Diabetes watcher

Let Them Debate, But You Decide: Low Carb or Low Calorie?

2006-06-20T14:11:00.000-07:00

There is a continuous debate over whether people with type 2 diabetes benefit from low carb diets. Naturally, the friends of the drug makers say no, but the low carb diet makers say yes. If you have diabetes or are predisposed to developing this disease then you had better decide now.

But how?

This is easy. There are two things (yeah, and even a third!) you need to bear in mind.

Diabetes is not caused by carbohydrates, so don't blame it on the carbs. Diabetes is the inability to metabolize carbs (glucose) properly.
Fat intake, on the other hand, is a big part of the complex lifestyle conditions that cause type 2 diabetes.
The drug industry does not want to die and the diet designers surely want to live - they strive for economic survival, and our financial patronage is their source of life.
Now, did you hear the ADA saying they don't really disclaim the benefits of low carb diets? Yes, everyone admits that fewer carbs per meal will nean less carbohydrate to spike your blood glucose level after a meal.

Low carb cannot be long-term

Who wants to spend the rest of their lives on a low carb diet? Who can, anyway? No one. It's a temporary solution. A kind of "quick fix."

Even though proponents of the low carb diet say "many people are essentially cured of their type 2 diabetes by low carbohydrate diets," the ADA refuses to endorse the low carb option. They say that they prefer to endorse a diet that people can live with long-term.

The benefits of a high fiber high carbohydrate diet has been shown in research repeatedly. If the type of carbohydrate is right, you can eat a whole lot without suffering the adverse effects. Refined or processed foods tend to elevate blood sugar levels quickly compared to high fiber content carbs.

Problem. Problem. Problem with low carbs

There is usually some problem with low carb diets, especially for diabetics. We know that dietary and body fats are a major culprit in the development of adult onset (type 2) diabetes. This has been shown in experiments by Dr. Anderson at the University of Kentucky. Healthy young men developed diabetic symptoms within two weeks on a high fat diet, whereas a control group on high sugar diet did not show a single symptom after eleven weeks in the experiment.

Given the popularity of the Western diet today the whole world is now more at risk for developing diabetes. You've got to be strong to resist what floats on the air from a fast food kitchen nowadays, especially if you spent most of your life eating that stuff. It's tantalizing.

But diabetics who have this kind of strength have been able to come off their medication and insulin shots. It is nearly impossible to live the rest of your life on low carb food. Many of these diets have been shown to have too much fat and protein content, anyway.

Limiting your carbs means lessening your calorie intake. But your energy has got to come from somewhere. Given what we know about the effects of excess fat and excess protein metabolism, every diabetic (actually, everyone) would do better staying away from these low carb, high fat, high protein options.

It seems clear that the safest option in the long term is the most natural: a complex high carbohydrate, high fiber diet with regular (daily) exercise. It takes a lot of work, but it works.

And it works for a long, healthy, long time. Ask the Okinawans and other groups who don't know what the word "retirement" means. I'll watch the low carb debate, but I want to be around until the truth is clear - I will choose high fiber high carbohydrate foods and build muscle while the argument grows.

Copyright © 2006 by Bentley Thompson

Bentley writes about lifestyle-related conditions such as diabetes, obesity, high cholesterol, and cardiovascular diseases. He advocates the anti-diabetes diet which he describes on his website. You may visit his website and blog using the following URLs: http://www.anti-diabetes-diet-supplements.com/ and http://choosehealthtoday.blogspot.com

The Emotional Impact of Diabetes

2006-06-20T14:08:00.001-07:00

Unless someone is diabetic, or very close to someone who is, they do not realize how life changing this disease can be. I believe one of the reasons this is, is because so many people are diagnosed with diabetes; that somewhere down the line, the seriousness of the disease, in people’s minds, have diminished.

Diabetes is a very serious and scary chronic illness. It is totally life changing for those diagnosed. Eating becomes literally a matter of life and death. And the way a person is use to eating is usually changed drastically.

The emotional stress one goes through seems to get ignored and lost in the endless information and directions of how to now live your life. This is not just merely staying alive – it’s trying to stay alive without ending up blind, on kidney dialysis, with severe nerve damage, or amputation, just to name a few.

My life was drastically affected by diabetes twelve years ago when my son, who is now 23, was just eleven years old, and diagnosed with juvenile diabetes.

He has always been hyperactive, so even when he was sick, he was active. I started to notice he was looking a little pale and losing weight, even though he ate constantly. I made him a doctor appointment for the next opening, which wasn’t until a month away. All of a sudden he started wetting the bed. The urine had a very strong odor. He also started complaining of headaches. At first I thought the complaints, was just an excuse for the eleven-year-old to stay out of school. But when they became so severe, I knew they were real. The second day his headaches were so severe, he stayed home from school. He presented no other symptoms, but he slept all day long. This was enough to definitely make me realize something was extremely wrong. I got out my diagnosis health encyclopedia books and after a few hours, I came down to two diagnosis, kidney trouble or diabetes, (this was before I became a nurse, so I was going only by his symptoms and the words on the page). It was about 6:30 at night, when I told my husband something was terribly wrong and I was taking our son to the emergency room.

When we arrived at the emergency room, my son had a hard time keeping his eyes opened. We were finally called to the back, where they started running several tests. Sure enough he was diagnosed with Type 1 Juvenile Diabetes. His blood sugar was well over 600. Normal blood sugar levels range from 90-110. The reason he was sleeping so much was because he was trying to slip into a diabetic coma. The doctor said that if I didn’t bring him in when I did, he would have went into a coma that night. They admitted him to ICU and kept a vigil on him for three days as insulin was delivered through IV. That was the day our lives changed forever; especially my eleven-year-old son’s.

It was over-whelming. Three main meals a day and three snacks a day; mandatory, with a minimum of two shots daily for the rest of his life. To say we were under stress, would be putting it mildly. My son put on a brave face, but about the fourth day after he was diagnosed, I had a heart to heart with him. The poor baby thought he had brought the diabetes on himself and was being punished for something he said. Meanwhile, my nine-year-old at home was going through her own personal hell. After speaking to her, I found out she was scared to death that he was going to die, and that she was next. This came from two children whose parents did talk to them and tried to explain everything to the best of their ability.

Our lives became rigid, at first -- as we tried to cope with the changes. My son, Eddie, could not just run off and play at his friend's house whenever he wanted, or was allowed. He had to make sure he was home to take his shots on time, to eat the regular meals and the snacks in-between. He was a hard player, he had to learn that if he didn't eat like he was supposed to, wheather he was hungry or not, he would end up getting shaky. If he did not get something in him quickly to raise his blood sugar, he may slip so low that an ambulance would have to be called to save his life, if I wasn't there with an emergency glucagon (intra-muscular sugar water) shot -- as he would get extremely lethargic and not be able to communicate, or to understand what was going on around him.

All these changes he was going through, made him feel like he was different than the other children. He was afraid to spend a night for quite some time after being diagnosed; because if his sugar went up too high at night, it could cause him to wet the bed. Something that an eleven-year-old would be horrified to do in front of his friends. We also had to make sure if he did go spend the night with a friend, that they had plenty of food. (Though, his back pack would be packed with extra food for snacks, it couldn't contain the main meals.) We also had to let the parents know he was diabetic, where they could keep an extra eye out. This would sometimes turn into a nightmare, as Eddie did not want to go around announcing he was diabetic. He also didn't like being treated differently if a mother was handing out sugared drinks or sugared snacks to the other kids.

As a mother, seeing him go through all of this, tore my heart out. When I did let him leave, I had to worry not only what every mother worries about when her children go off by themselves, but I had to worry if his sugar dropped too low, would he be able to make it home {b}in time{/b} to get something to eat? Even though he carried emergency glucose pills for low sugar, it does not work all the time. (Depending on how low his sugar is and if he is able to chew, and has enough sense to take them.) When your sugar drops extremely low, you are not aware of what you're doing. Many people have been suspected of being high on drugs, when it is their sugar causing the strange behaviour. It's a very scary thing to see, even more so do go through. I also had to worry if he would go off and drink sugar drinks and go to the store and get candy. This was not a simple concern, this could actually kill or disable him. When your sugar gets too high, you are damaging your organs -- and if you start spilling ketones, it becomes a very dangerous situation. It causes ketoacidosis which causes nausea, sometimes severe with projectile vomiting, stomach pains, confusion and drowsiness; because their body is over-worked and worn out. It's literally starving to death. They are also in danger of slipping into a diabetic coma. High sugar often does develop into Diabetic ketoacidosis -- (DKA) which is a life-threatening blood chemical (electrolyte) imbalance that develops in a person with diabetes when the cells do not get the sugar (glucose) they need for energy. As a result, the body breaks down fat instead of glucose and produces and releases substances called ketones into the bloodstream. Severe diabetic ketoacidosis can cause difficulty breathing, brain swelling (cerebral edema), coma, or death. This is also the time when diabetes is doing the most harm to all the organs -- which can lead to heart failure, kidney failure, blindness, neuropathy -- and the list goes on.

Eddie, who is now 23, has kept his sugar under good control, (not tight, sadly -- but good) where he has not had to be hospitalized too often. He mainly has to go into the hospital when he gets a bad illness, such as the flu or stomach virus. When a diabetic's body is stressed with illnesses, it causes the blood sugar to go erratic. High blood sugars read off the chart, even when they have not been able to eat -- then their blood sugar may suddenly drop to a dangerous low. It also makes it more difficult to control because they are not able to eat, or maybe even drink. For diabetics, this is not an option. They are hospitalized where they can receive I.V fluids, and keep a close check on their blood sugar readings. Which sometimes means being pricked in the fingers up to 8 times a day, for several days in a row.

Diabetes causes such a wide array of secondary illnesses. Including stunting growth in a growing child. Eddie lost a whole year of growing. When he was 13, he had the bones of an 11 1/2 yr. old. He was put on intra-muscular testoterone shots at home. Which he took a lot better than most adults would, every night for six months.

It hurts me now, as it has since the day he was diagnosed, to know that he may soon be experiencing some very bad health problems because of the diabetes. Problems start to arise mostly after being diabetic for five years. We are living on borrowed time with decent health -- as he now has had diabetes for twelve years. When he says his chest hurts him, I don't think, "Oh no, he may be getting bronchitis." I think, "Oh Lord, please let it be something as simple as bronchitis." When he tells me his feet hurt and his whole body aches -- I know it may be a sign of neuropathy. At 23 he experiences pains and aches no young adult should have to face. But I praise God for each day that goes by where he is still able to work and live life as close to a young adult as he possibly can. God has spared us from him having any serious conditions. I know that may change any day, but I can relish in each day it does not.

Then there are the emotional changes diabetes puts them through. The anger, restlessness, nervousness, inpatience -- imagine it, and it is effected. It plays roulette with their hormones, causing their emotions and temperment to go into extreme modes. Sadly, this seems to be most of the time. All this happens in all diabetics, but I am concentrating on Type 1, Juvenile Diabetes. Type 1, Juvenile on-set, varies from Type 2, adult on-set, because with type 1, your pancreas does not produce any insulin at all. With Type 2, it produces insulin, but not sufficient enough, or at a normal rate.

These emotional issues are just as important to deal with as the physical disease itself. The emotional needs must be addressed. Not only the needs of the person diagnosed, but the whole family, and if it’s a child, this includes the parents and siblings.

If you are living with diabetes, please make sure you get the emotional help you so need and deserve. It’s absolutely a necessity. You may have to live with diabetes, but make sure you have it under control, and that it does not control you. After all, it’s a matter of life and death – both physical and emotional.

Tracey Wilson is an author on http://www.Writing.Com/ which is a site for Creative Writers. Many of her writings can be found at http://www.writing.com/authors/intuey.

Diabetes and Menopause

2006-06-20T14:08:00.000-07:00

You might be thinking what is the connection between diabetes and the menopause? Well, for ladies reaching that certain age, it can be very traumic. Menopause is not necessarily a negative experience. It is sometimes called a "change of life" as there are a lot of changes going on in a woman's body, both as menopause approaches and afterwards.

The menopause marks an important transition into the last third of a woman's life. It gives the woman and her health professionals an opportunity to review health risks, plan preventive activities, and establish monitoring strategies. This is especially important in women with diabetes because of the compounding menopausal cardiovascular risk and those associated with diabetes. The importance of the menopause is often not appreciated by women with diabetes, nor by their health professionals, and opportunities to avoid future problems may be missed.

Menopause is a natural process that women go through as the child-bearing years come to an end and the ovaries cease to release eggs every month. Menopause is usually defined as the point when periods stop. Menopause is not an event, but a slow process, often lasting up to 10 years. It starts during the age of 40s (sometime late 30s) and the average age for most women to have their last period is 51, where the female sex hormones hormones, estrogen and progesterone, begin to decline.

How menopause affects diabetes
As you approach menopause, ovaries gradually stop producing the hormone estrogen and progesterone. Both of these hormones affect insulin which is the hormone produced by the pancreas that deliver glucose which is life sustaing to every cell in the body.

Decrease levels of estrogen and progesterone can:

Increase the blood sugar. This will be mostly during perimenopause where the body may become more resistant to insulin and this causes blood sugar level to rise.

Decrease the blood sugar. This will be during the time when you reach menopause. Where the levels of estrogen and progesterone decline permanently. Where the body may regain its sensitivity to insulin, which causes blood sugar levels to fall.

The hormone fluctuations that characterize menopause may wreak havoc on the hard-earned blood glucose control. With less progesterone, there may be greater insulin sensitivity and with less estrogen insulin resistance increases, and the lack of these hormones can also cause other changes which can worsen diabetes complications. For example, lowered estrogen levels increase the risks of cardiovascular disease, which is already higher for people who have diabetes, and osteoporosis.

Many symptoms are attributed to menopause, and the most common are hot flashes, disturbed sleep, night sweats and the decreased ability to think clearly. Both menopause and diabetes produce similar symptoms. Some mistake menopausal symptoms such as hot flashes, moodiness etc as the symptoms of low blood sugar, so that they incorrectly assume these symptoms are a result of low blood sugar and start consuming unnecessary calories which in turn raises the blood sugar and in advertently cause a surge in blood sugar

Because of diabetes women experience stronger and more frequent episodes of low blood sugar especially at night. This may affect their sleep, already interrupted by menopause – associated with hot flashes and night sweats. Such sleep deprivation causes fluctuations in blood sugar.

In order to combat this women choose to take hormone replacement therapy or HRT.These hormones (estrogen and progesterone) replace the hormones that the body no longer make. But this will not be possible in the case of women if she is a diabetic as these hormones affect the blood sugar. But these doses with HRT are so low and they do not cause much effect. In that case the diabetic medicine needs to be adjusted also .If the woman is exposed to these hormones it has benefits like

Protect the heart

Protect the bones from the loss of calcium which can lead to brittle bones.

Eliminate the symptoms such as hot flashes (which are easy to confuse with hypoglycemia) helps to sleep and think more easily.

Complications of Menopause

Majority of women will experience this complication but the intensity may vary within each women

Irregular bleeding

Hot flushes

Vaginal thinning and dryness

Osteoporosis

Heart diseases

Menopause is complete when you have not menstruated for 12 months. Women with type 1 diabetes experience menopause earlier than average. Women with type 2 diabetes may go through menopause later than average if they are above a healthy weight, as estrogen levels do not decrease as rapidly in women who are overweight.

This is one of the major problems in many women as they gain weight and become less active during this time, which compounds blood glucose control difficulties. So it is vitally important to plan a nutritious, low fat diet with calcium supplements if needed and physical activity. As these measures will lower the risk of cardiovascular disease by keeping the cholesterol level low and protect the bones against the thinning of osteoporosis. Regular exercise benefits the heart and bones, help to regulate weight, contributes to a sense of overall well-being and improvement in mood. Sedentary women are far more prone to coronary heart disease, obesity, high blood pressure, diabetes, and osteoporosis. They also suffer from chronic back pain, stiffness, insomnia, and irregularity. Depression is also a problem. Therefore exercise plays an important and beneficial role as it circumvent these problems and also achieve higher HDL cholesterol levels.

The Benefits of regular exercise

• Increases circulation, and improves the regulation of body temperature.

• Improves weight control by increasing basal metabolic rate and lean body mass.

• Reduces the risk of cardiovascular disease by strengthening the circulatory system, lowering blood pressure and maintaining a healthier blood cholesterol level.

• Increases strength and range of movement.

• Elevates your mood and controls stress.

• Reduces the likelihood of osteoporosis.

Some suggestions that may reduce the discomforts of menopause:

1.Eat well balanced meals that forms the basis for managing the diabetes

2.Cutting out caffeine which may help to reduce hot flashes.

3.Consuming more legumes and soy products which decreases the discomforts associated with menopause as these foods contain phytoestrogen (plant estrogen.

4.Last but not the least being physically active may help to increase energy levels and give you a mental lift.

Therefore menopause is an important phase in women’s life where she undergoes a lot of physical changes. The body goes through changes that can affect her social life, her feelings about herself, and functioning at work. Till recently menopause was often surrounded by misconceptions and myths, but it is a natural; step in the process of aging. So one should accept menopause and age gracefully – for "As a white candle in a holy place so is fine beauty of an aged face."

Benefits of Drinking Alcohol for Diabetes Type II

2006-06-20T14:06:00.000-07:00

Diabetes Mellitus comes in two forms, Type I and Type II. Unlike Diabetes Type I, Type II Diabetes Mellitus occurs later in life. The majority of Type II Diabetics are women. Documented in medical journals, drinking alcohol can lower the risks of complications for women who have Type II Diabetes Mellitus. A light to moderate amount of alcohol and life style enhancement has the greatest positive effect and will benefit a woman's future health.

The importance of alcohol and its dangers

The mechanism of alcohol's effects, in moderate amounts of about 2 drinks a day, can decrease the insulin resistance in women with Type II diabetes. In a normal situation, the insulin acts on the peripheral cells where the glucose or sugar is waiting to enter. The insulin binds to the cell and the glucose enters. Unfortunately, in this type of diabetes, the insulin does not bind to the cell where the insulin resistance takes place and the glucose can't go inside. This results in hyperglycemia which is most toxic to the body.

Beer and wine were shown to have greater benefit than hard liquor. On the other hand, too little or too much alcohol has been implicated as risk factors for this type of diabetes. It is dangerous to consume too much alcohol as this can lead to adverse effects such as hypoglycemia, inhibition of insulin secretion, pancreatitis, increased incidence of breast cancer, ketoacidosis, cirrhosis of the liver, and most notably, addiction.

Women who have experienced menopause are at even higher risk for Type II Diabetes. They are also at risk for cardiovascular disease. Alcohol's benefits are that it can increase the level of good cholesterol such as HDL, decrease platelet aggregation, and reduce incidence of myocardial infarction.

The French Paradox

In southwestern France they have high saturated fat diet. The French workers in this study have a 36 percent lower incidence of coronary artery disease when compared to similar U.S. workers. They have a high intake of red wine with antioxidants and they have shown lower platelet aggregation and lower atherosclerosis. As stated previously, this suggests that not only is alcohol good for Diabetes but good for the heart as well.

Lifestyle Changes

Drinking alcohol is not the only way to decrease the chances of acquiring Type II Diabetes. There are many other factors that influence the development of this disease. According to the New England Journal of Medicine researchers led by Dr. Hu, overweight and obesity is the single most important predictor of diabetes. They also say that "lack of exercise, a poor diet, current smoking, and abstinence from alcohol use were all associated with a significantly increased risk of diabetes." Obese women, who choose to exercise regularly and follow a healthy diet while abstaining from smoking, can decrease their chances of acquiring diabetes by 24 percent. It is 50 percent for overweight women.

Symptoms of Diabetes Type II

If you are concerned that you are at risk for Type II Diabetes, the following symptoms are clues that a follow up by your physician is necessary: Frequent urination, increased thirst, increased hunger, slow-healing wounds and sores, prolonged and unexplained fatigue, numbness or tingling of extremities, and gynecological fungal infections in women.

Conclusion

Type II Diabetes Mellitus is a serious illness that necessitates immediate care. There are many behavioral modifications that a woman can take to relieve some of the symptoms and overall illness of diabetes. Alcohol in moderate amounts is a first step and is important to decreasing insulin resistance and even helping the heart and cardiovascular system. Diet, exercise, and cessation of smoking are likewise important. Lifestyle changes are the first step. To begin, see your physician and start a plan of action to help yourself from a potentially debilitating disease and live a healthy and satisfying life.

Copyright 2006 Michael V. Gruber, MPH

Michael V. Gruber, MPH is a contributing author to My Nursing Degree Online, providing articles and resources for nurses looking for continuing education online. Find more information about earning your nursing degree online at: http://nursing.earnmydegree.com

Pre-Diabetes - Are You at Risk?

2006-06-20T07:14:00.000-07:00

The latest research reports that more than 40 million Americans have "pre-diabetes". Pre-diabetes (or Impaired Glucose Tolerance) is a combination of factors that you may have right now that puts you at a heightened risk for real, irreversible Type 2 diabetes in ten years. It is usually a combination of inactivity, a fat-laden diet, obesity and genetics that is responsible. When one has pre-diabetes, the level of glucose in the blood is over the normal limit but still has not reached diabetic limits yet.

Pre-diabetes is not diabetes per se and if you are diagnosed with it, it is not a death sentence. With exercise, weight loss and a healthy diet, pre-diabetic people can and have managed to bring down their glucose levels and have escaped the threat of an insulin-dependent life.

You won't necessarily know if you have pre-diabetes because it is asymptomatic. There are no big telltale signs that point toward it but it is of crucial importance to be tested for condition as soon as possible so you can curb it right away. If nothing is done during the pre-diabetic stage, it is very likely that the blood sugar levels will go awry and needlessly boost a person's risk of heart disease and eye damage, as well as a host of other difficult and expensive consequences.

Should you be screened for pre-diabetes? If you answer yes to any of the following questions, you should talk to your doctor about getting screened: Do you have relatives that have heart disease or Type 2 diabetes? Are you overweight? Do you have high blood pressure? Are you part of a "high-risk" group (African American, Latino and Asian)? Do you have more stored fat around your belly than your hips? If you're male, you should be checked if your waistline is more than 40 inches and if you're female, if your waistline is more than 35 inches. If you've had children, did you have diabetes when you were pregnant or deliver a baby that weighed more than nine pounds?

If you think you are pre-diabetic, your doctor will recommend that you go for a fasting plasma glucose test (FPG). To prepare for the FPG, you will be asked to fast for 10 hours before a blood sample is drawn first thing in the morning before breakfast. The normal level is below 100 mg/dl. If your have an FPG level between 100 and 125 mg/dl, you are considered pre-diabetic. But if your blood glucose level is 126 mg/dl or more, you can be considered a diabetic already.

To back up the FPG result, your doctor may ask you to take an oral glucose tolerance test (OGTT) that is similar to the FPG. This time however, you will be asked to drink a glucose-rich beverage and your blood glucose level measured 2 hours after. If normal, your blood glucose would be below 140 mg/dl two hours after the drink. If pre-diabetic, the blood glucose level is between 140 to 199 mg/dl. If your figure is above 200 mg/dl or more, you are considered diabetic. You should also have your cholesterol levels checked. High levels of triglycerides in the blood and low levels of "good" HDL cholesterol do not only put you at risk for diabetes, but also heart disease and certain cancers.

Knowing you are pre-diabetic is a blow for many people, but there is no reason to give up hope yet. More studies show that pre-diabetics who are aware of their condition can do a number of things that can prevent or delay the development of diabetes. The first thing to take care of is really an intense modification in lifestyle. Starting a modest exercise routine like walking for half an hour every day can trigger weight loss. Both exercise and weight loss are proven methods that slow the development of diabetes by returning blood glucose levels to normal in some people. You need not even reach your ideal body weight to reap benefits - a 15% reduction in weight can cut your risk of having full-fledged diabetes by almost 60 percent! This little change is twice as effective as taking medication. Start educating yourself about your condition. See your doctor regularly and meet with a registered dietician and an exercise specialist. Ask your doctor about some supplements like aspirin and niacin that you may benefit from.

Insulin resistance

2005-10-14T04:20:00.000-07:00

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Insulin resistance

In medicine, insulin resistance denotes a decompensation of glucose homeostasis where the tissues appear to be less responsive to insulin.

Contents
1 Pathophysiology
2 Investigation
2.1 Glucose tolerance testing (GTT)
2.2 Hyperinsulinemic euglycemic clamp
2.3 Alternatives
3 Causes of insulin resistance
4 Therapy
5 History
6 Sources
7 External links

Pathophysiology
In patients who use insulin, "insulin resistance" is production of antibodies against insulin that lead to lower-than-expected falls of glucose levels (glycemia) after a given dose of insulin.

Insulin resistance denotes decreased sensitivity of target cells (muscle, fat cells) to insulin. It is the metabolic cause of the very common "metabolic syndrome", which is the clustering of diabetes mellitus (type 2), hypertension, combined hyperlipidemia and central obesity in patients. It also underlies most processes behind the metabolic complications of polycystic ovarian syndrome (PCOS).

In a normal person, a small amount of insulin is produced after eating ("postprandial"), and it signals the body to absorb the sugars from the food at a steady rate. In an "insulin resistant" person the message does not get to the cells so the sugar remains in the blood for long periods of time while ever more insulin is released in an attempt to trigger the sugar-uptake. The sugar circulates in the blood for several hours and then is taken into the cells very rapidly, leading to a steep drop in blood sugar and a hypoglycaemic reaction several hours after the meal.

At a later stage, frank hyperglycemia develops as pancreatic β-cells are unable to produce adequate insulin to maintain normal blood sugar levels ("euglycemia").

Various disease states make the body tissues more resistant to the actions of insulin. Example include infection (TNFα) and acidosis. Recent research involves the relative roles of adipokines (the cytokines produced by adipose tissue) in modifying insulin resistance.

Insulin resistance and atherosclerosis often appear together. Insulin resistance in these patients can be detected not only by sophisticated tests but by some simple observations of hypertension, hyperglycaemia and dyslipidemia involving small dense low-density lipoprotein (sdLDL) particles.

These patients also have slightly decreased high-density lipoprotein (HDL) levels, impaired fibrinolysis, a hypercoagulable state and increased inflammatory cytokine levels.

Investigation

Glucose tolerance testing (GTT)
During a glucose tolerance test (GTT), which is generally used to diagnose diabetes mellitus type 2, the patient (who has been fasting) takes a fixed oral dose of glucose, and glucose levels are measured by fingerprick testing every 30 minutes of the following hours.

Interpretation depends on local guidelines, but glycemia exceeding 10 mmol/l is often considered diagnostic for diabetes.

OGTT can be normal or mildly abnormal in simple insulin resistance. Often, there are raised glucose levels in the early measurements, reflecting the loss of a postprandial (after the meal) peak in insulin production. Extension of the testing (for several more hours) will often reveal a hypoglycemic "dip", which is a result of an overshoot in insulin production after the failure of the physiologic postprandial insulin response.

Hyperinsulinemic euglycemic clamp
The gold standard for investigating and quantifying insulin resistance is the "hyperinsulinemic euglycemic clamp", so called because it measures the amount of glucose necessary to compensate for an increased insulin level without causing hypoglycemia. This was first reported by DeFronzo et al in 1979. The test is rarely performed in clinical care, but is sometimes used in medical research - for example, to assess the effects of different medications.

The procedure takes about 2 hours. Through a peripheral vein, insulin is infused at 0.06 units per kg body weight per minute. In order to compensate for the insulin infusion, glucose 20% is infused to maintain blood sugar levels between 5 and 5.5 mmol/l. The rate of glucose infusion is determined by checking the blood sugar levels every 5 minutes.

The rate of glucose infusion during the last 30 minutes of the test determines insulin sensitivity. If high levels (7.5 mg/min or higher) are required, the patient is insulin-sensitive. Very low levels (4.0 mg/min or lower) suggest that the body is resistant to insulin action. Levels between 4.1 and 7.4 mg/min are indetermined and might point at "impaired glucose tolerance", considered an early form of insulin resistance.

Alternatives
Given the complicated nature of the "clamp" technique (and the potential dangers of hypoglycemia in some patients), alternatives have been sought to simplify the measurement of insulin resistance. The first was the Homeostatic Model Agreement (HOMA), and a more recent method is the QUICKI (quantitative insulin check index). Both employ fasting insulin and glucose levels to calculate insulin resistance, and both correllate reasonably with the results of clamping studies.

Causes of insulin resistance
Obesity
Haemochromatosis
Polycystic ovarian syndrome (PCOS)
Hypercortisolism (e.g. steroid use or Cushing's disease)
Drugs (e.g. rifampicin, isoniazid, olanzapine, risperidone, progestogens, possibly alcohol)
Genes

Therapy
Both metformin and the thiazolidinediones improve insulin resistance. Exercise, weight loss, and a low glycemic index diet may help.

The Diabetes Prevention Program showed that exercise and diet were nearly twice as effective as metformin at reducing the risk of progressing to type 2 diabetes (Knowler et al 2002).

History
The concept that insulin resistance may be the underlying cause of diabetes mellitus type 2 was first advanced by Sir Harold Percival Himsworth in 1936.

Sources
DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance.d Am J Physiol; 1979;237:E214-23. PMID 382871.
Himsworth HP. Diabetes mellitus: its differentiation into insulin-sensitive and insulin-insensitive types. Lancet 1936;i:127-130.
Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 2002;346:393-403. PMID 11832527.
Dr. Andrew P. Selwyn. What data is available that shows insulin resistance as a risk factor of CVD? How compelling is it? CME on Diabetes
From Wikipedia, the free encyclopedia.
>>http://en.wikipedia.org/wiki/Insulin_resistance

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Insulin

2005-10-14T04:18:00.000-07:00

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Insulin

The structure of insulin
Red: carbon; green: oxygen; blue: nitrogen; pink: sulfur. The blue/purple ribbons denote the skeleton [-N-C-C-]n in the protein's amino acid sequence H-[-NH-CHR-CO-]n-OH where R is the part protruding from the skeleton in each amino acid.Insulin (Latin insula, "island", as it is produced in the Islets of Langerhans in the pancreas) is a polypeptide hormone that regulates carbohydrate metabolism. Apart from being the primary effector in carbohydrate homeostasis, it also has a substantial effect on small vessel muscle tone, controls storage and release of fat (triglycerides) and cellular uptake of both amino acids and some electrolytes. In this last sense, it has anabolic properties. Its concentration (more or less, prsence or absence) has extremely widespread effects throughout the body.

Insulin is used medically in some forms of diabetes mellitus. Patients with Type 1 diabetes mellitus depend on exogenous insulin (injected subcutaneously) for their survival because of an absolute deficiency of the hormone; patients with Type 2 diabetes mellitus have either relatively low insulin production or insulin resistance or both, and a non-trivial fraction of Type 2 diabetics eventually require insulin administration when other medications become inadequate in controlling blood glucose levels.

Insulin has the empirical formula C254H377N65O75S6.

Insulin structure varies slightly between species. Its carbohydrate metabolism regulatory function strength in humans also varies. Pig insulin is particularly close to the human one.

Contents
1 Discovery and characterization
2 Structure and production
3 Actions on cellular and metabolic level
4 Regulatory action on blood glucose
5 Signal transduction
6 The brain and hypoglycemia
7 Diseases and syndromes caused by an insulin disturbance
8 Insulin as a medication
8.1 Principles
8.2 Modes of administration
8.3 Dosage and timing
8.4 Types
8.5 Abuse
9 See also
10 External links

Discovery and characterization
In 1869 Paul Langerhans, a medical student in Berlin, was studying the structure of the pancreas under a new microscope when he noticed some previously unidentified cells scattered in the exocrine tissue. The function of the "little heaps of cells", later known as the Islets of Langerhans, was unknown, but Edouard Laguesse later argued that they may produce a secretion that plays a regulatory role in digestion.

Insulin crystalsIn 1889, the Polish-German physician Oscar Minkowski in collaboration with Joseph von Mehring removed the pancreas from a healthy dog to demonstrate this assumed role in digestion. Several days after the dog's pancreas was removed, Minkowski's animal keeper noticed a swarm of flies feeding on the dog's urine. On testing the urine they found that there was sugar in the dog's urine, demonstrating for the first time the relationship between the pancreas and diabetes. In 1901 another major step was taken by Eugene Opie, when he clearly established the link between the Islets of Langerhans and diabetes: Diabetes mellitus.... is caused by destruction of the islets of Langerhans and occurs only when these bodies are in part or wholly destroyed. Before this demonstration the link between the pancreas and diabetes was clear, but not the specific role of the islets.

Over the next two decades several attempts were made to isolate the secretion of the islets as a potential treatment. In 1906 Georg Ludwig Zuelzer was partially successful treating dogs with pancreatic extract, but unable to continue his work. Between 1911 and 1912 E.L. Scott at the University of Chicago used aqueous pancreatic extracts and noted a slight diminution of glycosuria, but was unable to convince his director and the research was shut down. Israel Kleiner demonstrated similar effects at Rockefeller University in 1919, but his work was interrupted by World War I and he was unable to return to it. Nicolae Paulescu, a professor of physiology at the Romanian School of Medicine published similar work in 1921 that was carried out in France, and it has been argued ever since by Romanians that he is the rightful discoverer.

However the practical extraction of insulin is credited to a team at the University of Toronto. In October 1920 Frederick Banting was reading one of Minkowski's papers and concluded that it was the very digestive secretions that Minkowski had originally studied were breaking down the secretion, thereby making it impossible to extract successfully. He jotted a note to himself Ligate pancreatic ducts of the dog. Keep dogs alive till acini degenerate leaving islets. Try to isolate internal secretion of these and relieve glycosurea.

He travelled to Toronto to meet with J.J.R. Macleod, who was not entirely impressed with his idea. Nevertheless he supplied Banting with a lab at the University, and an assistant, medical student Charles Best, and ten dogs, while he left on vacation during the summer of 1921. Their method was tying a ligature (string) around the pancreatic duct, and when examined several weeks later the pancreatic digestive cells had died and been absorbed by the immune system, leaving thousands of islets. They then isolated the protein from these islets to produce what they called isletin. Banting and Best were then able to keep a pancreatectomized dog alive all summer.

Macleod saw the value of the research on his return from Europe, but demanded a re-run to prove the method actually worked. Several weeks later it was clear the second run was also a success, and he helped publish their results privately in Toronto that November. However they needed six weeks to extract the isletin, dramatically slowing testing. Banting suggested they try to use fetal calf pancreas, which had not yet developed digestive glands, and was relieved to find this method worked well. With the supply problem solved, the next major effort was to purify the protein. In December 1921 Macleod invited the brilliant biochemist, James Collip, to help with this task, and within a month he felt ready to test.

On January 11, 1922, Leonard Thompson, a fourteen year old diabetic, was given the first injection of insulin. Unfortunately the extract was so impure that he suffered a severe allergic reaction and further injections were cancelled. Over the next 12 days Collip worked day and night to improve the extract, and a second dose injected on the 23rd. This was completely successful, not only in not having obvious side-effects, but in completely eliminating the symptoms of diabetes. However, Banting and Best never worked well with Collip, apparently seeing him as something of an interloper, and Collip left soon after.

Over the spring of 1922 Best managed to improve his techniques to the point where large quantities of insulin could be extracted on demand, but the extract remained impure. However they had been approached by Eli Lilly with an offer of help shortly after their first publications in 1921, and they took Lilly up on the offer in April. In November Lilly made a major breakthrough, and were able to produce large quantities of very pure insulin. Insulin was offered for sale shortly thereafter.

For this landmark discovery, Macleod and Banting were awarded the Nobel Prize in Physiology or Medicine in 1923. Banting, apparently insulted that Best was not mentioned, shared his prize with Best, and MacLeod immediately shared his with Collip. The patent for insulin was sold to the University of Toronto for one dollar.

The exact sequence of amino acids comprising the insulin molecule, the so-called primary structure, was determined by British molecular biologist Frederick Sanger. It was the first protein the structure of which was completely determined. For this he was awarded the Nobel Prize in Chemistry in 1958. In 1967, after decades of work, Dorothy Crowfoot Hodgkin determined the spatial conformation of the molecule, by means of X-ray diffraction studies. She also was awarded a Nobel Prize.

1. Preproinsulin (Leader, B chain, C chain, A chain); proinsulin consists of BCA, without L
2. Spontaneous folding
3. A and B chains linked by sulphide bonds
4. Leader and C chain are cut off
5. Insulin molecule remains
Structure and production
Insulin is synthesized in humans and other mammals within the beta cells (B-cells) of the islets of Langerhans in the pancreas. One to three million islets of Langerhans (pancreatic islets) form the endocrine part of the pancreas, which is primarily an exocrine gland. The endocrine part accounts for only 2% of the total mass of the pancreas. Within the islets of Langerhans, beta cells constitute 60–80% of all the cells.

Insulin is synthesized from the proinsulin precursor molecule by the action of proteolytic enzymes known as prohormone convertases (PC1 and PC2). Active insulin has 51 amino acids and is one of the smallest proteins known. Beef insulin differs from human insulin in three amino acid residues, and pork insulin in one residue. Fish insulin is also close enough to human insulin to be effective in humans. In humans, insulin has a molecular weight of 5734. Insulin is structured as 2 polypeptide chains linked by 2 sulfur bridges (see figure shown above). Chain A consists of 21, and chain B of 30 amino acids. Insulin is produced as a prohormone molecule – proinsulin – that is later transformed by proteolytic action into the active hormone.

The remaining part of the proinsulin molecule is called C-peptide. This polypeptide is released into the blood in equal amounts to the insulin protein. Since exogenous insulins contain no C-peptide component, serum levels of C peptide are good indicators of endogenous insulin production. C-peptide has recently been discovered to have itself biological activity; the activity is apparently confined to an effect on the muscular layer of the arteries.

Actions on cellular and metabolic level
The actions of insulin on the global human metabolism level include:

control of cellular intake of certain substances, most prominently glucose in muscle and adipose tissue (about 2/3 of body cells)
increase of DNA replication and protein synthesis via control of amino acid uptake
modification of the activity of numerous enzymes (allosteric effect)
The actions of insulin on cells include:

increased glycogen synthesis – insulin forces storage of glucose in liver (and muscle) cells in the form of glycogen; lowered levels of insulin cause liver cells to convert glycogen to glucose and excrete it into the blood. This is the clinical action of insulin which is useful in reducing high blood glucose levels as in diabetes.
increased fatty acid synthesis – insulin forces fat cells to take in glucose which is converted to triglycerides; lack of insulin causes the reverse
increased esterification of fatty acids – forces adipose tissue to make fats (ie, triglycerides) from fatty acid esters; lack of insulin causes the reverse
decreased proteinolysis – forces reduction of protein degradation; lack of insulin increases protein degradation,
decreased lipolysis – forces reduction in conversion of fat cell lipid stores into blood fatty acids; lack of insulin causes the reverse
decreased gluconeogenesis – decreases production of glucose from various substrates in liver; lack of insulin causes glucose production from assorted substrates in the liver and elsewhere
increased amino acid uptake – forces cells to absorb circulating amino acids; lack of insulin inhibits absorption
increased potassium uptake – forces cells to absorb serum potassium; lack of insulin inhibits absorption
arterial muscle tone – forces arterial wall muscle to relax, increasing blood flow, especially in micro arteries; lack of insulin reduces flow by allowing these muscles to contract

Regulatory action on blood glucose
Despite long intervals between meals or the occasional consumption of meals with a substantial carbohydrate load (e.g., half a birthday cake or a bag of potato chips), human blood glucose levels normally remain within a narrow range. In most humans this varies from about 70 mg/dl to perhaps 110 mg/dl (3.9 to 6.1 mmol/litre) except shortly after eating when the blood glucose level rises temporarily. In a healthy adult male of 75 kg with a blood volume of 5 litre, a blood glucose level of 100 mg/dl or 5.5 mmol/l corresponds to about 5 g (1/5 ounce) of glucose in the blood and approximately 45 g (1 1/2 ounces) in the total body water (which obviously includes more than merely blood and will be usually about 60% of the total body weight in men). This homeostatic effect is the result of many factors, of which hormone regulation is the most important.

There are two groups of mutually antagonistic metabolic hormones affecting blood glucose levels:

catabolic hormones (such as glucagon, growth hormone, and catecholamines), which increase blood glucose
and one anabolic hormone (insulin), which decreases blood glucose
Mechanisms which restore satisfactory blood glucose levels after hypoglycemia must be quick and effective because of the immediate serious consequences of insufficient glucose. This is because, at least in the short term, it is far more dangerous to have too little glucose in the blood than too much. In healthy individuals these mechanisms are indeed generally efficient, and symptomatic hypoglycemia is generally only found in diabetics using insulin or other pharmacologic treatment. Such hypoglycemic episodes vary greatly between persons and from time to time, both in severity and swiftness of onset. In severe cases prompt medical assistance is essential, as damage (to brain and other tissues) and even death will result from sufficiently low blood glucose levels.

Mechanism of glucose dependent insulin releaseBeta cells in the islets of Langerhans are sensitive to variations in blood glucose levels through the following mechanism (see figure to the right):

Glucose enters the beta cells through the glucose transporter GLUT2
Glucose goes into the glycolysis and the respiratory cycle where the high-energy ATP molecule is produced by oxidation
Dependent on blood glucose levels and hence ATP levels, the ATP controlled potassium channels (K+) close and the cell membranes depolarise
On depolarisation, voltage controlled calcium channels (Ca2+) open and calcium flows into the cells
An increased calcium level causes activation of phospholipase C, which cleaves the membrane phospholipid phosphatidyl inositol 4,5-bisphosphate into inositol 1,4,5-triphosphate and diacylglycerol.
Inositol 4,5-biphosphate binds to receptor proteins in the membrane of endoplasmic reticulum. This further raises the cell concentration of calcium.
Significantly increased amount of calcium in the cells causes release of previously synthesised insulin, which has been stored in secretory vesicles
The calcium level also regulates expression of the insulin gene via the calcium responsive element binding protein (CREB).
This is the main mechanism for release of insulin and regulation of insulin synthesis. In addition some insulin synthesis and release takes place generally at food intake, not just glucose or carbohydrate intake, and the beta cells are also somewhat influenced by the autonomic nervous system.

Substances that stimulate insulin release are also acetylholin, released from vagus nerve endings (parasympathetic nervous system), cholecystokinin, released by enteroendocrine cells of intestinal mucosa and gastrointestinal inhibitory peptide (GIP). The first of these act similarly as glucose through phospholipase C, while the last one acts through the mechanism of adenylate cyclase.

Sympathetic nervous system (α2 adrenergic agonists) inhibits the release of insulin.

When the glucose level comes down to the usual physiologic value, insulin release from the beta cells slows or stops. If blood glucose levels drop lower than this, especially to dangerously low levels, release of hyperglycemic hormones (most prominently glucagon from Islet alpha cells) forces release of glucose into the blood from cellular stores. The release of insulin is strongly inhibited by the stress hormone adrenalin (epinephrine).

Signal transduction
There are special transport channels in cell membranes through which glucose from the blood can enter a cell. These channels are, indirectly, under insulin control in certain body cell types. A lack of circulating insulin will prevent glucose from entering those cells (eg, in untreated Type 1 diabetes). However, more commonly there is a decrease in the sensitivity of cells to insulin (eg, the reduced insulin sensitivity characteristic of Type 2 diabetes), resulting in decreased glucose absorption. In either case, there is 'cell starvation', weight loss, sometimes extreme. In a few cases, there is a defect in the release of insulin from the pancreas. Either way, the effect is the same: elevated blood glucose levels.

Activation of insulin receptors leads to internal cellular mechanisms which directly affect glucose uptake by regulating the number and operation of protein molecules in the cell membrane which transport glucose into the cell.

Two types of tissues are most strongly influenced by insulin as far as the stimulation of glucose uptake is concerned: muscle cells (myocytes) and fat cells (adipocytes). The former are important because of their central role in movement, breathing, circulation, etc, and the latter because they accumulate excess food energy against future needs. Together, they account for about 2/3 of all cells in a typical human body.

The brain and hypoglycemia
Though other cells can use other fuels for a while (most prominently fatty acids), neurons are dependent on glucose as a source of energy in the non-starving human. They do not require insulin to absorb glucose, unlike muscle and adipose tissue and they have very small internal stores of glycogen. Thus, a sufficiently low glucose level first and most dramatically manifests itself in impaired functioning of the central nervous system – dizzness, speech problems, even loss of consciousness, are common. This phenomenon is known as hypoglycemia or, in cases producing unconsciousness, hypoglycemic coma (formerly termed insulin shock from the most common causative agent). Because endogenous causes of insulin excess (such as an insulinoma) are extremely rare naturally, the overwhelming majority of hypoglycemia cases are caused by human action (e.g. iatrogenic, caused by medicine), and are usually accidental. There have been a few cases reported of murder, attempted murder or suicide using insulin overdoses, but most insulin shock appears to be due to mismangement of insulin (didn't eat as much as anticipated, or exercised more than expected), or a mistake (e.g. 200 units of insulin instead of 20).

Causes of hypoglycemia are:

oral hypoglycemic agents (eg, any of the sulfonylureas, or similar drugs, which increase insulin release from beta cells in response to a particular blood glucose level)
external insulin (usually injected subcutaneously)

Diseases and syndromes caused by an insulin disturbance
There are several conditions in which insulin disturbance is pathologic:

diabetes mellitus – general term referring to all states characterized by hyperglycemia
type 1 – autoimmune-mediated destruction of insulin producing beta cells in the pancreas resulting in absolute insulin deficiency
type 2 – multifactoral syndrome with combined influence of genetic susceptibility and influence of environmental factors, the best known being obesity, age, and physical inactivity, resulting in insulin resistance in cells requiring insulin for glucose absorption. This form of diabetes is strongly inherited.
other types of impaired glucose tolerance (see the diabetes article)
insulinoma or reactive hypoglycemia

Insulin as a medication

Principles
Insulin is absolutely required for all animal (including human) life. The mechanism is almost identical in nematode worms (ie, C. elegans), fish, and in mammals. In humans, insulin deprivation due to the removal or destruction of the pancreas leads to death in days or at most weeks. Insulin must be administered to patients in whom there is a lack of the hormone for this, or any other, reason. Clinically, this is called diabetes mellitus type 1.

Harvesting pancreases from human corpses is not practical on a large scale, so insulin from cows, pigs or fish pancreases is used instead. All have 'insulin activity' in humans as they are nearly identical to human insulin (2 amino acid difference for bovine insulin, 1 amino acid difference for porcine). Insulin is a protein which has been very strongly conserved across evolutionary time. Differences in suitability of beef, pork, or fish insulin preparations for particular patients have been primarily the result of preparation purity and of allergic reactions to assorted non-insulin substances remaining in those preparations. Purity has improved more or less steadily since the 1920s, but allergic reactions have continued.

Human insulin can now be manufactured, using genetic engineering molecular biology techniques, in sufficient quantity for widespread clinical use, much reducing impurity reaction problems. Eli Lilly marketed the first such synthetic insulin, Humulin, in 1982. Genentech developed the technique Lilly used. NovoNordisk has also developed a genetically engineered insulin independently. Most insulins used clinically is produced this way, for it avoids the allergic reaction problem.

Modes of administration
Unlike many medicines, insulin cannot be taken orally. It is treated in the gastrointestinal tract precisely as any other protein; that is, reduced to its amino acid components, whereupon all 'insulin activity' is lost. There are research efforts underway to develop methods of protecting insulin from the digestive tract so that it can be taken orally, but none has yet reached clinical use. Instead insulin is usually taken as subcutaneous injections by single-use syringes with needles, or by repeated-use insulin pens with needles.

There are several difficulties with the use of insulin as a clinical treatment for diabetes:

mode of administration
selecting the 'right' dose and timing
selecting an appropriate insulin preparation (typically on 'speed of onset and duration of action' grounds)
adjusting dosage and timing to fit food amounts and types
adjusting dosage and timing to fit exercise undertaken
adjusting dosage, type, and timing to fit other conditions as for instance the increased stress of illness
the dosage is non-physiologic in that a subcutaneous bolus dosage of only insulin is given instead of the pancreas releasing insulin and C-peptide gradually and directly into the portal vein
it is simply a nuisance for patients to inject themselves once or several times a day
it may be dangerous in the case of mistake (most especially 'too much' insulin)
There have been several attempts to improve upon this mode of administering insulin as many people find injection awkward and painful. One alternative is jet injection (also sometimes used for some vaccinations) which has different insulin delivery peaks and durations as compared to needle injection of the same amount and type of insulin. Some diabetics find control possible with jet injectors, but not with hypodermic injection. There are also 'insulin pumps' of various types which are 'electrical injectors' attached to a semi-permanently implanted needle (ie, a catheter). Some who cannot achieve adequate glucose control by conventional injection (or sometimes jet injection) are able to with the appropriate pump.

An insulin pump is a reasonable solution for some. However there are several major limitations - cost, the potential for hypoglycemic episodes, catheter problems, and, thus far, no approvable means of controlling insulin delivery in the field based on blood glucose levels. If too much insulin is delivered or the patient eats less than normal, there will be hypoglycemia. On the other hand, if too little insulin is delivered by the pump, there will be hyperglycemia. Both of these can lead to potentially life-threatening conditions. In addition, indwelling catheters pose the risk of infection and ulceration. However, that risk can be minimized by keeping catheter sites clean. Thus far, insulin pumps require considerable care and effort to use correctly. However, some diabetics are able to keep their glucose in reasonable control only on a pump.

Researchers have produced a watch-like device that tests for blood glucose levels through the skin and administers corrective doses of insulin through pores in the skin of the patient. Both electricity and ultrasound have been found to make the skin temporarily porous. The insulin administration aspect remains experimental at this writing. The blood glucose test aspect of such 'wrist appliances' is, at this writing, commercially available essentially as described.

Another 'improvement' would be to avoid periodic insulin administration entirely by installing a self-regulating insulin source. For instance, pancreatic, or beta cell, transplantation. Transplantation of an entire pancreas (as an individual organ) is technically difficult, and is not common. Generally, it is performed in conjunction with liver or kidney transplant surgery. However, transplantation of only pancreatic beta cells is a possibility. It has been highly experimental (for which read 'prone to failure') for many years, but some researchers in Alberta, Canada, have developed techniques which have produced a much higher success rate (about 90% in one group). Beta cell transplant may become practical, and common, in the near future. Several other non-transplant methods of automatic insulin delivery are being developed in the research labs as this is written. None is currently close to clinical approval.

Inhaled insulin is under active investigation as are several other, more exotic, techniques.

Dosage and timing
The central problem for those requiring external insulin is picking the right dose of insulin and the right timing.

Physiological regulation of blood glucose, as in the non-diabetic, would be best. Increased blood glucose levels after a meal is a stimulus for prompt release of insulin from the pancreas. The increased insulin level causes glucose absorption and storage, reducing glycogen to glucose conversion, reducing blood glucose levels, and so reducing insulin release. The result is that the blood glucose level rises somewhat after eating, and within an hour or so returns to the normal 'fasting' level. Even the best diabetic treatment with human insulin, however administered, falls short of normal glucose control in the non-diabetic.

Complicating matters is that the composition of the food eaten (see glycemic index) affects intestinal absorption rates. Glucose from some foods is absorbed more (or less) rapidly than the same amount of glucose in other foods. And, fats and proteins both cause delays in absorption of glucose from carbohydrate eaten at the same time. As well, exercise reduces the need for insulin even when all other factors remain the same.

It is in principle impossible to know for certain how much insulin (and which type) is needed to 'cover' a particular meal in order to achieve a reasonable blood glucose level within an hour or two after eating. Non-diabetics' beta cells routinely and automatically manage this by continual glucose level monitoring and adjustment of insulin release. All such decisions by a diabetic must be based on general experience and training (ie, at the direction of a physician or PA, or in some places a specialist diabetic educator) and, further, specifically based on the individual experience of the patient. It is not straightforward and should never be done by habit or routine, but with care can be done quite successfully in practice.

For example, some diabetics require more insulin after drinking skimmed milk than they do after taking an equivalent amount of fat, protein, carbohydrate, and fluid in some other form. Their particular reaction to skimmed milk is different than other diabetics', but the same amount of whole milk is likely to cause a still different reaction even in that same person. Whole milk contains considerable fat while skimmed milk has much less. It is a continual balancing act for all diabetics, especially for those taking insulin.

It is important to notice that diabetics need more insulin than the usual -not less- during physical stress like infections or surgeries.

Types
Medical preparations of insulin (from the major suppliers – Eli Lilly and Novo Nordisk -- or from any other) are never just 'insulin in water'. Clinical insulins are specially prepared mixtures of insulin plus other substances. These delay absorption of the insulin, adjust the pH of the solution to reduce reactions at the injection site, and so on. Some recent insulins are not even precisely insulin, but so called insulin analogs. The insulin molecule in an insulin analog is slightly modified so that they are

absorbed rapidly enough to mimic real beta cell insulin (Lilly's is 'lispro', Novo Nordisk's is 'aspart'), or
steadily absorbed after injection instead of having a 'peak' followed by a more or less rapid decline in insulin action (Novo Nordisk version is 'Insulin detemir' and Aventis' version is 'Insulin glargine')
all while retaining insulin action in the human body.
The management of choosing insulin type and dosage / timing should be done by an experienced medical professional working with the diabetic.

Allowing blood glucose levels to rise, though not to levels which cause acute hyperglycemic symptoms, is not a sensible choice. Several large, well designed, long term studies have conclusively shown that diabetic complications decrease markedly, linearly, and consistently as blood glucose levels approach 'normal' patterns over long periods. In short, if a diabetic closely controls blood glucose levels (ie, on average, both over days and weeks, and avoiding too high peaks after meals) the rate of diabetic complications goes down. If glucose levels are very closely controlled, that rate can even approach 'normal'. The chronic diabetic complications include cerebrovascular accidents (CVA or stroke), heart attack, blindness (from proliferative diabetic retinopathy), toehr vascular damage, nerve damage from diabetic neuropathy, or kidney failure from diabetic nephropathy. These studies have demonstrated beyond doubt that, if it is possible for a patient, so-called intensive insulinotherapy is superior to conventional insulinotherapy. However, close control of blood glucose levels (as in intensive insulinotherapy) does require care and considerable effort, for hypoglycemia is dangerous and can be fatal.

A good measure of long term diabetic control (over approximately 90 days in most people) is the serum level of glycosylated hemoglobin (HbA1c). A shorter term integrated measure (over two weeks or so) is the so-called 'fructosamine' level, which is a measure of similarly glyclosylated proteins (chiefly albumin) with a shorter half life in the blood. There is a commercial meter available which measures this level in the field.

Abuse
There are reports that some patients abuse insulin by injecting larger doses that lead to mild hypoglycemic states. This is extremely dangerous and is essentially equivalent to suffocation experimentation. Severe acute or prolonged hypoglycemia can result in brain damage or death.

On July 23, 2004, news reports claim that a former spouse of a prominent international track athlete said that, among other drugs, the ex-spouse had used insulin as a way of 'energizing' the body. The intended implication would seem to be that insulin has effects similar to those alleged for some steroids. This is not so; eighty years of insulin use has given no reason to believe it to be in any respect a performance enhancer for non diabetics. Improperly treated diabetics are, to be sure, more prone than others to exhaustion and tiredness, and in some of these cases, proper administration of insulin can relieve such symptoms. However, insulin is not, chemically or clinically, a steroid, and its use in non diabetics is dangerous and always an abuse outside of a well-equipped medical facility.

However, when properly administered, insulin can restore body metabolism to something sufficiently close to normal to allow ahtletes to return to their former performance levels. Examples include Bill Talbert, the best male tennis player in the world for an extended time, Gary Hall Jr. the Olympic champion swimmer, at least one young professional Tour golfer, etc. Performace in other fields can also be maintained. Examples include Jerry Garcia of the Grateful Dead, and David Crosby, of Crosby, Stills & Nash.

See also
anatomy and physiolology
glucagon
pancreas
islets of Langerhans
endocrinology
forms of diabetes mellitus
diabetes mellitus
diabetes mellitus type 1
diabetes mellitus type 2
treatment
Diabetic coma
intensive insulinotherapy
insulin pump
conventional insulinotherapy
From Wikipedia, the free encyclopedia.
>>http://en.wikipedia.org/wiki/Insulin

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Anti-diabetic drug

2005-10-14T04:14:00.000-07:00

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Anti-diabetic drug

An anti-diabetic drug or oral hypoglycemic agent is used to treat diabetes mellitus. They usually work by lowering the glucose levels in the blood. There are different types of anti-diabetic drugs, and their use depends on the nature of the diabetes, age and situation of the person, as well as other factors.

Insulin is the only non-oral antidiabetic drug. It is the mainstay of treatment in type I diabetes, in which insulin production is impaired. In type II diabetes, it is used when oral medication has become ineffective.

Contents
1 Sulfonylureas
2 Meglitinides
3 Biguanides
4 Thiazolidinediones
5 Alpha glucosidase inhibitors
6 Experimental agents
7 Insulin by mouth
8 Reference

Sulfonylureas
Sulfonylureas were the first widely used oral hypoglycemic medications. They are insulin secretagogues, triggering insulin release by direct action on the KATP channel of the pancreatic beta cells. Seven types of these pills have been marketed in North America. Four, known as "first-generation" drugs, have been in use for some time, but not all remain available. Three "second-generation" drugs, are now more commonly used. They are stronger than first-generation drugs and have fewer side effects.

Sulfonylureas bind strongly to plasma proteins. Sulfonylureas are only useful in type II diabetes, as they work by stimulating endogenous release of insulin. They work best with patients over 40 years old, who have had diabetes mellitus for under ten years. They can not be used with type I diabetes, or diabetes of pregnancy. They can be safely used with biguanides and glitazones. The toxicity of these drugs on the whole is relatively low.

First-generation agents
Tolbutamide (Orinase)
Acetohexamide (Dymelor)
Tolazamide (Tolinase)
Chlorpropamide (Diabinese)
Second-generation agents
Glipizide (Glucotrol)
Glyburide (Diabeta, Micronase, Glynase)
Glimepiride (Amaryl)

Meglitinides
Meglitinides are related to sulfonylureas. The amplification of insulin release is shorter and more intense, and they are take with meals to boost the insulin response to each meal.

Repaglinide (Prandin)
Nateglinide (Starlix)

Biguanides
Biguanides reduce hepatic glucose output. Although it must be used with caution in patients with impaired liver or kidney function, metformin has become the most commonly used agent for type 2 diabetes in children and teenagers.

Metformin (Glucophage)
Phenformin (DBI): used in 1960-1980s, withdrawn due to lactic acidosis risk.

Thiazolidinediones
Thiazolidinediones, also known as "glitazones," bind to PPARγ, a type of nuclear regulatory protein involved in transcription of numerous genes regulating glucose and fat metabolism. They act as "insulin sensitizers" without increasing insulin secretion.

Rosiglitazone (Avandia)
Pioglitazone (Actos)
Troglitazone (Rezulin): used in 1990s, withdrawn due to hepatitis and liver damage risk.

Alpha glucosidase inhibitors
Alpha glucosidase inhibitors are "diabetes pills" but not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity. These agents slow the digestion of starch in the small intestine, so that glucose from the starch of a meal enters the bloodstream more slowly, and can be matched more effectively by an impaired insulin response or sensitivity. These agents are effective by themselves only in the earliest stages of impaired glucose tolerance, but can be helpful in combination with other agents in type 2 diabetes.

Miglitol (Glyset)
Acarbose (Precose)

Experimental agents
Many other potential drugs are currently in investigation by pharmaceutical companies. Some of these are simply newer members of one of the above classes, but some work by novel mechanisms. For example, at least one compound that enhances the sensitivity of glucokinase to rising glucose is in the stage of animal research.

Insulin by mouth
The basic appeal of oral hypoglycemic agents is that most people would prefer a pill to an injection. Unlike all the oral drugs described in this article, insulin is a protein. Protein hormones, like meat proteins, are digested in the stomach and gut.

However, the potential market for an oral form of insulin is enormous and many laboratories have attempted to devise ways of moving enough intact insulin from the gut to the portal vein to have a measurable effect on blood sugar. One can find several research reports over the years describing promising approaches or limited success in animals, and limited human testing, but as of 2004, no products appear to be successful enough to bring to market.[1]

Reference
Lebovitz HE. Therapy for Diabetes Mellitus and Related Disorders. 4th edition. Alexandria:American Diabetes Association, 2004.
From Wikipedia, the free encyclopedia.
>>http://en.wikipedia.org/wiki/Anti-diabetic_drug

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Immunologic Issues in Type 1 Diabetes

2005-10-02T22:10:00.000-07:00

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Immunologic Issues in Type 1 Diabetes
Zachary T. Bloomgarden, MD
This is the second in a series of reports on the American Diabetes Association (ADA) 61st Scientific Sessions held in Philadelphia, PA, in June 2001. It covers topics related to immunity and type 1 diabetes.

Jay Skyler, Miami, FL, presented the results of the parenteral substudy arm of the Diabetes Prevention Trial for Type 1 Diabetes (DPT-1), in which relatives of patients with type 1 diabetes, whose risk of type 1 diabetes is 10- to 20-fold greater than that of the general population, were screened for islet cell antibodies (ICAs) and enrolled in a study of insulin administration if they showed high risk of developing diabetes. Animal studies in female nonobese diabetic (NOD) mice have shown this to be an effective treatment, and in the early 1990s, Keller et al. (1) reported a pilot study of 12 individuals with a predicted risk of diabetes; 5 subjects were treated with insulin and 7 subjects declined treatment. By 2.5 years, all of those who declined treatment had developed diabetes; at 5 years, only half of the intervention group had the disease.

The DPT-1 was initiated in 1993. Screening began in February 1994 and randomization began in January 1995; 339 subjects were enrolled, with follow-up ending 13 April 2001. Screening of 89,827 relatives, with 84,228 samples analyzed, showed that 3,152 (3.7%) were ICA positive. A total of 2,103 subjects were staged, 535 having low first-phase insulin response. Of 372 subjects who were eligible for randomization, 339 were randomized. Skyler pointed out that 354 of the 3,152 ICA-positive individuals had actually already developed diabetes, with 156 identified before further testing. The projected annual event rate was 21%, and the actual finding was of 15.1% developing diabetes (in addition to those developing diabetes before randomization). Of the patients who developed diabetes, 60% were sibs, 25% were parents, 4% were offspring, and 8% were other relatives. All were ICA and insulin autoantibody (IAA) positive. At baseline, 48.1% were female, 45.4% were below age 10 years, 38.9% were 11–20 years of age, and 15.6% were over 21 years of age; 93.5% were Caucasian, reflecting the ethnic distribution of type 1 diabetes in the U.S., although ICA positivity was seen in 3% of relatives, regardless of ethnic background.

A total of 169 were in the intervention group, and 170 were observed. Individuals were followed for an average of 3.7 years. Of the subjects followed, 60% developed diabetes by 5 years. Those with impaired glucose tolerance (IGT) and those with normal glucose tolerance had a 22 and 10% rate of diabetes development per year, respectively. Those <6 years of age progressed at a rate similar to those aged 6–12 years. Those >15 years of age progressed at a much slower rate, which implies that studies confined to older individuals will need even larger numbers. Those with ICA alone progressed at a slower rate than those with the presence of more than one antibody.

Coming as a great disappointment to the audience, Skyler reported, "There was no impact of [parenteral] insulin therapy on delaying or preventing the onset of diabetes." Also, and again disappointingly, C-peptide showed no difference with or without treatment. The insulin intervention did cause some hypoglycemia. There were 93.6 presumed events (not documented but responding to carbohydrate ingestion) per 100 patient years in the treated patients, as opposed to 57 events in the control subjects. Documented hypoglycemia occurred in 59 vs. 11 patients/100 patient-years, and severe hypoglycemia did not occur. There was no difference between the groups in any measure of cognitive function, and those with definite hypoglycemia also had no change in cognitive function. Skyler suggested that, perhaps, this group was studied "too late." An ongoing oral antigen trial in subjects with a 5-year risk of 26–50% (less than that in the parenteral arm) is in progress and may be successful, despite the current study being negative.

Stoever et al. (1092-P) reported that the dose of subcutaneous insulin administered in the DPT-1 did not suppress endogenous insulin secretion, suggesting that failure of the study to prevent diabetes may be related to lack of ß-cell rest (abstract numbers refer to the Abstracts of the 61st Annual Meeting of the American Diabetes Association, Diabetes 50 [Suppl. 2]:1–A649). Insulin treatment in the study may, however, have suppressed the T-cell response to human islet proteins. Brooks-Worrell et al. (313-PP) studied a group of 16 patients in the DPT-1, showing that there was some immune effect of the intervention. T-cell responses to human islet proteins, measured using cellular immunoblotting, showed that five of six untreated patients showed response to a mean of eight islet antigens, while three of the insulin-treated patients showed no response and, on average, there was response to only one antigen, similar to that seen in individuals from a normal population. At follow-up, the untreated patients showed increasing response, while none of the 10 treated patients did so. Thus, insulin treatment may produce an immunosuppressive effect on T-cell proliferative responsiveness to islet proteins in subjects at high risk for developing clinical type 1 diabetes, although no clinical benefit was demonstrated.

Several studies at the ADA meeting did show hints of promising treatment strategies. Vitamin E given with nicotinic acid in a setting of tight glycemic control may lead to prevention of ß-cell loss in patients with new onset type 1 diabetes. Pozzilli et al. (287-PP) treated 56 patients with new onset type 1 diabetes (mean age 7.8 years) with intensive insulin and with 25 mg · kg-1 · day-1 nicotinic acid with or without 15 mg · kg-1 · day-1 vitamin E in a randomized controlled study. The addition of vitamin E reduced the insulin dose requirement and HbA1c and led to a C-peptide peak at 6 months of 0.38 vs. 0.27 nmol/l. Åkerblom et al. (17-LB) described the results of the second pilot study of the Finnish Trial to Prevent Diabetes in the Genetically At-Risk (TRIGR), with 208 newborn infants who had a first degree relative(s) with type 1 diabetes with the risk-associated HLA-DQB1 alleles (*02 and/or *0302) in the absence of protective alleles. After breast-feeding, the infants were randomized to either a casein hydrolysate or a conventional cow’s milk–based formula until the age of 6–8 months. Seroconversion to positive ICA was decreased by 67% and to positive IAA by 62%, with a 66% decrease in the likelihood of developing at least one positive antibody in the group fed the casein hydrolysate. To show a decrease in the rate of development of type 1 diabetes will require a large-scale clinical trial. In a fascinating animal study, Arany et al. (333-PP) reported an approach to preventing diabetes in the NOD mouse. The insulitis in this model is preceded by a decrease in ß-cell mass, and it is possible to increase ß-cell mass by supplementation of the mother during fetal development. Dietary taurine supplementation of the mothers was found to increase ß-cell mass, to decrease the histologic findings of insulitis, and to delay the onset of diabetes in the offspring. Whether this will prove applicable to human diabetes is uncertain.

A number of studies reported at the meeting gave additional information pertaining to the nature of the autoimmune defect in type 1 diabetes. Hummel et al. (314-PP) studied 1,920 offspring of patients with type 1 diabetes, with 1.1% of 1,514 having positive antibodies at 9 months, 3.2% of 1,154 positive at 2 years, and 7.3% of 550 positive at 5 years. The cumulative risk of diabetes was 3.2% from fathers and 2.0% from mothers at 5 years, a pattern that has been previously reported. Patterns of antibodies changed and the number of positive antibodies decreased with later onset, suggesting that those with earlier positive antibodies were at higher risk. Hathout et al. (336-PP) reported findings in 24 patients developing type 1 diabetes before age 5 years, at an average age of 2.6 years. Of these patients, 17% had positive ICA and 21% had positive GAD antibody, which is less than that seen in older children, but the prevalence of the high-risk HLA-DQA1 alleles *0501 and *0301 were 58.3 and 54.2%, rates higher than those in older children, suggesting differences in this young-onset group. Kukreja et al. (315-PP) reported a deficiency of natural killer T-cells in both patients with newly diagnosed and longstanding type 1 diabetes and in relatives with multiple positive autoantibodies, suggesting another immunologic hint as to pathogenesis. In mice and humans, the presence of reduced numbers of these cells has been associated with the development of autoimmune diseases. Kukreja also reported that the cells showed decreased secretion of interleukin (IL)-4 and -interferon after stimulation. Diez et al. (18-LB) studied the phenomenon related to self-tolerance of "self–antigen-presenting cells" present in both thymus and peripheral lymphoid organs, expressing autoantigens such as insulin, GAD, and tyrosine phosphatases (IA-2). Using a monoclonal antibody against proinsulin, they showed that such cells with a surface-staining pattern of proinsulin peptides were present in lymphoid organs and blood. Using flow cytometry analysis, they were able to show by use of two antibodies that cells expressing proinsulin were present in the spleen and peripheral blood. The cells expressed insulin mRNA and markers of antigen-presenting cells, such as CD11c, CD14, CD40, and HLA-DR, suggesting an important additional component of the prevention of islet cell autoimmunity.

C-peptide

C-peptide deficiency has been suggested to play a role in the complications of diabetes. A C-peptide receptor has been identified in the kidney, where it appears to function to reduce glomerular blood flow. Consistent with these findings, administration of C-peptide to type 1 diabetic patients has been observed to reduce the urinary albumin excretion. Fiorina et al. (343-PP) studied 16 patients with type 1 diabetes who had had combined islet and whole kidney transplants 4 years earlier. All of the patients had adequate renal function; nine had and seven did not have some degree of islet function. Although HbA1c was not significantly lower, C-peptide was seven time higher, erythrocyte Na-K ATPase was 30% higher, and urine albumin decreased from 109 to 85 mg/24 h versus an increase from 92 to 184 mg/24 h from the initial level after transplantation. The same group (618-P) compared nine patients with versus seven patients without C-peptide >0.5 ng/ml at least 1 year after kidney plus islet transplant, with similar HbA1c, creatinine, lipid, and blood pressure levels. Endothelium-dependent brachial artery dilation was 7.8 vs. 0.5%, basal nitric oxide (NO) production more than doubled, and carotid intima-media thickness was unchanged compared with an increase of 0.12 mm in the two groups, suggesting preservation of vascular function. In patients with type 2 diabetes, Saito et al. (730-P) reported C-peptide levels of 3.1 vs. 4.8 ng/ml in 15 with vs. 52 patients without microalbuminuria. Johansson et al. (1052-P) reported that infusion of C-peptide (5 pmol · kg-1 · min-1 for 60 min) to 8 men with type 1 diabetes improved systolic and diastolic myocardial function measured by pulsed tissue Doppler before and during dipyridamole stress. Bjork et al. (358-P) treated 56 children aged 7–17 years at onset of type 1 diabetes with either the K+ channel opener diazoxide to inhibit insulin release or with placebo for 3 months. Stimulated C-peptide levels were higher after treatment through 12 months, though similar to the control group at 24 months, suggesting the potential for preservation of endogenous insulin and C-peptide secretory function. A number of animal studies showed effects of C-peptide on nerve function. Cotter and Cameron (748-P) reported that C-peptide administration to streptozotocin (STZ)-diabetic rats caused 62 and 78% improvement in sciatic motor and saphenous sensory nerve conduction velocity, respectively, which was prevented by coadministration of the NO synthase inhibitor L-nitro-arginine. Sima et al. (242-OR) reported that C-peptide administration prevented the upregulation of the low-affinity insulin receptor seen in sciatic nerves in an animal model of type 1, but not type 2, diabetes. Sima et al. (770-P) administered human C-peptide in doses of 10, 100, 500, and 1,000 µg · kg-1 ·day-1 for 2 months in a rat type 1 diabetes model, showing a dose response in increasing nerve conduction velocity and Na+K+-ATPase activity and in preventing histological changes.

C-peptide and islet antibodies in diabetes management

Jerry Palmer, Seattle, WA, discussed the utilization of C-peptide in the treatment and management of type 1 diabetes. Because every insulin molecule is produced along with a C-peptide molecule, the measurement of C-peptide allows assessment of insulin secretion in insulin-treated patients, many of whom develop anti-insulin antibodies. Antibodies to C-peptide may, however, recognize proinsulin or proinsulin split products, leading to differences between findings of different studies. The limit of detection of most clinical assays is 0.1 pmol/ml. In pancreatectomized patients, glucagon-stimulated C-peptide is at the detection limit of the assay. However, patients with type 1 diabetes with sufficient endogenous insulin to improve glycemic control have levels of 0.2 pmol/ml, non-insulin requiring individuals may have levels of 0.6 pmol/ml, and normal levels may be at 1.0 pmol/ml; thus, small differences are meaningful. Palmer favored the use of stimulated C-peptide, though noted excellent correlation with fasting values, as some patients with very low fasting levels show responses to stimulation and some with higher fasting levels have flat responses. Measuring both fasting and stimulated levels is ideal. Comparing the response to intravenous (IV) glucagon, IV glucose, a mixed meal, and oral glucose, he noted that individuals with type 1 diabetes have little response to oral glucose and respond best to a mixed meal or IV glucose, with glucagon having the disadvantage of causing gastrointestinal side effects such as nausea. Reproducibility is a problem, with glucagon-stimulated C-peptide having 15% intrasubject variation in normal control subjects and greater variation in patients with diabetes, particularly as the ß-cell lesion changes over time, and they may have different basal glucose levels at different times of testing. One can use C-peptide and C-peptide clearance measurements to assess secretion of insulin, which is extracted to a variable degree by the liver.

C-peptide measurement is useful in distinguishing type 1 from type 2 diabetes, although this has become complicated in both children and adults who have both obesity and type 1 diabetes. Obesity increases insulin resistance, but does not protect against autoimmunity, and may result in type 1 diabetes presenting at a time when there is a greater degree of ß-cell function and, hence, higher C-peptide levels. Antibody-positive patients with type 2 diabetes show C-peptide levels similar to those in antibody-negative patients at diagnosis. Over several years, their C-peptide levels decrease more than those of antibody-negative patients. Stimulated C-peptide levels of 0.6 pmol/ml are useful in distinguishing between those with type 2 diabetes who do and do not require insulin, the former showing great overlap with type 1 diabetes in C-peptide levels.

C-peptide levels are related to the ability of type 1 diabetic patients to attain good glycemic control. In the Diabetes Control and Complications Trial (DCCT), from which patients with C-peptide levels >0.5 pmol/ml were excluded, 552 of the 855 subjects with diabetes for 1–5 years had standardized meal-stimulated levels <0.2 pmol/ml, and 303 had levels between 0.2 and 0.5 pmol/ml. Before study entry, the latter had HbA1c levels 1% lower than nonresponders, and this difference was maintained for 7 years in the DCCT. The C-peptide–positive group experienced less hypoglycemia, and other studies have shown an increased glucagon response to hypoglycemia for these patients. Comparing patients with C-peptide <0.1, 0.1–0.2, and >0.2 pmol/ml, the latter showed lower fasting glucose and HbA1c levels, and the insulin dose requirement was somewhat lower in the 0.1–0.2 pmol/ml group. It is not uncommon for patients with type 1 diabetes to "have amounts [. . .] that make any difference," Palmer noted, with almost half of the 4,000 patients screened for the DCCT having stimulated C-peptide >0.2 pmol/ml between 2 and 5 years after diagnosis. In the future, use of C-peptide for monitoring efficacy of treatments to preserve ß-cell function may be useful. Palmer pointed out that the assay is well standardized and that commercial C-peptide assays are usually reliable. Other uses of C-peptide may include the assessment of need for insulin in patients with type 2 diabetes who were transferred to insulin because of sulfonylurea failure.

Palmer answered a series of questions illustrating additional uses of C-peptide. As far as the measurement of fasting rather than stimulated C-peptide, he noted that their correlation shows an r value of 0.8. A fasting C-peptide concentration of 0.2 corresponds to a stimulated C-peptide level of 0.6 pmol/ml, but "the noise around 0.2 is a lot greater." Ideally, he said, C-peptide should be measured with a basal glucose of 120 mg/dl, as higher levels may stimulate ß-cells or, less typically, decrease C-peptide levels because of glucose toxicity. For stimulation, in addition to standardized mixed meals, one "can use a variety of nonglucose stimuli," including isoproterenol, arginine, and GLP-1. He commented that the measurement may be useful "whenever the patient’s diabetes is behaving unusually." As far as latent autoimmune diabetes of the adult (LADA), "type 1 1/2 diabetes," and other difficult-to-characterize forms, he suggested, "The classification system is in evolution. In the future, we will rely a bit more on immune markers." As far as the use of C-peptide to decide on insulin treatment for patients with type 2 diabetes, "most of the data come from the time when all we had was sulfonylureas." Patients who failed to respond to sulfonylureas and are receiving insulin treatment but have stimulated C-peptide >0.6 pmol/ml could be given a trial of oral agents. As far as the guidelines that C-peptide be used for determination of whether a specific patient be treated with insulin pumps, he noted that there is no evidence that this helps to determine who will and who will not benefit from insulin pump treatment. If the rationale is to distinguish between type 1 and type 2 diabetes, it would be more useful to measure antibodies.

William Winter, Gainesville, FL, discussed islet autoantibody markers in the diagnosis, prediction, and clinical course of autoimmune type 1 diabetes. He recalled the 1997 ADA recommendation that diabetes be divided into type 1, type 2, gestational, and a group of miscellaneous types, with type 1 diabetes divided into an autoimmune type (1A) and one with insulinopenia in the absence of islet autoantibodies (1B). Autoantibodies can be important in disease management, perhaps lessening the likelihood that an individual will develop ketoacidosis at onset of type 1 diabetes, or in determining whether a person with diabetes and obesity causing insulin resistance actually has type 1 or type 2 diabetes. Autoantibodies may play a role in determining prognosis for a patient or in assessing the risk for other family members.

The four major antibodies measured clinically, ICAs, IAAs, GAD antibodies (GADAs), and insulinoma-associated antibodies (IA2s), are just a subset of the many different ones that have been described. It is unlikely that any are pathogenic. ICA was first described over 25 years ago, requiring measurement by indirect fluorescence, which is labor intensive, requires intensive quality assurance efforts, and can best be performed with human pancreas specimens. Histologically, these polyclonal IgG antibodies react with all cells of the islet, recognizing a variety of antigens. At diagnosis, ICAs are present in 70–80% of Caucasians and in fewer African-Americans, with decreasing prevalence over time. ICAs are present in 0.4% of nondiabetic individuals and therefore show high specificity. ICAs are present in 2–3% of first-degree relatives and do not appear to occur in pediatric type 2 diabetes. They are found in LADA.

IAAs are the only ß-cell–specific autoantigens. Measurement must be performed before starting insulin treatment, as the assay cannot distinguish between induced antibodies and autoantibodies. GAD, the "64K autoantigen," converts glutamate to the neurotransmitter -amino-butyric acid and is ubiquitous in the central nervous system. Type 1 diabetes is associated with specific epitopes of GADAs. These are present at similar frequency to ICA at diagnosis. GADA persists after diagnosis, making it useful for patient assessment several years after disease onset. IA2 is a member of the protein tyrosine phosphatase family, a group of receptor and cytoplasmic signal transduction enzymes present in many cell types. ICA 512 recognizes the cytoplasmic portion of this antigen. IA2 is present in 60% of patients at the time of onset of type 1 diabetes. However, both GADA and IA2 are found in 2–3% of the normal population, making their specificity lower than that of ICA.

Winter noted that fewer than 15% of individuals with type 1 diabetes have an affected first-degree relative. A patient with type 1 diabetes has a 5% chance of a sibling being affected, and concordance in identical twins is 30–50%. Thus, environmental factors must play a role in disease onset. An example of this is the puzzling finding that the frequency of type 1 diabetes in offspring is higher if the father has type 1 diabetes than if the mother is affected. Antibodies provide the earliest markers of these environmental events, with islet autoantibodies being associated with the finding of insulitis on the cellular level. Subsequent clinically recognizable events are the abnormal first phase (1–3 min) insulin response to IV glucose, for which the individual needs to lose 50% of ß-cell mass, and the development of a frankly abnormal oral glucose tolerance test, which usually leads to clinical diabetes within 2 years. The DPT-1 showed that with close observation, type 1 diabetes is asymptomatic in 70% of patients at the time of onset. Winter pointed out that this schema of the natural history of type 1 diabetes need not occur in all individuals, and antibody measurement may assist in the assessment of prognosis for a given individual.

In family studies, individuals with higher ICA titers have greater risk of developing diabetes, and ICA-negative individuals have no risk of disease. ICA-positive schoolchildren who do not have a relative with type 1 diabetes have a rate of progression to type 1 diabetes similar to that of first-degree relatives, and younger individuals with positive antibodies have higher risk. Combining islet cell autoantibody measurements and IV glucose tolerance testing, with antibodies present and a low first-phase insulin response, there is a >50% risk at 5 years regardless of antibody titer. The presence of IAA with ICA increases risk. GADA and IA2 also predict type 1 diabetes; GADA is associated with a 50% 5-year risk, with risk increasing at higher antibody titers, and with greater numbers of positive antibodies. Winter concluded that ICA has the greatest ability to predict risk but requires a methodologically difficult assay and that GADA and IA2 are the most usable for population screening. Asked about the validity of assays in commercial laboratories, Winter recommended ascertaining which kit is being used by a given laboratory and whether it has been correlated with results in a research setting. He pointed out that enzyme-linked immunosorbent assay (ELISA) is not as good as the radioimmunoprecipitation assay, and that the use of monkey rather than human pancreas for ICA measurements probably gives less sensitivity for ICA.

A final important question is whether, after diagnosis, the presence of antibodies is associated with differences in the course of type 1 diabetes. ICAs are not associated with different clinical presentation or with different clinical findings during the initial year after diagnosis, but may be associated with lower C-peptide levels at 2 years. IA2 and the presence of multiple autoantibodies are also associated with lower C-peptide levels at 18–24 months. This has not been shown for IAA, and different studies have shown GADA to be either protective or harmful, so that further research in this area will be important.

Asked whether the classification schema should be redefined based on antibodies as well as clinical findings, Winter commented that some patients initially appearing to have type 1B subsequently show antibody positivity, and that when many antibodies are tested, >95% are positive to at least one, so that it is uncertain whether "type 1B" actually represents a different disease. Why bother determining antibodies, then, if you are going to treat with insulin anyway? "I’m certainly not here to tell you," he stated, "that every child needs autoantibody testing." Winter suggested, however, that those with evidence of autoimmunity may then be at higher risk of autoimmune disease of the thyroid, of pernicious anemia, and perhaps of adrenal insufficiency, and that "if you recognize that somebody has type 1 diabetes, 5–15% of relatives will develop type 1." He acknowledged that "the results of the DPT-1 created a bigger problem for us," as prior data suggested that insulin treatment would help patients with positive antibodies, but with the negative results of the trial one cannot state that "insulin is really good for the ß-cell" for such individuals, at least before onset of diabetes.

Immunology and type 1 diabetes

Tumor necrosis factor-.
In a symposium addressing mechanisms of development of type 1 diabetes, tumor necrosis factor (TNF), an inflammatory predictor of disease in type 1 diabetes, was highlighted. Icbald Grewal of Genentech, South San Francisco, CA, discussed the TNF supergene family and the role of TNF molecules and receptors in the pathogenesis of autoimmune diseases. Two ligands have been identified: one that is expressed in normal tissues at low levels and induces proliferation in certain tumors, and the other that is expressed in the immune system, T-cells, dendritic cells, monocytes, and macrophages; is involved in B-cell stimulation; and causes lupus-like autoimmune diseases when overexpressed. There are two receptors for these ligands, with activation leading to nuclear factor-B (NF-B) expression. Administration of antibodies to block the ligands, or the use of fusion proteins of the Fc portion of IgG with portions of the receptor, blocks IgM production by B-cells and decreases splenic IgG1 production, with activity in autoimmune arthritis and neurologic disease models. A question being studied concerns their effect in experimental and clinical type 1 diabetes.

John Corbett, St. Louis, MO, discussed the effects of cytokines produced in islets on ß-cell function and ß-cell destruction. Each islet contains 2,000 cells, of which <1% are macrophages. Macrophages activated by TNF- release IL-1ß, which binds to surface receptors on ß-cells, leading to production of inflammatory signals such as NF-B, which thereby leads to inducible NO synthase (INOS) activation in ß-cells. NO production decreases mitochondrial function, leading to decreased ATP levels and a reduction in insulin secretion. Aminoguanidine, which decreases NO synthase activation, attenuates this effect. Thus, it appears that a cascade occurs where TNF- signals macrophages, which in turn cause ß-cells to produce cytokines causing ß-cell damage by both apoptosis and, under stimulation by cytokines and NO, necrosis.

Richard Flavell, New Haven, CT, noted that autoimmune diseases occur when a repertoire exists of autoreactive cells capable of reacting with the tissue in question. Lymphocyte activation, perhaps because of viral infection or chronic inflammation, leads to tissue destruction when immunoregulatory mechanisms fail. TNF- is an important signal for lymphocyte infiltration. The biologic consequence of diabetes depends on genetic predisposition. Neonatal, but not subsequent, TNF administration exacerbates the disease, leading to acceleration of ß-cell apoptosis, dendritic cell infiltration, apoptotic fragments presenting via the dendritic cells to CD4 and CD8 T-cells, and the CD8 T-cells mediating ß-cell destruction. The additional factor TNF-related activation-induced cytokine appears to slow expression of disease by increasing levels of protective CD25 T-cells, which blocks further differentiation of the cytotoxic CD8 cells.

Additional studies of immunology and type 1 diabetes

In a study presented at the meeting, Herold et al. (134-OR) administered splenocytes from already diabetic NOD mice, a model of autoimmune diabetes, to nondiabetic NOD recipients. Diabetes developed in 88 vs. 14% of mice pretreated with a soluble form of the receptor for AGE (RAGE), which binds ligands and prevents their access to the cell surface receptor. The islets did not show inflammatory infiltrate or express TNF- or IL-1ß . Blockade of RAGE/ligand interaction may provide islet protection against development of diabetes or recurrence after islet transplantation. The same investigators (138-OR) treated 12 individuals with type 1 diabetes for <6 weeks with non-FcR binding anti-CD3 monoclonal antibody. At 1 month, circulating lymphocytes decreased to 24% of basal levels, but fever and an eczematoid rash responding to antihistamines and nonsteroidal anti-inflammatory drugs developed in 9 and 10 patients, respectively. IL-10 levels increased, suggesting activation of Th2 cells. HbA1c decreased from 9.4 to 6.2%, while falling from 8.3 to 7.7% in six control subjects, with meal-induced insulin secretion increasing in eight treated but only one untreated patient. Scholtz et al. (522-P) administered NBI-6024, an altered peptide ligand that has been shown to generate Th2-like cells that appear to block the autoreactive process in NOD mice, to 15 patients with type 1 diabetes, showing preliminary evidence of safety of this approach.

Krischer et al. (180-OR) administered oral insulin versus placebo for 1–3 years to 205 newly diagnosed antibody-positive type 1 diabetic patients, showing a trend to greater C-peptide secretory capacity with treatment. Braghi et al. (131-OR) reported that 9 of 36 patients receiving islet transplants showed an increase in antibodies to GAD consistent with reactivation of a quiescent autoimmune response. Contreras et al. (133-OR) administered Anti-F(Ab)2-immunotoxin, which ablates >99% of T-cells, with 50% recovery by 5 months, and the NF-B inhibitor deoxyspergualin, blocking proinflammatory cytokine release and dendritic cell maturation to seven rhesus monkeys with STZ-induced diabetes. After subsequent transplantation of islets from MHC class I and class II incompatible rhesus monkey donors, only two showed rejection, at 70 and 335 days, with the other five normoglycemic at 180, 386, 532, and 566 days. Genovese et al. (375-P) found GAD autoantibodies in 62 of 949 patients diagnosed as having diabetes after 40 years of age. Of antibody-positive patients, 61%—but 15% of those with negative antibodies—were treated with insulin, with HbA1c 7.8 vs. 7.0% and BMI 26.2 vs. 29.1 kg/m2, respectively, suggesting the importance of LADA in this population and the potential clinical benefit of GADA screening in adult-onset diabetes. In an interesting report on adverse effects of immunosuppressive treatment on the ß-cell, Montori et al. (1710-P) reviewed 10 randomized trials, 11 cohort studies, and 1 case-control study of diabetes developing after transplantation of a variety of organs, which occurred at 1 year in 4–18% of patients without previous diabetes. Non-Caucasian race was associated with a 4.6-fold increased risk, and tacrolimus treatment was associated with a 2.3-fold increased risk, with prednisone dose and age as additional factors. Individuals developing diabetes after transplantation had a 7.2-fold increase in fatal infections, with trends toward worse patient and graft survival. Evidence did not favor any specific therapeutic approach.

Islet transplantation

Ryan et al. (33-LB), Edmonton, Canada, presented an update (as of 1 April 2001) on the glycemic control of 15 patients with islet transplantation (two procedures in 11 and three in 4 patients) using a steroid-free immunosuppression regimen. Acute complications of transplantation included bleeding in two, portal vein thrombosis in one, and puncture of the gall bladder in one; none required surgery. All patients initially became insulin- free with measurable C-peptide. Glycemia deteriorated in four, necessitating insulin treatment after being off insulin for a median of 3 months, although in contrast to their prior glycemic lability, they showed stable glucose without hypoglycemia problems and required approximately one-half their pretransplant daily doses. One other patient requires insulin intermittently and is on oral hypoglycemic agents. The mean of the most recent HbA1c for the 11 patients not requiring insulin was 5.9%. The immunosuppressive therapy caused hypercholesterolemia in 9 of 15, a rise of serum creatinine in 2 of 15, a rise of urine protein excretion in 3 of the other 13, and acne in 5 of 15. Bretzel et al. (345-PP) reported data on 56 consecutive islet transplants from Giessen, Germany, 35 performed simultaneously with and 21 following renal transplant (SIK and IAK transplanted, respectively); all patients underwent only one procedure as opposed to the two or three in the Edmonton report. At mean 1-year follow-up, islet function (C-peptide >0.5 ng/ml) was seen in 80 and 47%, respectively, and the insulin dose decreased from 40 and 45 units pretransplant to 24 and 12 units, with no patient developing severe hypoglycemia, although only 17 vs. 21% were insulin independent. Bretzel mentioned that, excluding their cases, the International Islet Transplant Registry reports 31 and 26% functional islet allograft survival and 7% insulin independence at 1 year after islet transplantation for SIK and IAK recipients.

In an animal study, Lee et al. (286-PP) grafted polyethylene glycol to the capsule of rat pancreatic islets, which were then cocultured with spleen cells, showing decreased immunogenicity and improved survival, with maintained insulin secretory response to glucose, suggesting this as an approach for prevention of rejection. Kojima et al. (307-PP) transfected intestinal stem cells with genes for pancreatic-duodenal homeobox 1, which plays a role in ß-cell formation, and for islet factor-1, and exposed the cells to the peptide betacellulin, which promotes pancreatic ß-cell differentiation. Implanted in STZ-injected diabetic rats, the cells decreased glucose and increased insulin levels, suggesting another potential approach to islet therapy. Tanwani et al. (1714-P) administered troglitazone or glimepiride to STZ-diabetic rats after islet transplantation. Fasting glucose levels were 78 vs. 139 mg/dl and hyperglycemia developed after 130 vs. 58 days, suggesting enhanced functional survival of the islet graft when insulin resistance was reduced.

Footnotes

Zachary T. Bloomgarden, MD, is a practicing endocrinologist in New York, New York, and is affiliated with the Diabetes Center, Mount Sinai School of Medicine, New York, New York.

The first section of this article was published online as a portion of Bloomgarden ZT: Type 1 diabetes and autoimmunity. http://www.medscape.com/Medscape/CNO/2001/ADA. Accessed 29 July 2001.

Abbreviations: ADA, American Diabetes Association; DCCT, Diabetes Control and Complications Trial; DPT-1, Diabetes Prevention Trial for Type 1 Diabetes; GADA, antibody to GAD; IA2, insulinoma-associated antibody; IAA, insulin autoantibody; ICA, islet cell antibody; IGT, impaired glucose tolerance; IL, interleukin; iNOS, inducible nitric oxide synthase; IV, intravenous; LADA, latent autoimmune diabetes of the adult; NO, nitric oxide; NF-B, nuclear factor-B; RAGE, receptor for AGE; STZ, streptozotocin; TNF, tumor necrosis factor.

Reference

Keller RJ, Eisenbarth GS, Jackson RA: Insulin prophylaxis in individuals at high risk of type I diabetes. Lancet 341:927–928, 1993[Medline]
>>>http://care.diabetesjournals.org/cgi/content/full/24/12/2143
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Economic Costs of Diabetes in the U.S. in 2002

2005-10-02T22:06:00.000-07:00

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Economic Costs of Diabetes in the U.S. in 2002
American Diabetes Association
ABSTRACT

OBJECTIVE—Diabetes is the fifth leading cause of death by disease in the U.S. Diabetes also contributes to higher rates of morbidity—people with diabetes are at higher risk for heart disease, blindness, kidney failure, extremity amputations, and other chronic conditions. The objectives of this study were 1) to estimate the direct medical and indirect productivity-related costs attributable to diabetes and 2) to calculate and compare the total and per capita medical expenditures for people with and without diabetes.

RESEARCH DESIGN AND METHODS—Medical expenditures were estimated for the U.S. population with and without diabetes in 2002 by sex, age, race/ethnicity, type of medical condition, and health care setting. Health care use and total health care expenditures attributable to diabetes were estimated using etiological fractions, calculated based on national health care survey data. The value of lost productivity attributable to diabetes was also estimated based on estimates of lost workdays, restricted activity days, prevalence of permanent disability, and mortality attributable to diabetes.

RESULTS—Direct medical and indirect expenditures attributable to diabetes in 2002 were estimated at $132 billion. Direct medical expenditures alone totaled $91.8 billion and comprised $23.2 billion for diabetes care, $24.6 billion for chronic complications attributable to diabetes, and $44.1 billion for excess prevalence of general medical conditions. Inpatient days (43.9%), nursing home care (15.1%), and office visits (10.9%) constituted the major expenditure groups by service settings. In addition, 51.8% of direct medical expenditures were incurred by people >65 years old. Attributable indirect expenditures resulting from lost workdays, restricted activity days, mortality, and permanent disability due to diabetes totaled $39.8 billion. U.S. health expenditures for the health care components included in the study totaled $865 billion, of which $160 billion was incurred by people with diabetes. Per capita medical expenditures totaled $13,243 for people with diabetes and $2,560 for people without diabetes. When adjusting for differences in age, sex, and race/ethnicity between the population with and without diabetes, people with diabetes had medical expenditures that were 2.4 times higher than expenditures that would be incurred by the same group in the absence of diabetes.

CONCLUSIONS—The estimated $132 billion cost likely underestimates the true burden of diabetes because it omits intangibles, such as pain and suffering, care provided by nonpaid caregivers, and several areas of health care spending where people with diabetes probably use services at higher rates than people without diabetes (e.g., dental care, optometry care, and the use of licensed dietitians). In addition, the cost estimate excludes undiagnosed cases of diabetes. Health care spending in 2002 for people with diabetes is more than double what spending would be without diabetes. Diabetes imposes a substantial cost burden to society and, in particular, to those individuals with diabetes and their families. Eliminating or reducing the health problems caused by diabetes through factors such as better access to preventive care, more widespread diagnosis, more intensive disease management, and the advent of new medical technologies could significantly improve the quality of life for people with diabetes and their families while at the same time potentially reducing national expenditures for health care services and increasing productivity in the U.S. economy.

Abbreviations: ADA, American Diabetes Association • BLS, Bureau of Labor Statistics • CMMS, Centers for Medicare and Medicaid Services • GHPS, Group Health of Puget Sound • MEPS, Medical Expenditure Panel Survey • NHIS, National Health Interview Survey • PVFE, present value of future earnings • SSDI, Social Security Disability Insurance
>>>http://care.diabetesjournals.org/cgi/content/abstract/26/3/917?maxtoshow=&HITS=&hits=&RESULTFORMAT=1&andorexacttitle=and&fulltext=Diabetes&andorexactfulltext=and&searchid=1128315925478_8418&stored_search=&FIRSTINDEX=0&sortspec=relevance&resourcetype=1&journalcode=diacare

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Diabetes - The Basics

2005-10-02T22:04:00.000-07:00

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Diabetes - The Basics
by Nettie Mae

In simple terms DIABETES is the inability of the body to process sugars properly. When we eat or drink our PANCREAS produces a hormone called INSULIN. Insulin is released into the blood and helps to regulate the amount of glucose(sugar) in the bloodstream. Diabetes is a condition where this process does not function correctly. This is due to either:

- No insulin being produced, often called Type 1 diabetes, and requires the sufferer to use insulin injections, or...

- Insulin is produced but the body becomes RESISTANT to it. This renders the insulin ineffective. This is normally called Type 2 diabetes and is rapidly becoming more common.

Latest research shows that 2 in every 100 people have diabetes. Alarmingly half of these people do not even know they have it. Many people have diabetes without being aware of it because someone with diabetes looks no different from anyone else.

Someone can have diabetes for months or even years without realizing they have the condition. The danger is that while diabetes is not immediately life threatening the long term effects of high blood sugar can be damaging to one's health. Uncontrolled diabetes and prolonged high blood sugar levels can, in later life, cause problems to many organs including the kidneys, eyes, nerves and the heart. This may sound grim, however controlling blood sugar by a combination of medicine, diet and exercise will vastly reduce the long term complications.

The simplest way to check if you have diabetes is to arrange a blood sugar check with your doctor. A tiny sample of blood, obtained by pricking a finger is checked using a small electronic tester. A normal blood sugar level is generally between 72 - 126 mg/dl or 4 - 7 mmol/l (1 mmol/l = 18mg/dl). Diabetes is diagnosed when the body is unable to keep the blood sugar level within these limits. The unit of measurement used (mmol/l or mg/dl) will depend on which country you live in.

Diagnosis of diabetes can occur out of the blue during a routine check-up but more often it follows from the sufferer experiencing the "symptoms" of diabetes. These symptoms can be many or few, mild or severe depending on the individual.

The symptoms are:

NOTHING AT ALL (???) No this is not a typo. It is true many people do indeed feel no different and are astonished to discover they have diabetes. However even if you feel fine you must take your diabetes seriously and act on the doctor's advice.

THIRST (polydipsia) This is a very common symptom. Often it seems no matter how much you drink your mouth still feels as dry as Death Valley. The problem is compounded before diabetes is diagnosed by sufferers drinking copious amounts of...sugary drinks! Of course this only increases the blood sugar level and leads to increased thirst.

INCREASED URINATION (polyuria) Another very common symptom. Sufferers need to urinate often and pass large volumes each time. In addition this symptom takes no account of time so sleep is constantly disturbed by having to visit the bathroom during the night. It is a mistake to think this is caused by the increased thirst and drinking more..the opposite is true. High sugar levels in the blood spill over into the urine making it syrupy. To counter-act this water is drawn from the body causing dehydration and therefore thirst.

WEIGHT LOSS Glucose is the form of sugar which is the body's main fuel. Diabetics cannot process this properly so it passes into the urine and out of the body. Less fuel means the body's reserve tissues are broken down to produce energy with a resultant loss in weight.

Other symptoms include constipation, tiredness, lack of energy, tingling or pins and needles in the hands and feet, blurred vision and increased infections.

If you have experienced any of these symptoms it does not necessarily follow that you are diabetic however it might be advisable to visit your doctor to be sure.

If it does transpire that you have diabetes please do not panic. It can come as a shock and it will mean some changes in your life. While (currently) incurable it can be treated so the long term complications are reduced or even eliminated. As a result you may actually increase your health and life expectancy compared to previously when you were taking no care of your body whatsoever. It requires discipline and self-control however there is no reason why anyone with diabetes cannot live a full and perfectly normal life.

About the Author
Sick and tired of being Sick and Tired, Nettie Mae quit her 3rd shift factory job. To see what keeps her going, visit http://www.frutavida4u.com/nettiemae/.

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Do You Have Diabetes?

2005-10-02T21:57:00.000-07:00

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Do You Have Diabetes?
By Joshua Levine
Health Correspondent - Every 2nd Saturday

Diabetes mellitus, or high blood sugar, results from a deficiency of insulin, a hormone produced by the pancreas. When the body doesn't produce insulin or doesn't use it correctly, it can't make use of its main fuel -- sugar. Untreated, diabetes can lead to blindness, vascular disease, kidney disease, neuropathy, and other problems.
Almost every one of us knows someone who has diabetes. An estimated 16 million people in the United States have diabetes mellitus. About half of these people don't know they have it and are not receiving care for the disorder. Each year, about 800,000 people are diagnosed with this silent killer.

different types of diabetes

The 3 main types of diabetes are:

Type 1 diabetes
Type 2 diabetes
Gestational diabetes (for your women friends)

Type 1
Type 1 diabetes (also known as insulin-dependent diabetes mellitus or juvenile diabetes) is considered an autoimmune disease. An autoimmune disease results when the body's system for fighting infection (the immune system) turns against a part of the body. In diabetes, the immune system attacks the insulin-producing beta cells in the pancreas and destroys them. The pancreas then produces little or no insulin.

Someone with type 1 diabetes needs daily injections of insulin to live. At present, scientists do not know exactly what causes the body's immune system to attack the beta cells, but they believe that both genetic factors and viruses are involved. Type 1 diabetes accounts for about 5 to 10% of diagnosed diabetes in the United States.

Type 1 diabetes develops most often in children and young adults, but the disorder can appear at any age. Symptoms of type 1 diabetes usually develop over a short period, although beta cell destruction can begin years earlier.

Symptoms include: increased thirst and urination, constant hunger, weight loss, blurred vision, and extreme tiredness. If not diagnosed and treated with insulin, a person can lapse into a life-threatening coma.

Type 2
The most common form of diabetes is type 2 (also known as noninsulin-dependent diabetes mellitus or NIDDM). About 90 to 95% of people with diabetes have type 2. This form of diabetes usually develops in adults over the age of 40 and is most common among adults over age 55. About 80% of people with type 2 diabetes are overweight.

With type 2, the pancreas usually produces insulin, but for some reason, the body cannot use the insulin effectively. The end result is the same as for type 1 diabetes -- an unhealthy build-up of glucose in the blood and an inability of the body to make efficient use of its main source of fuel.

The symptoms of type 2 diabetes develop gradually and are not as noticeable as those in type 1.

Symptoms include: feeling tired or ill, frequent urination (especially at night), unusual thirst, weight loss, blurred vision, frequent infections, and slow healing of sores.

Gestational diabetes
Guys, please make sure your wives, girlfriends, sisters, or mothers read this part. Gestational diabetes develops or is discovered during pregnancy. This type usually disappears once the pregnancy is over, but women who have had gestational diabetes have a greater risk of developing type 2 diabetes later on in their lives.

what are your risks?

Diabetes is not contagious; people cannot "catch" it from one another. However, certain factors can increase one's risk of developing the disease. People who have family members with diabetes (especially type 2), are overweight, or are African American, Hispanic or Native American are all at greater risk of developing diabetes.
Type 1 diabetes occurs equally among men and women, but is more common in whites than in nonwhites. Data from the World Health Organization's Multinational Project for Childhood Diabetes indicates that type 1 diabetes is rare in most Asian, African, and American Indian populations. On the other hand, some northern European countries, including Finland and Sweden, have high rates of type 1 diabetes. The reasons for these differences are not known.

Type 2 diabetes is more common in older people, especially older women who are overweight, and occurs more often among African Americans, Hispanics, and American Indians. Compared with non-Hispanic whites, diabetes rates are about 60% higher in African Americans and 110 to 120% higher in Mexican Americans and Puerto Ricans. American Indians have the highest rates of diabetes in the world. Among Pima Indians living in the US, for example, half of all adults have type 2 diabetes.

The prevalence of diabetes is likely to increase because older people, Hispanics, and other minority groups, make up the fastest growing segments of the US population.

how do you manage it?

Before the discovery of insulin in 1921, all people with type 1 diabetes died within a few years after the appearance of the disease. Although insulin is not considered a cure for diabetes, its discovery was the first major breakthrough in diabetes treatment.
Today, daily injections of insulin are the basic therapy for type 1. Insulin injections must be balanced with meals and daily activities, and glucose levels must be closely monitored through frequent blood sugar testing.

Diet, exercise, and blood testing for glucose are also the basis for management of type 2. In addition, some people with type 2 diabetes take oral drugs or insulin to lower their blood glucose levels.

People with diabetes must take responsibility for their day-to-day care. Much of the daily care involves trying to keep blood sugar levels from going too low or too high. When blood sugar levels drop too low -- a condition known as hypoglycemia -- a person can become nervous, shaky and confused. Judgment can become impaired. Eventually, the person could pass out. The treatment for low blood sugar is to eat or drink something with sugar in it.

living with diabetes

On the other hand, a person can become very ill if blood sugar levels rise too high, a condition known as hyperglycemia. Hypoglycemia and hyperglycemia, which can occur in people with type 1 or type 2 diabetes, are both potentially life-threatening emergencies.
People with diabetes should be treated by a doctor (endocrinologist) who monitors them and checks for complications. In addition, people with diabetes often see ophthalmologists for eye examinations, podiatrists for routine foot care, dieticians for help in planning meals, and diabetes educators for instruction in day-to-day care.

In recent years, advances in diabetes research have led to better ways to manage diabetes and treat its complications. Major advances include:

New forms of purified insulin, such as human insulin produced through genetic engineering.
Better ways for doctors to monitor blood glucose levels and for people with diabetes to test their own levels at home.
Development of external and implantable insulin pumps that deliver appropriate amounts of insulin, replacing daily injections.
Laser treatment for diabetic eye disease, reducing the risk of blindness.
Successful transplantation of kidneys in people whose own kidneys fail due to the disease.
New drugs that treat type 2 diabetes and better ways to manage it through weight control.
Evidence that intensive management of blood glucose reduces and may prevent development of microvascular complications.
Demonstration that antihypertensive drugs called ACE-inhibitors prevent or delay kidney failure in people with diabetes.

steps to prevention & control

Eat well
Respect the 3 basic principles: quantity, quality and regularity. First, always watch how much you eat, especially foods that are high in carbohydrates. Second, include foods that contain lots of fiber in every meal, and limit food with high concentrations of fat. And finally, to better control your blood sugar, it's best to eat 3 meals a day and evenly distribute your carbs throughout the day.

Control your weight
When overweight people lose 4 to 9kg, they are better able to control their blood sugar. The risk of dying from cardiovascular diseases is 4 to 5 times greater among people who have diabetes than non-diabetics.

Get moving
People who exercise regularly have better control over their blood sugar levels. Hey, it also helps you lose those extra inches.

Check your blood sugar levels
Go to your doctor for regular check-ups and have your blood sugar levels checked out. If you already have diabetes, make sure to use your portable blood sugar indicator every day.

In addition to following this advice, it's important to see your physician regularly. And consult a dietician if you haven't already done so. These professionals will give you personalized guidance and tips, and motivate you to change some of your bad habits. After all, it's your own health we're talking about.

References: WebMd, Merck Frosst, HealthScout, LATimes.com

Article Suggested By:Viken Hagopian, Canada

Encouraging Women to Take Charge of Diabetes

2005-10-02T21:54:00.000-07:00

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Encouraging Women to Take Charge of Diabetes
By Michelle Meadows

November is National Diabetes Month, a perfect time to consider that about 2,200 people are diagnosed with diabetes every day, and that close to 800,000 will be diagnosed with the disease this year, according to the American Diabetes Association (ADA). Many people don't even know they have diabetes until they develop a serious complication such as blindness, kidney disease, nerve disease requiring amputation, heart disease, or stroke.

The Food and Drug Administration's Office of Women's Health, the ADA, the National Association of Chain Drug Stores, and 80 other organizations nationwide are planning a campaign that will focus on the early identification and control of diabetes. The campaign, scheduled for next year, will highlight the fact that about 8.1 million women in the United States have diabetes, and one-third of them don't know it.

Diabetes-related brochures, wallet-sized calendars, and recipe cards for nutritious meals will be distributed at grocery stores and pharmacies in 10 cities: Atlanta, Baltimore, Chicago, Dallas, Detroit, Indianapolis, Los Angeles, Miami, New Orleans, and Philadelphia.

Diabetes affects the body's ability to produce or respond to insulin. Insulin is a hormone that allows blood glucose (blood sugar) to enter the cells of the body and be used for energy. Diabetes falls into two main categories: Type 1, usually occurring during childhood or adolescence, and Type 2, the most common form of the disease, usually occurring in people older than 45.

A blood test can let you know in minutes whether you have diabetes, and "Get Tested" will be a key message of the campaign. The FDA encourages women to know the factors that put them at high risk for diabetes, including being overweight, being physically inactive, having a brother or sister with the disease, and being African American, Hispanic, Native American, Asian American, or Pacific Islander (see "Take the Risk Test").

Dezaree Pines-Wilusz, 47, of Bloomfield, Conn., has diabetes and recalls being amazed at reading a list of diabetes risk factors and checking them off one by one. She was overweight, is of African American and American Indian descent, and her father died of complications of diabetes. She also has a history of diabetes on her mother's side of the family.

For Pines-Wilusz, extreme exhaustion was the tip-off that something was wrong. As an insurance agent, she was used to keeping a hectic schedule. But in 1994, she felt like she'd been sapped of all her energy. "I found myself needing to come home in between business appointments or I would have to stop in the middle of vacuuming and rest," she says. Soon after reporting her unusual fatigue to the doctor, a test showed diabetes was the culprit.

Other warning signs of diabetes include frequent urination, unusual thirst, extreme hunger, unusual weight loss, and irritability. Recurring skin, gum, and bladder infections, blurred vision, cuts and bruises that are slow to heal, and tingling or numbness in the hands and feet are also possible symptoms. But often, people with Type 2 diabetes have no symptoms.

Other campaign messages will point out that diabetes is controllable and that women with diabetes should regularly check their blood sugar, that exercise is important, that women should use medicine wisely, and that a healthy diet for people with diabetes isn't so different than a healthy diet for anyone else. For example, lowering fat and cholesterol and eating lots of whole grains and vegetables are sound tips for everyone.

The FDA is also funding ongoing diabetes outreach through the Indian Health Service (IHS). "Portion control is an important message to get out to women in order to impact the escalating diabetes and obesity rates among American Indians and Alaska Natives," says Sandra Dodge, a women's health coordinator with the IHS. The agency is developing culturally-appropriate handouts to help American Indian women with diabetes manage portion sizes for meals. The project will target certain urban areas, as well as American Indian reservations. The overall prevalence of Type 2 diabetes is just over 12 percent in Native Americans versus 5 percent of the general population. In some tribes, half of the population has diabetes.

Diabetes is a unique condition for women. When compared with men, women have a 50 percent greater risk of diabetic coma, a condition brought on by poorly controlled diabetes and lack of insulin. Women with diabetes have heart disease rates similar to men, but more women with diabetes die from a first heart attack than do men with diabetes.

Diabetes also poses special challenges during pregnancy. Compared with women who don't have diabetes, women with diabetes are up to five times more likely to develop toxemia, a disorder marked by hypertension, protein in the urine, swelling, headache, and visual disturbances. Diabetes during pregnancy (gestational diabetes) results in an increased risk for problems such as high birth weight, birth defects, and other complications for the mother. Children born of mothers who developed gestational diabetes are more likely to be overweight or obese during adolescence and therefore are at greater risk for diabetes as well. Women who have had gestational diabetes are at increased risk for developing Type 2 diabetes later.

Birth control pills can affect blood glucose levels and diabetes control. And because women with diabetes are already at higher risk of infection, most women with diabetes should not use an intrauterine device because it may lead to infections.

It's difficult "always having at the back of your mind that this is a disease that could do so much damage and could even take you out of here," Pines-Wilusz says. "But it is also manageable." She takes the oral diabetes drug Glucophage (metformin), eats nutritious meals, and exercises regularly. "I know that controlling the disease reduces my risk of complications," Pines-Wilusz says.

"Losing weight is a constant battle," she adds, "but I'm working on it." Exercising, eating right, and sticking to a medication schedule are all part of learning how to take time for yourself. "We cannot let the stresses of everyday life get in the way of taking care of ourselves," says Pines-Wilusz. "We have to think about us, our future, the people we love. Nobody's going to do it for us."

For more information about diabetes, contact the American Diabetes Association at 1-800-342-2383 or visit www.diabetes.org. For tips to protect your eyes, heart, and feet, see "Diabetes: What to Know Head to Toe" (plain text version or printer-friendly PDF.)

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Take the Risk Test
Are you overweight?
Do you get little exercise?
Do you have high blood pressure? (130/80 or higher)
Do you have a brother or sister with diabetes?
Are you a woman who had diabetes when you were pregnant OR have you had a baby who weighed more than 9 pounds at birth?
Are you African American, Hispanic, Native American, Asian American, or Pacific Islander?
If you answered "yes" to any of these questions, ask your doctor for a diabetes test.

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Diabetes Prevention, Treatment

2005-10-02T21:53:00.000-07:00

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Diabetes Prevention, Treatment
By Linda Bren

Once seen only in adults, type 2 diabetes has been rising steadily in children and teens, especially black, Hispanic and American Indian adolescents, according to government reports from clinics nationwide. The longer a person has diabetes, the greater the chances of developing serious damage to the eyes, nerves, heart, kidneys, and blood vessels.

The Department of Health and Human Services (HHS), using revised American Diabetes Association guidelines, estimates that about 40 percent of Americans ages 40 to 74--or more than 41 million people--have "pre-diabetes," a condition in which people have higher than normal blood sugar levels but are not yet diagnosed as having diabetes.

The new estimate is more than double the previous estimate of 20.1 million people with pre-diabetes in this age group. Many people with pre-diabetes go on to develop type 2 diabetes within a decade.

HHS is working to reduce the health threat of diabetes that has already affected more than 18 million Americans--more than 6 percent of the U.S. population. Recent activities have focused on a new prevention campaign, a research symposium, and a study to identify the best treatment for type 2 diabetes in young people.

Targeting High-Risk Groups
In April 2004, HHS Secretary Tommy G. Thompson and the HHS-sponsored National Diabetes Education Program (NDEP) launched the first national multicultural diabetes prevention campaign, "Small Steps. Big Rewards. Prevent type 2 Diabetes."

"We need to act urgently to confront the epidemic of type 2 diabetes that is threatening Americans, especially minority populations," Thompson said in announcing the campaign. Blacks, Hispanics, American Indians and Alaska Natives, Asian-Americans and Pacific Islanders, and adults ages 60 and older are at particularly high risk for type 2 diabetes.

With type 2 diabetes, which accounts for up to 95 percent of all Americans with diabetes, either the body does not produce enough insulin, the hormone necessary to convert sugar and other food into energy, or the body's cells do not use insulin properly.

The campaign enlists the aid of community groups to help empower people at high risk to make modest lifestyle changes that can prevent or delay the onset of type 2 diabetes. Campaign materials, including consumer-friendly motivational tip sheets, are written in several languages specifically tailored for the high-risk groups.

"This campaign provides the tools to help those hardest hit by this growing epidemic to prevent the disease and its serious, deadly complications," said James R. Gavin III, M.D., Ph.D., chair of the NDEP and president of Morehouse School of Medicine in Atlanta . "If we are going to make a difference, we need to reach people where they live, work, and play, so we are partnering with community groups."

Targeting Prevention and Treatments
The exchange of ideas in scientific forums assists government regulators, researchers, and industry representatives in their efforts to prevent diabetes and improve the health of people with diabetes. One such forum, a two-day symposium sponsored by the Food and Drug Administration and the National Institutes of Health (NIH) in May 2004, included representatives from government, academia, research, industry, and diabetes patient advocacy groups.

"This conference will assist in generating ideas and identifying the kinds of problems we need to address if we're going to advance the development of innovative medical products," FDA Deputy Commissioner for Operations Janet Woodcock, M.D., said in her opening remarks at the symposium. "We need to translate scientific knowledge into new therapies to prevent and treat diabetes."

The rapid increase in the number of people with diabetes and those who are at risk for the disease is closely tracking the nation's escalating obesity rates. In March 2004, the Centers for Disease Control and Prevention (CDC) released a study that found that deaths due to obesity will soon overtake tobacco as the leading preventable cause of death. Overweight and obesity are key risk factors for developing type 2 diabetes.

"Research has clearly shown that losing 5 percent to 7 percent of body weight through diet and increased physical activity can prevent or delay pre-diabetes from progressing to type 2 diabetes," said Allen Spiegel, M.D., director of the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).

"Without intervention, 1 in 3 children born in the year 2000 will develop diabetes in their lifetime," said Frank Vinicor, M.D., M.P.H., director of the CDC's diabetes division. "For some of us, the risk is even higher. If that child is Hispanic and female, she has a 1 in 2 chance of developing diabetes in her lifetime. We need to get the word out that type 2 diabetes can be prevented."

The TODAY Study
The first clinical study sponsored by the NIDDK to focus on type 2 diabetes in young people has begun at 12 medical centers around the country. "Type 2 diabetes has increasingly become a problem in our young people," said NIH Director Elias A. Zerhouni, M.D. "This trial will give us the information we need to most effectively help these patients."

The five-year study, called Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY), will compare three treatments of type 2 diabetes in children and teens to determine how well and how long each treatment approach controls blood glucose levels. The treatments will involve FDA-approved diabetes drugs and lifestyle changes. Researchers plan to enroll 750 young people ages 10 to 17 who have been diagnosed with type 2 diabetes in the past two years.

TODAY is the first clinical study to look at the effects of intensive lifestyle change aimed at lowering weight by cutting calories and increasing physical activity in youths with type 2 diabetes. The American Diabetes Association is providing additional support for the study, which is also supported in part by LifeScan, GlaxoSmithKline, and Eli Lilly and Company.

"Obesity and type 2 diabetes are among the most serious health challenges facing America 's youth today," said Thompson. "We need to do all we can to develop strategies that encourage healthy eating and active lifestyles in our children."

Get Tested
A national survey conducted by the American Diabetes Association revealed that 7 out of 10 Americans are not aware of their blood glucose level, which is critical information for determining if a person has diabetes or pre-diabetes.

According to the NDEP, everyone over age 45 should consult with his or her health care provider about testing for pre-diabetes or diabetes. Those who are over 45 and overweight are strongly recommended for testing. Those younger than 45 who are overweight and have one or more of the other risk factors also should consult their health care provider about testing.

For More Information
American Diabetes Association
(800) DIABETES (342-2383)

Food and Drug Administration
Diabetes information page

Office of Women's Health
Take Time To Care ... About Diabetes

Información Rápida-Diabetes
Easy-to-read Spanish brochure

National Institute of Diabetes and Digestive and Kidney Diseases
National Diabetes Information Clearinghouse
(800) 860-8747

National Diabetes Education Program
Small Steps. Big Rewards. Prevent type 2 Diabetes campaign
(800) 438-5383

The TODAY study

Risk Factors for Diabetes
Age: Risk increases with age
Overweight: Body mass index (BMI) of 25 or higher (23 or higher if Asian-American, 26 or higher if Pacific Islander)
Blood pressure: 140 over 90 mm/Hg or higher
Cholesterol: Abnormal lipid levels-HDL cholesterol less than 40 mg/dL for men and less than 50 mg/dL for women; triglyceride level 250 mg/dL or higher
Family history of diabetes: Having a parent, brother, or sister with diabetes
Ethnicity: Black, American Indian, Alaska Native, Asian-American, Pacific Islander, or Hispanic heritage
History of diabetes in pregnancy or giving birth to a baby weighing more than 9 pounds
Inactive lifestyle: Exercise less than three times a week
Source: National Institute of Diabetes and Digestive and Kidney Diseases
>>http://www.fda.gov/fdac/features/2004/404_diabetes.html

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What Is Diabetes?

2005-10-02T07:54:00.000-07:00

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What Is Diabetes?

Provided by ehealthMD.com

Diabetes is a problem with the body's fuel system. It is caused by lack of insulin, a hormone made in the pancreas (an organ that secretes enzymes needed for digestion) that is essential for getting energy from food. There are two kinds of diabetes:

In type 1 diabetes, which usually starts in children, the body stops making insulin completely.
In type 2 diabetes, also called adult-onset diabetes, the body still makes some insulin, but cannot use it properly.

Most adults with diabetes have type 2; in fact, type 2 diabetes accounts for 90 percent of all diabetes cases.

How Insulin Works
Food is digested in the stomach and intestines, and carbohydrates are broken down into sugar molecules, or glucose. Glucose is then absorbed into the bloodstream, and blood glucose levels rise. This rise in blood sugar normally signals special cells in the pancreas, called beta cells, to release the right amount of insulin.

Insulin allows glucose and other nutrients (such as amino acids from proteins) to enter muscle cells. There, they can be stored for later or burned for energy.

When the body has a problem making insulin or the cells do not respond to insulin in the right way, diabetes results

Facts About Diabetes in Adults

About 16 million people in the U.S. have type 2 diabetes. Half those people are unaware that they have the condition.
Diabetes contributes to the deaths of more than 190,000 Americans per year.
Diabetes often leads to blindness, heart and blood vessel disease, strokes, kidney failure, amputations, and nerve damage.
Uncontrolled diabetes can complicate pregnancy and put a mother at risk for having a baby with birth defects.
In 1997, diabetes cost the United States $98 billion, including $54 billion in indirect costs (such as disability payments and lost work time) and $44 billion in direct medical costs.
Obesity raises the risk for diabetes by as much as 93%, and an inactive lifestyle can raise it by as much as 25%.

Last Reviewed: 2002 by YourMedicalSource.com

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Diabetes insipidus

2005-10-02T07:53:00.000-07:00

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Diabetes insipidus
From Wikipedia, the free encyclopedia.
Diabetes insipidus
ICD-10 code: E23.2
ICD-9 code: 253.5

Diabetes without a modifier usually refers to diabetes mellitus.
Diabetes insipidus (DI) is a disease characterized by excretion of large amounts of severely diluted urine, which cannot be reduced when fluid intake is reduced. It denotes inability of the kidney to concentrate urine. DI is caused by a deficiency of antidiuretic hormone, or by an insensitivity of the kidneys to that hormone.

Contents [hide]
1 Signs and symptoms
2 Diagnosis
3 Pathophysiology
4 Treatment
5 Sources

Signs and symptoms
Excessive urination and extreme thirst (especially for cold water) are typical for DI. Symptoms of diabetes insipidus are quite similar to those of severely deranged diabetes mellitus, with the distinction that the urine is not sweet and there is no hyperglycemia (elevated blood glucose). Blurred vision is a rarity.

The extreme urination continues throughout the day and the night. In children, DI can interfere with appetite, eating, weight gain, and growth as well. They may present with fever, vomiting, or diarrhea. Adults with untreated DI may remain healthy for decades as long as enough water is drunk to offset the urinary losses. However, there is a continuous risk of dehydration.

Diagnosis
In order to distinguish DI from other causes of excess urination, blood glucose, bicarbonate and calcium need to be tested. Electrolytes can show substantial derangement; hypernatremia (excess sodium levels) are common in severe cases. Urinalysis shows low electrolyte levels, and measurement of urine osmolarity (or specific gravity) is generally low.

A fluid deprivation test helps determine whether DI is caused by:

excessive intake of fluid
a defect in ADH production
a defect in the kidneys' response to ADH
This test measures changes in body weight, urine output, and urine composition when fluids are withheld. Sometimes measuring blood levels of ADH during this test is also necessary.

To distinguish between the main forms, desmopressin stimulation is also used; desmopressin can be taken by injection, a nasal spray, or a tablet. While taking desmopressin, a patient should drink fluids or water only when thirsty and not at other times, as this can lead to sudden fluid accumulation in central DI. If desmopressin reduces urine output and increases osmolarity, the pituitary production of ADH is deficient, and the kidney responds normally. If the DI is due to renal pathology, desmopressin does not change either urine output or osmolarity.

If central DI is suspected, testing of other hormones of the pituitary, as well as magnetic resonance imaging (MRI), is necessary to discover if a disease process (such as a prolactinoma) is affecting pituitary function.

Pathophysiology
Electrolyte and volume homeostasis is a complex mechanism that balances the body's requirements for blood pressure and the main electrolytes sodium and potassium. In general, electrolyte regulation precedes volume regulation. When the volume is severely depleted, however, the body will retain water at the expense of deranging electrolyte levels.

The regulation of urine production is the hypothalamus, which produces antidiuretic hormone (ADH or vasopressin) in the posterior lobe of the pituitary gland. In addition, it regulates the sensation of thirst as perceived by the cortex.

The main effector organ for fluid homeostasis is the kidney. In response to ADH, it concentrates urine in the distal tubule.

There are several forms of DI:

Central diabetes insipidus is due to damage to the hypothalamus of pituitary due to a tumor, stroke, neurosurgery or some rather rare causes (which include hemochromatosis, sarcoidosis and some genetic disorders). If the hypothalamus is damaged, the feeling of thirst may be completely absent.
Nephrogenic diabetes insipidus is due to the inability of the kidney to respond normally to ADH. There are hereditary causes (90% are due to mutations of the ADH V2 receptor, and 10% mutations of the aquaporin 2 water channel), but these are rare (incidence is around 4 per million live births). Most are male, because V2 receptor mutations are x-linked recessive defects. More common are acquired forms of NDI, which occur as a side-effect to some medications (such as lithium citrate and amphotericin B), as well as in polycystic kidney disease (PKD) and sickle-cell disease, and electrolyte disturbances such as hypokalaemia and hypercalcaemia. In some cases, no cause is found.
Dipsogenic DI is due to a defect or damage to the thirst mechanism, which is located in the hypothalamus. This defect results in an abnormal increase in thirst and fluid intake that suppresses ADH secretion and increases urine output. Desmopressin is ineffective, and can lead to fluid overload as the thirst remains.
Gestational DI only occurs during pregnancy. While all pregnant women produce vasopressinase in the placenta, which breaks down ADH, this can assume extreme forms in GDI. Most cases of gestational DI can be treated with desmopressin. In rare cases, however, an abnormality in the thirst mechanism causes gestational DI, and desmopressin should not be used.

Treatment
Central DI and gestational DI respond to desmopressin. In dipsogenic DI, desmopressin is not an option.

Desmopressin will be ineffective in nephrogenic DI. Instead, the diuretic hydrochlorothiazide (HCT or HCTZ) or indomethacin can improve NDI; HCT is sometimes combined with amiloride to prevent hyperkalemia. Again, the patient should be reminded only to drink fluids when thirsty, and not at other times.

Sources
The public domain document "Diabetes Insipidus", NIH Publication No. 01-4620, December 2000.
Retrieved from "http://en.wikipedia.org/wiki/Diabetes_insipidus"

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Diabetes mellitus

2005-10-02T07:51:00.000-07:00

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Diabetes mellitus
From Wikipedia, the free encyclopedia.
(Redirected from Diabetes)
Diabetes mellitus
ICD-10 code: E10-E14
ICD-9 code: 250

This article is about the disease that features high blood sugar. The other major but far less common diabetes is diabetes insipidus ("water diabetes", DI).
Diabetes mellitus is a medical disorder characterized by varying or persistent hyperglycemia (elevated blood sugar levels), especially after eating. All types of diabetes mellitus share similar symptoms and complications at advanced stages. Hyperglycemia itself can lead to dehydration and ketoacidosis. Longer-term complications include cardiovascular disease (doubled risk), chronic renal failure (it is the main cause for dialysis), retinal damage which can lead to blindness, nerve damage which can lead to erectile dysfunction (impotence), gangrene with risk of amputation of toes, feet, and even legs. The more serious complications are all more common in those with poor glycemic control.

The most important forms of diabetes are due to decreased production of insulin (diabetes mellitus type 1, the first recognized form), or decreased sensitivity of body tissues to insulin (diabetes mellitus type 2, the more common form). The former requires insulin injections, while the latter is generally managed with oral medication and only requires insulin if the tablets are ineffective.

Patient understanding and participation is vital as blood glucose levels change continuously, while successfully keeping blood sugar within normal limits has been compellingly shown to reduce or prevent development of some of the complications of diabetes. Other risk factors that can require addressing to reduce complications are: cessation of smoking, optimizing cholesterol levels, maintaining a stable body weight, controlling high blood pressure and engaging in regular exercise.

Contents
1 Statistics
2 Causes and types
2.1 The role of insulin
2.2 Type 1 diabetes mellitus
2.3 Type 2 diabetes mellitus
2.4 Type 3 diabetes mellitus
2.5 Gestational diabetes mellitus
2.6 Genetics
3 Diagnosis
3.1 Signs and symptoms
3.2 Diagnostic approach
3.3 Criteria for diagnosis
3.4 Diabetic ketoacidosis and coma
3.5 Hypoglycemia
4 Long-term complications
5 Management of the disease
5.1 Medication
5.2 Other treatment
5.3 Monitoring
6 Public health, policy and health economics
7 History
8 Etymology
9 References
10 See also
11 External links

Statistics
In 2004, according to the World Health Organization, more than 150 million people worldwide suffer from diabetes. Its incidence is increasing rapidly, and it is estimated that by the year 2025 this number will double. Diabetes mellitus occurs throughout the world, but is more common (especially type 2) in the more developed countries. The greatest increase in prevalence rate is, however, expected to occur in Asia and Africa, where most of the diabetic patients will be seen by 2025. The increase in incidence of diabetes in the developing countries follows the trend of urbanisation and life style changes.

Diabetes is in the top 10, and perhaps the top 5, of the most significant diseases in the developed world, and is gaining in significance (see big killers).

For at least 20 years, diabetes rates in North America have been increasing substantially. In 2002 there were about 18.2 million diabetics in the United States alone. The Centers for Disease Control has termed the change an epidemic. The National Diabetes Information Clearinghouse estimates that diabetes costs $132 billion in the United States alone every year.

Causes and types

The role of insulin

Mechanism of insulin release in normal pancreatic beta cells (ie, glucose dependence). Insulin production does not depend on blood glucose levels; insulin is stored pending releaseSince insulin is the principal hormone that regulates uptake of glucose into cells (primarily muscle and fat cells) from the blood, deficiency of insulin or its action plays a central role in all forms of diabetes.

Most of the carbohydrates in food are rapidly converted to glucose, the principal sugar in blood. Insulin is produced by beta cells in the pancreas in response to rising levels of glucose in the blood, as occurs after a meal. Insulin makes it possible for most body tissues to remove glucose from the blood for use as fuel, for conversion to other needed molecules, or for storage. Insulin is also the principal control signal for conversion of glucose (the basic sugar unit) to glycogen for storage in liver and muscle cells. Lowered insulin levels result in the reverse conversion of glycogen to glucose when glucose levels fall -- though only in the liver not muscle tissue. Higher insulin levels increase many anabolic ("building up") processes such as cell growth, cellular protein synthesis, and fat storage. Insulin is the principal signal in converting many of the bidirectional processes of metabolism from a catabolic to an anabolic direction.

If the amount of insulin produced is insufficient, if cells respond poorly to the effects of insulin (insulin insensitivity or resistance), or if the insulin itself is defective, glucose is not handled properly by body cells (about 2/3 require it) nor stored appropriately in the liver and muscles. The net effect is persistent high levels of blood glucose, poor protein synthesis, and other metabolic derangements.

Type 1 diabetes mellitus
Type 1 diabetes is most commonly diagnosed in children and adolescents, but can occur in adults as well. It is an autoimmune disorder, in which the body's own immune system attacks the beta cells in the Islets of Langerhans of the pancreas, destroying them or damaging them sufficiently to reduce insulin production. The autoimmune attack may be triggered by reaction to an infection, for example by one of the viruses of the Coxsackie virus family. A subtype of type 1 (identifiable by the presence of antibodies against beta cells) develops slowly and so is often confused with Type 2. In addition, a small proportion of type 1 cases has the hereditary condition maturity onset diabetes of the young (MODY).

Some poisons (e.g. certain rat poisons) work by selectively destroying certain types of cells, including pancreatic beta cells, thus producing "artificial" type 1 diabetes. Other pancreatic problems including trauma, pancreatitis or tumors (either malignant or benign) can also lead to loss of insulin production.

Currently, type 1 is treated with insulin injections, lifestyle adjustments, and careful monitoring of blood glucose levels using blood test kits. Insulin delivery is also available by an insulin pump, which allows the infusion of insulin 24 hours a day at preset levels, and the ability to program push doses (bolus) of insulin as needed at meal times. The treatment must be continued indefinitely. Experimental replacement of beta cells (by transplant) is being investigated in several research programs and may become clinically available in the future.

About 5-10% of all North American cases of diabetes are Type 1 diabetics. The fraction of type 1 diabetics in other parts of the world differs; this is likely due to both differences in the rate of type 1 and differences in the rate of other types, most prominently type 2. Most of this difference is not currently understood.

Formerly, type 1 diabetes was called "childhood" or "juvenile" diabetes or "insulin dependent" diabetes. Each term is a misnomer, especially since the obesity epidemic in recent years has led to increased incidence of type 2 diabetes in children and adolescents in the USA, and insulin is used in some type 2 cases.

Type 2 diabetes mellitus
Main Article diabetes mellitus type 2

Type 2 diabetes is characterized by "insulin resistance" as body cells do not respond appropriately when insulin is present. This is a more complex problem than type 1, but is sometimes easier to treat, since insulin is still produced, especially in the initial years. Type 2 may go unnoticed for years in a patient before diagnosis, since the symptoms are typically milder (no ketoacidosis) and can be sporadic. However, severe complications can result from unnoticed type 2 diabetes, including renal failure, and coronary artery disease.

Type 2 is initially treated by changes in diet and through weight loss. This can restore insulin sensitivity, even when the weight lost is modest e.g. around 5 kg (10 to 15 lb). The next step, if necessary, is treatment with oral antidiabetic drugs: the sulphonylureas, metformin, or (if these are insufficient) thiazolidinediones. When these have failed, insulin therapy may be necessary to maintain normal glucose levels.

Type 3 diabetes mellitus
One classification system called all other forms of diabetes that do not fit into type 1 or type 2 or gestational diabetes as type 3 diabetes. This nomenclature is rarely used.

Type 3A: genetic defect in beta cells.
Type 3B: genetically related insulin resistance.
Type 3C: diseases of the pancreas.
Type 3D: caused by hormonal defects.
Type 3E: caused by chemicals or drugs.

Gestational diabetes mellitus
Main article: Gestational diabetes mellitus

Gestational diabetes mellitus appears in about 2-5% of all pregnancies. It is temporary and fully treatable, but if untreated it may cause problems with the pregnancy, including macrosomia (high birth weight) of the child. It requires careful medical supervision during the pregnancy. In addition, about 20-50% of these women go on to develop type 2 diabetes.

Genetics
Both type 1 and type 2 diabetes are at least partly inherited. Type 1 diabetes appears to be triggered by infection, stress, or environmental factors (e.g. exposure to a causative agent). There is a genetic element in the susceptibility of individuals to some of these triggers which has been traced to particular HLA genotypes (i.e. genetic "self" identifiers used by the immune system). However, even in those who have inherited the susceptibility, type 1 diabetes mellitus seems to require an environmental trigger. A small proportion of type 1 diabetics carry a mutation that causes maturity onset diabetes of the young (MODY).

There is an even stronger inheritance pattern for Type 2 diabetes; those with type 2 ancestors or relatives have very much higher chances of developing Type 2. Concordance among monozygotic twins is close to 100%, and 25% of those with the disease have a family history of diabetes. It is also often connected to obesity, which is found in approximately 85% of (North American) patients diagnosed with that form of the disease, so inheriting a tendency toward obesity seems also to contribute. Age is also thought to be a contributing factor, as most type 2 patients in the past were older. The exact reasons for these connections are unknown.

Diagnosis

Signs and symptoms
Type 2 diabetes almost always has a slow onset (often years), but in type 1, particularly in children, onset may be quite fast (weeks or months). Early symptoms of type 1 diabetes are often polyuria (frequent urination) and polydipsia (increased thirst, and consequent increased fluid intake). There may also be weight loss (despite normal or increased eating), increased appetite, and irreducible fatigue. These symptoms may also manifest in Type 2 diabetes in patients who present with frank poorly controlled diabetes.

Thirst develops because of osmotic effects — sufficiently high glucose (above the 'renal threshold') in the blood is excreted by the kidneys but this requires water to carry it and causes increased fluid loss, which must be replaced. The lost blood volume will be replaced from water held inside body cells, causing dehydration.

Another common presenting symptom is altered vision. Prolonged high blood glucose causes changes in the shape of the lens in the eye, leading to blurred vision and, perhaps, a visit to an optometrist. All unexplained quick changes in eyesight should force a fasting blood glucose test. These are now quick (less than 5 minutes total), inexpensive (materials less than USD $1), and can be safely performed by almost anyone with trivial training.

Especially dangerous symptoms in diabetics include the smell of acetone on the patient's breath (a sign of ketoacidosis), Kussmaul breathing (a rapid, deep breathing), and any altered state of consciousness or arousal (hostility and mania are both possible, as is confusion and lethargy). The most dangerous form of altered consciousness is the so-called "diabetic coma" which produces unconsciousness. Early symptoms of impending diabetic coma include polyuria, nausea, vomiting and abdominal pain, with lethargy and somnolence a later development, progressing to unconsciousness and death if untreated.

Diagnostic approach
The diagnosis of type 1 diabetes and many cases of type 2 is usually prompted by recent-onset symptoms of excessive urination (polyuria) and excessive thirst (polydipsia), often accompanied by weight loss. These symptoms typically worsen over days to weeks; about 25% of people with new type 1 diabetes have developed a degree of diabetic ketoacidosis by the time the diabetes is recognized.

The diagnosis of other types of diabetes is made in many other ways. The most common are (1) health screening, (2) detection of hyperglycemia when a doctor is investigating a complication of longstanding, unrecognized diabetes, and less commonly (3) new signs and symptoms attributable to the diabetes.

Diabetes screening is recommended for many types of people at various stages of life or with several different risk factors. The screening test varies according to circumstances and local policy and may be a random glucose, a fasting glucose and insulin, a glucose 2 hours after 75 g of glucose, or a formal glucose tolerance test. Many health care recommendations for adults recommend universal screening at age 40 or 50 years, and sometimes occasionally thereafter. Earlier screening is recommended for those with risk factors such as obesity, family history of diabetes, high risk ethnicity (Hispanic [Latin American], American Indian, African American, Pacific Island, and South Asian ancestry).
Many medical conditions are associated with a higher risk of various types of diabetes and warrant screening. A partial list includes: high blood pressure, elevated cholesterol levels, coronary artery disease, past gestational diabetes, polycystic ovary syndrome, chronic pancreatitis, hepatic steatosis (fatty liver), cystic fibrosis, several mitochondrial neuropathies and myopathies, myotonic dystrophy, Friedreich's ataxia, some of the inherited forms of neonatal hyperinsulinism and many others. Risk of diabetes is higher with chronic use of several medications, including high dose glucocorticoids, some chemotherapy agents (especially L-asparaginase), and some of the antipsychotics and mood stabilizers (especially phenothiazines and some atypical antipsychotics).
Diabetes is often detected when a person suffers a problem frequently caused by diabetes, such as a heart attack, stroke, neuropathy, poor wound healing or a foot ulcer, certain eye problems, certain fungal infections, or delivering a baby with macrosomia or hypoglycemia.

Criteria for diagnosis
Diabetes mellitus is characterized by recurrent or persistent hyperglycemia, and is diagnosed by demonstrating any one of

two fasting plasma glucose levels above 7 mmol/l (125 mg/dl) on different days;
plasma glucose above 11.1 mmol/l (200 mg/dl) two hours after a 75 g glucose load; or
symptoms of diabetes and a random glucose above 11.1 mmol/l (200 mg/dl).
While not used for diagnosis, an elevated glucose bound to hemoglobin, HbA1c, of 6.0% or higher (2003 revised US standard); is a screening and treatment-tracking test reflecting average blood glucose levels over the preceding 90 days (approximately).

Diabetic ketoacidosis and coma
See more detail in the articles diabetic ketoacidosis and diabetic coma

Diabetic ketoacidosis (DKA) is an acute, dangerous complication and is always a medical emergency. Prompt proper treatment usually results in full recovery, though death can result from inadequate treatment or a variety of complications.

Hyperosmotic diabetic coma is another acute problem associated with improper management of diabetes mellitus. It has some symptoms in common with DKA, but a different cause, and requires different treatment. In anyone with very high blood glucose levels (usually considered to be above 16.6 mmol/l (300 mg/dl)) water will be osmotically driven out of cells into the blood. The kidneys will also be "dumping" glucose into the urine, resulting in concomitant loss of water, causing an increase in blood osmolality. The osmotic effect of high glucose levels combined with the loss of water will eventually result in such a high serum osmolality that the body's cells may become directly affected as water is drawn out from them. Electrolyte imbalances are also common. This combination of changes, especially if prolonged, will result in symptoms similar to ketoacidosis, including loss of consciousness. As with DKA, urgent medical treatment is necessary. This is the diabetic coma to which type 2 diabetics are prone; it is less common in type 1 diabetics.

Hypoglycemia
Hypoglycemia in diabetic patients almost always arises as a result of poor management of the disease either from too much or poorly timed insulin or oral hypoglycemics or too much exercise, not enough food, or poor timing of either. If blood glucose levels are low enough, the patient may become agitated, sweaty, and have many symptoms of sympathetic activation of the autonomic nervous system - they may experience feelings similar to dread and immobilized panic. Consciousness can be altered, or even lost, in extreme cases, leading to coma and/or seizures or even death and brain damage. Experienced diabetics can often recognise the symptoms early on - all diabetics should always carry something sugary to eat or drink as these symptoms can be rapidly reduced if treated early enough. In the case of children, this can be a type of candy disliked by the patient, to prevent concerns about unnecessary use.

Other ways of treating hypoglycemia include an injection of glucagon which causes the liver to convert its internal stores of glycogen to be released as glucose into the blood. Oral or intravenous dextrose can also be given. In most cases, recovery is rapid and troublefree. Longstanding hypoglycemia may require hospital admission to allow supervised recovery and adjustment of diabetic medications.

Long-term complications
Among the major risks of the disorder are chronic problems affecting multiple organ systems which will eventually arise in patients with poor glycemic control. Many of these arise from damage to the blood vessels. These illnesses can be divided into those arising from large blood vessel diseases, macroangiopathy, and those arising from small blood vessel disease, microangiopathy. Interestingly, small vessel disease is minimized by tight blood glucose control, but large vessel disease is unaffected by tight blood glucose control.

Small vessel disease complications:
proliferative retinopathy and macular edema which can lead to severe vision loss or blindness;
peripheral neuropathy which, particularly when combined with damaged blood vessesls, can lead to foot ulcers, and possibly progressing to necrosis, infection and gangrene, sometimes requiring limb amputation, see below
diabetic nephropathy (due to microangiopathy) which can lead to renal failure
Large vessel disease complications:
ischemic heart disease caused by both large and small vessel disease
stroke
peripheral vascular disease which contributes to foot ulcers and the risk of amputation
Diabetes mellitus is the most common cause of adult kidney failure worldwide. It also the most common cause of amputation in the US, usually toes and feet, often as a result of gangrene, and almost always as a result of peripheral vascular disease. Retinal damage (from microangiopathy) makes it the most common cause of blindness among non-elderly adults in the US. A number of studies have found that those with diabetes are more at risk for dry eye syndrome[1] [2] [3].

Management of the disease
Diabetes is a chronic disease with no cure (except experimentally in type 1 diabetics) as of 2005. Management of this disease may include lifestyle modifications such as achieving and maintaining proper weight, diet, exercise and foot care.

Medication
The most important is the hypoglycemic treatment with either oral hypoglycemics and/or insulin therapy. Nowadays, the goal for diabetics is to avoid or minimize chronic diabetic complications, as well as to avoid acute problems of hyperglycemia or hypoglycemia.

Adequate control of diabetes leads to a lower risk of the complications of uncontrolled diabetes which include kidney failure (requiring dialysis or transplant), blindness, heart disease and limb amputation.

There is emerging solid evidence that full-blown diabetes mellitus type 2 can be evaded in those with only mildly impaired glucose tolerance6.

Patients with type 1 diabetes mellitus require direct injection of insulin as their bodies cannot produce enough (or even any) insulin. As of 2005, there is no other clinically available form of insulin administration other than injection for patients with type 1: injection can be done by insulin pump, by jet injector, or any of several forms of hypodermic needle. There are several insulin application mechanisms under experimental development as of 2004. There have also been proposed vaccines for type I using glutamic acid decarboxylase (GAD), but these are currently not being tested by the pharmaceutical companies that have sublicensed the patents to them.

For type 2 diabetics, diabetic management consists of a combination of diet, exercise, and weight loss, in any achievable combination depending on the patient. Patients who have poor diabetic control after lifestyle modifications are typically placed on oral hypoglycemics. Some Type 2 diabetics eventually fail to respond to these and must proceed to insulin therapy.

Patient education and compliance with treatment is very important in managing the disease. Improper use of medications and insulin can be very dangerous causing hypo- or hyper-glycemic episodes.

Insulin therapy requires close monitoring and a great deal of patient education, as improper administration is quite dangerous. For example, when food intake is reduced, less insulin is required. A previously satisfactory dosing may be too much if less food is consumed causing a hypoglycemic reaction if not intelligently adjusted. In addition, exercise decreases insulin requirements as exercise increases glucose uptake by body cells whose glucose uptake is controlled by insulin. And vice versa. In addition, there are available several types of insulin with varying times of onset and duration of action.

Other treatment
As diabetes is a prime risk factor for cardiovascular disease, controlling other risk factors as well as the diabetes is one of the facets of diabetes management. Checking cholesterol, LDL, HDL and triglyceride levels may indicate hyperlipoproteinemia, which may warrant treatment with hypolipidemic drugs. Checking the blood pressure and keeping it within strict limits (using diet and antihypertensive treatment) protects against the retinal, renal and cardiovascular complications of diabetes. Regular follow-up by podiatrist or other foot health specialists is encouraged to prevent the development of diabetic foot.

Monitoring

An older style portable blood glucose meter. A blood sample is applied to an inserted strip (see image below) and color changes caused by reaction with blood glucose are measured by the meter.Optimal management of diabetes involves patients measuring and recording their own blood glucose testing at home. By keeping a diary of their own blood glucose measurements and noting the effect of food and exercise, patients can modify their lifestyle to better control their diabetes. For patients on insulin, patient involvement is important in achieving effective dosing and timing.

Relying on their own perceptions of symptoms of hyperglycemia or hypoglycemia is usually unsatisfactory as mild to moderate hyperglycemia causes no obvious symptoms in nearly all patients. Other considerations include the fact that, while food takes several hours to be digested and absorbed, insulin administration can have glucose lowering effects for as little as 2 hours or 24 hours or more (depending on the nature of the insulin preparation used and individual patient reaction). In addition, the onset and duration of the effects of oral hypoglycemic agents vary from type to type and from patient to patient.

A useful test that can be done in a doctor's clinic is the measurement of blood HbA1C levels. This is the ratio of glycosylated red blood cells in relation to the total number of red blood cells. Persistent raised plasma glucose levels causes the proportion of these cells to go up. This is a test that measures the average amount of diabetic control over a period originally thought to be about 3 months (the average red blood cell lifetime), but more recently thought to be about 2 to 4 weeks. In the non-diabetic, the HbA1C level ranges from 4.0-6.4%; patients with diabetes mellitus who manage to keep their HbA1C level below 7.0% are considered to have good glycaemic control.

Regular blood testing especially more so in type 1 diabetics is essential to keep a tight reign on the symptoms of the disease. There are many (at least 20+) different types of blood monitoring devices available on the market today; not every meter suits all patients and it is a specific matter of choice for the patient to find a meter that they personally find comfortable to use. The principle of the devices is the virtually the same, a small blood sample is collected by the patient by self-production using a lancing device (a sterile pointed needle) the blood is usually collected at the end point to a test strip. This test strip contains various chemicals which when the blood is applied creates a small electrical charge between two contacts. This charge will vary dependent on the glucose levels within the blood and its effect on the chemicals contained within the strip. In older glucose meters, the drop of blood is placed on top of a strip. A chemical reaction occurs and the strip changes color. The meter then measures the color of the strip optically.

It is this level that is measured and a result in either mg/dL (milligrams per deciliter in the USA) or mmol/L (millimoles per litre in Europe) of blood. The average normal person should have a glucose level of around 4.5 to 7.0 mmol/L (80 to 125 mg/dL). In the diabetic patient, more specifically type 2 patients, it is important to maintain good glucose control, with a before meal level of <6.1 mmol/L (<110 mg/dL) and a level two hours after the start of a meal of <7.8 mmol/L (<140 mg/dL)12.

A level of <3.8 mmol/L (<70 mg/dL) is usually described as a hypoglycaemic attack. Most diabetics 'know' when they're going to 'go hypo' and usually are able to eat some food or drink something sweet to raise levels. It is important to remember though, that a patient who is hyperglycemic (high glucose) can also become temporarily hypoglycemic under certain conditions (i.e. not eating regularly, or strenuous exercise, followed by fatigue).

Levels greater than 13-15 mmol/L (230-270 mg/dL) should be monitored closely and the patient is advised to seek urgent medical attention as soon as possible if this continues to rise after 2-3 tests.

Hyperglycemia is not as easy to detect as hypoglycemia and usually happens over a period of days rather than hours or minutes. If left untreated this can result in diabetic coma and death.

A blood glucose test strip for an older style (ie, optical color sensing) monitoring systemProlonged and elevated levels of glucose in the blood, which is left unchecked and untreated will, over time, result in serious diabetic complications and sometimes even death. It is therefore highly important that a diabetic patient checks their blood levels either daily or every few days to see what levels they are achieving over a given period of time. There is also computer software for the PC which is available from blood testing manufacturers which can display results and trends over time. Type 1 patients will have to check on a more regular daily basis due to insulin therapy, which is a fine art to master. The US Food and Drug Administration has also approved a non-invasive blood glucose monitoring device [4]. This allows checking blood glucose levels, while puncturing the skin as little as twice a day. Once calibrated with a blood sample, it pulls body fluids from the skin using small electrical currents, taking six readings an hour for as long as thirteen hours. It has not proven to be reliable enough, or convenient enough to be used in lieu of conventional blood monitoring. Other non-invasive methods like radiowaves, ultrasound and energy waves are also being tested.

These results are especially useful for the diabetic to present to their doctor or physician in the monitoring and control of the disease. Failure to maintain a strict regimen of testing can accelerate symptoms of the condition, and it is therefore imperative that any diabetic patient strictly monitor their glucose levels regularly.

Public health, policy and health economics
The Declaration of St Vincent was the result of international efforts to improve the care accorded to diabetics. Doing so is important if only economically. Diabetes is enormously expensive for healthcare systems and governments. In North America, it is the largest single non-traumatic cause in adults of amputation, blindness, and dialysis, all extremely expensive events.

Work in the Puget Sound area of North America (by the health organization Group Health) shows that, over its large and varied patient population, specially retaining medical information on diabetic patients, keeping it up to date, and basing their continuing care on that data reduced total healthcare costs for those patients by US$1000 per year per patient for the rest of life. Recognition of this reality drove the Hawkes Bay initiative which established such a system, and resulted in various activities throughout the world including the Black Sea Telediab project which produced elements of a distributed diabetic record and management system as an open source computer program.

History
Although diabetes has been recognized since antiquity, and treatments were known since the Middle Ages, the elucidation of the pathogenesis of diabetes occurred mainly in the 20th century7.

Until 1922, when insulin was first discovered and made clinically available, a clinical diagnosis of diabetes was an invariable death sentence, more or less quickly. Non-progressing type 2 diabetics almost certainly often went undiagnosed then; many still do.

The discovery of the role of the pancreas in diabetes is generally credited to Joseph Von Mering and Oskar Minkowski, two European researchers who, in 1889, found that when they completely removed the pancreas of dogs, the dogs developed all the signs and symptoms of diabetes and died shortly afterward. In 1910, Sir Edward Albert Sharpey-Schafer of Edinburgh in Scotland suggested diabetics were deficient in a single chemical that was normally produced by the pancreas - he proposed calling this substance insulin.

The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was not fully clarified until 1921, when Sir Frederick Grant Banting and Charles Herbert Best repeated the work of Von Mering and Minkowski but went a step further and managed to show that they could reverse the induced diabetes in dogs by giving them an extract from the pancreatic islets of Langerhans of healthy dogs8. They went on to isolate the hormone insulin from bovine pancreases at the University of Toronto in Canada.

This led to the availability of an effective treatment - insulin injections - and the first clinical patient was treated in 1922. For this, Banting et al received the Nobel Prize in Physiology or Medicine in 1923. The two researchers did not patent their discovery and insulin therapy rapidly spread around the world.

The distinction between what is now known as type 1 and type 2 diabetes was made by Sir Harold Percival (Harry) Himsworth in 1935; he published his findings in January 1936 in The Lancet9.

Other landmark discoveries7 include:

identification of sulfonylureas in 1942
the radioimmunoassay for insulin, as discovered by Rosalyn Yalow and Solomon Berson (gaining Yalow the 1977 Nobel Prize in Physiology or Medicine);
Reaven's introduction of the metabolic syndrome in 1988
identification of thiazolidinediones as effective antidiabetics in the 1990s.

Etymology
"Diabetes" is a Greek word meaning "a passer through; a siphon". "Mellitus" comes from the Greek word "sweet". Apparently, the Greeks named it thus because the excessive amounts of urine diabetics produce (when blood glucose is too high) attracted flies and bees because of the glucose content. The ancient Chinese tested for diabetes by observing whether ants were attracted to a person's urine; medieval European doctors tested for it by tasting the urine themselves, a scene occasionally depicted in Gothic reliefs.

It is probably important to note that passing abnormal amounts of urine is a symptom shared by several diseases (most commonly of the kidneys), and the single word diabetes is applied to many of them. The most common of them are diabetes insipidus and the subject of this article, diabetes mellitus.

References
Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977-86. Fulltext. PMID 8366922.
World Health Organisation, Department of Noncommunicable Disease Surveillance. Definition, Diagnosis and Classification of Diabetes Mellitus and its Complications. Geneva: WHO, 1999 (PDF)
UK Prospective Diabetes Study Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-53. PMID 9742976.
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See also
list of terms associated with diabetes
list of celebrities with diabetes
diabetes in cats and dogs
HbA1c

External links
MedlinePlus Diabetes from the U.S. National Library of Medicine
Children with Diabetes
MyWebMD Diabetes Section
Canadian Diabetes Association
Juvenile Diabetes Research Foundation
American Diabetes Association
International Diabetes Federation
WHO - The Diabetes Programme
Health A to Z Diabetes Type 2 Section
Health Canada Diabetes Type 2 Risk Evaluation
Center for Disease Control Diabetes Section
The Immunology of Diabetes Society
Informative Book on Basic and Clinical information on Type 1 Diabetes from Barbara Center for Childhood Diabetes
Journals on Basic and clinical research in Diabetes cure and care
Diabetes Type 2 Risks
Diabetes UK
Retrieved from "http://en.wikipedia.org/wiki/Diabetes_mellitus"

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