Effect of vitamin D replacement on indexes of insulin resistance in overweight elderly individuals: a randomized controlled trial

Background: It is unclear whether and at what dose vitamin D supplementation affects insulin resistance (IR). Objective: We sought to investigate whether vitamin D at doses higher than currently recommended decreases indexes of IR in an ambulatory population of overweight elderly subjects. Design: This double-blind, randomized, controlled multicenter trial enrolled 257 elderly overweight individuals aged >= 65 y with baseline 25-hydroxyvitamin D [25(OH)D] concentrations between 10 and 30 ng/mL. All subjects received 1000 mg calcium citrate/d, with vitamin D administered weekly at an equivalent dose of 600 or 3750 IU/d. The homeostasis model assessment (HOMA) of IR index at 1 y was the primary outcome. We also assessed the McAuley index. Results: In total, 222 subjects (55% women) with a mean +/- SD age and body mass index (BMI; in kg/m(2)) of 71 +/- 4 y and 30 +/- 4, respectively, completed the study. Subjects' baseline characteristics, including IR indexes, were similar across groups: 69% had prediabetes, 54% had hypertension (47% were taking antihypertensive medications), and 60% had hyperlipidemia, nearly half of whom were receiving lipid-lowering drugs. At 1 y, mean 6 SD serum 25(OH) D increased from 20 +/- 7 to 26 +/- 7 ng/mL in the low-dose arm (P < 0.0001) and from 21 +/- 8 to 36 +/- 10 ng/mL in the high-dose arm (P < 0.001). Median HOMA-IR indexes did not change compared with baseline concentrations and were similar in the high-[2.2 (IQR: 1.5, 2.9)] and low-dose [2.3 (IQR: 1.6, 3.3] treatment groups. Adjusted analyses showed that HOMA-IR was predicted by the baseline HOMA index and BMI but not by vitamin D dose, baseline serum 25(OH)D, or change in 25(OH)D. Conclusion: Vitamin D3 at 3750 IU/d did not improve HOMA-IR compared with the Institute of Medicine Recommended Dietary Allowance of 600 IU/d in elderly overweight individuals.