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Plasma Leptin Levels Are Associated with Coronary Atherosclerosis in Type 2 Diabetes

Cardiovascular Division (M.P.R., D.J.R., S.E.K.) and Division of Endocrinology, Diabetes and Metabolism (N.I., M.S.), Department of Medicine (M.L.W.), and the Center for Clinical Epidemiology and Biostatistics (M.P.R., A.R.L., S.E.K.), University of Pennsylvania School of Medicine; Department of Medicine, Section of Endocrinology, Diabetes and Metabolism (N.I.), Philadelphia Veterans Administration Medical Center; and Department of Medicine (M.S.), Pennsylvania Hospital, University of Pennsylvania Health System, Philadelphia, Pennsylvania 19104

Address all correspondence and requests for reprints to: Muredach Reilly, Cardiovascular Division, University of Pennsylvania Medical Center, 909 BRB 2/3, 421 Curie Boulevard, Philadelphia, Pennsylvania 19104-6160. E-mail: muredach{at}spirit.gcrc.upenn.edu.

Leptin signaling may promote atherothrombosis and lead to cardiovascular disease. However, whether leptin is associated with human atherosclerosis, distinct from thrombosis, is unknown. We determined the association of plasma leptin levels with coronary artery calcification (CAC), a measure of coronary atherosclerosis, in a cross-sectional study of type 2 diabetes. Leptin levels were associated with CAC after adjusting for established risk factors [odds ratio (95% confidence interval) for 5 ng/ml leptin increase: 1.31 (1.10–1.55); P = 0.002]. Leptin remained associated with CAC after further controlling for body mass index (BMI) [1.29 (1.07–1.55); P = 0.008], waist circumference [1.30 (1.09–1.57); P = 0.003], C-reactive protein (CRP) levels [1.28 (1.07–1.55); P = 0.008], and subclinical vascular disease [1.30 (1.08–1.57); P = 0.006]. Addition of BMI (P = 0.97), waist (P = 0.55), or CRP (P = 0.39) to a model with leptin failed to improve the model’s explanatory power, whereas addition of leptin to a model with BMI (P = 0.029), waist (P = 0.006), or CRP (P = 0.005) improved the model significantly. Plasma leptin levels were associated with CAC in type 2 diabetes after controlling adiposity and CRP. Whether leptin signaling promotes atherosclerosis directly or represents a therapeutic target for the prevention of atherosclerotic cardiovascular disease remains to be explored.

This work was supported in part by Grant M01-RR00040 from the National Center for Research Resources-National Institutes of Health (NIH) supporting the University of Pennsylvania General Clinical Research Center and by a pilot grant from the Penn Diabetes and Endocrinology Research Center (DK19525) (M.P.R.). M.P.R. is supported by National Center for Research Resources Grant 15532-02, Grant RO1 HL73278-01 from the NIH, and Grant H0204 from the W. W. Smith Charitable Trust.

Abbreviations: ABI, Ankle brachial indices; BMI, body mass index; CAC, coronary artery calcification; CRP, C-reactive protein; CVD, cardiovascular disease; DM, diabetes mellitus; EBT, electron beam tomography; EKG, electrocardiogram; HbA1c, hemaglobin A1c; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LR, likelihood ratio; MI, myocardial infarction; OR, odds ratio; PAOD, peripheral arterial obstructive disease.

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