Elevated Fetuin-A Concentrations in Morbid Obesity Decrease after Dramatic Weight Loss

Context: Morbid obesity (MO) is a risk factor for cardiovascular morbidity, mortality, and diabetes, which can be effectively reduced by bariatric surgery. The liver-secreted protein Fetuin-A is elevated in insulin resistance, is an independent predictor of type 2 diabetes and is associated with atherosclerosis. Objective: We studied Fetuin-A concentrations in patients with MO before and after weight loss induced by gastric bypass. Design: We conducted a cross-sectional study and a 16-month longitudinal study. Setting: This study was performed in secondary care. Patients, Subjects, and Intervention: We included 75 MO patients [65 women, body mass index (BMI) 45.6 +/- 8.1 kg/m(2)] and 38 healthy controls (21 women, BMI 26.0 +/- 5.5 kg/m(2)) in a cross-sectional study and investigated them before and about 16 months after gastric bypass surgery. Main Outcome Measures: Apart from measurements of blood pressure and routine laboratory parameters, a 75-g oral glucose tolerance test was performed. Insulin resistance was calculated by using homeostatic model assessment (HOMA). Results: Fetuin-A levels were significantly higher in MO (877 +/- 318 mu g/ml) than in controls (295 +/- 61 mu g/ml; P < 0.001). After surgery-induced weight loss (BMI 31.6 +/- 6.8 vs. 45.6 +/- 8.1 kg/m(2); P < 0.001), HOMA (2.0 +/- 1.2 vs. 6.6 +/- 6.3; P < 0.001) and Fetuin-A (710 +/- 350 vs. 877 +/- 318 mu g/ml; P < 0.001) decreased. Delta (Delta) Fetuin-A concentrations correlated with Delta fasting insulin (r = 0.710; P = 0.001), Delta 2-h insulin (r = 0.693; P = 0.005), and HOMA-insulin resistance (r = 0.684; P = 0.001). Conclusions: Fetuin-A is markedly increased in patients with MO. The reduction of Fetuin-A after weight loss could play an important role in the beneficial effects of gastric bypass surgery. (J Clin Endocrinol Metab 95: 4877-4881, 2010)