Completed Studies

Calcium and Vitamin for type 2 Diabetes Mellitus (CaDDM) Study

The Calcium and Vitamin D for type 2 Diabetes Mellitus  (CaDDM) study, funded by NIDDK grant R01DK076092, was a randomized clinical trial that examined the effects of vitamin D and/or calcium supplementation on cardiometabolic outcomes. The 2×2 factorial design tested the effect of vitamin D3 (2,000 IU once daily) and calcium carbonate (400 mg twice daily) supplementation on disposition index, an IVGTT-derived composite measure of beta cell function that accounts for insulin sensitivity, in participants with pre-diabetes.

In the CADDM study, adults at risk for type 2 diabetes or with early diabetes (not on medications) were randomized to receive 2,000 IU/day of vitamin D3 and/or 800 mg/day of calcium carbonate (2×2 factorial design) for 4 months.   The primary outcome was disposition index.  Secondary outcomes included: insulin sensitivity and insulin secretion, glucose tolerance, systemic inflammation, lipoprotein profile and blood pressure.

Results. Mean age was 57 years, BMI was 33 Kg/m2 and HbA1c was 5.9%, consistent with a pre-diabetes population. Vitamin D supplementation achieved a clear difference in 25OHD between vitamin D and no vitamin D arms of ~12 ng/mL (30.6 for vitamin D vs. 18.4 for no vitamin D; p<0.001). Both non-whites (n=20) and whites (n=72) responded to vitamin D, but the 25OHD difference between arms was larger in non-whites (~17 ng/mL) vs. whites (~11 ng/mL).

Vitamin D improved the primary outcome, disposition index (adjusted mean change from baseline, +300 in vitamin D vs. -126 in placebo; p=0.011). This represents an improvement of ~26% in the vitamin D arm vs. a worsening of ~14% in the no vitamin D arm. Consistent changes were observed in acute insulin release to glucose (AIRg) and insulin sensitivity (Si) (change in AIRg +62 vs. -36; p=0.046; change in Si, +76 in active vs. -44 in placebo; p=0.082) but only the difference in AIRg was statistically significant, indicating a predominant effect of vitamin D on beta cell function. The change in disposition index was consistent in whites (+156 for vitamin D vs. -136 for placebo) and non-whites (+326 vs. +58) indicating that the effect of vitamin D supplementation is independent of race.

Importantly, although the study was not powered for glycemic outcomes, HbA1c was lower – but not statistically significant – in the vitamin D arm (adjusted mean difference in HbA1c between the two arms -0.08%; p=0.081). Calcium supplementation alone did not have any significant effect on either disposition index or HbA1c and there was no vitamin D x calcium interaction. Results were published in the American Journal of Clinical NutritionAbstract available on PubMed

Ancillary Study to Nurses Health Study (NHS)

The Vitamin D Status and Incident Type 2 Diabetes study, funded by NIDDK grant R01DK078867, was an ancillary analysis within the Nurses Health Study, an ongoing large observational cohort in women, to assess the longitudinal association between vitamin D status and risk of developing type 2 diabetes. The working hypothesis was that vitamin D status, as measured by serum 25-hydroxyvitamin D level, is inversely associated with type 2 diabetes risk. The association was quantified in a nested case-control study design (600 cases of type 2 diabetes and 600 controls – matched by age and season of blood draw).

Results: After multivariate adjustment, including body mass index higher 25-hydroxyvitamin D concentration was associated with lower risk of type 2 diabetes. The odds ratio (OR) for incident diabetes in the top quartile of 25-hydroxyvitamin D (mean 33 ng/mL) vs. the bottom quartile (mean 14 ng/mL) was 0.52 (95%CI 0.33 to 0.83). The association was stronger among overweight/obese vs. normal weight women (OR 0.46 vs. 0.63 respectively). Spline regression models showed no apparent threshold and no deviation from linearity for the relation between 25-hydroxyvitamin D and incident diabetes, although the shape of the association suggested a stronger decrease in risk within the higher range of plasma 25-hydroxyvitamin D concentration, above 30-35 ng/mL. Results were published in Diabetes CareAbstract available on PubMed

Ancillary Study to Diabetes Prevention Program (DPP)

The Vitamin D Status in Relation to Incident Type 2 Diabetes and Cardiometabolic Risk study, funded by NIDDK grant R01DK079003, is an ancillary study to the Diabetes Prevention Program (DPP) with the following aims: (1) Measure the association between vitamin D status, as 25-hydroxyvitamin D, and incident t2DM [prospective analyses] in a case-cohort study design in adults within the Lifestyle and Placebo arms of the DPP. (2). Measure the association between vitamin D status and development of metabolic syndrome (and its individual components) and macrovascular disease [prospective analyses]. (3). Measure the association between vitamin D status and insulin secretion, insulin sensitivity and systemic inflammation [cross-sectional analyses].

Results: After multivariate adjustment, including for the DPP intervention, there was an inverse association between 25-hydroxyvitamin D and incident diabetes without an apparent plateau with the hazard ratio for incident diabetes being lowest (0.40; 95%CI, 0.20 to 0.81) in the highest (≥50 ng/mL) compared to the lowest category (<12 ng/mL) of 25-hydroxyvitamin D. The association was in the same direction in placebo vs. lifestyle arm and among whites vs. non-whites. Results were published in Diabetes CareAbstract available on PubMed

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