23-OR: The Effect of 14-Day Atorvastatin Treatment on Postprandial Glucose Metabolism in Healthy Males—A Link to Why Statin Therapy Increases the Risk of Type 2 Diabetes?

Background and Aim: Statins are LDL cholesterol-lowering drugs that are highly effective in the prevention of cardiovascular disease and death. Recently, it has become known that statin therapy increases the risk of type 2 diabetes, but the mechanism behind this phenomenon remains obscure. We evaluated the gluco-metabolic effects of statin therapy in healthy male individuals. Methods: In a placebo-controlled, double-blinded, randomized, cross-over study, we investigated the effect of 14 days of treatment with atorvastatin (40 mg once-daily for one week and 80 mg once-daily the second week) on fasting and postprandial concentrations of glucose, gluco-regulatory hormones and bile acid profiles in 15 healthy male individuals (age 25.6±3.8 years; BMI 24.7±2.8 kg/m 2 ; glycated hemoglobin A1c 4.8±0.2% (mean±SD)). Four-hour mixed meal tests were performed following each of the two 14-day treatment periods with placebo or atorvastatin, respectively. Results: Treatment with atorvastatin did not affect postprandial plasma glucose or insulin concentrations, but basal as well as postprandial concentrations of glucagon were increased compared to placebo. Postprandial plasma concentrations of the gut-derived incretin hormones glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 were increased after atorvastatin treatment compared to placebo. Also, postprandial concentrations of taurine-conjugated primary bile acids increased, whereas glycine-conjugated secondary bile acids decreased. Conclusion: In healthy male individuals, 14 days of atorvastatin treatment did not affect postprandial glucose tolerance or insulin concentrations. Fasting and postprandial glucagon concentrations were increased by atorvastatin treatment, which may point to hyperglucagonemia as a possible link between statin treatment and type 2 diabetes. Disclosure M.L. Thomasen: None. D.P. Sonne: None. M.L. Karhus: None. A. Bronden: Other Relationship; Self; AstraZeneca. B. Staels: None. J.J. Holst: Advisory Panel; Self; Novo Nordisk A/S. T. Vilsboll: None. F.K. Knop: Advisory Panel; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Novo Nordisk A/S, Sanofi. Consultant; Self; Amgen Inc., Carmot Therapeutics, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Novo Nordisk A/S. Speaker9s Bureau; Self; AstraZeneca, MedImmune, Merck Sharp & Dohme Corp., Mundipharma, Norgine, Novo Nordisk A/S. Funding Augustinus Fonden