Table 1: Reported associations of 25(OH)D with 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; T2DM: type 2 diabetes mellitus; NHANES III: National Health and Nutrition Examination Survey 1988–1994; CA: Caucasian American; AA: African American; MA: Mexican American; HOMA- : homeostasis model assessment of -cell function; HOMA-IR: homeostasis model assessment of insulin resistance; QUICKI: quantitative insulin sensitivity check index; HbA1c: glycosylated hemoglobin; WHR: waist-to-hip ratio; BIA: bioelectrical impedance.

Author, year (ref)Subjects’ characteristics Mean serum 25(OH)D Method to determine insulin outcomesAssociation of 25(OH)D with insulin outcomeCovariatesMajor limitations

(a) Insulin Secretion

Boucher 1995 [41]44 glucose-intolerant East London Asians, mean age 44.9 years, mean BMI: 25.9  27.5 nmol/LOGTTPositive association with postchallenge C-peptide and insulinAge, sex, BMINo measure of dietary intake or physical activity; indirect measures of adiposity and insulin secretion
Orwoll et al. 1994 [42]35 adults with T2DM, mean age: 61 years, mean BMI: 29.8  (ethnicity not reported) 35 7 nmol/LMeal challengeNo association with fasting or postchallenge glucose, insulin, C-peptide, or glucagonIndirect measure of insulin secretion; no adjustment for confounders
Scragg et al. 2004 [5]6228 NHANES participants (Caucasian, African, and Mexican American), ages 20 years79.6 36.8 nmol/L (CA) 49.1 37.5 nmol/L (AA) 66.0 41.5 nmol/L (MA)Fasting glucose and insulin (HOMA- )No association with HOMA- Age, sex, BMI, physical activity, season, HOMA-IRNo measure of dietary intake; indirect measures of adiposity and insulin secretion
Baynes et al. 1997 [4]142 Dutch men, mean age: 75.7 years42 29.1 nmol/LOGTTInverse association with postchallenge glucose and insulinSeason, physical activity, BMI, skinfolds, smoking, alcohol, and fish, fat, and oil consumptionNo adjustment for calcium consumption; indirect measure of adiposity
Chiu 2004 et al. [43]126 glucose-tolerant Asian, African, Caucasian, and Mexican American, mean age 26 6 years, mean BMI: 24.7  46.9 nmol/L (Asian American), 47.3 nmol/L (AA), 69.4 nmol/L (CA), 50.2 nmol/L (MA)Hyperglycemic clampInverse association with first- and second-phase insulin response (not significant after adjustment for insulin sensitivity index)Age, sex, ethnicity, BMI, WHR, blood pressure, season, insulin sensitivity indexNo measure of dietary intake or physical activity; indirect measure of adiposity
Kamycheva et al. 2007 [40]15 Norwegian subjects with secondary hyperparathyroidism, mean age: 62.9 years, mean BMI: 27.1  ; 15 sex-, age-, and BMI-matched controls58.4 nmol/L (patients) 61.9 nmol/L (controls)Hyperglycemic clampInverse association with 2nd phase insulin secretionSex, age, BMINo measure of dietary intake or physical activity; indirect measure of adiposity

(b) Insulin sensitivity/resistance

Scragg et al. 2004 [5]6228 NHANES participants (Caucasian, African, and Mexican American), ages 20 years79.6 36.8 nmol/L (CA) 49.1 37.5 nmol/L (AA) 66.0 41.5 mol/L (MA)Fasting glucose and insulin (HOMA-IR)Inverse association with HOMA-IR in Caucasian ( ) and Mexican Americans ( )Age, sex, BMI, physical activity, seasonNo measure of dietary intake; indirect measures of adiposity and insulin sensitivity
Chonchol and Scragg 2007 [45]14697 NHANES participants (Caucasian, African, and Mexican American), ages ≥ 20 years78 58.4 nmol/L (men) 71.6 61.5 nmol/L (women)Fasting glucose and insulin (HOMA-IR)Inverse association with fasting insulin and HOMA-IRAge, sex, ethnicity, BMINo measure of dietary intake or physical activity; indirect measures of adiposity and insulin sensitivity
Lu et al. 2009 [48]3262 Chinese adults (Nutrition and Health of Aging Population in China study), ages 50–70 years40.4 nmol/LFasting insulin  and glucose (HOMA-IR)Inverse association with fasting glucose, HbA1c, fasting insulin, and HOMA-IR.Age, sex, residence, season, education, physical activity, smoking, alcohol, family history, CRP, IL-6, BMINo measure of dietary intake; indirect measures of adiposity and insulin sensitivity
Gannagé-Yared et al. 2009 [47]381 Lebanese university students; ages 18–30 years; mean BMI: 23.9 4.1  77.4 31.2 nmol/LFasting insulin  and glucose (HOMA-IR)Inverse association with fasting glucose, fasting insulin, and HOMA-IR. Only glucose held after adjustment for all confounders.Sex, BMI, exerciseNo measure of dietary intake; indirect measures of adiposity and insulin sensitivity
Clifton-Bligh et al. 2008 [49]307 pregnant women of various ethnicities, mean age: 32.6 years53.8 23.9 nmol/LFasting insulin  and glucose (HOMA-IR)Inverse association with fasting insulin, glucose, and HOMA-IR but not after adjustment for confoundersAge, BMI, ethnicityNo measure of dietary intake or physical activity; indirect measures of adiposity and insulin sensitivity
Alemzadeh et al. 2008 [49]127 children (Caucasian, Mexican, and African American), mean age: 13 years, BMI 95th percentile for age59.9 23.2 nmol/LFasting insulin  and glucose (QUICKI), HbA1cInverse association with HbA1c, but not after adjustment for confoundersFat mass (BIA), age, sex, ethnicity, seasonNo measure of dietary intake or physical activity; indirect measures of adiposity and insulin sensitivity
McGill et al. 2008 [46]243 adults of various ethnicities (New Zealand), mean age: 47.6 years, mean BMI: 35.4  62.2 22.7 nmol/LFasting glucose  and HbA1cInverse association with HbA1c  and glucose (negated after removal of 3 outliers)Sex, age, ethnicity, season, BMINo measure of dietary intake or physical activity; indirect measures of adiposity and insulin sensitivity
Ford et al. 2005 [53]8421 NHANES participants, ages 20 years, multiple ethnicities74 nmol/L (range: 8.7–227.9 nmol/L)Fasting glucoseInverse association with fasting glucoseAge, sex, ethnicity, education, smoking, cotinine, cholesterol, abdominal obesity, triglyceridemia, low HDL, high blood pressureNo measure of dietary intake or physical activity; indirect measures of adiposity and insulin sensitivity
Need et al. 2005 [63]753 postmenopausal Caucasian (Australian) women, mean age: 63 years, mean BMI: 26.5  62 24.3 nmol/LFasting glucoseInverse association with fasting glucoseAge, BMINo measure of dietary intake or physical activity; indirect measures of adiposity and insulin sensitivity
Hyppönen et al. 2008 [64]6810 British Caucasian adults, age: 45 years, BMI variable53.8 nmol/L (men) 51.5 nmol/L (women)HbA1cInverse association with HbA1cSex, month, IGF-1, physical activity, smoking, alcohol, social class, abdominal obesity, BMINo measure of dietary intake; indirect measures of adiposity and insulin sensitivity
Baynes et al. 1997 [4]142 Dutch men, mean age: 75.7 years42 29.1 nmol/LOGTTInverse association with fasting insulin
Chiu et al. 2004 [43]126 glucose-tolerant Asian, African, Caucasian, and Mexican American, mean age 26 6 years, mean BMI: 24.7  46.9 nmol/L (Asian American), 47.3 nmol/L (AA), 69.4 nmol/L (CA), 50.2 nmol/L (MA)OGTT Hyperglycemic clampInverse association with postchallenge glucose; Positive association with insulin sensitivity indexAge, sex, ethnicity, BMI, WHR, blood pressure, seasonNo measure of dietary intake or physical activity; indirect measure of adiposity
Kamycheva et al. 2007 [40]15 Norwegian subjects with secondary hyperparathyroidism, mean age: 62.9 years, mean BMI: 27.1  and 15 sex-, age-, and BMI-matched controls58.4 15.3 nmol/L (patients) 61.9 18.5 nmol/L (controls)Hyperglycemic clampPositive association with insulin sensitivity index among all subjectsSex, age, BMINo measure of dietary intake or physical activity; indirect measure of adiposity
Lind et al. 1995 [51]34 Caucasian men, mean age: 63 years90 19 nmol/LEuglycemic clampPositive association with insulin sensitivity, inverse association with fasting insulinAge, BMI, WHR, serum creatinineNo measure of dietary intake or physical activity; indirect measure of adiposity
Lind et al. 1989 [52]10 Danish men with impaired glucose tolerance, ages 60–63 years107 62 nmol/LEuglycemic clampPositive association with insulin sensitivitySerum calcium, phosphate, magnesium, and other mineralsNo measure of dietary intake or physical activity; no adjustment for adiposity
Manco et al. 2005 [59]116 Caucasian, morbidly obese (mean BMI: 48.8  ) women before and after bariatric surgery, ages 20–35 yearsPre-surgery: 39.2 22.3 nmol/L, 5 years postsurgery: 27.4 16.4 nmol/L, 10 years postsurgery: 25.1 13.9 nmol/LEuglycemic clampNo association with insulin sensitivity before or after bariatric surgeryTriglycerides, fat mass, PTH, serum calcium, phosphorus, HDL, LDL, total cholesterolNo measure of dietary intake or physical activity