Advertisement

Effect of Statin Therapy on Incident Type 2 Diabetes Mellitus in Patients With Clinically Manifest Vascular Disease

Published:November 28, 2014DOI:https://doi.org/10.1016/j.amjcard.2014.11.021
      Several trials and cohort studies have shown an increased incidence of type 2 diabetes mellitus (T2DM) in patients using statins. Whether this only applies to patients at already high risk for the development of T2DM or for all patients is still a matter of debate. In the present prospective cohort study of 4,645 patients with established vascular disease without DM at baseline, 3,057 patients used statins at baseline, of whom 1,608 used intensive statin therapy, defined as statin therapy theoretically lowering low-density lipoprotein cholesterol with ≥40%. Cox proportional hazards models were used to estimate the risk of incident T2DM with (intensive) statin therapy. Statin therapy was associated with increased risk of incident T2DM (hazard ratio 1.63; 95% confidence interval 1.15 to 2.32) when adjusted for age, gender, body mass index, plasma high-density lipoprotein cholesterol, and plasma triglyceride levels. Intensive statin therapy tended to be related to a higher risk of T2DM compared with moderate statin therapy (hazard ratio 1.22; 95% confidence interval 0.92 to 1.61, adjusted for age, gender, body mass index, plasma high-density lipoprotein cholesterol, and plasma triglyceride levels). The increase in risk was regardless of the number of metabolic syndrome characteristics or insulin resistance but was particularly present in patients with low baseline glucose levels (<5.6 mmol/L; p for interaction 2.9 × 10−7). In conclusion, statin use increases the risk of incident T2DM in patients with clinically manifest vascular disease. The increase in risk was independent of the number of metabolic syndrome criteria and was even more pronounced in patients with low baseline glucose levels.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Baigent C.
        • Blackwell L.
        • Emberson J.
        • Holland L.E.
        • Reith C.
        • Bhala N.
        • Peto R.
        • Barnes E.H.
        • Keech A.
        • Simes J.
        • Collins R.
        Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials.
        Lancet. 2010; 376: 1670-1681
        • Reiner Z.
        • Catapano A.L.
        • De B.G.
        • Graham I.
        • Taskinen M.R.
        • Wiklund O.
        • Agewall S.
        • Alegria E.
        • Chapman M.J.
        • Durrington P.
        • Erdine S.
        • Halcox J.
        • Hobbs R.
        • Kjekshus J.
        • Filardi P.P.
        • Riccardi G.
        • Storey R.F.
        • Wood D.
        ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS).
        Eur Heart J. 2011; 32: 1769-1818
      1. Executive Summary of the Third report of the National cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and treatment of high blood cholesterol in Adults (Adult treatment Panel III).
        JAMA. 2001; 285: 2486-2497
        • Ridker P.M.
        • Danielson E.
        • Fonseca F.A.
        • Genest J.
        • Gotto Jr., A.M.
        • Kastelein J.J.
        • Koenig W.
        • Libby P.
        • Lorenzatti A.J.
        • MacFadyen J.G.
        • Nordestgaard B.G.
        • Shepherd J.
        • Willerson J.T.
        • Glynn R.J.
        Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial.
        Lancet. 2009; 373: 1175-1182
        • Sattar N.
        • Preiss D.
        • Murray H.M.
        • Welsh P.
        • Buckley B.M.
        • de Craen A.J.
        • Seshasai S.R.
        • McMurray J.J.
        • Freeman D.J.
        • Jukema J.W.
        • Macfarlane P.W.
        • Packard C.J.
        • Stott D.J.
        • Westendorp R.G.
        • Shepherd J.
        • Davis B.R.
        • Pressel S.L.
        • Marchioli R.
        • Marfisi R.M.
        • Maggioni A.P.
        • Tavazzi L.
        • Tognoni G.
        • Kjekshus J.
        • Pedersen T.R.
        • Cook T.J.
        • Gotto A.M.
        • Clearfield M.B.
        • Downs J.R.
        • Nakamura H.
        • Ohashi Y.
        • Mizuno K.
        • Ray K.K.
        • Ford I.
        Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials.
        Lancet. 2010; 375: 735-742
        • Preiss D.
        • Seshasai S.R.
        • Welsh P.
        • Murphy S.A.
        • Ho J.E.
        • Waters D.D.
        • DeMicco D.A.
        • Barter P.
        • Cannon C.P.
        • Sabatine M.S.
        • Braunwald E.
        • Kastelein J.J.
        • de Lemos J.A.
        • Blazing M.A.
        • Pedersen T.R.
        • Tikkanen M.J.
        • Sattar N.
        • Ray K.K.
        Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis.
        JAMA. 2011; 305: 2556-2564
        • Wang K.L.
        • Liu C.J.
        • Chao T.F.
        • Huang C.M.
        • Wu C.H.
        • Chen S.J.
        • Chen T.J.
        • Lin S.J.
        • Chiang C.E.
        Statins, risk of diabetes, and implications on outcomes in the general population.
        J Am Coll Cardiol. 2012; 60: 1231-1238
        • Culver A.L.
        • Ockene I.S.
        • Balasubramanian R.
        • Olendzki B.C.
        • Sepavich D.M.
        • Wactawski-Wende J.
        • Manson J.E.
        • Qiao Y.
        • Liu S.
        • Merriam P.A.
        • Rahilly-Tierny C.
        • Thomas F.
        • Berger J.S.
        • Ockene J.K.
        • Curb J.D.
        • Ma Y.
        Statin use and risk of diabetes mellitus in postmenopausal women in the Women's Health Initiative.
        Arch Intern Med. 2012; 172: 144-152
        • Waters D.D.
        • Ho J.E.
        • Boekholdt S.M.
        • DeMicco D.A.
        • Kastelein J.J.
        • Messig M.
        • Breazna A.
        • Pedersen T.R.
        Cardiovascular event reduction versus new-onset diabetes during atorvastatin therapy: effect of baseline risk factors for diabetes.
        J Am Coll Cardiol. 2013; 61: 148-152
        • Zaharan N.L.
        • Williams D.
        • Bennett K.
        Statins and risk of incident diabetes in a primary care population.
        Br J Clin Pharmacol. 2013; 75: 1118-1124
        • Ridker P.M.
        • Pradhan A.
        • MacFadyen J.G.
        • Libby P.
        • Glynn R.J.
        Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial.
        Lancet. 2012; 380: 565-571
        • Simons P.C.
        • Algra A.
        • van de Laak M.F.
        • Grobbee D.E.
        • van der G.Y.
        Second manifestations of ARTerial disease (SMART) study: rationale and design.
        Eur J Epidemiol. 1999; 15: 773-781
        • Weng T.C.
        • Yang Y.H.
        • Lin S.J.
        • Tai S.H.
        A systematic review and meta-analysis on the therapeutic equivalence of statins.
        J Clin Pharm Ther. 2010; 35: 139-151
        • Hou R.
        • Goldberg A.C.
        Lowering low-density lipoprotein cholesterol: statins, ezetimibe, bile acid sequestrants, and combinations: comparative efficacy and safety.
        Endocrinol Metab Clin North Am. 2009; 38: 79-97
        • Carter A.A.
        • Gomes T.
        • Camacho X.
        • Juurlink D.N.
        • Shah B.R.
        • Mamdani M.M.
        Risk of incident diabetes among patients treated with statins: population based study.
        BMJ. 2013; 346: f2610
        • Guerrero-Romero F.
        • Simental-Mendia L.E.
        • Gonzalez-Ortiz M.
        • Martinez-Abundis E.
        • Ramos-Zavala M.G.
        • Hernandez-Gonzalez S.O.
        • Jacques-Camarena O.
        • Rodriguez-Moran M.
        The product of triglycerides and glucose, a simple measure of insulin sensitivity.
        J Clin Endocrinol Metab. 2010; 95: 3347-3351
        • Mihaylova B.
        • Emberson J.
        • Blackwell L.
        • Keech A.
        • Simes J.
        • Barnes E.H.
        • Voysey M.
        • Gray A.
        • Collins R.
        • Baigent C.
        The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials.
        Lancet. 2012; 380: 581-590
        • Wang K.L.
        • Liu C.J.
        • Chao T.F.
        • Chen S.J.
        • Wu C.H.
        • Huang C.M.
        • Chang C.C.
        • Wang K.F.
        • Chen T.J.
        • Lin S.J.
        • Chiang C.E.
        Risk of new-onset diabetes mellitus versus reduction in cardiovascular events with statin therapy.
        Am J Cardiol. 2014; 113: 631-636
        • Ko D.T.
        • Wijeysundera H.C.
        • Jackevicius C.A.
        • Yousef A.
        • Wang J.
        • Tu J.V.
        Diabetes mellitus and cardiovascular events in older patients with myocardial infarction prescribed intensive-dose and moderate-dose statins.
        Circ Cardiovasc Qual Outcomes. 2013; 6: 315-322
        • Nielsen S.F.
        • Nordestgaard B.G.
        Statin use before diabetes diagnosis and risk of microvascular disease: a nationwide nested matched study.
        Lancet Diabetes Endocrinol. 2014; 2: 894-900
        • Dorresteijn J.A.
        • Boekholdt S.M.
        • van der G.Y.
        • Kastelein J.J.
        • LaRosa J.C.
        • Pedersen T.R.
        • DeMicco D.A.
        • Ridker P.M.
        • Cook N.R.
        • Visseren F.L.
        High-dose statin therapy in patients with stable coronary artery disease: treating the right patients based on individualized prediction of treatment effect.
        Circulation. 2013; 127: 2485-2493
        • Reaven G.M.
        Insulin resistance, the insulin resistance syndrome, and cardiovascular disease.
        Panminerva Med. 2005; 47: 201-210
        • Abdul-Ghani M.A.
        • Tripathy D.F.
        • DeFronzo R.A.
        Contributions of beta-cell dysfunction and insulin resistance to the pathogenesis of impaired glucose tolerance and impaired fasting glucose.
        Diabetes Care. 2006; 29: 1130-1139
        • Corrao G.
        • Ibrahim B.
        • Nicotra F.
        • Soranna D.
        • Merlino L.
        • Catapano A.L.
        • Tragni E.
        • Casula M.
        • Grassi G.
        • Mancia G.
        Statins and the risk of diabetes: evidence from a large population-based cohort study.
        Diabetes Care. 2014; 37: 2225-2232