Insulin Resistance and Diabetes

by Hans R. Larsen, MSc ChE

Fatigue, frequent urination, abnormal thirst, increased appetite, blurred vision, and slow healing of skin, gum and urinary infections are common symptoms of insulin resistance and type 2 diabetes. Diabetes mellitus is the most common endocrine disorder in the world today. It is estimated that over 16 million American suffer from the disease[1]. Diabetes manifests itself through abnormally high blood glucose levels and comes in two major forms - insulin-dependent (type 1) and non-insulin-dependent (type 2). Type 1 diabetes most often occurs before the age of 20 years and involves progressive destruction of insulin-producing cells in the pancreas. Type 2 diabetes is usually diagnosed after the age of 40 years and is primarily caused by a defect in the mechanism that governs the uptake of glucose by individual cells. The treatment of type 1 involves daily insulin injections while type 2 can often be managed by diet and exercise.

Type 2 diabetes is, by far, the most common and accounts for approximately 90% of all cases. It has a fairly strong genetic component and should always be suspected in obese individuals since about 90% of all diabetics are obese. Fatigue, frequent urination, abnormal thirst, increased appetite, blurred vision, and slow healing of skin, gum and urinary infections are common symptoms of type 2 diabetes.

Diagnosis
Prior to 1997 diabetes was suspected if an individual had a least two fasting glucose readings of 140 mg/dL (7.8 mmol/L) on two separate occasions. In 1997 the American Diabetes Association lowered the diabetes cut-off point to 126 mg/dL (7 mmol/L) on two separate occasions. So now the "rules" are[2]:

• Fasting glucose level less than 110 mg/dL is considered normal
• Fasting glucose level between 110 and 126 mg/dL indicates impaired glucose tolerance (insulin resistance)
• Fasting glucose level at or above 126 mg/dL indicates diabetes.

The World Health Organization (WHO) recommends the 2-hour oral glucose tolerance test. The interpretation of its results is[2]:

• 2-hour reading of less than 140 mg/dL (7.8 mmol/L) is normal
• 2-hour reading of between 140 and 200 mg/dL is indicative of impaired glucose tolerance
• 2-hour reading of 200 mg/dL or greater is indicative of diabetes.

The National Institutes of Health recommends that diabetes should be suspected only if at least two readings in the 2-hour period are equal to or greater than 200 mg/dL.

There is evidence that food intake during the two days prior to the glucose tolerance test can materially affect the results. It is best to eat a diet rich in complex carbohydrates and avoid an excessive intake of protein and fats[3].

Epidemiological studies have found that an elevated level of glycosylated hemoglobin (HbA1c) is a strong indicator of an increased risk for vascular disease. Glucose binds to the pigment in red blood cells (hemoglobin) whenever new cells are generated. The proportion of hemoglobin molecules that contains glucose can be used as a measure of the average blood sugar level over the past four months (the average lifetime of a red blood cell). Unfortunately, the test for HbA1c is not very reproducible between individual testing laboratories so a good deal of interpretation is required on the part of the physician. The current recommendation is that glycosylated hemoglobin should be below 7%[2,4].

The R-R interval study is another important test used in the investigation of diabetes. It evaluates the functioning of the vagus nerve and is very similar to a standard electrocardiogram (ECG). The R-R interval is the difference in heart rate between a deep inhalation and a deep exhalation. A healthy young person may have as much as a 75% drop in heart rate when going from inhaling to exhaling while a diabetic may show little or no difference. Little or no difference indicates that the vagus nerve may have been damaged by long-term exposure to high glucose levels. This damage plays a major role in a number of diabetes complications such as digestive problems, arrhythmias, erectile dysfunction (impotence), and delayed stomach-emptying[4].

People with type 2 diabetes may have developed impaired kidney function so it is important to have a through evaluation of kidney function. Creatinine clearance and microalbuminaria are the two tests most frequently used here. It is also advisable to have homocysteine levels checked. High levels are a potent risk factor for heart disease, stroke and many other conditions[4].

Mechanism of insulin resistance and type 2 diabetes
Insulin is released by the pancreas in response to the presence of sugar (glucose) in the blood stream. Glucose gets into the blood through consumption of sugar or sugar-containing foods or via the breakdown of carbohydrates into simple sugars. Insulin is a chemical messenger that acts on the walls of the cells to cause the release, from within the cell, of special protein molecules - the so-called GLUT-4 transporters. The GLUT-4 transporters rise to the cells' outer membranes where they grab hold of the glucose molecule and transport it into the interior of the cell. Here the glucose is used to produce energy and any excess is converted into fat[5].

This process functions flawlessly in non-diabetic persons resulting in a steady glucose level in the blood stream usually between 60 and 115 mg/dL with an average of 85 mg/dL.

In diabetics glucose levels are not under control and can reach levels of 250 mg/dL or higher. Patients with type 1 (insulin-dependent) diabetes produce little or no insulin because the beta-cells in the pancreas, which normally produce the hormone, have been destroyed. Patients with type 2 (non-insulin-dependent) diabetes, on the other hand, usually produce an adequate amount of insulin, but for some reason the mechanism whereby the insulin summons the GLUT-4 transporters does not function. The result is that both glucose and insulin levels in the blood remain high. The same problem is experienced by persons with insulin resistance (impaired glucose tolerance), but to a lesser degree.

Complications in diabetes
The most serious problem with high glucose levels is that the excess glucose tends to bind to proteins and cause them to become "sticky". This process is called glycosylation and is a major factor in atherosclerosis and other diabetes complications. The higher than normal insulin levels (hyperinsulinemia) experienced by people with insulin resistance or type 2 diabetes are also highly detrimental. They interfere with the normal metabolism of fats and cause an increase in the production of very-low-density cholesterol, a potent risk factor for heart disease. High insulin levels also encourage the formation of blood clots and thereby increase the risk of heart attacks. Finally, high insulin levels can lead to hypoglycemia (low blood sugar levels)[5].

Long-term, uncontrolled high blood sugar levels can lead to a number of serious complications, among them kidney failure, hypertension, diabetic retinopathy (eye disease), neuropathy (nerve disease), heart disease, peripheral vascular disease (intermittent claudication), stroke, diabetic foot disease, and erectile dysfunction[5].

Prevention of type 2 diabetes
It is estimated that 35% of all cases of impaired glucose tolerance eventually progress to full-blown diabetes. Researchers at the Finnish National Public Health Institute believe that this progression can be halted by fairly simple lifestyle modifications. Their study involved 522 middle-aged, overweight men and women with a mean age of 55 years. The members of the intervention group were given individualized goals on how to reduce weight (by 5% or more), how to decrease total fat intake and saturated fat intake (to 30% and 10% of energy consumed respectively), how to increase fiber intake, and how to exercise effectively for at least 30 minutes a day. The control group was given some general advice, but no personalized attention. After four years 11% of the members of the intervention group had developed diabetes as compared to 23% in the control group. None of the 49 members in the intervention group or the 15 members of the control group who reached four out of the five goals developed diabetes. On the other hand, diabetes did develop in the 48 subjects in the control group and the 13 in the intervention group who did not achieve any of the five goals. The researchers conclude that type 2 diabetes can be prevented by changes in lifestyle among people with impaired glucose tolerance[6].

Researchers at the National Center for Chronic Disease Prevention and Health Promotion in the USA report that vitamin supplementation helps prevent diabetes. Their study, which involved 9573 men and women between the ages of 25 and 74 years, began in 1971-1975 and was continued for 20 years. At the end of the study 1010 (11%) of the participants had developed diabetes. All the participants were asked if they used supplements (vitamins, minerals, and other supplements) at the beginning of the study and again 10 years into the study. Regular vitamin users were found to have a 24% lower risk of developing diabetes than did non-users even when adjusted for the effects of age, race, education, smoking, blood pressure, cholesterol, body mass index, exercise, alcohol consumption, fruit and vegetable intake, fat intake and total energy intake. The risk reduction was somewhat smaller for women (16%) than for men (30%). The risk reduction for the participants who supplemented with both vitamins and minerals was even more impressive at 33%. The researchers speculate that vitamin-E, chromium, and magnesium may be particularly effective in preventing diabetes. They modestly conclude "the judicious use of vitamins may play a role in the prevention of diabetes"[7].

Researchers at Kuopio University in Finland report that a low intake of vitamin E is a significant risk factor for the development of type 2 diabetes. Their study involved 944 Finnish men aged 42 to 60 years who were free of diabetes when tested between March 1984 and December 1989. Four years later 45 of the men had developed clinically confirmed diabetes. The researchers found that men with a below average intake of vitamin E had an almost four times greater risk of developing diabetes than did men with a higher than average intake. They conclude that oxidative stress (free radical attacks) plays an important role in the development of diabetes and suggest that vitamin E supplementation may be useful in the primary prevention of the disease[8].

Researchers at the Harvard School of Public Health have found that a high intake of trans-fatty acids (hydrogenated oils, margarine) markedly increases the risk of developing diabetes. They believe that replacing trans-fatty acids in the diet with non-hydrogenated, polyunsaturated fatty acids would substantially reduce the incidence of type 2 diabetes, perhaps by as much as 40%[9,10].

Researchers at the Harvard Medical School believe that regular exercise is an important tool in both the prevention and treatment of type 2 diabetes. They cite a study involving 87,253 nurses that found women who exercised vigorously once a week had a 37% lower risk of developing diabetes than did women who exercised less than once a week. A 16% lower risk persisted even after adjusting for degree of obesity (BMI), family history of diabetes, and other variables. Similarly, a study of over 21,000 male physicians found that men who exercised vigorously once a week had a 30% lower risk of developing type 2 diabetes than men who exercised less than once a week; this correlation held even after adjustment for age, smoking, hypertension, high cholesterol levels, and obesity (BMI). A recently published Swedish study found that men with impaired glucose tolerance (a forerunner for diabetes) could cut their risk of developing full-blown diabetes by two thirds by following a diet and exercise program. The researchers conclude that people can reduce their risk of developing diabetes by anywhere from 30 to 50% merely by following a regular, moderate or vigorous exercise program[11].

It is clear that the development of type 2 diabetes is, to a large extent, preventable if concerted, timely action is taken.

For those who already have the disease treatment aimed at maintaining blood glucose levels within normal or near-normal levels is a must. The treatment involves frequent monitoring of glucose levelscombined with a special diet and the use of pharmaceutical drugs or supplements. Glucose levels should be measured at least twice a day - before breakfast and before dinner. Until a glucose profile is established it may also be advisable to measure it 2 hours after meals and at bedtime. The measurements can be done at home using a computerized glucose meter or the newly developed GlucoWatch[12].

Conventional treatment
Diet, exercise, and oral hypoglycemic agents are the mainstay of conventional treatment of insulin resistance and type 2 diabetes. The diet emphasizes the avoidance of simple sugars and an increased intake of fiber. There is no agreement on the preferred proportion of carbohydrates, proteins and fat. Some experts believe that a diet deriving 40% of energy from carbohydrates, 30% from protein, and 30% from fat is optimum while others advocate 60% carbohydrates, 20% protein, and 20% fat[13-15].

Exercise at the recommended heart rate for aerobic exercise is very important. Exercise helps to reduce insulin levels and lowers cholesterol and triglyceride levels as well as blood pressure[11,16,17]. Many patients with insulin resistance or type 2 diabetes can actually revert to a non-diabetic state just by exercising and following a proper diet. For those who cannot oral hypoglycemic agents are prescribed.

The oldest and most commonly prescribed drugs are the sulfonylureas (Micronase, Diabinese, Tolinase, Orinase, etc.). The primary effect of these drugs is to increase insulin secretion; they also slightly enhance the cells' ability to take in glucose. Obviously, as a deficiency in insulin is rarely a problem for type 2 diabetics the effectiveness of these drugs is somewhat limited. Sulfonylureas also have the potential for many quite serious side effects. Among the more common are hypoglycemia, weight gain, gastrointestinal problems, hypothyroidism, and skin rashes. They also increase the risk of heart disease and circulatory problems and are a definitely not for people with congestive heart failure[18].

Newer drugs such as metformin (Glucophage) and the thiazolidinediones (Avandia, Actos, Rezulin) aim to increase the cells' sensitivity to insulin and thereby facilitate the removal of glucose from the blood stream. Unfortunately, these drugs also have the potential for some very serious side effects such as an increase in blood pressure, increase in death from heart disease, lactic acidosis, weight gain, increase in low-density cholesterol (thiazolidinediones) and liver damage[18].

The potentially devastating side effects of these drugs can, of course, be completely avoided by replacing them with natural supplements as is done in alternative treatment of insulin sensitivity and type 2 diabetes.

Alternative treatment
The diet recommended by alternative practitioners is generally higher in complex carbohydrates, about 60% of total energy intake, than is the diet recommended in conventional medicine. Legumes, oat bran, nuts, seeds, pears, apples, and vegetables are particularly important because of their high fiber content. It is also important to emphasize foods with a low glycemic index as these release insulin more slowly and therefore tend to avoid hyperinsulinemia. Dr. Julian Whitaker's book "Reversing Diabetes" contains detailed diet instruction and numerous recipes for diabetes-friendly meals[13].

Several supplements have been found highly useful in the treatment of insulin resistance and type 2 diabetes. An adequate intake of vitamins and minerals is essential for diabetes patients.

Vitamin C is particularly important. Many diabetics are deficient in this important vitamin. Vitamin-C helps prevent glycosylation of proteins and the accumulation of damaging sorbitol. An intake of 2000 mg/day is recommended either in divided doses or in time-release capsules[16,19,20,21].

Vitamin E improves glucose metabolism and insulin sensitivity in doses from 800 to 1200 IU/day[16,21,22].

Chromium lowers glucose levels and helps prevent glycosylation; it also lowers cholesterol levels. Recommended dose is 200 microgram twice a day. Chromium picolinate is the preferred form[16,21,23-25].

The B vitamins, especially vitamin B6 and vitamin B12, are important in preventing diabetes complications as is folic acid[16,21].

Diabetics do not absorb magnesium well so supplementation with 200 mg three times a day may be required to avoid deficiency. Magnesium citrate and maleate are the preferred forms[16,21,26].

Lipoic acid is a powerful antioxidant and also improves insulin sensitivity by increasing the activity of the GLUT-4 transporters. The recommended dosage is 100 mg three times a day[21,27].

Vanadium may well be the most important supplement for diabetics and people with impaired insulin resistance. It is able to activate GLUT-4 transporters just like insulin. Doses of 50-100 mg/day of vanadyl sulfate have been found very effective in lowering glucose levels. However, supplementation with these relatively large doses of vanadiumcan result in a rapid drop in blood glucose so should only be undertaken under the supervision of a knowledgeable physician[21,28].

Recent work carried out at the University of Toronto has shown that American ginseng (Panax quinquefolius) is able to prevent the spike in blood sugar that follows a meal. A daily dosage of 500 mg (taken with breakfast) should be sufficient[29,30].

Many diabetics are deficient in the hormone DHEA (dehydroepiandrosterone) and may benefit significantly from supplementation. Evening primrose oil, fish oil, flax oil, onions and garlic, and several herbal supplements have also been found useful in blood sugar control[16,31,32].

A regular exercise program, proper diet, and the judicious use of natural supplements can be highly effective in keeping blood glucose levels under control and thus prevent the long-term complications accompanying uncontrolled diabetes.