Understanding How Statins Prevent Cardiovascular Disease but Increase Diabetes Risk

by Amanda Chase, PhD
January 3, 2022

Most have heard of statins and know it is a drug used to help decrease cholesterol levels. Many even take statins, as they are among the most prescribed medication in the world. By decreasing cholesterol levels, statins can help decrease plaque buildup that can lead to heart attack, heart disease, and/or stroke (collectively referred to as atherosclerotic cardiovascular disease or ASCVD). Statins are usually well-tolerated, although data from clinical trials suggests that use of statins can lead to a small increased risk of type 2 diabetes (T2DM). Diabetes can itself be a risk-factor for cardiovascular disease, making this a potentially serious side-effect of statins. T2DM is when your body cannot regulate the use of sugar as fuel as usual. Normally, food is broken down into sugar that enters the blood stream. Insulin is released by the pancreas (secreted) to help blood sugar enter cells in muscle and fat to be used for energy. In the abnormal situation of insulin resistance, sugar that enters the bloodstream is not able to get into cells and the pancreas releases even more insulin to get the blood sugar into cells. Over time, the pancreas cannot keep up with the demand for more insulin and T2DM develops.

While it is understood that statins can lead to T2DM, how it does that is not known. A team of Cardiovascular Institute member researchers, led by first author Fahim Abbasi and senior author Joshua Knowles, conducted a clinical trial to begin to understand how statins can lead to T2DM. Their findings were recently published in Artheriosclerosis, Thrombosis, and Vascular Biology. Specifically, they wanted to know if statins increase insulin resistance (cells stop responding to insulin and do not take blood sugar in) or decrease insulin secretion (less insulin is available to help cells take up the blood sugar).

The team recruited volunteers from the San Francisco Bay Area who were eligible for statin treatment for prevention of ASCVD, but who did not already have diabetes. Eligible participants were given a high dose of atorvastatin (a statin) for 10 weeks.

Overall project process. Recruited participants were treated with a high-level of statin (atorvastatin) for 10-weeks. They found that it could lead to diabetes by increasing both insulin resistance and insulin secretion.

The team then looked for changes in insulin resistance and/or insulin secretion to understand how the statin treatment affected both. They found that high-dose statin treatment for 10 weeks increases both insulin resistance and insulin secretion. The main reason for diabetes following statin treatment is likely the increase in insulin resistance, and the increase in insulin secretion is likely to compensate for increased insulin resistance. This information will make it easier for researchers to understand the mechanism by which statins can lead to T2DM, which will allow for the creation of ways to avoid such side-effects.

Other Cardiovascular Institute member researchers are Cindy Lamendola, Chelsea Harris, Vander Harris, Ming-Shian Tsai, Pragya Tripathi, Fakhar Abbas, Gerald Reaven, Michael Snyder, and Sun Kim. Peter Reaven from the University of Arizona was also part of the research team.

Fahim Abbasi, MD

Joshua Knowles, MD, PhD