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Insulin Resistance and Clinical Trials

Polycystic Ovary Syndrome

Insulin resistance is a condition that is getting more and more recognition as an important cause of many other diseases. These include diabetes, many cases of hypertension, atherosclerotic heart disease and polycystic ovary syndrome. As we learn more and more about insulin resistance, our understanding is changing profoundly the way we see health and disease in many adult and pediatric patients. For example, some experts recently noted that insulin resistance is the leading cause of heart attack in the United States. Therefore, gaining a good understanding of this problem and its treatments may be very important for many of us.

The Nature of Insulin Resistance

Insulin is a protein hormone, which is secreted by the pancreas and has many functions in the body. One of these functions is to stimulate muscle to take up sugar and fat to take up the building blocks of fat, called fatty acids.This is the way that insulin lowers blood sugar and regulates how the body uses or stores fats for energy.

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Some people have an inherited defect in this particular, food storage action of insulin. This problem occurs because of a variety of possible defects that occur in how insulin stimulates muscle or fat cells to take up glucose or fatty acids from the blood and store these nutrients. This problem is called insulin resistance, or a resistance in muscle and fat to the stimulation by insulin.

In addition, liver is a target of insulin action. Insulin exerts a number of metabolic effects in the liver. One of them is to reduce the production of sugar or glucose by the liver. When a person is fasting, and the body needs energy, the liver can take proteins and fats and convert them to sugar. This metabolic function of the liver is called gluconeogenesis. Insulin reduces this function of the liver. In people with insulin resistance, this function of insulin is defective, and, despite the presence of insulin, the liver produces glucose.

Insulin Resistance and Insulin Excess

When a person develops insulin resistance, the pancreas attempts to cope with the apparent reduction in insulin effect by secreting more insulin. Thus, insulin resistant patients tend to have higher blood levels of insulin than normal people.

However, insulin resistance is associated with other metabolic changes, almost all adverse. These people develop increases in blood pressure, in part, because insulin causes salt and water retention by the kidneys. Insulin-resistant people also develop various abnormalities in cholesterol and fat (triglyceride) metabolism. And, for a variety of reasons, pre-menopausal, insulin-resistant women develop changes in ovarian hormone secretion.

Changes in Ovarian Hormone Secretion and Polycystic Ovary Syndrome (PCOS) The ovary secretes estrogens, progesterone, and, usually, modest amounts of a weak male sex hormone, known as DHEA (dihydroepiandrosterone). Usually, the ovary is stimulated to secrete these hormones by two pituitary hormones, FSH (follicle stimulating hormone) and LH (lutenizing hormone). There is a monthly rhythm to the secretion of these two pituitary hormones, which causes the normal monthly cycle of estrogen and progesterone secretion.

In insulin resistance and polycystic ovary, LH secretion is excessive and prolonged. This leads to the cystic development of multiple ovarian follicles and to increased DHEA secretion. The DHEA is converted to testosterone by other tissues. The more severe the insulin-resistance, the more severe these abnormalities in ovarian function are.

Treatment of Insulin-Resistance and Polycystic Ovary Syndrome

There are two primary components of treatment of insulin resistance and PCOS. The first is diet. The second is the drug, metformin (brand name, Glucophage), which is also used in the treatment of diabetes.

Weight loss is the most important part of treatment. The more weight the insulin-resistant person loses, the less severe the insulin resistance becomes. In addition, studies suggest that eating high calorie diets, or eating simple sugars or high-fat foods will cause temporary increases in insulin resistance, which may last for hours.

Metformin is a drug, which makes liver and, to a lesser degree, muscle more sensitive to the action of insulin. As this occurs, serum levels of insulin decline. The lower serum insulin levels become, the more normal ovarian hormone secretion becomes.

 

Pregnancy and PCOS

Rates of ovulation in women with PCOS are markedly reduced. In addition, the risk of fetal loss during the first trimester in PCOS women is increased. Recently, there has been some use of metformin to treat these problems in fertility in women with PCOS. Preliminary studies suggest that metformin may increase the likelihood of pregnancy in PCOS and that it may reduce the risk of fetal loss. There is much more data to suggest that metformin does not appear to be harmful to the fetus if taken during pregnancy. Finally, very early data suggests that metformin reduces the risk of diabetes during pregnancy in PCOS women. These are exciting data, but they are preliminary. However, women with concerns about PCOS may wish to watch these developments over time.

New Insulins Make Headway Toward Release

Current information suggests that some of the coming insulins are closer to being released. There are three new insulins on the horizon:

Novolog (Novo-Nordisk Corporation) – an ultra-fast acting insulin, similar to Humulog (Eli Lilly Corporation)

Glargine or Lantus™ (Aventis Pharmaceuticals) – an ultra-long lasting insulin, taken once per day, which provides a base of insulin action

Inhaled Insulin (Pfizer and Inhale Pharmaceuticals) – a product breathed as an asthma inhaler to provide fast-acting insulin coverage. These new insulins will expand the many therapeutic choices for insulin coverage.

 

Healthy Eating

This section of our website is dedicated to all of us who like good food and, yet, are worried about our health. We will be updating this section periodically. We are always happy to have suggestions and new recipes for our food section.

 

Current Recommendations About Meal Planning

There are few things about diet that have changed as often or as much as the recommendations about carbohydrate intake. Currently, this is a major professional and public focus of concern in diets for diabetes. However, there have been a number of other changes in attitudes toward diet, which are at least as interesting, including the use of carbohydrate counting, acceptance of strict versus reasonable protocol diets, and considerations regarding vitamin and nutrient supplementation.

 

How the Nutritional Program May Be Planned

Years ago, we were all dedicated to the concept that diet for diabetic people should be designed by a strict protocol. The most widely used protocol was the Exchange Diet. This was used with almost all persons with diabetes without any clear documentation that this approach was more effective. In 1983, Pickert et al reported that dietary programs, which advocated easy-to-follow and reasonable suggestions were more commonly followed by patients than exchanges. The landmark study on diabetes complications, the Diabetes Control and Complications Trial (DCCT), demonstrated that patients given simple, reasonable suggestions on menu planning did at least as well as patients on strict dietary protocols, such as exchanges. Therefore, there are now more varied and possible approaches to diet, which are acceptable, than there used to be. While this change from one to many approaches has confused many diabetic people, the flexibility that has resulted from this is probably quite positive. However, diabetic patients may benefit from reassurances that the many approaches now advocated represent the current trend, rather than a lack of expertise on the part of their health providers.

 

Carbohydrate Content of the Diet

Most diabetes health professionals divide carbohydrates into “simple” and “complex” carbohydrates. Simple carbohydrates are sugars, such as table sugar, fruit sugar (fructose), milk sugar (maltose), and the body’s primary sugar, glucose. Complex carbohydrates are starches. These not only occur in starchy foods, as breads and pasta, but also in many vegetables.

The current, “standard” recommendation for carbohydrate in diabetic patients is to eat slightly more than half of all daily calories as complex carbohydrates. It is desired to limit simple sugars as much as possible. Therefore we suggest that patients include some bread, rice, potatoes, pasta and/or vegetables in each meal. We also suggest that patients avoid foods high in simple sugars as much as possible, including drinks sweetened with sugar. Fruit juices would be part of that group of foods to avoid, since they are concentrated fruit sugar (fructose). In addition, so-called “diabetic sweets” with fructose would be foods to be limited or avoided. (Sweets with sorbitol, aspartame, or saccharin are acceptable).

Recently, there have been a number of diets that have become popular, which advise a limitation of all carbohydrates. The most popular of these is the Adkins Diet. Another such diet is the “Sugar Busters Diet“. These diets suggest a significant restriction in carbohydrate intake to a total elimination of carbohydrate intake. Acceptance of these diets among specialists, interested in diabetes, is limited; however, there has been an impact of all the discussion about carbohydrates. Many health professionals interested in diabetes have started to advise a lower intake of carbohydrates than has been suggested during the last ten or more years.

The advantage of the low-carbohydrate diets seems to be a possible improvement in rates of weight loss. However, the rates of weight loss have not been studied in a comparative fashion.

Part of the focus on carbohydrate has been a new technique to control food intake in diabetes. This is called carbohydrate counting. Carbohydrate counting is used to determine pre-meal doses of fast-acting insulin. The grams of carbohydrate at each meal are calculated, and the dose of rapid-acting insulin adjusted, based on the carbohydrate load.

The advantages of carbohydrate counting include its reliability as a method to adjust pre-meal doses of insulin if the person is eating the sort of diet recommended by the American Diabetes Association. This system does not work well if the person is eating a very low carbohydrate diet, because most of the calories in the diet are not from carbohydrates. The advantages also include its relative ease for those patients who wish to do this sort of program.

The disadvantages include its unreliability in persons who are eating low carbohydrate diets. Some people feel that this is cumbersome. The system also requires that the person take a pre-meal insulin dose to adjust for increased carbohydrates.

 

Tomatoes and Healthy Eating

There is new information on tomatoes and healthy eating. Tomatoes are a rich source of an anti-oxidant called lycopenes. Lycopenes are a newly appreciated group of anti-oxidants, which may provide important cardiovascular protection in diabetic patients. Instead of taking morning medication with fruit juice, it may be healthier to take a glass of tomato or vegetable juice. People with hypertension should be careful though about the salt content of these beverages.