How to Identify Individuals at Enhanced Risk for Developing Statin-Associated Type 2 Diabetes

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Presented by: Gerald Reaven, MD
Professor of Medicine (Active Emeritus)
September 15, 2016

More than 200 million people around the world take statin drugs to lower cholesterol levels and reduce the risk of heart attack or stroke. Statins interfere with the synthesis of low-density lipoprotein (LDL), the “bad” cholesterol that is a prime suspect in heart disease. Even if LDL cholesterol levels are normal, statins are often prescribed when other factors put you at higher risk.

But studies have shown that statins also can increase the risk of developing type 2 diabetes. About 10 percent of statin users develop the disease.

Type 2 diabetes, or noninsulin-dependent diabetes, is a chronic condition that affects how sugar (glucose) is metabolized. Insulin, a hormone made by the pancreas, helps deliver the glucose into your body’s cells for energy. When the pancreas doesn’t make enough insulin or the cells do not respond properly (insulin resistance), excess sugar builds up in the bloodstream and may eventually cause severe damage to the organs and life-threatening complications.

“Statins are really good drugs with amazing benefits and few complications,” said Gerald Reaven, MD, professor emeritus of cardiovascular medicine, who spoke at a presentation sponsored by the Stanford Health Library. “Their clinical benefits are greater than any adverse effects, and it would be a shame to not use them properly.”

The trick, he said, is to identify the people most at risk and monitor their progress more carefully. But how do you figure out who those patients are?

Tracking Risk Factors
Statins could theoretically increase risk of type 2 diabetes by increasing a person’s insulin resistance and/or impairing the pancreas’ ability to secrete insulin. Though most people with insulin resistance do not get diabetes, they do show some degree of glucose intolerance, which is predictive of pre-diabetes or diabetes.

Dr. Reaven is internationally known for identifying Syndrome X, also known as metabolic syndrome or Insulin Resistance Syndrome, which is a condition linked to an increased risk of diabetes and heart disease. There is a cluster of abnormalities that frequently develop in non-diabetic people who are insulin resistant, including some degree of glucose intolerance (prediabetes), increased blood pressure, and higher triglycerides (TG).

Statins are used to lower LDL cholesterol concentrations to decrease the risk of heart attack or stroke. In earlier research Dr. Reaven and his colleagues had shown that people with high LDL cholesterol were a mixed group: some had high LDL alone, whereas others had high LDL PLUS a high TG. More importantly, the group with only high LDL cholesterol was generally insulin sensitive, while those with a high LDL cholesterol and a high TG were insulin resistant.

Since insulin-resistant people are at increased risk of developing diabetes, Dr Reaven and his associates figured that the best way to identify those at greatest risk to develop diabetes with statin treatment would be those who were most insulin resistant. Though direct measurements of insulin resistance are too complicated to be of use in a clinical setting, combining prediabetes with an elevated TG concentration can help to identify insulin resistant individuals.

They hypothesized that patients who do not have prediabetes and have normal TG concentration are at very low risk of developing diabetes with statin usage, while those with one or another abnormality are at intermediate risk, and those who have both prediabetes and a high TG are at greatest risk. They then were able to confirm this hypothesis by applying it to previously published studies of statin treatment.

Patients who need statins should take them regardless of the risk of diabetes, said Dr. Reaven. His work shows that two simple measurements—fasting plasma glucose and TG concentrations—provide physicians and patients with an estimate of this risk and the ability to tailor clinical monitoring with this information in mind. The greater the risk, the more often patients should be assessed for diabetes and the greater the effort to initiate lifestyle changes that can reduce risk of type 2 diabetes.

Statins can be prescribed without concern to people diagnosed with type 2 diabetes since they are already being treated for the condition, he added.

About the Speaker
Gerald Reaven, MD, is a professor emeritus of medicine (cardiovascular medicine), and a renowned investigator of insulin resistance and diabetes who was the first to identify and describe Syndrome X, now known as metabolic syndrome. He co-authored Syndrome X: The Silent Killer in 2001 about Syndrome X and its repercussions on cardiovascular disease. Dr. Reaven is the former chief of the Division of Endocrinology and Metabolism, the Division of Gerontology, and the divisions of Endocrinology-Metabolism-Gerontology.

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About Dr. Reaven

Cardiovascular Health

Stanford Cardiovascular Medicine