Short-term Intervention Of Metformin In Xinjiang Uygur Patients With Type 2 Diabetes Or IFG; The Influence Of OCT1 Gene Polymorphisms On The Metformin Response In Patients With Type 2 Diabetes Or Impaired Glucose Metabolism

Objective: To take a week-long intervention in Uygur patients with type 2 diabetes or IFG screened from Second Jikun hospital and Kashidonglu community medicine service, Urumqi, China and their surrounding districts,with metformin the widely used anti-diabetes drug. To examine the effects of metformin on plasma glucose, total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and triglyceride in relation with R61C,G465R and 420del variants of OCT1 (gene encoding organic cation transporter 1, mainly locating in liver, which is metformin's major target) in Uygur patients. It is expected that a possible R61C, G465R as well as 420del genotype correlated with the clinical response of metformin be rendered through the trying to explain the relation between the clinical response of metformin and variants in OCT1, while have possible positive effects on the development of personalized medicine. Method: A total of 22 patients recruited from Second Jikun hospital and Kashidonglu community medicine service, Urumqi, China and their surrounding districts with type 2 diabetes or IFG were treated with metformin (2000 mg/day) for 1 week. In all, R61C , G465R and 420del of OCT1 gene were examined using DNA extracted from whole blood and PCR-RFLP. Data concerning with gene and metformin treatment were handled by t-test. Result: After metformin treatment, there were increases both in FPG and LDL (P=0.011and P=0.013 respectively). To divide all participants into mutant and wild groups, according to the polymorphisms of R61C, G465R and 420del respectively, as well as carriers with one of the mutant genetypes at least and carriers with none of the mutant sites. Analysis made to compared FPG, Chol, TG, and LDL and HDL between carriers of wild genotypes and carriers of other genotypes showed no statistic significance both before the metformin treatment and after the treatment. The same is the case with changes of FPG, Chol, TG, and LDL and HDL of wild genotype carriers and variant genotype carriers, except of LDL changes (P=0.05) in patients grouped by G465R polymorphisms and TG changes (P=0.03) in subjects differed by 420del genotypes. Conclusion: In this study it is suggested that OCT1 gene polymorphisms have little contribution to the clinical efficacy of blood glucose control by metformin among Uygur people with type 2 diabetes or IFG, but possible relationship with the clinical efficacy on fat metablism by metformin.