Fetuin-A does not explain ethnic disparity in cardiometabolic risk factors and subclinical atherosclerosis between Hispanics and non-Hispanic whites.

BACKGROUND: Fetuin-A has been associated with insulin resistance and inversely related with vascular calcification. The present study evaluated whether serum fetuin-A explains the ethnic disparity in the subclinical atherosclerosis and risk for diabetes between healthy Hispanic and non-Hispanic white (NHW) subjects. METHODS: Fetuin-A was measured in serum of 76 age-matched healthy males (41 NHW, 35 Hispanics). Body mass index, blood pressure, serum lipoprotein cholesterol and triglyceride levels, coronary artery calcium (CAC), fasting glucose and insulin concentrations, and plasma glucose levels 2 h after a 75-g oral glucose tolerance test were measured in all participants. Insulin resistance was estimated using the homeostasis model assessment (HOMA). RESULTS: Fasting insulin, fasting and 2-h serum glucose, and HOMA values were all significantly higher in Hispanics (p < 0.05 for all), yet CAC trended lower and the prevalence of very high CAC (>400 Agatston score) was lower (P = 0.03). There was no statistically significant difference in serum fetuin-A when comparing Hispanics and NHW (P = 0.12). Furthermore, there was no correlation between fetuin-A levels and CAC (P = 0.9). CONCLUSIONS: Serum fetuin-A concentration was not associated with measures of insulin resistance or with preclinical atherosclerosis in Hispanics and NHW. These data indicate that the disparity in prevalence of insulin resistance, type 2 diabetes, and subclinical atherosclerosis between Hispanics and NHW does not appear attributable to differences in fetuin-A concentrations.

Exenatide suppresses postprandial elevations in lipids and lipoproteins in individuals with impaired glucose tolerance and recent onset type 2 diabetes mellitus.

OBJECTIVE: Chronic exenatide treatment in type 2 diabetes is associated with improved glucose control and fasting lipid levels, as well as weight loss. Less established is whether exenatide directly reduces postprandial lipid and lipoprotein levels without the reduction in body weight or fasting glucose and triglycerides levels that frequently occur with prolonged therapy. Therefore, the effect of a single injection of exenatide on postprandial lipids, remnant lipoproteins, and apolipoproteins was studied. METHODS: A double-blinded, randomized, placebo-controlled, crossover study was conducted in 35 subjects (31 men and 4 women) with impaired glucose tolerance (n=20) or recent onset type 2 diabetes (n=15). A single subcutaneous injection of exenatide (10 microg) or normal saline was administered just prior to a high-calorie, fat-enriched breakfast meal. Concentrations of triglycerides (TG), apolipoproteins B-48 and CIII, non-esterified fatty acids (NEFA), and remnant lipoprotein (RLP) cholesterol and TG in serum or plasma were measured prior to the injection and for up to 8 h postprandially. RESULTS: Exenatide markedly reduced postprandial elevation of TG, apolipoproteins B-48 and CIII, RLP-cholesterol and RLP-triglyceride (all p<0.001). Postprandial declines in NEFA were less pronounced but persisted longer with exenatide compared to placebo (p<0.05). These effects of exenatide were not affected either by glucose tolerance status or by treatment with statins. CONCLUSION: These results demonstrate that exenatide acutely and profoundly inhibits postprandial excursions of proatherogenic lipids and lipoproteins and may offer additional cardiovascular risk reduction (NCT00974272).