Source/Disclosures
Disclosures: Holden and one other study author report they received grant support from the Canadian Institute for Health Research, OKPO Renal and Sanofi.
June 05, 2020
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Statin use may lead to ‘unintended consequence’ of insulin resistance

Source/Disclosures
Disclosures: Holden and one other study author report they received grant support from the Canadian Institute for Health Research, OKPO Renal and Sanofi.
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A cohort of Canadian adults prescribed statins, and hydrophilic statins, in particular, had higher levels of insulin resistance compared with non-statin users, according to findings published in the Journal of the Endocrine Society.

“There is emerging data to suggest that by inhibiting the production of intermediates of cholesterol biosynthesis, statins also inhibit the mevalonate pathway and impede the production of vitamin K2 in peripheral tissues,” Rachel M. Holden, MD, a nephrologist and associate professor in the department of medicine at Queen’s University in Kingston, Ontario, Canada, and colleagues wrote in the study background. “There is growing evidence to suggest that vitamin K2 plays a key role in glucose homeostasis as well as vascular calcification. On this background, we hypothesized that statin use would be associated with both insulin resistance and vascular calcification in community-dwelling participants of a large longitudinal study of osteoporosis.”

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In an observational study, Holden and colleagues analyzed data from 609 adults participating in the Canadian Multicentre Osteoporosis Study with follow-up data at year 10 (mean age, 71 years, 74% women; 33% with diabetes; 44% with hypertension). Participants reported information on statin use and specific statin type at year 10 (n = 150 statin users). Researchers used homeostatic model assessment of insulin resistance (HOMA-IR) to measure insulin resistance in participants without diabetes at year 10 (n = 164); fasting glucose and serum insulin were also measured. Abdominal aortic calcification was assessed on lateral spine radiographs using the Framingham method in 187 participants at year 10.

Researchers evaluated the association between statin use and abdominal aortic calcification among participants at 10 years. Researchers also explored the impact of the hydrophilicity vs. lipophilicity of specific statin drugs on outcomes as a secondary analysis.

Within the cohort, median HOMA-IR was 2.6 for statin users and 1.7 for nonusers (P < .001). Median abdominal aortic calcification score was 4.5 for statin users and 2 for nonusers.

In analyses stratified by statin type, researchers found that HOMA-IR was higher among hydrophilic statin users compared with lipophilic statin users (P < .05). Compared with non-statin users, HOMA-IR was similarly higher among participants prescribed hydrophilic statins with propensity score stratification (P < .001) and without propensity score stratification (P < .001), and was also higher among participants prescribed lipophilic statins with propensity score stratification (P < .05) and without propensity score stratification (P < .01).

Lipophilic statins include atorvastatin, simvastatin, lovastatin, fluvastatin, cerivastatin and pitavastatin; hydrophilic statins include rosuvastatin and pravastatin.

In a separate assessment of participants prescribed rosuvastatin, researchers observed that HOMA-IR was higher vs. those prescribed lipophilic statins, in analyses with propensity score matching (P < .001) and without (P < .001).

“Statins, widely prescribed drugs to lower cholesterol, may have unintended consequences related to glucose homeostasis that could be relevant in healthy aging,” the researchers wrote. “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.”