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 bet a(3)-adrenergic receptor gene on weight loss, body fat distribution, g lycemic control, and insulin resistance in obese type 2 diabetic patie nts. RESEARCH DESIGN AND METHODS - We measured body weight, waist-to-h ip ratio (WHR), adjusted resting metabolic rate, fasting blood glucose , fasting serum insulin levels, insulin resistance index (fasting gluc ose X fasting insulin/22.5), and HbA(1c) levels before and after 12 we eks of obesity treatment in 61 obese women with type 2 diabetes. The M val polymorphism of the beta(3)-adrenergic receptor gene was determine d by polymerase chain reaction-restriction fragment length polymorphis m analysis. RESULTS - Of obese type 2 diabetic patients, those with th e mutation (n = 24) had a higher WHR (P < 0.001), a lower adjusted met abolic rate, and higher blood glucose levels, serum insulin levels, in sulin resistance index (P < 0.001), and HbA(1c) levels (P = 0.016), Fu rthermore, patients with the mutation had smaller decreases in body we ight, WHR, insulin resistance index, and HbA(1c) levels after the weig ht-loss program compared with patients without the mutation (n = 37). even though food intake, exercise, and serum thyroid hormone levels we re similar in both groups. CONCLUSIONS - These present findings show t hat the Trp64Arg allele of the beta(3)-adrenergic receptor gene may pr edict difficulty in losing body weight, lowering WHR, and improving gl ycemic control and insulin resistance in obese patients with type 2 di abetes.