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)DDeterminant of insulin/glucose metabolismRoute, dose, and form of vitamin D administration Length of intervention Follow-up 25(OH)D OutcomeMajor 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/m2OGTTOral, 2000 IU/d cholecalciferol6 monthsIncreased insulin area and insulinogenic indexNot 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/LOGTTIntravenous, 100,000 IU cholecalciferolSingle dose, follow-up 8–12 weeks later33.7 18.5 nmol/LIncrease in postchallenge insulin and C-peptideNot 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/LIVGTTOral, 1332 IU cholecalciferol/d1 month63.3 31 nmol/LIncreased first-phase insulin secretionNot randomized, placebo-controlled; small sample size
Inomata et al. 1986 [67]14 Japanese T2DM subjects, mean age 54.3 yearsOGTT2  alphacalcidiol versus placebo3 weeksImproved insulin secretion (area under the curve) and reduced free fatty acid concentrations25(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)IVGTTOral, 3 μg/d 4 daysNo change in insulin secretionNot 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/LMeal challenge1 μg/d versus placebo4 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-peptide40,000 IU cholecalciferol/wk versus placebo6 months118.3 nmol/L (treatment) 57.2 nmol/L (placebo)No change in insulin secretionSample 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 placebo6 weeks71.6 nmol/L (treatment) 30.6 nmol/L (placebo)No change in insulin secretionIndirect measure of insulin secretion

(b) Insulin sensitivity

De Boer et al. 2008 [71]795–866 postmenopausal women of various ethnicities, ages 50–79 years43.7 nmol/L (median)Fasting insulin and glucose (HOMA-IR)Oral, 400 IU cholecalciferol 1000 mg calcium versus placebo6 yearsNo change in fasting glucose, insulin, or HOMA-IR; no change in diabetes riskPostintervention 25(OH)D not reported; indirect measure of insulin sensitivity
Nilas and Christiansen 1984 [72]151 Danish postmenopausal women, ages 45–54 yearsBlood glucoseOral, 2000 IU/d cholecalciferol 500 mg/d calcium versus 0.25  alphacalcidiol 500  calcium versus placebo2 yearsNo change in blood glucose25(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 placebo6 months118.3 nmol/L (treatment) 57.2 nmol/L (placebo)No change in fasting glucose, insulin, HOMA-IR, or HbA1cSample 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/LFasting insulin and glucose (HOMA-IR)Oral, 1332 IU cholecalciferol/d1 month63.3 31.0 nmol/LNonsignificant decrease in HOMA-IRNot 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 placebo3 yearsTreatment: 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 IFGIndirect 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)OGTTOral, 3 doses of 120,000 IU cholecalciferol fortnightly versus placebo6 weeks71.6 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 valuesIndirect 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/LOGTT, fasting insulin and glucoseOral, 2 doses of 100,000 IU cholecalciferol1 month (Follow-up 2 weeks after 2nd dose)90.3 4.3 nmol/LNo change in fasting glucose, postchallenge insulin, Avignon’s insulin sensitivity, QUICKI, or HOMA-IRNot 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/LOGTTOral, 25(OH)D loading dose of 200  g 10 2 weeks36 6 nmol/L 35 3 nmol/LDecrease in fasting insulin and postchallenge insulin only in subjects with epilepsyNot 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 yearsIVGTTOral, 2  alphacalcidiol18 months78 43 nmol/LNo change in insulin sensitivityNot 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)IVGTTOral, 0.75  alphacalcidiol versus placebo3 months104.8 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 clampOral, 1.5  1,25(OH)D/d versus placebo7 daysNo change in insulin sensitivity25(OH)D not reported; small sample size