| BackgroudResearch on glucose and lipid metabolic has been a hot topic in the field of diabetes.Synergy for diabetes and dyslipidemia may further increase the risk for the morbidity and mortality of cardiovascular disease.To understand the prevalence of different types of dyslipidemia in diabetes can help identify high-risk population of diabetes and cardiovascular disease.Insulin plays an important role in the balance regulation of glucose and lipids metabolic and insulin resistance(IR)is a major pathological feature of diabetes.Plenty of evidences suggested that lipids related indicators were associated with IR.However,due to the different study subjects and no consideration of different glycemia status,there are inconsistencies among those studies.Since the progress of IR is closely related to glucose and lipid metabolic,it is necessary to discuss the relationship between lipid parameters and IR among different glycemia status.A variety of lipid metabolites are involved in the process of IR and it is possible to find potential biomarker associated with IR by analyzing these metabolites.Phospholipids are essential components of cell membranes and have important biological function.Animal models and dietary studies have showed that phospholipids play an important role in the pathogenesis of IR.ObjectivesThis study will investigate the prevalence of dyslipidemia among different glycemic status,and provide the basis data for further study of glucose and lipid metabolic.To investigate the relationship between lipids related indicators and IR,and explore the surrogate markers of IR for pre-diabetes and normal glucose participants.The aim of this study is to perform plasma phospholipids analysis and explore the relationship between phospholipids and IR,and identify potential phospholipid markers associated with IR.MethodsA total of 175152 participants aged 18 and above were included in present study,which come from the China National Chronic Diseases and Nutrition Survey(2015).According to the ADA criteria(2010),the participants were divided into previously diagnosed diabetes,newly-diagnosed diabetes,pre-diabetes and normal glucose participants.According to Chinese Guideline on Prevention and Treatment of Dyslipidemia in Adults(2016),clinical classification of dyslipidemia included hypercholesterolemia,hypertriglyceridemia,mixed hyperlipaemia,low HDL cholesterolemia and high LDL cholesterolemia.Dyslipidemia was defined as suffering any one of hypercholesterolemia,hypertriglyceridemia and low HDL cholesterolemia.The prevalence of dyslipidemia was estimated with PROC SURVEYFREQ.A total of 30967 participants aged 18 and above who had insulin measurements were included in present study.Pearson correlation or Spearman order correlation was performed to analyze lipids related indicators correlated with insulin and HOMA-IR.Two-level logistic regression model was performed to analyze the association between lipids related indicators and IR.ROC curve was performed to assess the discrimination of lipids related indicators to detect IR.A total of 1053 participants aged 45-59 were randomly selected from large cities.Seven categories phospholipids(PG、PE、PC、PI、SM、LPC and LPE),including 199 kinds of phospholipids,were analyzed by LC-MS.PERMANOVA analysis and Random Forest regression analysis were performed to analyze the relationship between plasma phospholipids with insulin and HOMA-IR.Results1.The prevalence dyslipidemia in adults with previously-diagnosed diabetes,newly-diagnosed diabetes,pre-diabetes and normal glucose participants were 58.0%,58.9%,43.8%and 31.1%,respectively,which displayed mainly high LDL cholesterolemia and hypertriglyceridemia.The prevalence of different type’s dyslipidemia increased with the elevated BMI and WC.The prevalence of awareness,treatment and control all showed a lower level in different glycemic status,expecially for newly-diagnosed diabetes participants.2.Levels of insulin and HOMA-IR showed highest in newly-diagnosed diabetes and lowest in normal glycemic participants(P<0.001).Insulin and HOMA-IR showed positive correlations with TG,TC/HDL-C,LDL-C/HDL-C and TG/HDL-C,LAP,V VAI and TyG index(P<0.001),and negative correlation with HDL-C(P<0.001)in different glycemic status.For normal glycemic participants,levels of insulin and HOMA IR were positively correlated with TC,LDL-C,and Non-HDL-C,while negatively correlated with the TC and LDL-C(P<0.001)in pre-diabetes.3.Among normal glycemic participants,the prevalent of IR increased with the elevated quartiles of TG,Non-HDL-C,TC/HDL-C,LDL-C/HDL-C,TG/HDL-C,LAP,VAI and TyG index,but decreased with elevated quartiles of HDL-C(Ptrend<0.001).Compared with the lowest quartile of TG,HDL-C,Non-HDL-C,TC/HDL-C and TG/HDL-C,LDL-C/HDL-C,LAP,VAI and TyG index,the risk of IR in the highest quartile were 3.37(2.81-4.04),0.32(0.27-0.39),1.23(1.05-1.45),2.36(1.98-2.82),3.96(3.27-4.80),2.12(1.78-2.52),3.54(2.78-4.52),4.23(3.42-5.24)and 3.66(3.00-4.46)after multivariate adjustment.The ROC curve analyses showed that the area under the ROC curve(AUC)was 0,71(0.69-0.72),0.73(0.72-0.75),0.73(0.72-0.74)and 0.71(0.70-0.73)for TG/HDL-C,LAP,VAI and TyG index.4.As for pre-diabetes participants,the prevalent of IR increased with the elevated quartiles of TG,TC/HDL-C,LDL-C/HDL-C,TG/HDL-C,LAP,VAI and TyG index,but decreased with elevated quartiles of TC,LDL-C and HDL-C(Ptrend<0.001)-Compared with the lowest quartile of TC,TG,LDL-C,HDL-C,TG/HDL-C,LAP,VAI and TyG index,the risk of IR in the highest quartile were 0.62(0.51-0.74),1.92(1.58-2.33),0.66(0.55-0.80),0.47(0.38-0.57),2.33(1.91-2.85),2.06(1.61-2.63),2.38(1.92-2.95)and 2.02(1.65-2.47)after multivariate adjustment.The ROC curve analyses showed that the AUC was 0.73(0.72-0.75)and 0.72(0.71-0.74)for LAP and VAI.5.A total of 7 categories phospholipids including 199 kinds of phospholipids(5 kinds of PG,53 kinds of PE,60 kinds of PC,18 kinds of PI,30 kinds of SM,11 kinds of LPE and 22 kinds of LPC),were analyzed by LC-MS.The total concentration of all kinds of phospholipids in plasma was 236.9 mg/dl.6.PERMANOVA analysis showed that there was an association between plasma phospholipids with insulin and HOMA-IR(Q=6.60×10-4).Insulin was correlated with 109 kinds of plasma phospholipids(Q<0.05),while HOMA-IR was correlated with 111 kinds of plasma phospholipids(Q<0.05).Insulin and HOMA-IR were both positively correlated with PG,LPE C14:0 and LPC C14:0,while negatively correlated with plasmalogen(including PE[P],PC[P]and LPC[P]),and other LPE and LPC(Q<0.05).7.Random Forest regression analysis showed that 199 kinds of phospholipids explained 23.1%the change of HOMA-IR.According to the score of variable importance,a total of 8 phospholipids markers[PG(36:1),LPC(18:1),LPC(20:2),PE(36:1),LPC(20:1),LPC(14:0),PE(40:6)and PG(36:2)]were screened to be associated with HOMA-IR.ConclusionThe prevalence dyslipidemia in adults with previously-diagnosed diabetes,newly-diagnosed diabetes,pre-diabetes and normal glucose participants were 58.0%,58.9%,43.8%and 31.1%,respectively.The main types of dyslipidemia were low HDL cholesterolemia and hypertriglyceridemia.The prevalence of awareness,treatment and control was lower in different glycemic status,expecially for newly-diagnosed diabetes participants.It is suggested that the prevention and treatment of diabetes and dyslipidemia should be strengtheined.The relationship between lipids related indicators and IR was different between pre-diabetes and normal glucose participants,which mainly manifested in TC and LDL-C.It is necessary to discuss the relationship between lipids related indicators and IR among different glycemia status.In the future,large cohort study needs to be discussing the association between lipids related indicators and IR.Among normal glucose participants,TG/HDL-C,LAP,VAI and TyG index were the best markers predicting the risk of IR,while LAP and VAI were the best markers in pre-diabetes.These indicators will be validated through large cohort study and might be a part of the primary prevention of diabetes.The concentration of 199 kinds of phospholipids in plasma was 236.9 mg/dl,and these phospholipids explained 23.1%of the change of HOMA-IR.This means that phospholipids was closely associated with HOMA-IR and play a key role in the development of IR and diabetes.Eight phospholipids markers can provide valuable information for the basic research of IR and diabetes. |
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