Effects Of Vitamin D On Glycolipid Metabolism,Inflammation And Carotid Intima-media Thickness In Patients With Type 2 Diabetes Mellitus

Objective:With the development of social economy,the obvious improvement of people's living standard and the increase of life span,the prevalence of Diabetes mellitus(DM)has increased rapidly year by year.DM and its complications not only seriously affect the health and quality of life of patients,but also bring huge economic burden to the society.DM is related to the increased risk of cardiovascular disease(CVD),which is the main cause of death and disability in type 2 diabetes mellitus(T2DM).ADA guidelines have emphasized the importance of controlling cardiovascular risk factors in preventing or reducing the risk of atherosclerotic cardiovascular disease in diabetic patients.It is known that pathological mechanisms related to diabetes and atherosclerosis include age,dyslipidemia,hyperglycemia inflammation and increased oxidative stress.In recent years,carotid intima-media thickness(CIMT)is considered as a subclinical marker of atherosclerosis in type 2diabetes mellitus,which can be used to predict the incidence of cardiovascular and ischemic stroke in the future.Although the treatment of blood glucose and blood lipid has been actively controlled,it still can not prevent the occurrence and development of diabetes and its vascular complications.Therefore,new treatment indicators are urgently needed to predict the risk of the development of Diabetes Atherosclerosis.Vitamin D deficiency is a global concern.There are about one billion people in the world whose vitamin D level has decreased.More and more studies have shown that vitamin D not only affects bone metabolism,but also is closely related to CVD,hypertension,dyslipidemia and T2DM.However,most of the existing reports are cross-sectional studies.At present,there are few prospective studies on the protective effect of vitamin D on diabetic macroangiopathy.Therefore,we first study the prevalence of vitamin D deficiency in type 2 diabetic patients through cross-sectional study;then we choose the type 2 diabetic patients accompanied by vitamin D deficiency or deficiency with stable blood glucose and lipid level to receive layered vitamin D supplementation treatment,and observe the changes of glycolipid metabolism indexes,inflammatory factors,oxidative stress indexes and CIMT before and after treatment.The aim is to explore the best concentration of vitamin D in nonskeletal health benefits and the possible mechanism of its effect on carotid intima-media thickness.(1)To analyze the level of 25(OH)D and the prevalence of vitamin D deficiency in type 2 diabetic patients,and to explore the correlation between the level of 25(OH)D and the clinical characteristics of blood glucose and blood lipid in type 2 diabetic population;(2)The changes of blood glucose,blood lipid,inflammatory factors,oxidative stress index and CIMT were compared before and after treatment.The influencing factors of CIMT were analyzed by logistic regression analysis.To explore the possible mechanism and the best range of the effect of vitamin D on carotid intima-media thickness,so as to provide more data and theoretical basis for better prevention and treatment of diabetic macroangiopathy.Methods:Part?:Based on clinical practice,this study investigated 1800 type 2 diabetes patients with Hb A1c between 5.0-8.5%in our hospital from January 2017 to December 2018,collected general clinical data of patients,collected blood from vein to detect serum 25 hydroxyvitamin D[25(OH)D],blood glucose,blood lipid and other biochemical indicators,and explored the distribution of serum 25(OH)D and the prevalence of vitamin D deficiency in type 2 diabetes.According to the quartile of serum 25(OH)D level,the population characteristics of each group were compared.The differences of vitamin D level,blood glucose metabolism index and blood lipid metabolism index were analyzed,and the relationship between 25(OH)D level and blood glucose and blood lipid was discussed by Spearman correlation analysis.Part?:From January 2017 to June 2018,400 T2DM patients with 25(OH)D<30ng/ml in our hospital were selected,which were with the relatively stable blood glucose and lipid level in the past year,then randomly divided into two groups:control group and intervention group,the control group was given the maintenance of the original treatment plan+lifestyle guidance;the intervention group,based on the original treatment plan+lifestyle guidance,according to the level of 25(OH)D,was given the layered vitamin D supplement treatment:if 25(OH)D<10 ng/ml,was given the oral vitamin D₃ 1200 IU/day;if 25(OH)D 10-20 ng/ml,was given the oral vitamin D₃ 800 IU/day;25(OH)D 20-30 ng/ml,oral vitamin D₃ 400 IU/day.The safety evaluation and vitamin D supplement dose adjustment were carried out every three months.After 12 months of intervention,the same indexes as the baseline[25(OH)D,blood glucose,blood lipid,inflammatory factor,oxidative stress index,CIMT]were retested.The changes of all indexes were analyzed before and after treatment,and the influencing factors of CIMT and the suitable range of vitamin D for optimal extra-skeletal effects were discussed.Results:Part?:(1)The average concentration of 25(OH)D in type 2 diabetic patients was(17.83±8.01)ng/ml.Only 6.61%of the patients had adequate vitamin D level[25(OH)D?30ng/ml],66.01%of the patients had low vitamin D level[25(OH)D<20 ng/ml].(2)The prevalence of vitamin D deficiency was 15.72%in patients under 40 years old,17.11%in patients between 40 and 60 years old,and 33.28%in patients over 60 years old.The prevalence of vitamin D deficiency increased with age.(3)According to the serum 25(OH)D quartile,the patients were divided into four groups:Q1(9.17±2.02)ng/ml,Q2(14.37±1.35)ng/ml,Q3(19.17±1.69)ng/ml,Q4(28.54±6.67)ng/ml.There was the highest 25(OH)D level,the youngest patients,the shortest clinical course,and the lowest prevalence of vitamin D deficiency in winter and spring in Q4 group(P<0.05).(4)There were statistical significance in Fasting Blood Glucose(FBG),Triglyceride(TG)and Total cholesterol/High density lipoprotein-cholesterol(TC/HDL)levels between the four groups(P<0.05).There were decreased Body mass index(BMI),Homeostasis model assessment-insulinresistance index(HOMA-IR),Hemoglobin(Hb A1c)levels with the increase of vitamin D level,but there was no significant difference(P>0.05).(5)Pearson correlation analysis showed that 25(OH)D was negatively correlated with TC/HDL,FBG and HOMA-IR(P<0.05).After adjusting for factors such as age,gender,BMI and clinical course,TC/HDL(r=-0.010,P=0.035),and FBG(r=-0.071,P=0.048)were still negatively correlated with 25(OH)D.Part?:1.Baseline:There was no significant difference in age,sex constituent ratio,serum 25(OH)D level,course of disease,BMI,blood pressure,glycolipid metabolism index,PTH,inflammatory factors,oxidative stress index and CIMT between the intervention group and the control group.2.Intervention effect:?After 12 months of intervention,the level of 25(OH)D in the intervention group increased from(15.12±6.97)ng/ml to(33.77±4.75)ng/ml,and there was statistical difference in 25(OH)D level between the two groups,and there was significant difference in the ratio of vitamin D deficiency between the two groups(P>0.05).?At the end of the study,the serum PTH level of the intervention group(29.71±7.47 pg/ml)was lower than that of the control group(33.77±9.49 pg/ml),the difference was statistically significant(P<0.05).?TG and TC/HDL levels were significantly lower in the intervention group(P<0.05).?FBG level was significantly lower in the intervention group(P<0.05).The level of Hb A1c in the intervention group decreased,but there was no difference between two groups(P>0.05).?The levels of IL-2,IL-6 and TNF–?were significantly lower in the intervention group(P<0.05).?The levels of TAOC,SOD and GSH-Px were significantly higher,and the level of MDA was significantly lower in the intervention group(P<0.05).?The CIMT level in the intervention group was lower than that in the control group(P<0.05).(8)The logistic regression analysis with CIMT as the dependent variable indicated that age(OR=0.002,95%CI:-0.000-0.003,p=0.047;)?TC/HDL(OR=-0.024,95%CI:0.051-0.064,p=0.044;)?IL-6(OR=-0.006,95%CI:-0.002-0.001,p=0.032;)?TNF-?(OR=0.001,95%CI:0.000-0.002,p=0.046;)?25(OH)D(OR=-0.003,95%CI:0.003-0.007,p=0.046;)?TAO-C(OR=-0.085,95%CI:0.001-0.031,p=0.039;)?GSH-PX(OR=-0.005,95%CI:0.001-0.006,p=0.044;)had linear relationships with CIMT after adjusting other confounding factors and were independent risk factors of CIMT.Conclusions:1.This cross-sectional analysis shows that type 2 diabetes patients generally have vitamin D deficiency or lack,and the proportion of patients in winter and spring is higher.2.Layered vitamin D₃ supplementation can effectively improve the level of serum vitamin D and increase the proportion of adequate vitamin D.3.After vitamin D supplementation,the serum 25(OH)D level was maintained at about 30ng/ml,which could reduce the fasting blood glucose level of type 2 diabetic patients;improve the blood lipid profile(reduce LDL,TC/HDL);reduce the level of inflammatory factors(IL-2,IL-6,TNF-?);improve the indicators of oxidative stress(TAOC,SOD,GSH-Px levels increased significantly,and MDA levels decreased significantly);thus reduce CIMT and delay the occurrence and development of diabetes angiopathy in diabetic population.