Study On Serum Leptin And Tumor Necrosis Factor Level As Well As Tumor Necrosis Facotr-α Promotor Gene Polymorphism With Insulin Resistance And Type 2 Diabetes

Objective: Insulin resistance (IR) is an important mechanism in type 2 diabetes. IR hyper-insulinemia the deficiency of islet cell will result in type 2 diabetes. It was reported that leptin, TNF a produced from adipose tissue have took part in the development of IR. Gene polymorphism is an ubiquitous phenomenon in the human genome. The synthesis and function of gene product can be influenced by genetic variation in some degrees. Different genetic background made different people got various susceptibility to some kinds of diseases to the clinical treatment. It was reported that there is a G-A mutation at the -308bp of the promoter region of tumor necrosis factor a gene(TNF a -P).So we have investigated the relationship between serum leptin, TNF a level, tumor necrosis factor a promotor gene polymorphism with insulin resistance and type 2 diabetes in the hans of Hebei province.Methods: In this study 118 patients with type 2 diabetes as defined by ADA criteria were examined(61 men, mean age 56.03+9.62;57 women, mean age 58.00 +8.81).theywere newly diagnosed or treated irregularly. 78 normal person were made as control group(41 men, mean age 55.12 + 10.58;37 women, mean age54.22+4.73).The two groups were divided into two subgroups respectively according to body mass index(BMI)(BMI 25/BMI<25):obesities with type 2 diabetes ,non-obesities with type 2 diabetes; obesities of normal control, non-obesities of normal control. The two groups were divided into two subgroups respectively on the basis of the Nco I gene-type:TNFl with type 2 diabetes(restriction site presence GG), TNF2 with type 2 diabetes(GA); TNF1 of normal control(GG), TNF2 of normal control(GA).A fragment of 107bp DNA sequence in promoter of TNF a gene was measured by polymerize chain reaction. After PCR amplification of DNA fragment PCR products were digested with Nco I restriction enzyme and electrophoresed on a 6%nondenatured polyacrylamide gel . Nco I restriction fragment length polymorphism was detected by ethidium bromide staining.Serum leptin TNF a level were measured by radio-immunoassay.Results:(l)There were significant differences in TNF a, Leptin HbA, SBP DBP HDL ISI between type 2 diabetes and normal control(P<0.01 or P<0.05).(2)Stepwise multiple regression analysis revealed that TNF a ?HbAiC TG SBP were significantly correlated with insulin sensitivity index(ISI).(3)All subjects weredivided into two groups on the basis of the Nco I gene-type: TNF a ,. Leptin TG were significantly higher in TNF2 than in TNF 1;whereas ISI was lower than TNFl(p<0.05).(4)In type 2 diabetes group: TNF a Leptin TG were higher in TNF2 than in TNF1(p<0.05);whereas ISI was lower than TNFl(p<0.05). HbAi^ SBP were higher in obesities than in non-obesities, HDL-c was lower than non-obesities.(5)In normal control group: TNF a Leptin TG were higher in TNF2 than in TNFl(p<0.05);whereas ISL HDL-c were lower in TNF2(p<0.05). TNF a Leptin, TG. SBP were higher in obesities (p<0.05),however ISI - HDL-c were lower in obesities.(6)Genotype distribution and allele frequency of the TNF a promoter gene polymorphism were not significantly different between type 2 DM patients and normal controls.Conclusions:(l)TNF a , HbAc, TG, SBP have a strong association with ISI. (2)There was an IR in obesities.In normal controls there were TNF a Leptin TG SBP increase , HDL-c insulin sensitivity decline in obesities as compared with non-obesities. However in type 2 diabetes HbAiC. SBP were higher, HDL-c was lower in obesities than in non-obesities. TNF a TG were not significantly different between obesities and non-obesities in type 2 DM patients. It is may be that most type 2 diabetes-obesity or not-have IR. (3)TNF a , Leptin, TG were higher in TNF2 than in TNF1; whereas ISI was lower in TNF2. It indicated that TNF2 have some correlated with IR.