Study Of Association Between Plasma TNF-α, Polymorphism Of TNF-α Gene, Plasma Leptin And Insulin Resistance In Type 2 Diabetes Mellitus

ObjectiveTo explore the association between TNF- a -308 polymorphism, plasma TNF-a , plasma leptin and insulin resistance in type 2 diabetes mellitus. Methods1. Several biochemical parameters were measured, including fasting glucose, triglyceride and total cholesterol,et al.2. The level of fasting plasma insulin, TNF- a, leptin were examined by means of radioimmunoassay. Insulin resistance was determined using HOMA index(HOMA-IR=FPG X FINS/22.5).3. Genomic DNA was extracted from peripheral blood.4. The 308th specified gene fragment of TNF- a was amplified by polymerase chain reaction(PCR). PCR products were digested with Ncol restriction enzyme and electrophoresed on a polyarylamide gel to determine the genotype.5. Homa insulin resistance index was regarded as dependent variable, and age, serum total cholesterol, triglyceride, high density lipoprotein, genotype of TNF-a, plasma TNF-a and leptin were regarded as independent variables.Multiple stepwise regression was performed to study the influencing factor ofinsulin resistance.Results1. FPG,TNF-a , Leptin and HOMA-IR of type 2 diabetes mellitus were significantly higher than those of control group, while insulin was significantly lower than that of control group.2. Frequencies of GG+GA genotype in type 2 diabetes mellitus and control group were 30% and 13% respectively, and A allele frequency was 16% and 7%. Both GG+GA genotype frequency and A allele frequency of type 2 diabetes mellitus were significantly higher than those of control group(p<0.05).3. FPG,TNF-a , Leptin, FINS and HOMA-IR of GG+GA genotype were significantly higher than those of GG genotype.4. The first multiple stepwise regression suggested that HOMA-IR was positively associated with TNF-a , TNF- a genotype and leptin. The second multiple stepwise regression suggested that leptin was positively associated with TNF-a and BMI.Conclusion1. TNF- a gene G308A mutation was associated with type 2 diabetes mellitus in South Fujian. A allele carrier may be involved in insulin resistance by increasing the release of TNF- a , which resulted in type 2 diabetes mellitus.2. Both TNF-a and leptin were involved in insulin resistance. TNF-a may result in insulin resistance by increasing plasma leptin.