Statins are associated with increased insulin resistance and secretion
Open accessAbstract
Objective: Statin treatment reduces the risk of atherosclerotic cardiovascular disease but is associated with a modest increased risk of type 2 diabetes, especially in those with insulin resistance or prediabetes. Our objective was to determine the physiological mechanism for the increased type 2 diabetes risk. Approach and Results: We conducted an open-label clinical trial of atorvastatin 40 mg daily in adults without known atherosclerotic cardiovascular disease or type 2 diabetes at baseline. The co-primary outcomes were changes at 10 weeks versus baseline in insulin resistance as assessed by steady-state plasma glucose during the insulin suppression test and insulin secretion as assessed by insulin secretion rate area under the curve (ISRAUC) during the graded-glucose infusion test. Secondary outcomes included glucose and insulin, both fasting and during oral glucose tolerance test. Of 75 participants who enrolled, 71 completed the study (median age 61 years, 37% women, 65% non-Hispanic White, median body mass index, 27.8 kg/m2). Atorvastatin reduced LDL (low-density lipoprotein)-cholesterol (median decrease 53%, P<0.001) but did not change body weight. Compared with baseline, atorvastatin increased insulin resistance (steady-state plasma glucose) by a median of 8% (P=0.01) and insulin secretion (ISRAUC) by a median of 9% (P<0.001). There were small increases in oral glucose tolerance test glucoseAUC (median increase, 0.05%; P=0.03) and fasting insulin (median increase, 7%; P=0.01). Conclusions: In individuals without type 2 diabetes, high-intensity atorvastatin for 10 weeks increases insulin resistance and insulin secretion. Over time, the risk of new-onset diabetes with statin use may increase in individuals who become more insulin resistant but are unable to maintain compensatory increases in insulin secretion.
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Statin exposure possibly exacerbates the risk to develop diabetes in individuals with TS, who are already at high risk for metabolic derangement.
“Statin exposure possibly exacerbates the risk to develop diabetes in individuals with TS, who are already at high risk for metabolic derangement.479,480”
From Clinical practice guidelines for the care of girls and women with Turner syndrome. (2024) · cites this paper as [480]
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Clinical practice guidelines for the care of girls and women with Turner syndrome.
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- Authors
- Abbasi, F., Lamendola, C., Harris, C. S., Harris, V., Tsai, M.-S., Tripathi, P., Abbas, F., Reaven, G. M., Reaven, P. D., Snyder, M. P., Kim, S. H., & Knowles, J. W.
- Affiliations
- Stanford Medicine (US)
- Stanford Diabetes Research Center (US)
- University of Arizona (US)
- Corresponding author
- Knowles, Joshua W.
- ORCID
- Venue
- Arteriosclerosis Thrombosis and Vascular Biology
- Published
- 2021-11
- Volume
- 41
- Issue
- 11
- Pages
- 2786-2797
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC8551023
- OpenAlex
- W3194954047
- Cited by
- 98
- References
- 67
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 19 · 2023: 30 · 2022: 17 · 2021: 1
- FWCI
- 15.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (UL1TR003142)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK116750, R01DK106236, R01DK120565, P30DK116074, P30DK020579)
- National Center for Advancing Translational Sciences
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- statins, atorvastatin, insulin resistance, insulin secretion, type 2 diabetes risk, prediabetes, insulin suppression test, oral glucose tolerance test, fasting insulin, LDL cholesterol lowering
- MeSH terms
- Atorvastatin, Adult, Aged, Blood Glucose, Diabetes Mellitus, Female, Humans, Insulin, Insulin Resistance, Lipids, Male, Middle Aged, Prospective Studies, Risk Factors, Time Factors, Biomarkers, Treatment Outcome, Risk Assessment, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Dyslipidemias
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