The goal of this analysis was to evaluate the ability of insulin resistance, identified by the presence of prediabetes mellitus (PreDM) combined with either an elevated triglyceride (TG >1.7 mmol/l) or body mass index (BMI ≥27.0 kg/m2), to identify increased risk of statin-associated type 2 diabetes mellitus (T2DM). Consequently, a retrospective analysis of data from subjects without diabetes in the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels randomized controlled trials was performed, subdividing participants into 4 experimental groups: (1) normal fasting glucose (NFG) and TG ≤1.7 mmol/l (42%); (2) NFG and TG >1.7 mmol/l (22%); (3) PreDM and TG ≤1.7 mmol/l (20%); and (4) PreDM and TG >1.7 mmol/l (15%). Comparable groupings were created substituting BMI values (kg/m2 <27.0 and ≥27.0) for TG concentrations. Patients received atorvastatin or placebo for a median duration of 4.9 years. Incident T2DM, defined by developing at least 2 fasting plasma glucose (FPG) concentrations ≥126 mg/dl, an increase in FPG ≥37 mg/dl, or a clinical diagnosis of T2DM, was observed in 8.2% of the total population. T2DM event rates (statin or placebo) varied from a low of 2.8%/3.2% (NFG and TG ≤1.7 mmol/l) to a high of 22.8%/7.6% (PreDM and TG >1.7 mmol/l) with intermediate values for only an elevated TG >1.7 mmol/l (5.2%/4.3%) or only PreDM (12.8%/7.6%). Comparable differences were observed when BMI values were substituted for TG concentrations. In conclusion, these data suggest that (1) the diabetogenic impact of statin treatment is relatively modest in general; (2) the diabetogenic impact is accentuated relatively dramatically as FPG and TG concentrations and BMI increase; and (3) PreDM, TG concentrations, and BMI identify people at highest risk of statin-associated T2DM.
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- Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials.Lancet. 2010; 375: 735-742
- Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis.JAMA. 2011; 305: 2556-2564
- Predictors of new-onset diabetes in patients treated with atorvastatin: results from 3 large randomized clinical trials.J Am Coll Cardiol. 2011; 57: 1535-1545
- Statins are diabetogenic—myth or reality?.Atheroscler Suppl. 2012; 13: 1-10
- 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
- Banting lecture 1988. Role of insulin resistance in human disease.Diabetes. 1988; 37: 1595-1607
- Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians.N Engl J Med. 1993; 329: 1988-1992
- Relationship between several surrogate estimates of insulin resistance and quantification of insulin-mediated glucose disposal in 490 healthy nondiabetic volunteers.Diabetes Care. 2000; 23: 171-175
- Is there a simple way to identify insulin-resistant individuals at increased risk of cardiovascular disease?.Am J Cardiol. 2005; 96: 399-404
- Evaluation of fasting plasma insulin concentration as an estimate of insulin action in nondiabetic individuals: comparison with the homeostasis model assessment of insulin resistance (HOMA-IR).Acta Diabetol. 2014; 51: 193-197
- Wanted!: a standardized measurement of plasma insulin concentration.Arterioscler Thromb Vasc Biol. 2011; 31: 954-955
- Differences in cardiovascular risk factors, insulin resistance, and insulin secretion in individuals with normal glucose tolerance and in subjects with impaired glucose regulation: the Telde Study.Diabetes Care. 2005; 28: 2388-2393
- Isolated impaired fasting glucose and peripheral insulin sensitivity: not a simple relationship.Diabetes Care. 2008; 31: 347-352
- Risk of new-onset diabetes and cardiovascular risk reduction from high-dose statin therapy in pre-diabetics and non-pre-diabetics: an analysis from TNT and IDEAL.J Am Coll Cardiol. 2015; 65: 402-404
- Relationship between obesity, insulin resistance, and coronary heart disease risk.J Am Coll Cardiol. 2002; 40: 937-943
- Evidence for an independent relationship between insulin resistance and fasting plasma HDL-cholesterol, triglyceride and insulin concentrations.J Intern Med. 1992; 231: 25-30
- Intensive lipid lowering with atorvastatin in patients with stable coronary disease.N Engl J Med. 2005; 352: 1425-1435
- High-dose atorvastatin after stroke or transient ischemic attack: the Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) Investigators.J Cardiometab Syndr. 2008; 3: 68-69
- Standards of medical care in diabetes–2015: summary of revisions.Diabetes Care. 2015; 38: S4
- Pravastatin and the development of diabetes mellitus: evidence for a protective treatment effect in the West of Scotland Coronary Prevention Study.Circulation. 2001; 103: 357-362
- Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin.N Engl J Med. 2002; 346: 393-403
- Effect of change in body weight on incident diabetes mellitus in patients with stable coronary artery disease treated with atorvastatin (from the treating to new targets study).Am J Cardiol. 2014; 113: 1593-1598
- 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.Diabetologia. 2015; 58: 1109-1117
- HMG-coenzyme A reductase inhibition, type 2 diabetes, and bodyweight: evidence from genetic analysis and randomised trials.Lancet. 2015; 385: 351-361
- Association between familial hypercholesterolemia and prevalence of type 2 diabetes mellitus.JAMA. 2015; 313: 1029-1036
- Effects of niacin on glucose control in patients with dyslipidemia.Mayo Clin Proc. 2008; 83: 470-478
Published online: August 12, 2016
Accepted: July 28, 2016
Received in revised form: July 28, 2016
Received: June 9, 2016
Drs. Kohli and Knowles contributed equally to this work.
See page 1280 for disclosure information.
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