Clinical Impact of the Leptin to Soluble Leptin Receptor Ratio on Subclinical Carotid Atherosclerosis in Patients with Type 2 Diabetes

Abstract

The adipocyte-derived hormone leptin plays a key role in the regulation of food intake and energy expenditure. Recent studies have suggested that leptin is also involved in the pathogenesis of obesity-associated atherosclerosis and cardiovascular disease. In this study, we investigated the associations of leptin and the soluble leptin receptor (sOb-R) with atherosclerosis in patients with type 2 diabetes. Three hundred seventeen type 2 diabetic subjects were enrolled in this cross-sectional study. Fasting plasma leptin and sOb-R concentrations were measured by enzyme-linked immunosorbent assays. The intima-media thickness (IMT) of the common carotid artery was measured by ultrasound. The IMT was significantly associated with sOb-R concentrations, age, diabetes duration, serum creatinine (sCre) levels, and systolic blood pressure (SBP), but not with leptin concentrations or the leptin/sOb-R ratio. The concentrations of leptin (r=0.478, p<0.001) and the sOb-R (r= -0.404, p<0.001) and the leptin/sOb-R ratio (r=0.501, p<0.001) were strongly correlated with IMT in subjects treated with insulin for glycemic control, but not in those treated with diet alone or oral hypoglycemic agents. Multiple regression analysis, including age, sex, diabetes duration, body mass index, SBP, HbA1c, triglycerides, LDL-cholesterol, sCre, smoking, and insulin therapy, revealed that plasma leptin and the leptin/sOb-R ratio were independently associated with IMT in subjects treated with insulin. Plasma leptin and the leptin/sOb-R ratio are associated with atherosclerosis in patients with type 2 diabetes on insulin therapy, and these associations were independent of obesity and other cardiovascular risk factors.