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 Nutrition. Abstract available on PubMed