Vitamin D, insulin secretion, sensitivity, and lipids: results from a case-control study and a randomized controlled trial using hyperglycemic clamp technique

Abstract

Objective: Vitamin D deficiency is associated with an unfavorable metabolic profile in observational studies. The intention was to compare insulin sensitivity (the primary end point) and secretion and lipids in subjects with low and high serum 25(OH)D (25-hydroxyvitamin D) levels and to assess the effect of vitamin D supplementation on the same outcomes among the participants with low serum 25(OH)D levels.

Research design and methods: Participants were recruited from a population-based study (the Tromsø Study) based on their serum 25(OH)D measurements. A 3-h hyperglycemic clamp was performed, and the participants with low serum 25(OH)D levels were thereafter randomized to receive capsules of 20,000 IU vitamin D(3) or identical-looking placebo twice weekly for 6 months. A final hyperglycemic clamp was then performed.

Results: The 52 participants with high serum 25(OH)D levels (85.6 ± 13.5 nmol/L [mean ± SD]) had significantly higher insulin sensitivity index (ISI) and lower HbA(1c) and triglycerides (TGs) than the 108 participants with low serum 25(OH)D (40.3 ± 12.8 nmol/L), but the differences in ISI and TGs were not significant after adjustments. After supplementation, serum 25(OH)D was 142.7 ± 25.7 and 42.9 ± 17.3 nmol/L in 49 of 51 completing participants randomized to vitamin D and 45 of 53 randomized to placebo, respectively. At the end of the study, there were no statistically significant differences in the outcome variables between the two groups.

Conclusions: Vitamin D supplementation to apparently healthy subjects with insufficient serum 25(OH)D levels does not improve insulin sensitivity or secretion or serum lipid profile.

Trial registration: ClinicalTrials.gov NCT00809744.

FIG. 1.

Flowchart showing recruitment of participants, randomization, and completion.

FIG. 2.

Results from a 3-h hyperglycemic clamp in 104 subjects with low serum 25(OH)D (○) and 50 subjects with high serum 25(OH)D (■). A: Mean (95% CI) ln serum insulin. B: Mean (95% CI) infused glucose. C: Mean (95% CI) plasma glucose.

FIG. 3.

First phase insulin release (AUC 0–10 min), second phase insulin release (AUC 120–180 min), M, and ISI from a 3-h hyperglycemic clamp comparing participants with low and high serum 25(OH)D at baseline, and at baseline and after completion in the RCT. Data are geometric means. A: Subjects with low serum 25(OH)D (n = 104) (black bars) and high serum 25(OH)D (n = 50) (white bars) levels at baseline. B: Subjects with low serum 25(OH)D (n = 49) randomized to high dose vitamin D₃ at baseline (black bars) and after 6 months (white bars). C: Subjects with low serum 25(OH)D (n = 45) randomized to placebo at baseline (black bars) and after 6 months (white bars). *P < 0.05.

FIG. 4.

Baseline (A–C) and final (D–F) results in completers of the RCT comparing 6 months of high dose vitamin D₃ (n = 49) (■) and placebo (n = 45) (○) in vitamin D–insufficient participants. A and D: Mean (95% CI) ln serum insulin. B and E: Mean (95% CI) infused glucose. C and F: Mean (95% CI) plasma glucose.