Effects of Trp64Arg Mutation in the β3-Adrenergic Receptor Gene on Weight Loss, Body Fat Distribution, Glycemic Control, and Insulin Resistance in Obese Type 2 Diabetic Patients

Abstract

OBJECTIVE To investigate the effects of Trp64Arg mutation in the β₃-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 × 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 β₃-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 β₃-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.