Lipasin (also known as C19ORF80, RIFL, ANGPTL8 and betatrophin) is a newly discovered circulating factor that regulates lipid metabolism and promotes pancreatic β-cell proliferation. Whether circulating levels of lipasin in humans are altered in a) type 2 diabetes; b) obesity and c) the postprandial state, however, is unknown. The current study aimed to compare serum lipasin levels in those who were a) non-diabetic (N = 15) or diabetic (BMI- and age-matched; N = 14); b) lean or obese (N = 53 totally) and c) fasting and 2 hours following a defined meal (N = 12). Serum lipasin levels were determined by the enzyme-linked immunosorbent assay. Lipasin levels [mean ± SEM] were increased by more than two fold (P < 0.001) in the diabetic patients (5.56 ± 0.73 ng/mL) as compared to the control subjects (2.19 ± 0.24 ng/mL). Serum lipasin levels were positively correlated with BMI (rho = 0.49, P < 0.001) and showed a 35% increase 2 hours following a defined meal (P = 0.009). Therefore, lipasin/betatrophin is nutritionally-regulated hepatokine that is increased in human type 2 diabetes and obesity.