Intervention Study Of Calcitriol In Patients With Type 2 Diabetes Mellitus And Cognitive Dysfunction

OBJECTIVE: To investigate the risk factors and clinical risk indicators of Mild cognitive impairment(MCI)in patients with type 2 diabetes,and to evaluate the association between vitamin D deficiency and MCI in diabetic patients.Patients with type 2 diabetes mellitus with MCI were treated with calcitriol for 6 months and the Mo CA scores and other clinical characteristics were measured and compared before and after the treatment.METHODS: 1.173 patients with type 2 diabetes comparing recent memory loss were enrolled and divided into normal cognition(NC group)(n=79 cases)(Mo CA>=26 points)and mild cognitive dysfunction group(mild Cognitive impairment,MCI group)(n=94 cases)(Mo CA <25 points)in this study.Data of their body weight,BMI,waist circumference,hip circumference,waist-to-hip ratio,blood glucose,glycosylated hemoglobin,blood lipids(TG,TC,HDL-C,LDL-C),renal function(creatinine,uric acid,urea nitrogen),fasting C-peptide,Aβ1-40,Aβ1-42,IGF-1,25(OH)D,PTH levels,common carotid artery RI,Mo CA score,brain MRI and other clinical parameters were measured and collected.We compared the differences of clinical parameters between the two groups2.Forty patients with diabetes mellitus who matched the gender,age,and duration of diabetes in the NC group and the MCI group underwent head MRI.The Fazekas score was evaluated according to the T2(flair)image.3.85 patients with MCI and type 2 diabetes who had 25(OH)D levels below 30 ng/ml joined the intervention process.They were divided into treatment group(N=43 cases,conventional hypoglycemic therapy + calcitriol 0.25 ug bid po)and control group(N=42 cases,conventional hypoglycemic treatment only).The fasting C-peptide,Aβ1-40,Aβ 1-42,IGF-1,blood glucose,blood glucose,glycosylated hemoglobin,blood lipids(TG,TC,HDL-C,LDL-C),renal function(creatinine,uric acid,urea nitrogen)levels and common carotid artery ultrasonography of the patients before and after intervention were compared and analyzed.RESULTS: 1.At baseline there were no significant differences in gender,age,smoking history,alcohol abuse history,sleep status,and BMI between the NC group and the MCI group(P>0.05).Patients in the control group had higher education level,lower systolic blood pressure,shorter duration of DM,lower waist-to-hip ratio,and higher proportion of patients who had daily sun exposure for more than half an hour(P<0.05).C-peptide,triglyceride,25(OH)D,IGF-1,Aβ1-42/ Aβ1-40 in the control group were significantly higher than those in the MCI group(P<0.05),Hb A1 c,total cholesterol,high-density cholesterol,PTH,Aβ1-40 and serum calcium were significantly lower than in the MCI group(P < 0.05).The bilateral RI and IMT in the control group were lower than those in the MCI group,and the proportion of carotid plaques was lower(P<0.05).Mo CA scores in diabetic patients were positively correlated with education years,C-peptide,TG,25(OH)D,IGF-1,Aβ1-40,and were negatively correlated with duration of diabetes,history of hypertension,insomnia,SBP,FPG,Hb A1 c,TC,HDL-C,PTH,Ca,P,Aβ1-42/ Aβ1-40,RI(right),RI(left),IMT(right),IMT(left),carotid plaque.After adjusting for gender,age,education,and duration of diabetes,25(OH)D,IGF-1,Aβ1-40,Ca,C peptide,and systolic blood pressure were independently associated with Mo CA(R2=0.448).Multiple regression analysis was performed in 94 patients with diabetes mellitus with MCI after adjusting for gender,age,education,and duration of diabetes,and it showed that IGF-1 and insomnia were independently associated with Mo CA(R2=0.240).2.After the 6 months of treatment and follow-up,two patients in the treatment group and two in the control group did not complete the follow up.MoCA scores in the treatment group was significantly higher than that at baseline state in treatment group,and abstract and delayed recalls increased significantly(P < 0.05).The total score,spatial and executive ability,naming,attention,language,delayed recall,and orientation scores of the treatment group were significantly higher than those of the control group.In the control group,after 6 months of follow-up,a decrease in attention and orientation ability was observed.Comparing with the baseline,SBP,DBP,TC,LDL-C,Hb A1 c,and PTH of patients in treatment group significantly decreased,and C-peptide,BUN,calcium,25(OH)D,IGF-1,and Aβ1-40 significantly increased..After 6 months of follow-up,comparing with the control group,patients in the treatment group had lower BMI,PTH,and UA,calcium,IGF-1,25(OH)D,and higher levels of Aβ1-40.Carotid ultrasound results suggested that the bilateral RI and IMT in the treatment group were significantly lower than that at baseline.However,after follow-up,the results showed that only the left IMT was significantly lower in the treatment group than in the control group.CONCLUSIONS: 1.Type 2 diabetic patients with MCI have significantly lower25(OH)D,IGF-1,and Aβ1-40,and results of carotid ultrasound suggested a significant increase in bilateral RI and IMT.MRI imaging showed that the Fazekas score of patients with MCI was significantly increased and they were more prone to develop to white matter lesions.2.The cognitive function of patients with type 2 diabetes is independently associated with levels of 25(OH)D,Aβ1-40,C-peptide,IGF-1,SBP,and bilateral IMT.3.Treatment with calcitriol can significantly improve the cognitive function of patients with type 2 diabetes mellitus with vitamin D deficiency.4.After treatment with calcitriol,the PTH and BMI of patients were significantly lower than those in the control group,and IGF-1,25(OH)D and Aβ1-40 were elevated.The improvement of cognitive function may be related to changes of these clinical parameters.