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Effects of vitamin D and calcium supplementation on pancreatic ? cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial.

ABSTRACT: BACKGROUND:A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies, but evidence from trials is lacking. OBJECTIVE:We determined whether vitamin D supplementation, with or without calcium, improved glucose homeostasis in adults at high risk of diabetes. DESIGN:Ninety-two adults were randomly assigned in a 2-by-2 factorial-design, double-masked, placebo-controlled trial to receive either cholecalciferol (2000 IU once daily) or calcium carbonate (400 mg twice daily) for 16 wk. The primary outcome was the change in pancreatic ? cell function as measured by the disposition index after an intravenous-glucose-tolerance test. Other outcomes were acute insulin response, insulin sensitivity, and measures of glycemia. RESULTS:Participants had a mean age of 57 y, a body mass index (BMI; in kg/m(2)) of 32, and glycated hemoglobin (Hb A(1c)) of 5.9%. There was no significant vitamin D × calcium interaction on any outcomes. The disposition index increased in the vitamin D group and decreased in the no-vitamin D group (adjusted mean change ± SE: 300 ± 130 compared with -126 ± 127, respectively; P = 0.011), which was explained by an improvement in insulin secretion (62 ± 39 compared with -36 ± 37 mU · L(-1) · min, respectively; P = 0.046). Hb A(1c) increased less, but nonsignificantly, in the vitamin D group than in the no-vitamin D group (0.06 ± 0.03% compared with 0.14 ± 0.03%, respectively; P = 0.081). There was no significant difference in any outcomes with calcium compared with no calcium. CONCLUSION:In adults at risk of type 2 diabetes, short-term supplementation with cholecalciferol improved ? cell function and had a marginal effect on attenuating the rise in Hb A(1c). This trial was registered at clinicaltrials.gov as NCT00436475.

SUBMITTER: Mitri J

PROVIDER: S-EPMC3142723 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature

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Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial.

Mitri Joanna J Dawson-Hughes Bess B Hu Frank B FB Pittas Anastassios G AG

The American journal of clinical nutrition 20110629 2

<h4>Background</h4>A suboptimal vitamin D and calcium status has been associated with higher risk of type 2 diabetes in observational studies, but evidence from trials is lacking.<h4>Objective</h4>We determined whether vitamin D supplementation, with or without calcium, improved glucose homeostasis in adults at high risk of diabetes.<h4>Design</h4>Ninety-two adults were randomly assigned in a 2-by-2 factorial-design, double-masked, placebo-controlled trial to receive either cholecalciferol (2000 ...[more]

PMID: 21715514

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Project description:To examine whether combined vitamin D and calcium supplementation improves insulin sensitivity, insulin secretion, ?-cell function, inflammation and metabolic markers.6-month randomized, placebo-controlled trial.Ninety-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).Daily 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.Insulin sensitivity (HOMA2%S, Matsuda index), insulin secretion (insulinogenic index, area under the curve (AUC) for C-peptide) and ?-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-?; IL-6; adiponectin; total and undercarboxylated osteocalcin.Participants 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 ?-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.Daily vitamin D and calcium supplementation for 6 months may not change OGTT-derived measures of insulin sensitivity, insulin secretion and ?-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.Australian New Zealand Clinical Trials Registry ACTRN12609000043235.

Project description:Background: The prevalence of type 2 diabetes has increased dramatically in recent decades. Increasing brown adipose tissue (BAT) mass and activity has recently emerged as an interesting approach to not only increase energy expenditure, but also improve glucose homeostasis. BAT can be recruited by prolonged cold exposure in lean, healthy humans. Here, we tested whether cold acclimation could have therapeutic value for patients with type 2 diabetes by improving insulin sensitivity. Methods: Eight type 2 diabetic patients (age 59.3±5.8 years, BMI 29.8±3.2 kg/m2) followed a cold acclimation protocol, consisting of intermittent cold exposure (6 hours/day, 14-14.5 °C) for 12 consecutive days. Before and after cold acclimation, cold-induced BAT activity was assessed by [18F]FDG-PET/CT scanning, insulin sensitivity at thermoneutrality by a hyperinsulinemic-euglycemic clamp, and muscle and WAT biopsies were taken. Results: Cold-induced BAT activity was low, but increased in all patients upon cold acclimation (SUV from 0.40±0.29 to 0.63±0.78, p<0.05). Interestingly, insulin sensitivity showed a very pronounced 40% increase upon cold acclimation (glucose rate of disappearance from 14.9±4.1 to 20.5±6.9 μmol kg-1 min-1, p<0.05). A 40% increase in insulin sensitivity cannot be explained by BAT glucose uptake, in fact basal skeletal muscle GLUT4 content and translocation was markedly increased after cold acclimation, without effects on insulin signaling or AMPk activation. Conclusions: Regular mild cold exposure has marked effects on insulin sensitivity, which are accompanied by small increases in BAT activity and more pronounced effects on skeletal muscle. These data suggest a novel therapeutic option for the treatment of type 2 diabetes. Microarray analysis was performed on abdominal subcutaneous white adipose tissue samples from human type 2 diabetic patients before, and after 10 days of cold acclimation. A total of 14 samples, from 7 subjects, were used for the microarray analysis.

Project description:Background This study investigated whether single nucleotide polymorphisms (SNPs) reported by previous genome-wide association studies (GWAS) to be associated with impaired insulin secretion, insulin resistance, and/or type 2 diabetes are associated with disposition index, the homeostasis model assessment of insulin resistance (HOMA-IR), and/or development of diabetes following a pregnancy complicated by gestational diabetes mellitus (GDM). Methods Seventy-two SNPs were genotyped in 374 women with previous GDM from Southern Sweden. An oral glucose tolerance test was performed 1–2 years postpartum, although data on the diagnosis of diabetes were accessible up to 5 years postpartum. HOMA-IR and disposition index were used to measure insulin resistance and secretion, respectively. Results The risk A-allele in the rs11708067 polymorphism of the adenylate cyclase 5 gene (ADCY5) was associated with decreased disposition index (beta = − 0.90, SE 0.38, p = 0.019). This polymorphism was an expression quantitative trait loci (eQTL) in islets for both ADCY5 and its antisense transcript. The risk C-allele in the rs2943641 polymorphism, near the insulin receptor substrate 1 gene (IRS1), showed a trend towards association with increased HOMA-IR (beta = 0.36, SE 0.18, p = 0.050), and the T-allele of the rs4607103 polymorphism, near the ADAM metallopeptidase with thrombospondin type 1 motif 9 gene (ADAMTS9), was associated with postpartum diabetes (OR = 2.12, SE 0.22, p = 0.00055). The genetic risk score (GRS) of the top four SNPs tested for association with the disposition index using equal weights was associated with the disposition index (beta = − 0.31, SE = 0.29, p = 0.00096). In addition, the GRS of the four SNPs studied for association with HOMA-IR using equal weights showed an association with HOMA-IR (beta = 1.13, SE = 0.48, p = 9.72874e−11). All analyses were adjusted for age, body mass index, and ethnicity. Conclusions This study demonstrated the genetic susceptibility of women with a history of GDM to impaired insulin secretion and sensitivity and, ultimately, to diabetes development.

Dataset Information

Effects of vitamin D and calcium supplementation on pancreatic ? cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial.

Publications

Effects of vitamin D and calcium supplementation on pancreatic β cell function, insulin sensitivity, and glycemia in adults at high risk of diabetes: the Calcium and Vitamin D for Diabetes Mellitus (CaDDM) randomized controlled trial.

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