Studies have indicated that statins have been associated with the development of diabetes and atherosclerotic plaque calcification with cardiac disease. According to results from a study published in the Journal of the Endocrine Society, the use of statin therapy is also associated with elevated levels of insulin resistance in older patients.

In this observational study, the goals were to investigate the association between statin use and insulin resistance using the homeostatic model assessment of insulin resistance (HOMA-IR) in patients without diabetes who participated in the observational Canadian Multicenter Osteoporosis Study at Year 10 and to explore the association between statin use and abdominal aortic calcification assessed on lateral spine radiographs. 

The study cohort included 609 individuals (median age 71 years, 74% women), of whom 152 were statin users and 457 were nonusers. The study indicated that statin users had considerably higher HOMA-IR levels (2.6 [95% CI, 1.9-4.4] vs. 1.7 [95% CI, 1-2.9] in nonusers; P <.001). In addition, abdominal aortic calcification scores were substantially greater in statin users compared with those in nonusers. Researchers used a general linear model, and statin use was associated with higher levels of HOMA after stratified propensity score (PS) adjustment (β = 1.52 [1.18-1.95], P <.01). Hydrophilic statin users (n = 9) and lipophilic statin users (n = 30) had higher HOMA compared with nonstatin users (n = 125) ([β = 2.29 (1.43-3.68), P <.001] and [β = 1.36 (1.04-1.78), P <.05]), respectively, in general linear models after stratified PS adjustment.

Statin use was associated with abdominal aortic calcification without stratifying by PS in the Wilcoxon test but was no longer significant when stratified by PS. The researchers noted that the negative effect on insulin resistance has historically been tied to the lipophilicity of statins, but HOMA-IR was considerably greater in hydrophilic statin users compared with lipophilic statin users (β = 1.79; 95% CI, 1.15-2.79; P <.05). However, the researchers noted that 73% of hydrophilic statin users in this cohort were receiving rosuvastatin, a high-potency hydrophilic statin that has been linked to the highest risk for type 2 diabetes mellitus compared with other statins, which may have clarified the discrepancy.

The researchers concluded that “Statins may have unintended consequences related to glucose homeostasis that could be relevant in healthy aging. In those individuals with risk factors for diabetes, consideration for choosing non-lipophilic statins and avoidance of rosuvastatin and lipophilic statins may provide the intended cardiovascular protection without the increased incidence of insulin resistance.” 

The researchers also recognized several study limitations, including the cross-sectional design, potential unobserved or inaccurately measured confounders, missing data on cholesterol levels or statin doses, and a study population limited to community-living individuals.

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