The Effect Of Hyperinsulinemia And Plasma Glucose On All-cause And CVD Death

AimsTo characterize the effect of hyperinsulinemia and plasma glucose on all-cause and cardiovascular disease(CVD)death.MethodsIn 1986,110,660 participants recruited from Daqing,China,were conducted diabetes screening.Glycemic status was classified based on oral glucose tolerance test(OGTT)using 1985 World Health Organization(WHO)criteria.630 had newly diagnosed diabetes(NDD),576 had impaired glucose tolerance(IGT),and a sample of 519 persons with normal glucose tolerance(NGT),age-sex matched with the IGT group,was selected for control.The all-cause and CVD death were assessed from 1986 to 2016.Participants with full data on 2-h plasma glucose(2hPG)and insulin secretion afterload at baseline were selected in the present analysis.Therefore,a total of 462 individuals in the original Da Qing Diabetes and IGT Study were enrolled,including 180 with NGT and 282 with IGT.They were divided into G1(low insulin low glucose),G2(high insulin low glucose),G3(low insulin high glucose)and G4(high insulin high glucose)groups according to medians of 2hPG and the area under the curve(AUC)insulin at baseline.Cox proportional hazards analyses were used to calculate hazard ratio(HR)between groups and estimate cumulative incidences after adjusting confounding factors.ResultsDuring 30 years of follow-up,all-cause mortality in G1,G2,G3 and G4 was 8.11,13.53,14.58 and 18.64 per 1000 person-years,respectively,and CVD mortality was 7.92,13.22,14.27,and 18.11 per 1000 person-years,respectively.After adjusting age,sex,smoking,and total cholesterol(TC),G4 had the highest cumulative incidence of all causes or CVD death(allcause death:45.7%,95%CI 38.1-52.4;CVD death:31.9%,95%CI 22.939.8),G2(all-cause death:37.7%,95%CI 30.2-44.4;CVD death:26.3%,95%CI 17.9-33.9)and G3(all-cause death:39.2%,95%CI 31.8-45.8;CVD death:24.2%,95%CI 16.1-31.6)had similar incidence,and G1 had the lowest incidence(all-cause death:26.9%,95%CI 19.6-33.6;CVD death:14.9%,95%CI 7.8-21.4).Compared with G1,the highest risk was observed in G4 for all-cause(HR:2.32,95%CI 1.45-3.69,P=0.0004)and CVD death(HR:2.68,95%CI 1.35-5.29,P=0.005).The increased risk of all-cause death was similar in groups with elevated insulin alone(G2)or plasma glucose alone(G3)(HR[G2 vs G1]:1.65,95%CI 1.02-2.67,P=0.04;HR[G3 vs G1]:1.76,95%CI 1.11-2.81,P=0.01),and the same phenomenon was observed for CVD deaths.When G2 and G3 were compared,the risk of all-cause death(HR:1.07,95%CI 0.70-1.64,P=0.76)and CVD death(HR:0.91,95%CI 0.501.67,P=0.77)were similar in the two groups.ConclusionsIn this post-hoc study,participants with elevated insulin level were related to the same increased all-cause and CVD mortality risk as elevated glucose level,implying that strategies should be paid more attention on targeting not only better glycemic control,but also eliminating hyperinsulinemia and improving insulin resistance,in order to achieve better long-term outcomes.