Environmental Risk Factor And Cardiovascular Risk Of Impaired Glucose And Lipid Metabolism

BackgroundChronic metabolic diseases including diabetes,obesity and dyslipidemia have become one of the major threats to human health globally,and the key pathological characteristic is impaired glucose and lipid metabolism.Glucose and lipid metabolism is both affected by genetic and environmental factors,adverse environmental exposure plays an important role in inducing impaired glucose and lipid metabolism.Meanwhile,as a stressful metabolic disturbance with fat accumulation in hepatocytes,nonalcoholic fatty liver disease(NAFLD)is closely linked with diabetes owing to shared pathogenic mechanism.The coexistence of NAFLD and diabetes may aggravate glucose and lipid metabolic disturbances,consequently resulting in adverse clinical outcomes.We aim to examine the effect of environmental endocrine-disrupting chemical bisphenol A(BPA)on glucose and lipid homeostasis,and to systemically evaluate bidirectional associations between impaired glucose metabolism and NAFLD as well as related cardiovascular risk.Methods1.Urinary BPA relative to impaired glucose and lipid metabolism:This cohort study comprised Chinese adults aged?40 years from Songnan Community,Baoshan,Shanghai.At baseline and follow-up,participants received a standard questionnaire,anthropometric measurement,and an OGTT.Laboratory tests measured fasting glucose,2-h glucose,fasting insulin,based on which HOMA-IR and HOMA-?were calculated.Total BPA concentrations in morning spot urine were measured.Repeated-measures analysis was performed to evaluate associations of BPA with glucose and lipid homeostasis.2.Impaired glucose metabolism and NAFLD:This cohort study comprised Chinese adults aged?40 years from Jiading District.At baseline and follow-up,all participants underwent a detailed questionnaire,anthropometric measurement,and an OGTT.Laboratory tests measured fasting glucose,2-h glucose,and Hb A_1c.NAFLD was ascertained by hepatic ultrasonography.Bidirectional associations between impaired glucose metabolism and NAFLD were evaluated using longitudinal data.3.Cardiovascular risk associated with diabetes and NAFLD:The participants from Jiading cohort received carotid ultrasound and vascular function tests for the assessment of subclinical atherosclerosis.At follow-up,the composite of incident fatal or nonfatal CVD were ascertained.Cardiovascular risk associated with diabetes and NAFLD as well as their conexistance on cardiovascular outcomes were evaluated.Results1.Urinary BPA was independently associated with glucose homeostasis and serum lipids.Each tenfold increase in urinary BPA concentrations was associated with a 3.39%increase in fasting glucose(95%CI 2.24%,4.55%)and an 11.6%decrease in HOMA-?(95%CI-15.8%,-7.18%)in women,especially among those with overweight or obesity.Besides,urinary BPA was positively associated with LDL-C levels and inversely associated with levels of HDL-C and TG.Sustained high BPA at baseline and follow-up was associated with increased odds of developing hyper-LDL cholesterolemia.2.There were bidirectional relationships between impaired glucose metabolism and NAFLD.Compared with those with normal glucose metabolism,participants with diabetes had an increased risk of NAFLD(RR=1.27,95%CI:1.02–1.57)and reduced likelihood of resolution of NAFLD(RR=0.73,95%CI:0.60–0.88).In nondiabetic population,2-h glucose was positively associated with NAFLD incidence,while fasting and 2-h glucose were inversely associated with resolution of NAFLD.Glycemic deterioration conferred increased risk of developing NAFLD and reduced likelihood of resolution of NAFLD,and the strongest associations were found for individuals who developed diabetes.Moreover,compared with those without NAFLD,participants with NAFLD had an increased risk of diabetes(RR=1.54,95%CI:1.28–1.87).Incident NAFLD or resolution of NAFLD was also associated with diabetes and prediabetes.3.Diabetes was associated with arterial stiffness and carotid plaque,and an increased risk of CVD events.After stratified by NAFLD status,diabetes conferred an excess risk of CVD events in participants without NAFLD.However,NAFLD patients with severe fibrosis or NAFLD patients with a diabetes duration of?5 years had a higher CVD risk.Furthermore,the risk of arterial stiffness was higher in NAFLD patients and increased with advanced fibrosis.During follow-up,NAFLD and advanced fibrosis were not associated with CVD events,independent of diabetes status.Conclusions1.Urinary BPA was associated with impaired glucose and lipid homeostasis,suggesting that BPA exposure might be an environmental risk factor of glucose and lipid disorders;2.Diabetes and NAFLD are mutually affected.In nondiabetic population,2-h glucose was a predictor for NAFLD incidence and resolution.There was a graded association between glycemic deterioration and NAFLD incidence and resolution.These results highlight the importance of maintaining long-term normoglycemia for prevention and improvement of NAFLD and vice versa;3.Diabetes was associated with subclinical atherosclerosis and CVD,but NAFLD was only associated with subclinical atherosclerosis.There was lack of interaction between diabetes and NAFLD regarding CVD.Hence,early detection of diabetes and timely intervention is important for both individuals with and without NAFLD to effectively lower CVD risk.