Response to Comment on Krul-Poel et al. Effect of Vitamin D Supplementation on Glycemic Control in Patients With Type 2 Diabetes (SUNNY Trial): A Randomized Placebo-Controlled Trial. Diabetes Care 2015;38:1420–1426

We thank Bellastella et al. (1) for their interest in our recently published double-blind, randomized, placebo-controlled trial in patients with type 2 diabetes who were treated with either vitamin D₃ (50,000 IU/month) or placebo for 6 months (2). These patients were well controlled at baseline (HbA_1c was 6.8 ± 0.5% [51 ± 6 mmol/mol] and 6.8 ± 0.5% [51 ± 5 mmol/mol] in the vitamin D and placebo groups, respectively). After 6 months of treatment with vitamin D, no improvement was seen in the glycemic control despite an adequate increase of serum 25-hydroxyvitamin D [25(OH)D] (60.6 nmol/L at baseline to 101.4 nmol/L at 6 months). As mentioned by Bellastella et al., a small subgroup of patients with severe vitamin D deficiency [serum 25(OH)D <30 nmol/L] had a small but statistically significant decrease in HbA_1c.

We acknowledge that the effect of treatment is higher in patients with high HbA_1c at baseline (3). The small study performed by Soric et al. (4) showed that treatment with vitamin D₃ (2,000 IU daily) for 12 weeks did not improve the glycemic control when the baseline HbA_1c was between 7.0 and 7.9% (in six patients) and between 8.0 and 8.9% (in five patients). In five patients with HbA_1c ≥9.0%, an HbA_1c decrease of 1.4% was seen. Unfortunately, no serum 25(OH)D levels were reported at baseline or after treatment Taken together, evidence from the trials shows no effect of vitamin D₃ supplementation on glycemic control in patients with type 2 diabetes. Nevertheless, studies including patients with severe vitamin D deficiency and/or poorly regulated type 2 diabetes are necessary.

Age-related declines of testosterone and other anabolic hormones are well described and have been linked to increased diabetes risk. As the vitamin D receptor is also expressed in the testis (and the hypothalamus and pituitary gland), serum vitamin D levels may have an effect on gonadal functioning, especially in those with type 2 diabetes (5). Unfortunately, we did not measure the testosterone levels, but we will do so in the near future.