Effects of Combined Calcium and Vitamin D Supplementation on Insulin Secretion, Insulin Sensitivity and β-Cell Function in Multi-Ethnic Vitamin D-Deficient Adults at Risk for Type 2 Diabetes: A Pilot Randomized, Placebo-Controlled Trial

Abstract

ObjectivesTo examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, β-cell function, inflammation and metabolic markers.Design6-month randomized, placebo-controlled trial.ParticipantsNinety-five adults with serum 25-hydroxyvitamin D [25(OH)D] ≤55 nmol/L at risk of type 2 diabetes (with prediabetes or an AUSDRISK score ≥15) were randomized. Analyses included participants who completed the baseline and final visits (treatment n = 35; placebo n = 45).InterventionDaily calcium carbonate (1,200 mg) and cholecalciferol [2,000–6,000 IU to target 25(OH)D >75 nmol/L] or matching placebos for 6 months.MeasurementsInsulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, area under the curve (AUC) for C-peptide) and β-cell function (Matsuda index x AUC for C-peptide) derived from a 75 g 2-h OGTT; anthropometry; blood pressure; lipid profile; hs-CRP; TNF-α; IL-6; adiponectin; total and undercarboxylated osteocalcin.ResultsParticipants were middle-aged adults (mean age 54 years; 69% Europid) at risk of type 2 diabetes (48% with prediabetes). Compliance was >80% for calcium and vitamin D. Mean serum 25(OH)D concentration increased from 48 to 95 nmol/L in the treatment group (91% achieved >75 nmol/L), but remained unchanged in controls. There were no significant changes in insulin sensitivity, insulin secretion and β-cell function, or in inflammatory and metabolic markers between or within the groups, before or after adjustment for potential confounders including waist circumference and season of recruitment. In a post hoc analysis restricted to participants with prediabetes, a significant beneficial effect of vitamin D and calcium supplementation on insulin sensitivity (HOMA%S and Matsuda) was observed.ConclusionsDaily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity, insulin secretion and β-cell function in multi-ethnic adults with low vitamin D status at risk of type 2 diabetes. However, in participants with prediabetes, supplementation with vitamin D and calcium may improve insulin sensitivity.Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12609000043235

Effect of Vitamin D Supplementation on Some Inflammatory Biomarkers in Type 2 Diabetes Mellitus Subjects: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…After the intervention period, the mean TNF-α concentration decreased in 6 included studies, but an opposite trend was noted in the control group in 4 studies [25,27,28,34], other 2 studies [29,32] had similar trends in the control group. Nevertheless, only in 2 studies, the changes of TNF-α between the intervention group and the control group in the end of the intervention was statistically significant [28,29] (Table 2).…”

“…Compared with the baseline, vitamin D supplementation could increase the concentrations of 25(OH) D 3 in almost each of the intervention groups at the end of the trials achieving the mean levels between 17.6 ng/mL [22] and 95 ng/mL [27] (Table 2). There was no significant difference in FBG in the vitamin Characteristics of randomized controlled trials included in this meta-analysis Dalan et al [30] D intervention group between the baseline and the end of the trials (Table 2).…”

“…The vitamin D supplementation was used once a week in 2 studies [23,28]. The vitamin D supplementation combined with other supplements for intervention in 4 studies [24,[27][28]34] (Table 1).…”

Impact of vitamin D supplementation on C-reactive protein; a systematic review and meta-analysis of randomized controlled trials

“…In two of the studies, particciopants were summplemned with ergocalciferol at a dose of 50,000 IU at baseline for 26 [30] or 12 [31] weeks. In three studies, calcium supplements had also been administered in doses of 200 [32], 1000 [33], 1200 [34] mg/d, respectively.…”

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“…Henceforth it activates the pancreatic β cell function through the activation of Vitamin D receptor and by regulating peroxisome proliferator activated receptor (PPAR). Vitamin D may also affect insulin secretion and sensitivity indirectly by regulating extracellular calcium concentration in the beta cells and peripheral insulin-target tissues 10,11 Though arthritis is a major risk factor for the development of glucose intolerance and diabetes, prevalence and clinical associations are not well documented yet. Hence in the present study we planned to assess the role of vitamin D in the progression of prediabetes and other metabolic disorders in rheumatoid arthritis patients with prediabetic condition…”