Metabolic Markers to Predict Incident Diabetes Mellitus in Statin-Treated Patients (from the Treating to New Targets and the Stroke Prevention by Aggressive Reduction in Cholesterol Levels Trials).
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.
Division of Cardiology, Department of Medicine, Kaiser Permanente, Denver, Colorado; Division of Cardiology, Department of Medicine, University of California, San Francisco, San Francisco, California.
Payal
P
Kohli
Division of Cardiovascular Medicine and Cardiovascular Institute, Department of Medicine, Stanford University, Stanford, California. Electronic address: knowlej@stanford.edu.
Joshua W
JW
Knowles
Division of Cardiovascular Medicine and Cardiovascular Institute, Department of Medicine, Stanford University, Stanford, California.
Ashish
A
Sarraju
Division of Cardiology, Department of Medicine, University of California, San Francisco, San Francisco, California.
David D
DD
Waters
Division of Cardiovascular Medicine and Cardiovascular Institute, Department of Medicine, Stanford University, Stanford, California.
Gerald
G
Reaven
D000069059:Atorvastatin / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000378:metabolism*; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D015994:Incidence; D007333:Insulin Resistance; D002546:Ischemic Attack, Transient / Q000188:drug therapy; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D011236:Prediabetic State / Q000188:drug therapy* / Q000378:metabolism*; D012189:Retrospective Studies; D020521:Stroke / Q000188:drug therapy
D015415:Biomarkers; D001786:Blood Glucose; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids; D000069059:Atorvastatin