Statin treatment increased the risk of type 2 diabetes by 46%, attributable to decreases in insulin sensitivity and insulin secretion.
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1 von :49 Download PDF (277 KB) View Article Diabetologia May 2015, Volume 58, Issue 5, pp Date: 10 Mar 2015 Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort Abstract Aims/hypothesis The aim of this work was to investigate the mechanisms underlying the risk of type 2 diabetes associated with statin treatment in the population-based Metabolic Syndrome in Men (METSIM) cohort. Methods A total of 8,749 non-diabetic participants, aged years, were followed up for 5.9 years. New diabetes was diagnosed in 625 men by means of an OGTT, HbA 1c 6.5% (48 mmol/mol) or glucoselowering medication started during the follow-up. Insulin sensitivity and secretion were evaluated with OGTT-derived indices. Results Participants on statin treatment (N = 2,142) had a 46% increased risk of type 2 diabetes (adjusted HR 1.46 [95% CI 1.22, 1.74]). The risk was dose dependent for simvastatin and atorvastatin. Statin treatment significantly increased 2 h glucose (2hPG) and glucose AUC of an OGTT at follow-up, with a nominally significant increase in fasting plasma glucose (FPG). Insulin sensitivity was decreased by 24% and insulin secretion by 12% in individuals on statin treatment (at FPG and 2hPG <5.0 mmol/l) compared with individuals without statin treatment (p < 0.01). Decreases in insulin sensitivity and insulin secretion were dose dependent for simvastatin and atorvastatin. Conclusions/interpretation Statin treatment increased the risk of type 2 diabetes by 46%, attributable to decreases in insulin sensitivity and insulin secretion.
2 von :49 Article Metrics 4 Citations 144 Social Shares Co-published with European Association for the Study of Diabetes
3 3 von :49 125_2015_3528_MOESM1_ESM.pdf (83KB) ESM Fig 1: (PDF 82 kb) 125_2015_3528_MOESM2_ESM.pdf (71KB) ESM Table 1: (PDF 71 kb) 125_2015_3528_MOESM3_ESM.pdf (75KB) ESM Table 2: (PDF 75 kb) 125_2015_3528_MOESM4_ESM.pdf (90KB) ESM Table 3: (PDF 90 kb) 125_2015_3528_MOESM5_ESM.pdf (92KB) ESM Table 4: (PDF 92 kb) References 1. Cholesterol Treatment Trialists (CTT) Collaborators, Kearney PM, Blackwell L et al (2008) Efficacy of cholesterol-lowering therapy in 18,686 people with diabetes in 14 randomised trials of statins: a meta-analysis. Lancet 371: View Article 2. Cholesterol Treatment Trialists (CTT) Collaborators, Baigent C, Blackwell L et al (2010) Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 376: View Article 3. Freeman DJ, Norrie J, Sattar N et al (2001) Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study. Circulation 103: View 4. Ridker PM, Danielson E, Fonseca FA et al (2008) Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med 359: View 5. Culver AL, Ockene IS, Balasubramanian R et al (2012) Statin use and risk of diabetes mellitus in postmenopausal women in the Women s Health Initiative. Arch Intern Med 172: View 6. Rajpathak SN, Kumbhani DJ, Crandall J, Barzilai N, Alderman M, Ridker PM (2009) Statin therapy and risk of developing type 2 diabetes: a meta-analysis. Diabetes Care
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5 5 von :49 sensitivity in non-diabetics: a systematic review and meta-analysis. Diabetes Res Clin Pract 87:98 107View 20. Moutzouri E, Liberopoulos E, Mikhailidis DP et al (2011) Comparison of the effects of simvastatin vs. rosuvastatin vs. simvastatin/ezetimibe on parameters of insulin resistance. Int J Clin Pract 65: View 21. Yada T, Nakata M, Shiraishi T, Kakei M (1999) Inhibition by simvastatin, but not pravastatin, of glucose-induced cytosolic Ca 2+ signalling and insulin secretion due to blockade of L-type Ca 2+ channels in rat islet β-cells. Br J Pharmacol 126: View CentralPubMed 22. Ishikawa M, Okajima F, Inoue N et al (2006) Distinct effects of pravastatin, atorvastatin, and simvastatin on insulin secretion from a beta-cell line, MIN6 cells. J Atheroscler Thromb 13: View 23. Stancakova A, Javorsky M, Kuulasmaa T, Haffner SM, Kuusisto J, Laakso M (2009) Changes in insulin sensitivity and insulin release in relation to glycemia and glucose tolerance in 6,414 Finnish men. Diabetes 58: View CentralPubMed 24. American Diabetes Association (2006) Diagnosis and classification of diabetes mellitus. Diabetes Care 29(Suppl 1):S43 S Matsuda M, DeFronzo RA (1999) Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 22: View 26. Sukhija R, Prayaga S, Marashdeh M et al (2009) Effect of statins on fasting plasma glucose in diabetic and nondiabetic patients. J Investig Med 57: PubMed 27. Rautio N, Jokelainen J, Oksa H et al (2012) Do statins interfere with lifestyle intervention in the prevention of diabetes in primary healthcare? One-year follow-up of the FIN-D2D project. BMJ Open 2:e001472View CentralPubMed 28. Navarese EP, Buffon A, Andreotti F et al (2013) Meta-analysis of impact of different types and doses of statins on new-onset diabetes mellitus. Am J Cardiol 111: View Title Increased risk of diabetes with statin treatment is associated with impaired insulin sensitivity and insulin secretion: a 6 year follow-up study of the METSIM cohort Journal Diabetologia Volume 58, Issue 5, pp
6 von :49 Cover Date DOI /s Print ISSN X Online ISSN Publisher Springer Berlin Heidelberg Additional Links Topics Register for Journal Updates Editorial Board About This Journal Manuscript Submission Internal Medicine Metabolic Diseases Keywords Human Physiology 2-h glucose Fasting glucose HbA1c Insulin resistance Insulin sensitivity Statin Type 2 diabetes Industry Sectors Pharma Chemical Manufacturing Health & Hospitals Biotechnology Finance, Business & Banking Electronics
7 7 von :49 IT & Software Telecommunications Consumer Packaged Goods Authors Henna Cederberg (1) Alena Stančáková (2) Nagendra Yaluri (2) Shalem Modi (2) Johanna Kuusisto (1) Markku Laakso (1) Author Affiliations 1. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland and Kuopio University Hospital, P.O. Box 1627, 70211, Kuopio, Finland 2. Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland Continue reading... To view the rest of this content please follow the download PDF link above. Over 9 million scientific documents at your fingertips Springer International Publishing AG, Part of Springer Science+Business Media
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