This letter concerns the secondary analysis (1) of the Vitamin D and Type 2 Diabetes (D2d) study (2). The D2d study was a randomized controlled trial to determine whether vitamin D supplementation (4,000 IU per day) reduced the risk of diabetes among adults with prediabetes (2). In an intention-to-treat analysis, vitamin D nonsignificantly reduced new-onset diabetes by 12% compared with the placebo (2). A secondary analysis was subsequently performed that evaluated hazard ratios (HRs) of developing diabetes in the entire cohort stratified by different achieved levels of vitamin D (1). When adjusted for treatment assignment only (vitamin D or placebo [model 1]) and compared with the cohort of achieving the vitamin D sufficient range of 50–75 nmol/L, those in the highest two cohorts of achieved vitamin D levels of 100–124 nmol/L and ≥125 nmol/L had significantly decreased HRs of 0.65 and 0.41, respectively (1). The results were progressively adjusted for the following potential confounders: baseline BMI, race (model 2); sex, age (model 3); baseline physical activity (model 4); and baseline statin use (model 5). All of these adjustments lowered the HRs of model 1 of the 100–124 nmol/L and ≥125 nmol/L cohorts by only 0.08 and 0.06, respectively, suggesting that these potential confounders did not play a large role.

Weight loss is the most important factor in delaying or preventing the development of diabetes in individuals with prediabetes (3). It seems possible that those participants who achieved the highest vitamin D levels in the D2d study were the most compliant with the supplementation, and therefore might also have been the most compliant with the lifestyle recommendations given to people with prediabetes. Could the authors provide us with the effect of weight change as a potential confounder in their secondary analysis of the D2d study?

Duality of Interest. No potential conflicts of interest relevant to this article were reported.

1.
Dawson-Hughes
B
,
Staten
MA
,
Knowler
WC
, et al.;
D2d Research Group
.
Intratrial exposure to vitamin D and new-onset diabetes among adults with prediabetes: a secondary analysis from the Vitamin D and Type 2 Diabetes (D2d) study
.
Diabetes Care
2020
;
43
:
2916
2922
.
2.
Pittas
AG
,
Dawson-Hughes
B
,
Sheehan
P
, et al
.
D2d Research Group. Vitamin D supplementation and prevention of type 2 diabetes
.
N Engl J Med
2019
;
381
:
520
530
3.
Knowler
WC
,
Barrett-Connor
E
,
Fowler
SE
, et al.;
Diabetes Prevention Program Research Group
.
Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin
.
N Engl J Med
2002
;
346
:
393
403
.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at https://www.diabetesjournals.org/content/license.