Abstract

BACKGROUND
Rosiglitazone(RSG) is known as a potent agonist for the PPARgamma. It improves glycemic control by improving insulin sensitivity in peripheral tissues. And it is associated with body weight gain. The Pro12Ala polymorphism of the gene encoding the peroxisome proliferator-activated receptor(PPAR)gamma2 has recently been shown to be associated with insulin sensitivity. This study was performed to evaluate the body weight change during the long term rosiglitazone treatment and the role of PPARgamma2 polymorphism, Pro12Ala as an indicator to predict the clinical response of RSG in type 2 diabetes patients. METHOD: The study subjects were 214 type 2 diabetic patients(117 male, 97 female) who were received a daily 1 year course of 4 mg RSG combined with sulfonylurea or metformin. The Pro12Ala polymorphism of the PPARgamma2 was determined by the restriction fragment length polymorphism(RFLP) method. Body weight, height, waist circumference, fasting glucose, insulin, c-peptide and lipid profile were measured. RESULTS: After RSG treatment, body weight change was 2.4 +/- 3.8%, 4.5 +/- 9.8% of baseline body weight at 12, 24 weeks respectively. Body weight gains were increased to 5.6 +/- 10.1% at the end of 1 year. The HbA1C, serum insulin level and HOMA index were decreased following the rosiglitazone therapy. The allele frequency of the Ala12Pro polymorphism of the PPARgamma2 was 0.016. The number of Ala12Pro variant of the PPARgamma2 was too low to predict clinical response of RSG. Body weight gain was correlated with basal fasting plasma glucose, post-prandial 2 hour glucose and HbA1c level(p<0.05). There was no correlation between baseline body weight and change. CONCLUSION: This results showed that Pro12Ala polymorphism was not acceptable for the predictor of RSG induced weight gain and clinical response. However, body weight gain was increased in who had high glucose level, and correlated positively with glucose decrease. 1st 3 month weight gain was best predictor of weight change during 1 year.

• Keywords: Rosiglitazone;body weight;peroxisome proliferator-activated receptor(PPAR)gamma2;