Association Of Plasma Transthyretin Levels And Risk Of Type 2 Diabetes Mellitus And Impaired Glucose Regulation

Objective: Plasma transthyretin was a biochemical index that routinely evaluated protein nutrition status in the body.Previous studies mainly focused on the relationship between plasma transthyretin levels and complications and prognosis of type 2 diabetes mellitus(T2DM)patients.Data on the relationship between transthyretin levels and the risk of T2 DM were insufficient and inconclusive.Therefore,this study aimed to investigate the association between plasma transthyretin levels and newly diagnosed type 2 diabetes mellitus(T2DM)and impaired glucose regulation(IGR)in a Chinese population.Methods: After individual matching and frequency matching for sex and age(± 3 years),a total of 3,325 participants,including 1,244 newly diagnosed T2 DM patients,837 newly diagnosed IGR patients and 1,244 individuals with normal glucose tolerance(NGT)were recruited in the case-control study.Diagnostic criteria was in accordance with the recommendation of World Health Organization in 1999.Plasma transthyretin concentrations were determined by Autoanalyser using immunoturbidimetric method.We used multivariate conditional and non-conditional Logistic regression analysis to estimate the independent association of plasma transthyretin concentrations with the risk of T2 DM and IGR.We further conducted a restricted cubic spline to evaluate potential dose-effect relationship.Results: Plasma transthyretin concentrations were significantly higher in T2 DM and IGR patients compared with the control subjects(229.01 ± 53.69 mg/L,246.97 ± 64.77 mg/L and 246.50 ± 63.01 mg/L in NGT,T2 DM and IGR group,respectively,P < 0.001).In a crude model,comparing with the lowest quartile of plasma transthyretin concentrations,the odds ratios(95% confidence intervals)of T2 DM and IGR in the highest quartile were 2.23(1.76,2.82)and 2.00(1.56,2.71),respectively.After adjustment for sex,age,body mass index,waist circumference,family history of diabetes,educational levels,smoking status,drinking status,physical activity,history of hypertension and hyperlipidemia,and plasma total protein levels,the odds ratios(95% confidence intervals)of T2 DM and IGR were 2.04(1.53,2.71)and 2.17(1.63,2.88),respectively.In stratified analyses,the positive association of plasma transthyretin with T2 DM and IGR was consistently observed across all categories except stratifying by sex,smoking status and drinking status.Furthermore,a potential nonlinear trend was observed between plasma transthyretin and risk of T2 DM and IGR.When plasma transthyretin levels were above 302.10 mg/L and 281.67 mg/L,plasma transthyretin levels were significantly associated with increased risk of T2 DM and IGR.Moreover,plasma transthyretin levels were positively related to fasting plasma glucose(? = 0.10,P < 0.001),high-density lipoprotein cholesterol(? = 0.04,P = 0.046),low-density lipoprotein cholesterol(? = 0.06,P < 0.001)and total cholesterol(? = 0.07,P < 0.001)after multiple adjustment.Conclusions: Our results demonstrated that plasma transthyretin levels were positively associated with risk of T2 DM and IGR in a non-linear manner.When plasma TTR levels were higher than 302.10 mg/L and 281.67 mg/L,high plasma TTR levels were positively associated with the increased risk of T2 DM and IGR.Plasma transthyretin may be a promising biomarker for T2 DM and IGR in future.Moreover,the results will help people to properly supplement protein and balance nutrition.