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 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
) 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
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
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 μ g/d
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
(ethnicity not reported) 35
7 nmol/L Meal challenge 1 μ g/d
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
(treatment), 31.3
(placebo) 60
14 nmol/L (treatment) 58.5
21 nmol/L (placebo) Fasting insulin and glucose (HOMA-
) 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
(treatment), 26
(placebo) 36.5
14.6 nmol/L (treatment) 30
12.5 nmol/L (placebo) Fasting insulin and glucose (HOMA-
) 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 (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
alphacalcidiol
500
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
(treatment), 31.3
(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
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
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
(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
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
g
10
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
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
(treatment), 28.2
(placebo) 92.4
23.5 nmol/L (treatment) 97.3
72.4 nmol/L (placebo) IVGTT Oral, 0.75
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
— Euglycemic clamp Oral, 1.5
1,25(OH)D/d versus placebo 7 days — No change in insulin sensitivity 25(OH)D not reported; small sample size
