Higher circulating omentin is associated with increased risk of primary cardiovascular events in individuals with diabetes

Aims/hypothesis Higher concentrations of the adipokine omentin are associated with lower levels of cardiometabolic risk factors in experimental and cross-sectional studies, but with higher risk of type 2 diabetes and cardiovascular diseases in population-based cohort studies. However, it is unknown whether high omentin concentrations are associated with increased risk of cardiovascular events in people with established diabetes. Therefore, the present study investigated the association between serum omentin concentrations and the risk of cardiovascular events in individuals with diabetes. Methods This prospective study was based on participants of the German ESTHER cohort with diabetes and without previous cardiovascular event. The ESTHER cohort consists of individuals aged 50-75 years at baseline who were recruited by their general practitioners. After exclusion of individuals with serum C-reactive protein >= 10 mg/l (>= 95.24 nmol/l), the final analysis population consisted of 933 individuals. At baseline, serum omentin concentrations were measured by ELISA. Cox regression models were fitted to estimate HRs and their corresponding 95% CIs for associations of omentin tertiles with a composite endpoint of cardiovascular events and separately with incident myocardial infarction, stroke and cardiovascular death. Results During 14 years of follow-up, 228 individuals experienced a primary cardiovascular event (myocardial infarction, stroke or cardiovascular death). After comprehensive adjustment for age, sex, BMI, metabolic and lifestyle factors and medication use, HRs (95% CIs) for the 2nd and 3rd tertile of omentin compared with the 1st tertile were: 1.24 (95% CI 0.86, 1.79) and 1.63 (1.15, 2.32) (p(trend) = 0.005) for the composite cardiovascular endpoint; 1.39 (0.78, 2.47) and 1.71 (0.98, 2.99) (p(trend) = 0.065) for incident myocardial infarction; 1.40 (0.78, 2.53) and 2.05 (1.17, 3.58) (p(trend) = 0.010) for incident stroke; and 1.43 (0.85, 2.40) and 1.72 (1.04, 2.83) (p(trend) = 0.040) for cardiovascular death. Effect estimates and p values were almost unaltered after additional adjustment for adiponectin. Conclusions/interpretation Higher omentin concentrations are associated with an increased risk for cardiovascular events in individuals with diabetes after adjustment for multiple cardiovascular risk factors. Given data from preclinical studies, it appears possible that this association reflects a compensatory, but insufficient upregulation of omentin concentrations as a response to stimuli that increase cardiovascular risk.