Study On The Relationship Between Insulin Resistance, Proinsulin And Coronary Heart Disease

Objective: To determine insulin resistance and proinsulin levels in patients with coronary heart disease (CHD) and explore the relationships of them to other cardiovascular risk factors such as: dyslipidemia, disturbance of fibrinolysis-coagulation system, endothelial dysfunction and polymorphism of angiotensin converting enzyme (ACE) gene.Methods: 66 CHD patients who were identified by coronary angiography constituted the case group and the control group was composed of 42 persons with normal coronary angiography result.The plasmatic lipid concentration and blood glucose were measured. High specific BA-ELISA assays for PI and TI were used. The fasting serum PI and TI were detected in CHD patients and control subjects and insulin resistance was assessed by HOMA index. The activity of PAI-1 and vWF were detected by ELISA assays. Genomic DNA was extracted from peripheral blood leukocytes in all subjects. Polymerase chain reaction (PCR) wrer carried out to detect the gene polymorphism of ACE.The clinical characteristics of the two groups were compared by unpaired student's test. The PI levels, HOMA index, and theactivity of PAI-1 and vWF were compared by covariate variance analysis. Pearson linear correlation and partial correlation analysis were used to investigate the relationship between PI, HOMA index and dyslipidemia in CHD patients. The relationships of serum PI, HOMA index to activity of PAI-1 and vWF were investigated by Pearson linear correlation and multiple regression analysis. The levels of PI and HOMA index among different genotype groups were compared by ANOVA. The frequency of alleles and genotype were analyzed by X2 test.Results: The levels of PI and HOMA index were significantly higher in CHD patients than those in controls. The levels of PI was positively correlated with TG, LDL, apoB and negatively with HDL and apoA while HOMA index positively with Lp(α) ,apoB and negatively with HDL and apoA by Pearson linear correlation. After adjusting age, sex and BMI, the correlation aforementioned disappeared or weakened.The activity of PAI-1 was positively related with HOMA index and PI levels, so was that of vWF. In multiple regression, PAI-1 was still positively related with HOMA index and PI while the relationship of vWF to PI and HOMA index disappeared.The genotype distributions of case and control groups in this study were within Hardy-Weinberg equilibrium. There was nosignificant difference among ACE genotypes in PI levels and HOMA index. The distribution of ACE genotype was not significantly different between different PI groups. There was also no significant difference between different HOMA groups. Conclusions: CHD patients have hyperproinsulinemia and insulin resistance and the relationship between PI and CHD is much closer. There is relationship between PI, HOMA index and dyslipidemia. PI levels in CHD patients is more strongly associated with dislipidemia.The activity of PAI-1 in CHD patients is independently correlated with insulin resistance and there is no independent correlation between vWF and insulin resistance. PAI-1 is independently correlated with PI and the role of PI on CHD seems to be mediated by the dysfunction of fibrinolysis system.There is no relationship between polymorphism of ACE gene and insulin resistance. They may play separated role on the development of CHD. There is also no significant difference between ACE genotype and PI levels in CHD patients.