Effects of Trp64Arg mutation in the beta(3)-adrenergic receptor gene on weight loss, body fat distribution, glycemic control, and insulin resistance in obese type 2 diabetic patients

OBJECTIVE - To investigate the effects of Trp64Arg mutation in the beta(3)-adrenergic receptor gene on weight loss, body fat distribution, glycemic control, and insulin resistance in obese type 2 diabetic patients. RESEARCH DESIGN AND METHODS - We measured body weight, waist-to-hip ratio (WHR), adjusted resting metabolic rate, fasting blood glucose, fasting serum insulin levels, insulin resistance index (fasting glucose X fasting insulin/22.5), and HbA(1c) levels before and after 12 weeks of obesity treatment in 61 obese women with type 2 diabetes. The Mval polymorphism of the beta(3)-adrenergic receptor gene was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS - Of obese type 2 diabetic patients, those with the mutation (n = 24) had a higher WHR (P < 0.001), a lower adjusted metabolic rate, and higher blood glucose levels, serum insulin levels, insulin resistance index (P < 0.001), and HbA(1c) levels (P = 0.016), Furthermore, patients with the mutation had smaller decreases in body weight, WHR, insulin resistance index, and HbA(1c) levels after the weight-loss program compared with patients without the mutation (n = 37). even though food intake, exercise, and serum thyroid hormone levels were similar in both groups. CONCLUSIONS - These present findings show that the Trp64Arg allele of the beta(3)-adrenergic receptor gene may predict difficulty in losing body weight, lowering WHR, and improving glycemic control and insulin resistance in obese patients with type 2 diabetes.