Statins associated with increased risk of diabetes in high-risk individuals

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Researchers recommend that patients at high risk for diabetes be monitored during statin therapy.
Researchers recommend that patients at high risk for diabetes be monitored during statin therapy.

Statins are associated with nearly a 30% increased risk of type 2 diabetes among individuals who are at high risk for the disorder, according to a study in BMJ Open Diabetes Research & Care.

Jill Crandall, MD, from the Department of Medicine and Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York, and colleagues conducted the Diabetes Prevention Program Outcomes Study (DPPOS), a long-term follow-up to the Diabetes Prevention Program (DPP), a randomized clinical trial that tested interventions to prevent or delay the development of diabetes mellitus in high-risk individuals.

The researchers assessed 3,234 patients from 27 clinical centers in the United States—about 50% were members of ethnic or racial minority groups, and 20% were aged 60 years and older. Eligibility criteria included persons aged 25 years and older, a body mass index (BMI) of ≥24 kg/m2 (≥22 kg/m2 in Asian–Americans), and fasting plasma glucose levels between 95 and 125 mg/dL and impaired glucose tolerance (IGT) (2-hour 75-g postload glucose of 140 to 199 mg/dL).

Eligible participants received standard advice regarding healthy diet and physical activity and were randomly assigned to an intensive lifestyle intervention, metformin, or placebo. At the end of the main trial (mean follow-up, 3.2 years), all subjects were offered a group-administered version of the lifestyle intervention and were invited to enroll in the DPPOS. For the DPPOS, all participants were offered quarterly lifestyle sessions, the former metformin group received open-label metformin, and the former intensive lifestyle group was offered 2 additional lifestyle programs per year. Findings are based on data collected up to August 31, 2008, with a median follow-up of 10 years from randomization to the most recent evaluation. 

The researchers found that the cumulative incidence of statin initiation prior to a diagnosis of diabetes was 33% to 37% among the randomized treatment groups at 10 years. Statin use was associated with an increased diabetes risk irrespective of treatment group, and the pooled hazard ratio (HR) for incident diabetes was 1.36 (1.17 to 1.58).

“In this analysis, statin use was associated with a clear increase in diabetes risk in the cohort as a whole, with point estimates of the HRs suggesting this risk is increased by close to 30%,” Dr Crandall's group stated. “This augmented risk was only modestly attenuated with adjustment for variables related to the indication for statin treatment, suggesting that the indications for therapy were not themselves major contributors to diabetes risk. Participants who were prescribed statins had modestly higher levels of glucose at baseline, yet this also did not explain the higher rates of diabetes among statin users. Our data suggest the statin-associated diabetes risk did not differ significantly by treatment group, based on a test of statistical interaction.”

The investigators also found evidence of increased deterioration in insulin secretion in statin users, although this was only statistically demonstrated in participants who were randomized to the lifestyle arm.

“This pattern is consistent with previously described metabolic changes underlying progression to diabetes among high-risk individuals and with our observation that participants in the DPP/DPPOS lifestyle arm who progressed to diabetes had a higher genetic risk score, which largely reflects polymorphisms related to beta cell functioning,” the investigators commented. “Overall, this suggests an acceleration of typical glycemic deterioration, rather than a unique or statin-specific mechanism.”

Reference

Crandall JP, Mather K, Rajpathak SN, Goldberg RB, Watson K, Foo S, et al. Statin use and risk of developing diabetes: results from the Diabetes Prevention Program. BMJ Open Diab Res Care. 2017;5:e000438. doi:10.1136/ bmjdrc-2017-000438

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