Associations Of Serum Polyfluoroalkyl Substances Levels With Incident Cardiovascular Disease Risk Among Patients With Type 2 Diabetes: A Nested Case-control Study

Objective:Perfluoroalkyl Substances（PFAS）are endocrine disruptors which are widely used in working and living environments.After being absorbed by human body,they can interfere glucose and lipid metabolism,thus causing harm to human health.At present,the association between PFAS and the risk of Cardiovascular Disease（CVD）has attracted extensive attention.Some cross-sectional epidemiological studies have shown that PFAS is positively related with incident CVD.CVD is a major complication and cause of death among patients with diabetes,but there are few prospective studies on the association between PFAS and cardiovascular disease complications among patients with type 2diabetes.Perfluorooctanoic Acid（PFOA）and Perfluorooctane Sulfonate（PFOS）are the two fluorides that have been studied most recently.Therefore,in this study,serum PFOA and PFOS levels were used as internal exposure markers to explore the relationship between serum PFAS levels and incident cardiovascular complications among patients with type 2diabetes.Methods:A nested case-control study design was used in this study.Based on Dongfeng-Tongji cohort,a total of 989 patients with CVD（749 patients with coronary heart disease and 240 patients with stroke）and 989 controls free of CVD and tumor were 1:1matched on sex and age（within 2 years）.Incident cardiovascular disease among the diabetic population,including coronary heart disease and stroke,was defined as the outcome.The concentrations of serum PFOA and PFOS at baseline were determined by High Performance Liquid Chromatography Coupled with Mass Spectrometry.The baseline serum PFOA and PFOS levels with skewness distribution were logarithmically transformed and then included into the model for analysis.Conditional Logistic regression model was used to analyze the relationship between serum PFOA and PFOS levels and incident CVD among patients with type 2 diabetes mellitus,and unconditional Logistic regression model was used to analyze the interaction between various diabetes or CVD traditional risk factors and serum PFOA or PFOS levels in the occurrence of CVD complications among patients with type 2 diabetes mellitus.Results:A total of 1978 subjects（989 pairs）were included in this study,with an average age of 66.27 years,of which 50.8%were males.The detection rates of serum PFOA and PFOS were both 99.9%.And the median serum PFOA concentrations were 1.06 ng/m L and 1.19 ng/m L,while the median serum PFOS concentrations were 12.63 ng/m L and 13.54ng/m L,in the diabetic group and the control group respectively.Compare epidemiological information and biochemical indexes of baseline population:in group with CVD complications,BMI（25.47 kg/m²）,FPG（8.56 mmol/L）,total cholesterol（5.37 mmol/L）,triglyceride（1.78 mmol/L）,LDLC（3.20 mmol/L）,SBP（138.59 mm Hg）,DBP（78.45mm Hg）,diabetes duration（4 years）were significantly higher than those in control group,BMI（24.98 kg/m²）,FPG（8.25 mmol/L）,total cholesterol（5.27 mmol/L）,triglyceride（1.62mmol/L）,LDLC（3.11 mmol/L）,SBP（133.51 mm Hg）,DBP（76.75 mm Hg）,diabetes duration（2.22 years）.Meanwhile,e GFR levels at baseline were lower in the group with CVD complications（74.86 m L/min/1.73m²）than in the control group（76.69m L/min/1.73m²）.In addition,the prevalence of hypertension（75.4%）,hyperlipidemia（63.6%）,and the usage rate of hypoglycemic drugs and insulin（51.7%）in group with new CVD complications was higher than that in control group hypertension（64.4%）,hyperlipidemia（58.1%）,and the usage rate of hypoglycemic drugs and insulin（43.6%）.After adjusting for diabetes and cardiovascular traditional disease risk factors,serum PFOA levels were negatively correlated with the incident CVD complications among paticents with type 2 diabetes,with the highest tertile of Odds Ratios（ORs）value was 0.66(95%CI:0.52～0.85,P_trend=0.002)compared with the first tertile.For each 1 SD increase in serum Ln-PFOA,the risk of CVD complications was reduced by 15%,ORs value was 0.85（95%CI:0.76～0.95）.In the stratified analysis of baseline fasting glucose levels,the negative association between serum PFOA levels and diabetic cardiovascular disease was only found in the group with higher baseline glucose levels(P_interaction=0.048).In the group with baseline fasting glucose levels≥7.00 mmol/L,The third tertile of OR value was 0.61(95%CI:0.45～0.82,P_trend=0.001),and the risk of cardiovascular disease complications decreased by 20%for each one standard deviation increase in serum Ln-PFOA,ORs value was 0.80（95%CI:0.70～0.91）.However,there was no significant correlation between t serum PFOS levels and the incident diabetic CVD complications,with the highest tertile of ORs was 0.81（95%CI:0.60～1.08）.The stratified analysis results of different population groups maintained no significant correlation.Conclusions:Serum PFOA levels are inversely associated with the incident cardiovascular complications among paticents with type 2 diabetes mellitus.But further research is needed to confirm this relationship and clarify the underlying mechanisms.