The Association Of Serum 25-Hydroxyvitamin D₃ And Nonalcoholic Fatty Liver Disease In Type 2 Diabetes Mellitus

Background and ObjectivesNonalcoholic fatty liver disease?NAFLD?is a clinical syndrome closely related to type 2 diabetes mellitus,obesity and metabolic syndrome.It has a complex pathogenesis and is often associated with overweight and dyslipidemia.A large number of studies have shown that these characteristics are related to insulin resistance?IR?.The incidence of type 2 diabetes mellitus?T2DM?has increased at an alarming rate throughout the country and the world,and its pathogenesis is mainly related to insulin resistance and impaired insulin secretion.NAFLD occurs extensively in the T2DM,and both are often combined with the onset.If T2DM is combined with NAFLD,blood glucose levels will worsen,will make chronic complications of diabetes more serious,and will increase the development of nonalcoholic steatohepatitis?NASH?and even liver cancer.Vitamin D is an important hormone involved in the regulation of bone and mineral metabolism.Recently,some studies have found its role in non-skeletal metabolic diseases such as diabetes and nonalcoholic fatty liver disease.There may be potential biological interactions between vitamin D deficiency and diabetes and nonalcoholic fatty liver.This study was designed to compare serum 25-hydroxyvitamin D₃[25?OH?D₃],glucose metabolism,and liver function level in healthy individuals,type 2 diabetic patients,type 2 diabetic patients with nonalcoholic fatty liver disease by retrospective analysis.To investigate the relationship between serum25-hydroxyvitamin D₃ and type 2 diabetes mellitus with non-alcoholic fatty liver.In addition,the indicators of glucose metabolism,liver related indicators and fatty liver progression were explored by comparing the indicators before and after treatment with vitamin D3 and calcium carbonate.Object and MethodsA total of 238 patients with type 2 diabetes who were admitted to the Department of Endocrinology,Second Affiliated Hospital of Zhengzhou University from June 2017 to June 2018,and 30 healthy subjects from the same period were selected as the healthy control group.238 patients with type 2 diabetes were divided into two groups:type 2 diabetes mellitus group?n=111?and type 2 diabetes mellitus with nonalcoholic fatty liver group?n=127?.Patients in T2DM group were randomly divided into two subgroups according to whether they were treated with vitamin D₃ or calcium intervention:[group A1?55 cases?:no treatment;group A2?56cases?:treated with vitamin D₃ drops 800U/day and calcium carbonate D₃ tablet1.25g/day?containing calcium 500 mg,vitamin D₃ 200U?],The patients were followed up for 24 weeks.All participants received the consent of the Hospital Ethics Committee and signed the informed consent form.The general clinical data of 268 subjects were collected,including age,sex,height,weight,systolic blood pressure?SBP?,diastolic blood pressure?DBP?,and duration of diabetes mellitus,and so on.Biochemical indexes such as 25?OH?D₃,fasting insulin?FINS?,and glycosylated hemoglobin?HbA1C??%?,fasting blood glucose?FPG?,liver function,blood lipids and other biochemical indicators,and biochemical indicators after vitamin D and calcium intervention were recorded.Statistical analysis was performed using SPSS 20.0 software.The measurement data are expressed as mean±standard deviation??x±s?.The comparison between the multiple groups satisfies the one-way ANOVA for the homogeneity test of variance,and the LSD method is used for the pairwise comparison.If the homogeneity of the variance is not met,the rank sum is used.The Kruskal-wallis method was used to compare the two pairs;the two groups were compared using an independent sample t test.Counting data were expressed as frequency and percentage,using?² test;Pearson correlation analysis was used to analyze the correlation between 25?OH?D₃ and various biochemical indicators,and Spearman correlation analysis was used to analyze the correlation between 25?OH?D₃ and nonalcoholic fatty liver disease.The paired-sample t-test was used before and after intervention.The non-alcoholic fatty liver was used as the dependent variable,and the risk factors were used as the independent variables for logistic regression analysis.The test level?=0.05.Results?1?General clinical data comparisonThere were no significant differences in age,smoking positive rate drinking positive rate and sex ratio among type 2 diabetes mellitus group,non-alcoholic fatty liver group and healthy control group?P>0.05?;Compared with the control group and the type 2 diabetic group,the body mass index?BMI?of the type 2 diabetes mellitus with non-alcoholic fatty liver group was significantly higher than that of the control group and type 2 diabetes mellitus group?P<0.05?.?2?Comparison of blood biochemical indexesCompared with type 2 diabetes mellitus group,the levels of alanine aminotransferase?ALT?,serum uric acid?SUA?,serum calcium?Ca?,FINS,fasting C-peptide?FC-P?,insulin resistance index?ISR?,triglyceride?TG?in type 2 diabetic patients with non-alcoholic fatty liver were significantly higher than that in type 2diabetes mellitus group,and the level of 25?OH?D₃ was lower than that in type 2diabetes mellitus group,the difference was statistically significant?P<0.05?;Compared with the control group,the levels of HbA1c,ALT,retinol binding protein?RBP?,FPG,FINS,ISR,TG in type 2 diabetic patients with non-alcoholic fatty liver were significantly higher than that in the control group,and the levels of 25?OH?D₃,FC-P,were lower than that in the control group,and the difference was statistically significant.?P<0.05?;Compared with the control group,the levels of HbA1c,urea nitrogen?BUN?,cystatin C,FPG,HOMA-IR in type 2 diabetic patients with non-alcoholic fatty liver were significantly higher than that in the control group,and the levels of 25?OH?D₃,FC-P,Ca were lower than that in the control group,and the difference was statistically significant.?P<0.05?;the other indicators had no statistical significance?P>0.05?.?3?Analysis of the correlation between serum 25?OH?D₃ levels and nonalcoholic fatty liver disease in patients with type 2 diabetesCorrelation analysis of serum 25?OH?D₃ with non-alcoholic fatty liver showed that 25?OH?D₃ was negatively correlated with nonalcoholic fatty liver disease?r=-0.154,P=0.018?.?4?Analysis of the correlation between serum 25?OH?D₃ levels and clinical indicators in patients with type 2 diabetesCorrelation analysis of serum 25?OH?D₃ with clinical indicators showed that serum 25?OH?D₃ was negatively correlated with HOMA-IR?r=-0.161,P=0.013?,TG?r=-0.148,P=0.022?,and the course of diabetes mellitus?r=-0.161,P=0.013?.?5?Logistic regression analysis of risk factors for NAFLD in patients with type 2 diabetesTaking nonalcoholic fatty liver as the dependent variable,course of disease,BMI,BUN,creatinine,uric acid,cystatin C,liver function,retinal binding protein,blood lipids,glycosylated hemoglobin,fasting blood glucose,fasting C peptide,fasting insulin,Insulin resistance index and 25-hydroxyvitamin D₃ were independent variables.After adjusting for confounding factors,the results showed that BMI and ALT were risk factors for NAFLD,?P=0.009,95%CI:1.033¹.250;P=0.011,95%CI:1.016¹.129?,and 25?OH?D₃ was protective factor for NAFLD,?P=0.006,95%CI:0.848⁰.967?.?6?Changes in indicators after intervention of vitamin D₃ and calcium carbonate111 patients with type 2 diabetes mellitus were randomly divided into A1 group and A2 group.A1 group was not treated,A2 group was treated with vitamin D₃ drop?800U/day?and calcium carbonate D₃ tablet 1.25g/day?calcium 500mg,vitamin D₃200U?for 24 weeks.3 cases in A1 group did not completed the trial because they could not insist to withdraw,a total of 52 cases completed the trial,and 4 cases in A2group did not completed the trial because they could not insist to withdraw,a total of52 cases completed the trial.There were no significant differences in sex composition,age,course of disease,BMI and 25?OH?D₃ between the two groups?P<0.05?.Compared with pretreatment,the level of FPG,HOMA-IR in A1 group was lower,the level of FPG,FINS,HOMA-IR was lower,and the level of 25?OH?D₃was higher in A2 group?P<0.05?.After intervention,Compared with the non-intervention group?A1?group,the serum 25?OH?D₃ level in the intervention group?A2?group was significantly higher than that in the non-intervention group?A1?,while the insulin and insulin resistance index levels were significantly decreased in the intervention group,and the difference was statistically significant?P<0.05?.?7?Comparison of progression of non-alcoholic fatty liver disease after vitamin D3 and calcium carbonate interventionAfter intervention,the intervention group?A2 group?had 5 cases of nonalcoholic fatty liver new development,and 7 cases of non-intervention group?A1group?.The difference was not statistically significant?P>0.05?.Conclusions?1?In patients with type 2 diabetes mellitus,serum 25?OH?D₃ levels were associated with NAFLD;?2?In patients with type 2 diabetes mellitus,serum 25?OH?D₃ was a protective factor for NAFLD;?3?vitamin D₃ and calcium carbonate intervention can improve insulin resistance in type 2 diabetic patients with non-alcoholic fatty liver;?4?vitamin D₃ and calcium carbonate intervention treatment did not improve the progression of non-alcoholic fatty liver in type 2 diabetes mellitus in the short term.