Association Of Overweight,Obesity And Type 2 Diabetes With The Risk Of Cardio-Cerebrovascular Diseases

Objectives:With the changes in the spectrum of disease worldwide,chronic non-communicable diseases,represented by cardio-cerebrovascular diseases?CVD?,have become a global public health problem.Overweight?including obesity?and type2 diabetes mellitus?T2DM?have been the important risk factors for CVD.We aimed to estimate the incidence of CVD,examine the relationship between the single and combined effects of overweight and T2DM on the risk of CVD,and further explore whether genetic and early-life environmental factors play a role in this association.Methods:A total of 40812 CVD-free twin individuals who were from the Swedish Twin Registry?STR?and participated in the Screening Across the Lifespan Twin Study?SALT??a full-scale screening that gathered data on an extended set of variables via computer-assisted telephone interview?during 1998-2002 were followed up till Dec.31,2014 to identify the incident CVD cases.Information on weight and height was collected through the interview or STR based on self-report.Overweight was defined as body mass index?BMI?>=25 kg/m².T2DM was assessed based on self-repot,anti-diabetic medication use and the inpatient registry.CVD diagnoses including heart diseases?coronary heart disease;heart failure;atrial fibrillation and other cardiac arrhythmias?and cerebrovascular disease?CBD??cerebral infarction;transient ischemic attack;intracerebral hemorrhage and subarachnoid hemorrhage?were ascertained from the National Patient Registry.Data were analyzed as following:?1?we estimated the incidence of CVD according to the date of diagnosis of new cases during the follow-up period;?2?we conducted a classical?unmatched?case-control analysis among all participants using generalized estimating equation?GEE?model.Further,all the subjects were divided into four groups?overweight/obesity-and T2DM-free,only overweight/obesity,only T2DM and both overweight/obesity and T2DM?.Using the first group as reference,the risk of CVD in other three groups were estimated by GEE model;?3?we conducted co-twin matched case-control analysis for CVD-discordant twin pairs using conditional logistic regression;?4?we used logistic regression to test the difference in ORs from GEE model and conditional logistic regression to explore the role of genetic background and early life environments in the association of overweight/obesity and T2DM with CVD.Results:?1?Of the participants?n=40812?,during the follow-up period,11301 had incident CVD,8983 had incident heart diseases,and 4351 had incident CBD.The cumulative incidence and incidence density of CVD were 27.69%and 23.49/1000person-years,respectively.The cumulative incidence and incidence density of heart diseases were 22.01%and 18.21/1000 person-years,respectively;and the cumulative incidence and incidence density of CBD were 10.66%and 8.34/1000 person-years,respectively.The cumulative incidence and incidence density of CVD were increased with age(P_trend<0.001),and higher in male than in female?P<0.001?.?2?In multi-adjusted GEE model,both overweight/obesity?OR=1.085,95%CI:1.028-1.145?and T2DM?OR=2.963,95%CI:2.657-3.304?were significantly associated with the risk of CVD.?3?In joint effect analysis,compared with overweight/obesity-and T2DM-free group,ORs?95%CIs?of CVD were 1.098?1.039-1.161?for overweight/obesity or T2DM,1.060?1.002-1.112?for only overweight/obesity,2.181?1.784-2.667?for only T2DM,and 3.500?3.041-4.028?for overweight/obesity plus T2DM.?4?In co-twin matched case-control analysis,the association of overweight/obesity and T2DM with CVD were attenuated,ORs?95%CIs?of CVD were 1.129?0.998-1.276?and 3.627?2.735-4.810?,respectively.And overweight/obesity-T2DM significantly associated with the risk of CVD?OR=4.429,95%CI:2.402-8.167?.The differences in ORs from the GEE and co-twin control analysis were significant for overweight/obesity associated with the risk of CVD?OR=1.108,95%CI:1.033-1.188,P=0.004?,but not for the association of T2DM?OR=1.196,95%CI:0.975-1.456,P=0.081?or overweight/obesity plus T2DM?OR=1.062,95%CI:0.748-1.468,P=0.727?with CVD.Conclusions:During 1998-2002 to 2014,the cumulative incidence of CVD in the study population was almost 30%,and incidence density of CVD were 23.49/1000person-years.Overweight/obesity and T2DM are associated with an increased risk of CVD,especially when overweight/obesity and T2DM occur together.Genetic background and early life environmental factors appeared to play a role in the association of overweight/obesity with CVD,but not in the association of T2DM or overweight/obesity plus T2DM with CVD.