Table 2.
Effects of vitamin D intervention on insulin secretion and sensitivity/resistance. To convert nmol/L to ng/mL, divide by 2.496. 25(OH)D: 25-hydroxyvitamin D; OGTT: oral glucose tolerance test; IVGTT: intravenous glucose tolerance test; T2DM: type 2 diabetes mellitus; 1, 25(OH)2 D3: 1,25-dihydroxyvitamin D3 or calcitriol; HOMA-β: homeostasis model assessment of β-cell function; NFG: normal fasting glucose; IFG: impaired fasting glucose; HOMA-IR: homeostasis model assessment of insulin resistance; HbA1c: glycosylated hemoglobin.
| Author, year (ref) | Subject characteristics | Baseline 25(OH)D | Determinant of insulin/glucose metabolism | Route, dose, and form of vitamin D administration | Length of intervention | Follow-up 25(OH)D | Outcome | Major limitations |
|---|---|---|---|---|---|---|---|---|
| (a) Insulin secretion | ||||||||
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| ||||||||
| Gedik et al. 1986 [65] | 4 vitamin D deficient women (Turkey), mean age: 32.7 years, mean BMI: 22.8 kg/m2 | — | OGTT | Oral, 2000 IU/d cholecalciferol | 6 months | — | Increased insulin area and insulinogenic index | Not randomized, placebo-controlled; 25(OH)D not assessed; small sample size |
| Boucher et al. 1995 [41] | 22 glucose-intolerant East London Asians, mean age 44.9 years, mean BMI: 25.9 kg/m2) | 9.0 ± 4.5 nmol/L | OGTT | Intravenous, 100,000 IU cholecalciferol | Single dose, follow-up 8–12 weeks later | 33.7 ± 18.5 nmol/L | Increase in postchallenge insulin and C-peptide | Not randomized, placebo-controlled |
| Borissova 2003 [66] | 10 Bulgarian women with T2DM, mean age: 53.8 years, mean BMI: 30.9 kg/m2 | 35.3 ± 15.1 nmol/L | IVGTT | Oral, 1332 IU cholecalciferol/d | 1 month | 63.3 ± 31 nmol/L | Increased first-phase insulin secretion | Not randomized, placebo-controlled; small sample size |
| Inomata et al. 1986 [67] | 14 Japanese T2DM subjects, mean age 54.3 years | — | OGTT | 2 μg/d alphacalcidiol versus placebo | 3 weeks | — | Improved insulin secretion (area under the curve) and reduced free fatty acid concentrations | 25(OH)D not reported; small sample size |
| Zofková and Stolba 1990 [68] | 13 vitamin D-sufficient adults, mean age: 33.4 years (ethnicity not reported) | — | IVGTT | Oral, 3 μg/d 1,25(OH)2D3 | 4 days | — | No change in insulin secretion | Not randomized, placebo-controlled; 25(OH)D not reported; small sample size |
| Orwoll et al. 1994 [42] | 35 adults with T2DM, mean age: 61 years, mean BMI: 29.8 kg/m2 (ethnicity not reported) | 35 ± 7 nmol/L | Meal challenge | 1 μg/d 1, 25(OH)2D versus placebo | 4 days | — | No change, but tendency towards better insulin secretion in recently diagnosed subjects (within 3 years) | Postintervention 25(OH)D not assessed |
| Jorde and Figenschau 2009 [69] | 32 Norwegian adults with insulin and metformin-controlled T2DM, ages 21–75, mean BMI: 32.8 kg/m2 (treatment), 31.3 kg/m2 (placebo) | 60 ± 14 nmol/L (treatment) 58.5 ± 21 nmol/L (placebo) | Fasting insulin and glucose (HOMA-β) and c-peptide | 40,000 IU cholecalciferol/wk versus placebo | 6 months | 118.3 nmol/L (treatment) 57.2 nmol/L (placebo) | No change in insulin secretion | Sample size insufficient based on power calculations; indirect measure of insulin secretion |
| Nagpal et al. 2009 [70] | 100 Asian Indian, centrally-obese males, age ≥ 35 years, BMI: 26.7 kg/m2 (treatment), 26 kg/m (placebo) | 36.5 ± 14.6 nmol/L (treatment) 30 ± 12.5 nmol/L (placebo) | Fasting insulin and glucose (HOMA-β) | Oral, 3 doses of 120,000 IU cholecalciferol fortnightly versus placebo | 6 weeks | 71.6 nmol/L (treatment) 30.6 nmol/L (placebo) | No change in insulin secretion | Indirect measure of insulin secretion |
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| (b) Insulin sensitivity | ||||||||
|
| ||||||||
| De Boer et al. 2008 [71] | 795–866 postmenopausal women of various ethnicities, ages 50–79 years | 43.7 nmol/L (median) | Fasting insulin and glucose (HOMA-IR) | Oral, 400 IU cholecalciferol + 1000 mg calcium versus placebo | 6 years | — | No change in fasting glucose, insulin, or HOMA-IR; no change in diabetes risk | Postintervention 25(OH)D not reported; indirect measure of insulin sensitivity |
| Nilas and Christiansen 1984 [72] | 151 Danish postmenopausal women, ages 45–54 years | — | Blood glucose | Oral, 2000 IU/d cholecalciferol + 500 mg/d calcium versus 0.25 μg/d alphacalcidiol + 500 mg/d calcium versus placebo | 2 years | — | No change in blood glucose | 25(OH)D not reported; indirect measure of insulin sensitivity |
| Jorde and Figenschau 2009 [69] | 32 Norwegian adults with insulin and metformin-controlled T2DM, ages 21–75, mean BMI: 32.8 kg/m2 (treatment), 31.3 kg/m2 (placebo) | 60 ± 14 nmol/L (treatment) 58.5 ± 21 nmol/L (placebo) | Fasting insulin and glucose (HOMA-IR) | 40,000 IU cholecalciferol/wk versus placebo | 6 months | 118.3 nmol/L (treatment) 57.2 nmol/L (placebo) | No change in fasting glucose, insulin, HOMA-IR, or HbA1c | Sample size insufficient based on power calculations; indirect measure of insulin sensitivity |
| Borissova et al. 2003 [66] | 10 Bulgarian women with T2DM, mean age: 53.8 years, mean BMI: 30.9 kg/m2 | 35.3 ± 15.1 nmol/L | Fasting insulin and glucose (HOMA-IR) | Oral, 1332 IU cholecalciferol/d | 1 month | 63.3 ± 31.0 nmol/L | Nonsignificant decrease in HOMA-IR | Not randomized, placebo-controlled; indirect measure of insulin sensitivity |
| Pittas et al. 2007 [73] | 314 Caucasian American adults, mean age: 71.2 years, mean BMI: 26.7 kg/m2 | Treatment: 81.4 ± 3.7 nmol/L (NFG), 71.2 ± 5.2 nmol/L (IFG); Placebo: 70.6 ± 2.8 nmol/L (NFG), 81.2 ± 4.7 (IFG) | Fasting insulin and glucose (HOMA-IR) | Oral, 700 IU cholecalciferol + 500 mg calcium versus placebo | 3 years | Treatment: 111 nmol/L (NFG), 102.4 nmol/L (IFG); Placebo: 69.7 nmol/L (NFG), 73.4 nmol/L (IFG) | Improved HOMA-IR in subjects with IFG | Indirect measure of insulin sensitivity |
| Nagpal et al. 2009 [70] | 100 Asian Indian, centrally-obese males, age ≥ 35 years, BMI: 26.7 kg/m (treatment), 26 kg/m2 (placebo) | 36.5 ± 14.6 nmol/L (treatment) 30 ± 12.5 nmol/L (placebo) | OGTT | Oral, 3 doses of 120,000 IU cholecalciferol fortnightly versus placebo | 6 weeks | 71.6 nmol/L (treatment) 30.6 nmol/L (placebo) | Increased insulin sensitivity (3-hour oral glucose insulin sensitivity index); no change in indices derived from fasting glucose and insulin values | Indirect measure of insulin sensitivity |
| Tai et al. 2008 [74] | 33 primarily Caucasian adults, mean age 55 years, mean BMI: 24.1 kg/m2 | 39.9 ± 8.6 nmol/L | OGTT, fasting insulin and glucose | Oral, 2 doses of 100,000 IU cholecalciferol | 1 month (Follow-up 2 weeks after 2nd dose) | 90.3 ± 4.3 nmol/L | No change in fasting glucose, postchallenge insulin, Avignon's insulin sensitivity, QUICKI, or HOMA-IR | Not randomized, placebo-controlled; indirect measures of insulin sensitivity |
| Nyomba et al. 1986 [75] | 10 Belgian subjects with epilepsy (mean age: 56 years), and 15 elderly subjects (mean age: 78 years) | 17 ± 9.5 nmol/L; 19 ± 19.4 nmol/L | OGTT | Oral, 25(OH)D loading dose of 200 μg + 10 μg/d | 2 weeks | 36 ± 6 nmol/L 35 ± 3 nmol/L | Decrease in fasting insulin and postchallenge insulin only in subjects with epilepsy | Not randomized, placebo-controlled; small sample size; indirect measure of insulin sensitivity |
| Lind et al. 1989 [52] | 14 normal-weight, Danish men with impaired glucose tolerance, ages 60–63 years | — | IVGTT | Oral, 2 μg/d alphacalcidiol | 18 months | 78 ± 43 nmol/L | No change in insulin sensitivity | Not randomized, placebo-controlled; baseline 25(OH)D not assessed; small sample size |
| Ljunghall et al. 1987 [76] | 65 vitamin D sufficient, Caucasian men with impaired glucose tolerance, ages 61–65 years, mean BMI: 27.5 kg/m2 (treatment), 28.2 kg/m2 (placebo) | 92.4 ± 23.5 nmol/L (treatment) 97.3 ± 72.4 nmol/L (placebo) | IVGTT | Oral, 0.75 μg/d alphacalcidiol versus placebo | 3 months | 104.8 ± 20.7 nmol/L (treatment) 134.8 ± 119.8 nmol/L (placebo) | No change in insulin sensitivity | — |
| Fliser et al. 1997 [77] | 18 healthy German males, mean age: 26 years, mean BMI: 22.4 kg/m2 | — | Euglycemic clamp | Oral, 1.5 μg 1,25(OH)D/d versus placebo | 7 days | — | No change in insulin sensitivity | 25(OH)D not reported; small sample size |