Cholesterol disorder offers clues about statins and diabetes

A study published in the March 10 issue of JAMA may help unravel the possible relationship between statin use and the increased risk of diabetes. If confirmed, the findings may provide a pathway for new treatments.  

Joost Besseling, MD, of the Academic Medical Centre in Amsterdam, and colleagues noted that statins increase cellular cholesterol uptake while the low-density lipoprotein receptor mutations behind familial hypercholesterolemia impede cholesterol uptake. They also observed that people with familial hypercholesterolemia tend to be less likely to develop type 2 diabetes.

To evaluate the association between the two conditions, they accessed data from 1994 to 2014 in a Dutch registry for familial hypercholesterolemia. The national program screened people suspected of having the genetic disorder using DNA testing; if the person was found to be a carrier of the mutation, then their first-degree relatives were approached for genetic testing. Initiated in 1994, the program also measured lipids, although not consistently until 2004. Participants self-reported if they had type 2 diabetes.

Their analysis included 25,137 participants with familial hypercholesterolemia and 38,183 relatives who were not affected. Type 2 diabetes prevalence was lower in those with familial hypercholesterolemia (1.75 percent vs. 2.93 percent in their unaffected relatives) with an inverse-dose response based on severity. Carriers of mutations for the most severe phenotype had the lowest prevalence (1.12 percent).

Besseling et al placed the increased risk of diabetes with statin use at 9 percent, although they added that the biological mechanism behind that association is not well understood. “Our findings support the hypothesis that the common pathway in familial hypercholesterolemia and statin therapy—cellular cholesterol uptake—plays a role in the development of type 2 diabetes, perhaps because increased intracellular cholesterol levels are detrimental for pancreatic beta cell function,” they wrote.

They acknowledged the study was observational but the potential for confounding was minimized by the random nature of an inherited disease. They recommended longitudinal studies; if their findings are confirmed, the results might spur the development of treatments for type 2 diabetes that target pancreatic beta cells.