Cholecalciferol Preserves Beta-Cell Function in Type 1 Patients

In the 38-patient study, those taking 2,000 IU of cholecalciferol every day were significantly more likely to maintain C-peptide secretion during 18 months of treatment compared to patients in a placebo group. (Given that C-peptide is a by-product of insulin production by pancreatic beta cells, the researchers used it as a marker of residual beta-cell function.)

According to Dr. Monica A. L. Gabbay of Sao Paolo Federal University and colleagues, the treatment group also had a higher levels of peripheral CCL2 (chemokine ligand 2) and more regulatory T cells, which together "may collaborate to delay the autoimmune destruction of the beta cells."

In a report of the study, they note that participants were all taking insulin, and all had fasting serum C-peptide levels of 0.6 ng/mL or higher at the study's outset.

Given the lack of potential toxicity of cholecalciferol, the supplement should be recommended for all patients with new onset disease (within six months of clinical diagnosis) and residual beta cell function.

Previous research has linked vitamin D3 supplementation to a lower risk of type 1 diabetes, Dr. Gabbay and her colleagues write, although two clinical trials found no effect of supplementation with 1,25(OH)2D3. "Nevertheless," they add, "the dose and mechanism of action of cholecalciferol in this condition are still under discussion."

At 18 months, 18.7% of the patients in the cholecalciferol group had undetectable fasting levels of C-peptide (0.1 ng/mL or less), compared to 62.5% of the placebo group. And 6.2% of cholecalciferol patients had undetectable levels of postmeal stimulated C-peptide at 18 months, compared to 37.5% of the placebo group.

At 12 months, mean CCL2 levels were higher in treated patients (184.6 vs. 121.4 pg/mL), as was regulatory T-cell percentage (4.55% vs 3.34%).

Dr. Gabbay's group will be tracking these patients to see how long the effect persists. The research team also wants to know if higher doses of vitamin D could produce better results, and whether adding vitamin D to other beta-cell-protecting drugs could help improve beta cell function in patients with residual beta cell function who have had type 1 diabetes for a longer period of time.

In an editorial, Dr. Sheela N. Magge of the Children's Hospital of Philadelphia, notes that, "Although the current study by Gabbay et al is a small, preliminary study, its significant effect on stimulated C-peptide level in such a small sample size is notable." She added that it's "somewhat worrisome" that patients treated with vitamin D3 had a 160% increase in IA-2 titers, despite a 60% drop in glutamic acid decarboxylase autoimmune antibodies.

Other questions raised by the study, Dr. Magge points out, include why vitamin D levels also increased in the placebo group, and why previous clinical trials using the active form of vitamin D in T1DM patients showed no effect.

"Despite these issues, the most encouraging aspect of the study by Gabbay et al is that supplementation with 2000 IU of vitamin D3, thought by most to be relatively harmless, may actually help preserve insulin secretion," Dr. Magge added.

Arch Pediatr Adolesc Med 2012;166:601-607