| Type 2 diabetes mellitus(T2DM)is a disease with endocrine and metabolic disorders which seriously endanger human health.Impaired fasting glucose and impaired glucose tolerance are the intermediate phases from normal glucose tolerance to T2DM.With the improvement of people's living standards,changes in dietary patterns,the aging population and the increasing incidence of obesity,the prevalence of T2DM is increasing year by year.According to estimation of the World Health Organization(WHO),there will be 366 million people with diabetes worldwide by 2030,and there will be a large number of people with IFG/IGT.Oxidative stress and endoplasmic reticulum stress(ERS)play important roles in the occurrence of diabetes Selenium is an essential trace element in human body.Its main function was played by 25 kinds of selenoproteins,some of which have antioxidant and ERS regulation function.Therefore,selenium may affect the occurrence of T2DM in these two ways.However,there was a great difference in the results of animal and epidemiological results study on the relationship between selenium and T2DM.In 25 selenoproteins,the function of selenoprotein P was mainly to transport selenium produced by liver to other parts of our body.A gene polymorphism site of rs7579 located in the 3 'untranslated region of the SEPP gene can affect the full length isoform expression of the protein,the full length isoform has a stronger ability to transport selenium,thus affecting the concentration and activity of representative selenium biomarkers,thereby affecting the prevalence of diseases.Therefore,the aim of this study was to investigate the relationship between plasma selenium level,SEPP rs7579 gene polymorphism as well as their interactions with T2DM.The main research contents are as follows:Part ? Association of plasma selenium concentration with risk of type 2 diabetes mellitusSection 1 Association of plasma selenium concentration with risk of type 2 diabetes mellitus Objectives:To investigate the association of plasma selenium concentration with risk of type 2 diabetes mellitus(T2DM).Methods:Fasting blood glucose(FPG)was tested by GOD-POD method,fasting plasma insulin(FPI)was measured by means of electrochemical luminescence immunoassay(ECLIA),assessment of HOMA-IR and HOMA-beta by using the homeostasis model(HOMA)evaluation method.Plasma selenium levels were measured by inductively coupled plasma mass spectrometry(ICP-MS).Results:(1)?A total of 5392 subjects were enrolled in this study,with 2630 T2DM patients and 2762 normal glucose toleranc(NGT)subjects.When compared with subjects with NGT,patients with T2DM had a significantly increase in HOMA-IR(T2DM 4.26±0.13 vs.NGT 2.17±0.11;P<0.001)and a significantly decrease in HOMA-p(T2DM 44.40±1.78vs.NGT 103.37±5.01;P<0.001).(2)?The average plasma selenium concentration in patients with T2DM and subjects with NGT were 98.O1 ±25.37?96.72±21.05 ?g/L.The multi-variable-adjusted ORs comparing the four selenium quintiles(<79.62,79.63-90.31,99.81-112.67,>112.68 ?g/L)with the middle quintiles(<90.32-99.80 ?g/L)were 1.68(1.35.2.08),1.01(0.82.1.24),1.15(0.93.1.41)and 1.86(1.51,2.29)for T2DM,respectively.(3)In the three selenium lower quintiles,the multivariable-adjusted OR for T2DM across 5?g/L higher plasma selenium was 0.81(0.78-0.85).In the three selenium higher quintiles,the multivariable-adjusted OR for T2DM across 5?g/L higher plasma selenium was 1.21(1.18-1.25).Conclusions:Both deficiency and over-nutrition of selenium may lead to the occurrence of T2DM.Section 2 Association of plasma selenoprotein P concentration with risk of type 2 diabetes mellitusObjectives:To investigate the association of plasma selenoprotein P(SEPP)concentration with risk of T2DM.Methods:Plasma SEPP concentration was measured by ELISA.Results:A total of 1293 subjects were enrolled,with 610 T2DM patients and 683 NGT subjects.The multivariable-adjusted ORs comparing the two higher SEPP tertiles(4.8-5.96,>5.96 mg/L)with the lowest SEPP tertiles were 0.83(0.66,1.10),1.31(1.00,1.68)for T2DM,respectively.Conclusions:Both deficiency and over-nutrition of SEPP may lead to the occurrence of T2DM.Section 3 Association of the plasma selenium concentration and T2DM with oxidative stress statusObjectives:To investigate oxidative stress status in relation to plasma selenium concentration and T2DM.Methods:Plasma malondialdehyde(MDA)was determined by thiobarbituric acid(TBA)colorimetric method.Results:(1).Plasma MDA was significantly higher in patients with T2DM than NGT subjects(T2DM 6.52±0.18 nmol/L vs.NGT 5.79±0.12 nmol/L;P=0.001).(2).We combined(79.63-90.31,<90.32-99.80,99.81-112.67?g/L)together as 79.62-112.67?g/L).When compared with<79.62 ?g/L,79.62-112.67(<79.62 ?g/L 6.27±2.95 nmol/L vs.79.62-112.67 ?g/L 5.81 ±3.24nmol/L,P<0.001)and(>112.67?g/L(<79.62 ?g/L>6.27±2.95 nmol/L vs.>112.67?g/L 5.89±2.93 nmol/L,P=0.018)had a lower MDA.Conclusions:There is a strong association between the status of lipid peroxidation and risk of T2DM,and the decreased selenium concentration may be related to the increased lipid peroxidation.Part II Association of the SEPP rs7579 polymorphism with risk of type 2 diabetesObjective:To investigate the association of the SEPP rs7579 polymorphism with risk of T2DM?Methods:The genotyping of gene was done by using TaqMan method.The expression of SEPP isoform was obtained by Western blot.(1)?Overall,the ORs of diabetes comparing GG and GA genotypes with AA genotype were 0.90(0.65,1.24)and 0.80(0.58,1.12),respectively.However,the ORs of diabetes comparing GG and GA genotypes with AA genotype were 0.49(0.24,0.98)and 0.44(0.22,0.90)in the lowest quintile.(2)?The adjusted ORs of T2DM per each 5 ?g/L increment of plasma selenium were 0.94(0.90,0.98),0.93(0.91,0.99)and 0.75(0.58,0.98)for GG,GA and AA in the lower three quintiles.(3)?In the lowest quintile,the AA genotype had a significantly lower proportion of the 60-kDa isoform than carries of GA/GG genotype in the control group(P=0.046)but not T2DM group(P=0.393).Conclusions:Participants with the AA genotype in rs7579 may have higher risk of T2DM in a low selenium status and may relate to a lower proportion of the 60-kDa isoform and a lower SEPP transportation function. |
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