The Impact Of Vitamin D Status On Insulin Resistance And Bone Metabolism In Patients With Type 2 Diabetes And Its Potential Mechanisms

Background and ObjectivesRecently vitamin D was proven to be closely related to morbidity and development of type 2 diabetes.The relationship between vitamin D status and insulin resistance was conflicting.Insulin and insulin sensitizers(thiazolidinediones)were not excluded,therefore could have affected the results of the previous studies.Vitamin D affected bone metabolism and bone density resulting in osteopenia and osteoporosis.The effect of vitamin D supplement on insulin resistance is also conflicting in previous researches.Serum 25-hydroxy vitamin D[25(OH)D]concentration is used to evaluate the vitamin D status.There are several purposes of this study.One is to investigate the relationship between insulin resistance and serum 25(OH)D concentrations in type 2 diabetes patients.This is done by exploring the relationship between serum vitamin D status,bone metabolism and insulin resistance,and the possible mechanism in non-osteoporosis type 2 diabetes patients.Also,by exploring whether vitamin D decreases insulin resisitance after supplementation of calcitriol by suppressing the inflammation reaction.Subjects and Methods1.This study included 117 patients with type 2 diabetes that were randomly selected.Three of the female patients refused 25(OH)D concentration and intact parathyroid hormone test.The following parameters were measured:25(OH)D,fasting blood glucose(FBG),fasting blood insulin(FINS),parathyroid hormone(iPTH),calcium(Ca),phosphorus(P),homeostatic model assessment of insulin resistance(HOMA-IR),glomerular filtration rate(eGFR)were performed.Vitamin D deficiency was defined as 25(OH)D concentration of?20ng/mL(?50nmol/L),Vitamin D insufficiency was defined as a 25(OH)D concentration between 20ng/mL(50nmol/L)and 30ng/mL(75 nmol/L).The normal serum 25(OH)D concentration was defined as ?30ng/mL(?75nmol/L).The cases were divided into three groups:group 1(G1)with 25(OH)D?20ng/mL,group 2(G2)with a 25(OH)D concentration ranging from 20 ng/mL to 30 ng/mL,and group 3(G3)with 25(OH)D?30 ng/mL.SPSS 19.0 software was used for statistical analysis.Least-Significant Difference test(LSD-t test)was used to analyze the comparision of 25(OH)D and ?-cell function indices(FINS,HbAlc)for G1,G2,G3 subjects.Multiple linear regression analysis was used to examine the association between serum 25(OH)D concentration and insulin resistance.HOMA-IR was analyzed as a dependent variable with the other significantly associated variables[25(OH)D,eGFR,BMI,age]as independent variables,and a p value<0.05 was considered significant.2.This study included 109 patients with type 2 diabetes and without osteoporosis.The following parameters were measured:25(OH)D,calcium,phosphorus,bone alkaline phosphatase(BALP),insulin-like growth factor-1(IGF-1),et al.SPSS 19.0 software was used for statistical analysis.Multiple linear regression analysis was used to examine the associations below:(1)association between serum 25(OH)D concentrations and insulin resistance,HOMA-IR,analyzed as dependent variable with the other significantly associated variables[25(OH)D,eGFR,BMI,age]as independent variables,(2)association between serum 25(OH)D concentrations and bone metabolism indices(calcuim,phosphorus,BALP and IGF-1),25(OH)D analyzed as dependent variable with the other significantly associated variables(calcuim,phosphorus,BALP,IGF-1,eGFR,BMI,age)as independent variables,(3)association between insulin resistance and bone metabolism indices(calcuim,phosphorus,BALP and IGF-1),HOMA-IR analyzed as dependent variable with the other significantly associated variables(calcuim,phosphorus,BALP,IGF-1 eGFR,BMI,age)as independent variables.3.We randomly included 39 subjects with type 2 diabetes and 36 of the subjects successfully finished the medication and visit.The following parameters were measured:25(OH)D,insulin-like growth factor-1(IGF-1),tumor necrosis factor-a(TNF-a),and monocyte chemoattractant protein-1(MCP-1).Subjects received calcitriol one tablet per day(Rocaltrol,calcitriol 0.25?g/d)for 3 months and then the measurements mentioned above were repeated.Results1.The average serum 25(OH)D value was 21.40±10.68ng/mL(53.1±26.35nmol/L),below the sufficiency cutoff value of 30ng/mL(75nmol/L).The prevalence of vitamin D deficiency[25(OH)D<50 nmol/L]was 52.6%of the total study subjects.There was a negative correlation between 25(OH)D and HOMA-IR(?=-0.314,p=0.001)adjusted by age,BMI,eGFR.2.In 109 T2DM without osteoporosis there was a negative correlation between 25(OH)D and IGF-1(?=0.581,p= 0.000),positive correlation between 25(OH)D and BALP(?=-0.182,p=0.021)adjusted by age,BMI,eGFR,a negative correlation between 25(OH)D and HOMA-IR(?=-0.349,p=0.000)adjusted by age,BMI,eGFR,a negative correlation between HOMA-IR and IGF-1(?=-0.376,p=0.000),and a positive correlation between HOMA-IR and BALP(?=0.232,p=0.013),adjusted by age,BMI,eGFR.3.The research included 36 Chinese patients with type 2 diabetes.Before and after the medication of calcitriol,25(OH)D concentrations(p=0.000),HOMA-IR levels(p=0.046),MCP-1 levels(p=0.014),TNF-a levels(p=0.001)were significantly decreased,respectively.Before and after the medication of calcitriol,calcium(p =0.180)and phosphorus levels(p=0.712),calcuim-phosphorus product(p=0.326),IGF-1 levels(p=0.230)and BALP(p=0.880)did not change significantly.Conclusion1.Vitamin D deficiency is common in patients with type 2 diabetes.Better vitamin D status may be protective of glucose homeostasis since 25(OH)D was negatively associated with insulin resistance in patients with Type 2 diabetes.2.Insulin resistance increased when 25(OH)D concentrations decreased,which enhanced bone turnover in patients with type 2 diabetes without osteoporosis.Decrease of 25(OH)D concentrations probably resulted in insulin resistance,and enhanced bone turnover which increased the risk of osteoporosis.3.Supplement of calcitriol could possibly increase the 25(OH)D concentrations and ameliorate insulin resistance by suppressing the inflammation reaction.