What Causes Diabetes?

What Causes Diabetes? is a chapter in my book, "Take Charge of your Diabetes" Here's a section of this chapter. 

More than 95% of diabetics are Type 2. The root cause for Type 2 diabetes is a disease process in your body known as insulin resistance. Therefore, insulin resistance is the underlying problem for the great majority of diabetic patients.

Fewer than 5% of diabetics have Type 1 diabetes. The total destruction of insulin-producing cells in the pancreas is the underlying cause for Type 1 diabetes.

However, as they age, many Type 1 diabetics also suffer from insulin resistance. Therefore, all Type 1 diabetics should pay close attention to this discussion of insulin resistance.

Toward the end of this chapter, I will also discuss what causes Type 1 diabetes in more detail.


Insulin Resistance Syndrome

Insulin Resistance Syndrome is the most common medical condition affecting the world today. It is estimated that well over 100 mllion Americans have it and don’t know it. Worldwide, there is an epidemic of this devastating disease. And most people have never heard of it.

For a long time we have known that obesity, high blood pressure, and cholesterol disorder tend to cluster in a person who subsequently develops Type 2 diabetes or has a heart attack or stroke. What we didn’t know was the link between these medical conditions. In the last twenty years, there has been tremendous research in this field. Now we know the missing link is insulin resistance, hence the name Insulin Resistance Syndrome.

Insulin Resistance Syndrome (IRS) is also known as Metabolic Syndrome or Syndrome X. I prefer Insulin Resistance Syndrome because it clearly defines the underlying disease process. Syndrome X sounds to me like the title of a Hollywood movie: catchy, but ultimately a bit confusing. Metabolic Syndrome does not fully convey the serious nature of this condition, either.


The Major Components of Insulin Resistance Syndrome (IRS)

The major components of Insulin Resistance Syndrome include:

• Being overweight, especially around the waistline; this is also called abdominal obesity (a waistline of more than 35 inches in females and more than 40 inches in males; in Asians, these numbers are 32 and 35 inches respectively)

• Low HDL cholesterol (less than 50 mg/dl in females; less than 40 mg/dl in males)

• High triglycerides (more than 150 mg/dl)

• High blood pressure (more than 130/85 mm Hg, even in a physician’s office)

• Impaired glucose tolerance (blood glucose between 140 mg/dl and 200 mg/dl at two hours after 75 grams of a glucose drink in an oral glucose tolerance test*)

• Impaired fasting glucose (a fasting blood glucose level between 100 mg/dl and 125 mg/dl). Many people with impaired fasting glucose or impaired glucose tolerance eventually develop diabetes. Therefore, these conditions are also known as prediabetes.

• Diabetes (a fasting blood glucose level of more than 125 mg/dl or a two-hour blood glucose level of more than 200 mg/dl in an oral glucose tolerance test)

• Increased tendency for clot formation, which can cause an acute heart attack or stroke

• High insulin level in the blood

• Increased uric acid level in the blood (which can cause gout)

• Fatty liver (an abnormal deposition of fat in the liver that an cause liver dysfunction)

•Women with Polycystic Ovary Syndrome (PCO syndrome); symptoms include irregular menses, excessive facial hair growth, and acne

You don’t have to have all of these conditions to fit the diagnosis of Insulin Resistance Syndrome. Most individuals with IRS have abdominal obesity, low HDL cholesterol, and high triglycerides. In more advanced stages of insulin resistance, patients also develop high blood pressure and prediabetes or diabetes.

What combination of these metabolic disorders you have depends upon the severity and duration of insulin resistance in your body and your body’s ability to produce large amounts of insulin to meet the challenge of insulin resistance. Some people have a limited ability to produce large amounts of insulin. These patients usually develop diabetes at a younger age—in their thirties and forties or even in their teens. Others have an extraordinary ability to produce large amounts of insulin. These patients do not develop diabetes until late in life. They may die of a heart attack or stroke before they develop diabetes.

These metabolic disorders also cluster in family members. For example, a mother may have high blood pressure while her son may have diabetes and suffered a heart attack. An aunt may have diabetes and her niece may have high blood pressure and low HDL cholesterol.

Initially, people with IRS don’t have any symptoms and therefore are under the impression that there is nothing wrong with them. Then one day, they show up in the emergency room of a hospital with an acute heart attack. Family and friends wonder how it could have happened to such a (seemingly) healthy person.


The Causes of Insulin Resistance Syndrome

The main reasons people develop Insulin Resistance Syndrome are:

• Genetic predisposition

• Obesity

• Aging

• Lack of exercise

• Stress

Genetics play an important role in determining the degree of insulin resistance. While no one is immune to this syndrome, certain ethnic groups, such as Native American Indians, African

Americans, Latinos, and Asians, have a higher prevalence of insulin resistance than Caucasians. Make no mistake though. Large numbers of Caucasians also suffer from this disease. Asians often develop this syndrome even at a relatively normal weight. One in four Latinos is diagnosed with diabetes by the age of forty-five.

Abdominal obesity is a key player in most patients with Insulin

Resistance Syndrome, especially in younger individuals. Obesity

and diabetes have increased at an alarming rate in the last decade.

According to recent statistics from the Centers for Disease Control (CDC), the prevalence of obesity in the U.S. increased by 61% from 1991 to 2000. During the same period, diabetes increased by 49% with a 76% increase in people aged thirty to thirty-nine, according to a study published in 2001 in the Journal of the American Medical Association.1 Obesity in children and adolescents is also rapidly increasing. Children as young as five have exhibited signs of insulin resistance.

As we age, insulin resistance worsens. That is why diabetes, high blood pressure, heart disease, and stroke are so prevalent in people

over the age of fifty. In the U.S., seniors are the most rapidly expanding segment of society, which is contributing to the fast rate at which insulin resistance is increasing. Forty percent of adult Americans suffer from Insulin Resistance Syndrome, according to estimates published in 2003 in the Endocrine Practice, the official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists.2 This number increases to 50% by age seventy. In other words, every other American over the age of seventy has Insulin Resistance Syndrome.

These estimates are rather conservative due to the methodology used. In real life, this disease is even more prevalent.

Lack of exercise is another major factor that causes worsening of insulin resistance. Too many of us have become couch potatoes, glued to the ever-present television or computer. The only workout we get is from pressing the remote control for the television or maneuvering the mouse on our computer. Our lifestyles have become too sedentary. An interesting study was published in the Archives of Internal Medicine in 2001.3 The investigators studied 37,918 men between the ages of forty and seventy-five over a period of ten years and found that the risk for development of diabetes was directly related to time spent watching television.

Stress plays a major role in the worsening of insulin resistance.

Stress directly causes an increase in two hormones in the body, cortisol and catecholamines. Both of these hormones worsen insulin resistance. People who are stressed (as most of us are to some extent) often overeat despite knowing the health hazards of obesity. Increase in weight further worsens insulin resistance. This is how stress indirectly affects insulin resistance.

Think of insulin resistance as five guys controlling a speeding train. All five of them must halt to stop the deadly train called Insulin Resistance Syndrome. Unfortunately, two out of the five (genetics and aging) are out of your control.

That is the reason why diet, exercise, and stress management alone are generally inadequate to prevent diabetes and the other complications of Insulin Resistance Syndrome. You need to add vitamins and drugs to effectively treat this deadly disease


Insulin Resistance and How It Damages Your Body

There is a tremendous amount of clinical evidence to show that

insulin resistance is the root cause for coronary artery disease, stroke, diabetes, and high blood pressure. Insulin resistance causes narrowing of the blood vessels throughout your body. In the heart, it leads to heart attacks; in the brain, it causes stroke and dementia; and in the legs, it causes poor circulation and, ultimately, amputation.

Insulin has several actions in the body, one of which is to drive glucose from the blood into the muscle cells, where it is used as a fuel for energy.

Recall the image from chapter 1 of the cell as a small room and a blood vessel as a hallway outside of the room. Glucose, the delivery person, moves through the hallway but is unable to enter the room because the door is closed. Insulin works as the doorman, opening the door for glucose to enter the cell. In individuals with insulin resistance, the door hinges of the cell are rusty, making it difficult for insulin to open the door easily.

Now, instead of one doorman, you need three or four. This is insulin resistance. Your body produces excessive insulin to compensate for the door’s resistance.

A high level of insulin may keep your blood glucose normal, but is not good for the rest of your body. A high level of insulin causes high blood pressure. This association between high insulin levels and the development of high blood pressure has been confirmed by several researchers.

 A high level of insulin is also associated with a high risk for heart disease. This association has been documented by several excellent clinical studies—The Helenski Policeman Study, the Paris Prospective Study, and the Danish Study.


How does insulin cause heart disease?

Insulin stimulates smooth muscle cell growth in the walls of arteries and causes thickening and stiffness of arterial walls, which, in turn, contributes to narrowing of blood vessels.

Hypertension (high blood pressure) itself causes further narrowing of the blood vessels.

Narrowed blood vessels lead to heart attacks and strokes. 


Insulin Resistance and Cancer

A high level of insulin also leads to the growth of tumors in the body. Several clinical studies have shown a high prevalence of cancer in people with Insulin Resistance Syndrome. Certain cancers, especially breast cancer, colon cancer, and prostate cancer have been linked to insulin resistance.

An excellent, large clinical study, known as the American Nurses Health Study was published in Diabetes Care in 2003.9 In this study, 111,488 American female nurses who were thirty to fifty-five years old and free of cancer in 1976 were followed through 1996 for the occurrence of Type 2 diabetes and through 1998 for breast cancer. Women with Type 2 diabetes (a component of Insulin Resistance Syndrome) were found not have diabetes. 


Insulin Resistance and Diabetes

As long as your pancreas can churn out lots of extra insulin, your blood glucose will remain in the normal range. This “overworked pancreas” scenario can go on for years in apparently healthy individuals. This phenomenon was brilliantly studied in nondiabetic children of diabetic parents and published in 1990 in the Annals of Internal Medicine.10

Eventually, your pancreas can’t continue to produce large amounts of insulin to compensate for rising insulin resistance. What causes this decline in insulin production by the pancreas is undergoing intense research at this time. We know that genetics play a significant role. Free fatty acids (a product from the breakdown of fat) have also been shown to cause damage to the insulin producing cells (beta cells) of the pancreas.11

Once insulin production by the pancreas starts to decline, your blood glucose levels start rising, initially only after meals. This stage is known as impaired glucose tolerance (IGT). At this stage, your fasting blood glucose is usually normal. Impaired glucose tolerance can only be diagnosed if you have an oral glucose tolerance test.

Several years later, your blood glucose starts rising even in the fasting state. This occurs due to insulin resistance in the liver.

Normally your liver produces glucose during a fasting state, such as at night time. Insulin keeps this glucose production in check. However, when there is resistance to the action of insulin, this glucose production by the liver gets into high gear and your fasting blood glucose starts to rise.

If your fasting blood glucose rises into the range of 100–125

mg/dl, it is known as impaired fasting glucose (IFG).

Impaired glucose tolerance and impaired fasting glucose are

early stages in the development of diabetes and, therefore, are also known as prediabetes.

Ultimately, a diagnosis of diabetes is made when your fasting blood glucose is more than 125 mg/dl or when your blood glucose is more than 200 mg/dl two hours after a glucose drink in an oral glucose tolerance test. 


Insulin Resistance and Cholesterol Disorder

Another role that insulin plays is to keep fat where it belongs: inside fat cells. In individuals with abdominal obesity, there is resistance to the action of insulin at the level of the fat cells. Consequently, an increased amount of fat escapes from the fat cells and enters the blood stream.

A breakdown product of this fat is free fatty acids. Thus, in individuals with insulin resistance, there is a high level of free fatty acids in the blood. The liver takes up these free fatty acids and converts them into VLDL cholesterol (very low density lipoproteins).

These cholesterol particles are rich in triglycerides, which is why individuals with insulin resistance have a high level of triglycerides.

When VLDL particles interact with HDL (good cholesterol) particles, VLDL exchanges its triglycerides for the cholesterol of HDL particles. This results in a decrease in HDL cholesterol. These triglycerides-enriched HDL particles also break down easily, which further lowers HDL levels. That is why individuals with insulin resistance end up with low HDL cholesterol.

HDL cholesterol is popularly known as the good cholesterol as it sweeps out the built-up gunk (technically known as plaque) inside the blood vessels. If your HDL is low, you have a decreased number of “sweepers,” which means less cleansing and, therefore, more gunk buildup inside your blood vessels. This leads to narrowing of the blood vessels.

VLDL particles also give rise to the formation of another cholesterol particle, known as IDL (intermediate density lipoprotein), which then converts to LDL (low density lipoproteins).

LDL particles in individuals with insulin resistance are of Type B, which means that they are small, dense, and get deposited in the walls of blood vessels more easily and are, therefore, more harmful. LDL, VLDL, and IDL particles deposit in the arterial wall and cause narrowing of the vessel wall.

On average, many years of insulin resistance go by before a diagnosis of diabetes is made.

During this time, narrowing of the blood vessels takes place due to low HDL cholesterol, Type B LDL cholesterol, elevated IDL and VLDL cholesterol, high insulin levels, and high blood pressure. Narrowing of the blood vessels leads to heart attacks and strokes. Many people die of a heart attack before they are diagnosed with diabetes. Most people have developed advanced narrowing of the blood vessels by the time they are diagnosed with diabetes.  


The Cause of Type 1 Diabetes

Type 1 diabetes occurs as a result of the total destruction of beta cells (the insulin producing cells) in the pancreas. This destruction of beta cells in the pancreas takes place because your own immune system has gone wild.

Normally your immune system recognizes anything foreign in your body, such as a virus, and gets rid of it. In patients who ultimately develop Type 1 diabetes, the immune system mistakenly thinks that the beta cells of your pancreas don’t belong to you and, therefore, must be destroyed. So it starts attacking the beta cells of your own pancreas. Basically, your own immune system turns against you. That is why we call it an autoimmune disorder.

Gradually beta cells start dying out and insulin production starts declining. Ultimately, there is very little or no insulin production.

At that point, you must have the administration of insulin to survive. If Type 1 diabetic patients don’t receive insulin, they can rapidly lapse into a coma. They can die if proper treatment is not initiated in time.

Why does the immune system turn against itself and start attacking the beta cells of the pancreas? The exact answer is not entirely clear but here are some explanations.

Some individuals are genetically predisposed to this immune destruction of the beta cells, but this process has to be triggered by some factor in the environment.

The possible triggering factors include a viral illness, childhood immunizations, baby formula, preservatives in food, pesticides, and other unrecognized environmental factors.

Stress also plays an important role in weakening the immune system.

Vitamin D deficiency appears to play a significant role in the causation of Type 1 diabetes.


Patients with Type 1 diabetes are also at high risk for other autoimmune disorders that include:  

• Autoimmune thyroid disease, which can result in an underactive thyroid (also known as Hashimoto’s thyroiditis) or an overactive thyroid (also known as Grave’s disease)

• Impairment of vitamin B12 absorption from the intestines, resulting in vitamin B12 deficiency that may manifest as pernicious anemia; weakness, tingling, and numbness of toes and fingers; unbalanced gait; and dementia.

• Autoimmune adrenalitis resulting in adrenal failure (also known as Addison’s disease),manifesting as severe fatigue and low blood pressure

• Autoimmune oophoritis resulting in premature menopause

• Lupus and Rheumatoid arthritis.


This article was written by Sarfraz Zaidi, MD, FACE. Dr. Zaidi specializes in Diabetes, photoEndocrinology and Metabolism.

Dr. Zaidi is an assistant Clinical Professor of Medicine at UCLA and Director of the Jamila Diabetes and Endocrine Medical Center in Thousand Oaks, California.

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