Myonectin Predicts the Development of Type 2 Diabetes

Context: Myonectin has been identified as a myokine, expressed predominantly in skeletal muscle. However, its clinical implications are largely unknown. Objective: The aim of this study is to investigate the relationship between myonectin (C1q tumor necrosis factor-α-related protein isoform 15) and type 2 diabetes mellitus (T2DM) in cross-sectional and interventional studies. Design: In a separate study, oral glucose tolerance tests, a 45-minute bout of exercise, lipid infusions, and euglycemic-hyperinsulinemic clamps (EHCs) were performed to investigate the association of myonectin with homeostasis model assessment of insulin resistance (HOMA-IR) and T2DM. Circulating myonectin was measured by enzyme-linked immunosorbent assay. Patients: One hundred four newly diagnosed T2DM (nT2DM), 109 impaired glucose tolerance (IGT), and 128 healthy individuals were recruited for this study. Results: nT2DM and IGT subjects had higher circulating myonectin concentrations than normal subjects (82.3 ± 47.6 and 68.9 ± 46.6 vs. 45.2 ± 23.5 µg/L, P < 0.05 or P < 0.01). It was also found that in nT2DM individuals, circulating myonectin was higher than in IGT subjects. Plasma myonectin correlated positively with waist/hip ratio, percentage of body fat, triglyceride, fasting blood glucose, 2-hour blood glucose after glucose overload, fasting insulin, hemoglobin A1c, and HOMA-IR and negatively with the insulin sensitivity index in all of the study population. Multivariate logistic regression analysis revealed that circulating myonectin levels were significantly correlated with IGT and T2DM. A 45-minute bout of exercise did not change circulating myonectin levels in healthy, young individuals. Circulating myonectin levels were not significantly altered in response to an oral glucose challenge or EHC. In addition, acute elevated free fatty acid levels induced by lipid infusion had no effects on circulating myonectin. Conclusions: These data suggest that myonectin may be a useful marker in predicting the development of prediabetes and diabetes.