Circulating Betatrophin Concentrations Are Decreased in Human Obesity and Type 2 Diabetes

Context: Betatrophin is a secreted protein recently involved in beta-cell replication with a potential role in type 2 diabetes mellitus (T2D). Objective: The aim of the present study was to compare the circulating concentrations of betatrophin in human obesity and T2D. Design, Setting, and Participants: Serum concentrations of betatrophin were measured by ELISA in 153 subjects: 75 obese normoglycemic subjects (OB-NG), 30 obese subjects with impaired glucose tolerance (OB-IGT), and 15 obese subjects with T2D (OB- T2D) matched by sex, age, and body adiposity, in comparison with 33 lean normoglycemic individuals (LN-NG). Results: Circulating levels of betatrophin were significantly decreased in obese individuals and further diminished in IGT and T2D participants (LN-NG, 45.1 +/- 24.4 ng/mL; OB-NG, 26.9 +/- 15.4 ng/mL; OB-IGT, 18.3 +/- 10.7 ng/mL; OB- T2D, 13.5 +/- 8.8 ng/mL; P < .001). A marked sexual dimorphism was found, with betatrophin levels being significantly higher in women than in men (males, 21.1 +/- 16.0 ng/mL; females, 34.1 +/- 20.1 ng/mL; P < .001). Interestingly, betatrophin levels were positively correlated with the quantitative insulin sensitivity check index (r = 0.46; P < .001) and with high-density lipoprotein-cholesterol concentrations (r = 0.51; P < .001). Conclusions: We conclude that serum betatrophin is decreased in human obesity, being further reduced in obesity- associated insulin resistance. Betatrophin levels are closely related to obesity-associated cardiometabolic risk factors, emerging as a potential biomarker of insulin resistance and T2D.