Effect of Vitamin D Supplementation on Glucose Homeostasis among Type 2 Diabetic Patients: A Randomized Clinical Trial

Abstract

Background: Type 2 diabetes mellitus (T2DM) is a major endocrine metabolic disorder, which is highly prevalent in all ages of people in Bangladesh, who are suffering from vitamin D deficiency. Aims: The purpose of this study was to examine how vitamin D supplementation impacts glucose homeostasis in individuals with Type 2 Diabetes who are deficient in vitamin D. Materials and Methods: To find the vitamin status in T2DM, a pilot study was conducted among 23 T2DM patients. Vitamin D deficiency (VDD) was prevailing in the 100% T2DM of both sexes, 78.3% were deficient (10-30 ng/ml), and the rest 21.7% were severely deficient (<10 ng/ml). A singleblind prospective randomized clinical trial was conducted among 124 vitamin D deficient Type 2 diabetic patients comprising vitamin D supplementation to 61 T2DM and 63 T2DM patients during the period of 2020 and 2021. Patients were randomly recruited from Z.H Sikder Women’s Medical College and Popular Diagnostic Center, Dhaka under defined inclusion and exclusion criteria. The vitamin D deficient T2DM treatment group of patients received 20,000 IU vitamin D capsules (D-Rise, Beximco Pharmaceuticals) and placebo or control patients received ‘placebo’ at every 5th day for 12 weeks with a follow-up at 6 weeks simultaneously. Analysis of fasting blood glucose (FBG), fasting blood insulin (FBI), glycated hemoglobin (HbA1C), Cxv reactive protein (CRP), serum calcium, 25(OH) vitamins D, malondialdehyde (MDA) and superoxide dismutase (SOD) have been estimated at the time of recruitment, at 6th weeks and 12-weeks of vitamin D supplementation (end line). Collection of socio-demographic information, anthropometric data, collection, and laboratory analysis of blood specimens were carried out at the same schedules as of the vitamin D-supplemented subjects. In addition, simple sugar/carbohydrate restriction for foods and performing physical activity were advised and monitored at the timelines. 'Two-way repeated measure ANOVA mixed models' (GLM/general linear model) and ‘Fixed-Effect Regression Model using dummy variable’ were used in statistical analyses with SPSS, version 26 for measuring the significant changes of different biochemical parameters (as predictor variables) across timelines (denoted as within groups) and between groups (treatment versus placebo) following the 12 weeks vitamin D supplementation. ‘Multiple linear Regression’ analysis was also used for building multivariate models, with vitamin D as a dependent variable, where necessary. Results: Present study outlined significant correction of vitamin D status among vitamin D-deficient T2DM patients. As defined by the Endocrine Society (deficient <30 ng/ml, sufficient ≥30 ng/ml) mean vitamin D or 25 (OH)D3 level was increased from deficient (baseline: 14.5±6.1 ng/mL) to a sufficient level (end line 35.8±7.5 ng/mL) effectively (P=.000) in the treatment group as compared to placebo. Moreover, end-line 25-hydroxy vitamin D levels were significantly higher in the treatment group as compared to placebo (treatment: 35.8 ±7.5 ng/mL versus placebo: 20.05±5.2 ng/mL, p=0.001) and baseline to end-line changes in the placebo group was independent (Baseline:19.5 ± 8.8 ng/mL vs end line: 20.05 ± 5.2 ng/mL, p = 0.965). Regarding FBG present study showed after vitamin D supplementation, baseline mean FBG gradually decreased significantly (P<0.001) from 10.9 mmol/L (±3.5) to 8.42 mmol/L (±1.7) at the end line in the treatment group as compared to placebo. Additionally, mean HbA1C gradually decreased (P=0.004) from baseline (8.97±1.9) to the end line (8.5±1.6) only in treatment while changes in placebo were independent (p=0.587). Other biochemical indices such as FBS, Fasting Insulin, HOMA-IR, HOMA-β, Calcium, SOD, MDA, and CRP which also showed significant changes within timelines and between groups (treatment versus placebo) even in short interventions except HbA1C for placebo (P=.587); Calcium and FBI level between treatment and placebo respectively (p=0.08 and P>0.05). However, vitamin D supplementation showed no significant impact on sociodemographic variables, BMI (Kg/m2), co-morbidity, and Stress- related characteristics between treatment and control groups as those variables are somewhat independent (p>0.05) both at baseline and end-line. Multivariate analysis showed 44.4% variation for different biochemical predictors of vitamin D (overall R2-change=44.4%, F=19.17, P<0.001) and revealed that FBG, CRP, and MDA (P<.05) were inversely associated with vitamin D levels of T2DM patients. In contrast, SOD and calcium are significant positive predictors of changing Vitamin D levels over 3 months of intervention. However, important glycemic indices -HbA1C, FBI and derived parameters (HOMA 𝛽, HOMA-IS, HOMA-IR) were not significant predictors of variation in Vitamin D level analysis in the treatment group as compared to placebo. Surprisingly, after adjusting physical activity level (PAL) multiple regression analysis showed the increment of HOMA-IS and SOD along with reduction of FBG and MDA were changed vitamin D levels over the timelines. Similarly, an increment of vitamin D was also found associated with reduced FBG and MDA while adjusting for total calorie consumption among vitamin D-deficient T2DM patients. Conclusion and Recommendation: Vitamin D supplementation to vitamin D deficient type 2 diabetic patients had significantly improved their vitamin D levels. It supported the glycemic indices to maintain glucose homeostasis in type 2 diabetic patients. Effective awareness of adequate intake of vitamin D as well as consumption of natural vitamin D-rich foods and physical activity would help Type 2 diabetic mellitus patients to support glucose homeostasis.