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

Abstract

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.

Newly Discovered Adipokines: Pathophysiological Link Between Obesity and Cardiometabolic Disorders

“…The European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam study showed that higher levels of omentin-1 were related to an increased risk of stroke in metabolically healthy participants ( Menzel et al, 2016 ). Recent 14 years of follow-up in a prospective study on diabetes without a previous cardiovascular event showed that higher omentin-1 concentrations are associated with a higher risk for CVD events, incidence of primary stroke, and incidence of cardiovascular death even after adjustment for cardiovascular risk factors ( Niersmann et al, 2020 ). As mentioned above, a highly heterogeneous association between omentin-1 and CMD has been reported.…”

Association of Circulating Omentin-1 with Osteoporosis in a Chinese Type 2 Diabetic Population

“…Omentin-1, a newly identified adipokine in human visceral omental adipose tissue, is extensively involved in the regulation and maintenance of a wide variety of physiological and pathological processes, including insulin sensitivity, energy expenditure, blood pressure, glycolipid metabolism, inflammatory response, neuroendocrine activity, immunity, homeostasis, angiogenesis, endothelial and cardiovascular function, reproduction, and recently bone metabolism [ 6 , 7 , 11 ]. In the present study, we firstly found that T2DM patients with osteoporosis had significantly higher circulating omentin-1.…”

“…Circulating omentin-1 was associated with inflammatory disease, obesity, IR, diabetes and diabetic vascular complications, hypertension, hyperlipidemia, metabolic syndrome, polycystic ovary syndrome, obstructive sleep apnea syndrome, chronic obstructive pulmonary disease, endothelial dysfunction, and atherosclerosis and related cardiovascular diseases such as ischemic heart disease [ 6 – 11 ], all of which have been proposed to be implicated in the pathogenesis of osteoporosis [ 3 , 12 , 13 ]. Moreover, it has been reported that serum omentin-1 inversely correlates with leptin and positively correlates with adiponectin and vitamin D [ 7 , 9 , 14 ], whereas the abovementioned cytokines have also been suggested to be involved in bone metabolism [ 14 ]. Thus, we postulated that omentin-1 may be associated with the regulation of bone metabolism and might play a pivotal role in the pathogenesis of osteoporosis.…”

Cardiovascular autonomic neuropathy in patients with type 2 diabetes mellitus and its association with serum omentin and leptin

“…This may be due to an inadequate upregulation of omentin level in response to stimuli that raise the cardiovascular risk in patients with diabetes. [ 17 ]…”