Implications of Circulating Meteorin-like (Metrnl) Level in Human Subjects with Type 2 Diabetes

Aims: Meteorin-like (Metrnl) was recently identified as a novel adipomyokine induced by exercise and cold exposure. Metrnl improves glucose tolerance, increases systemic energy expenditure, induces white adipose browning, and promotes anti-inflammatory gene programs in obese/diabetic mice. However, the relationship of Metrnl with diabetes and cardiometabolic risk variables in humans has not been explored.

Methods: In 800 subjects (400 patients with type 2 diabetes and 400 non-diabetes), Metrnl concentration was measured with an enzyme-linked immunosorbent assay, and the correlations of Metrnl level with anthropometric parameters, lifestyle factors, body composition values, and laboratory measurements were assessed.

Results: Metrnl concentration was significantly higher in patients with diabetes than in those without diabetes [median (inter-quartile range); diabetes: 1219.9 (1020.6, 1535.6), non-diabetes: 1131.2 (993.1, 1313.6) pg/ml, P < .001]. After adjustment for age and sex, Metrnl level was significantly associated with fasting plasma glucose, blood pressure, lipid profile, and eGFR, but not with BMI or percent body fat. Multiple stepwise regression analysis exhibited that Metrnl level was independently associated with diabetes status (P < .001), eGFR (P < .001), and total cholesterol (P = .026) (R = 0.127). In multiple logistic regression analysis, the odds ratio for the risk of diabetes was 3.53 (95% confidence interval: 2.04-6.10) in the highest tertile of Metrnl compared to the lowest after adjustment for confounding factors.

Conclusions: This study is the first to demonstrate that Metrnl level is elevated in human subjects with type 2 diabetes and is inversely related to various cardiometabolic risk factors, including renal function.