By Elizabeth Cloutman

Insulin resistance is the cause of Type 2 diabetes, also a major factor in developing cardiovascular disease

About 10 to 20 percent of the population inherits the tendency to become insulin-resistant. While most people might be aware that insulin resistance is the cause of Type 2 (adult onset) diabetes, they may not know it has even more far-reaching effects on the body.

Insulin resistance appears to be a major contributor to cardiovascular disease as well as some other medical conditions. About 15 years ago, Stanford medical researchers, led by Gerald Reaven, named the cluster of symptoms caused by insulin resistance Syndrome X.

Two local physicians, Randolph Linde and Dominick Curatola, spoke recently about the symptoms, causes and treatment of Syndrome X. Linde is a clinical associate professor of medicine at Stanford and an endocrinologist at the Palo Alto Medical Foundation. Curatola is a Los Altos cardiologist, who is on the clinical faculty at Stanford.

Syndrome X describes a cluster of symptoms, including high blood pressure, high triglycerides, decreased high-density lipoproteins (HDL) and obesity, which tend to appear together in genetically predisposed individuals and increase their risk for cardiovascular disease.

HDL, known as the “good” cholesterol, and triglycerides are the components of fat found in the blood.

Insulin affects the body’s ability to maintain appropriate levels of glucose in the blood. “The pancreas makes the hormone insulin, which binds to receptors in your cells,” Curatola said. “In insulin resistance, the receptors don’t work well and glucose in the blood becomes high. Think of insulin as a key and the receptors as a keyhole. In insulin resistance, the key doesn’t fit.”

To compensate for high glucose levels, the pancreas produces more insulin. During a June 11 public seminar at PAMF, Linde explained that while some hormones, such as thyroid, affect only one particular organ, “there are many potential tissues that respond to insulin.”

These other organ systems are not insulin-resistant, and the result of their response to excessive insulin is the cluster of symptoms known as Syndrome X.

The physiology of insulin resistance is complex, Linde explained. People with insulin resistance tend to have abdominal visceral fat - fat that collects around the abdominal organs.

Insulin resistance leads to an excessive release of fatty acids. These fatty acids block insulin-mediated glucose uptake in muscle. Therefore, blood glucose rises, stimulating the production of more insulin.

Organs that retain normal insulin sensitivity go into “overdrive,” Linde said. For example, the effects of excess insulin on the sympathetic nervous system cause high blood pressure. The increased level of fatty acids in the liver leads to higher levels of triglycerides, lower levels of HDL and increased low-density - “bad” cholesterol - lipoproteins (LDL).

The endothelium, the lining of the arterial walls, is also affected by excess insulin, increasing the risk of arterial blood clots, which can cause heart attacks or strokes.

Type 2 diabetes develops when the pancreas ultimately “burns itself out” from the excessive demand for insulin production, Curatola said.

Insulin resistance appears to begin at a young age and increases with age.

Insulin resistance also seems to be a major factor in the development of polycystic ovary syndrome, Linde said.

Some research indicates it might also increase the risk of prostate, colon and breast cancer.

If you have a family history of diabetes and cardiovascular disease, you begin by discussing Syndrome X with your primary care physician. A fasting blood test will reveal if you have excessive blood levels of insulin.

Weight loss, diet, aerobic exercise and treatment with several different types of drugs appear to be highly effective in prevention and treatment of syndrome X.

Weight loss reduces the amount of visceral abdominal fat and thus is important, Linde noted.

Aerobic exercise is also key. Even moderate aerobic exercise is very beneficial in improving insulin resistance, he added. “Walking 30 minutes a day, five times a week has been shown to be very beneficial.”

Researchers have found the population of Southern Europe and the Mediterranean area are much less prone to diabetes and cardiovascular disease because of their diet.

A Mediterranean diet includes fish rich in omega 3 oils, such as tuna and salmon; olive oil; nuts; vegetables; plus a limited amount of fruit and high-fiber grains. Fish oil supplements can also be helpful. “It’s important not to eat a lot of processed foods, flour and sugar,” Curatola added.

Certain medications have proven very helpful in treating Syndrome X. Statins and fibrates improve triglyceride and HDL levels. ACE inhibitors and ARBs, used in treating high blood pressure, seem to protect kidney function.

Curatola said that because he has a family history of Type 2 diabetes and early heart disease, he takes an ACE inhibitor as a preventative measure.

Linde advised that patients with insulin resistance also use insulin-sensitizing drugs, such as Avandia, Glucophage or Actos, even if they have not yet developed Type 2 diabetes.

If you want to learn more about Syndrome X or the Mediterranean diet, there are several books available. These include two available in paperback: “Syndrome X, the Silent Killer” by Gerald Reaven, Terry Kirsten Strom and Barry Fox (Fireside, 2001); and “The Mediterranean Diet” by Marissa Cloutier and Eve Adamson (Avon, 2001).