The Effect of Vitamin D Supplementation on Insulin Sensitivity: A Systematic Review and Meta-analysis
Article Figures & Tables
Figures
- Figure 1
Flowchart diagram for study selection of systematic review (based on PRISMA guideline). FPG, fasting plasma glucose.
- Figure 2
Forest plot of the effect of vitamin D supplementation on insulin sensitivity. Horizontal lines span individual study 95% CIs. Diamonds represent the combined study standardized (Std.) mean value and the corresponding 95% CI values. df, degrees of freedom; ISI, insulin sensitivity index; IV, inverse variance. ‡Vitamin D3 1,600 IU/day (41). ¶Vitamin D3 3,200 IU/day (41).
- Figure 3
Forest plots of the effect of vitamin D supplementation on postprandial glucose (A) and serum vitamin D level (B). Horizontal lines span individual study 95% CIs. Diamonds represent the combined study standardized mean value and the corresponding 95% CIs. 2OGTT, 2-h oral glucose tolerance test; df, degrees of freedom; IV, inverse variance. ‡Vitamin D3 1,600 IU/day (41). ¶Vitamin D3 3,200 IU/day (41).
Tables
- Table 1
Characteristics of randomized controlled trial studies included in the meta-analysis
Author (year) Study location N subjects (Tx/Px) Sex Ethnicity BMI (kg/m2) Health status Vitamin D levels at baseline (nmol/L) Vitamin D levels after intervention (nmol/L) Type of vitamin D; mode of delivery; dose (IU/day) Vitamin D analytical measures Duration (months) Outcome measured Mitri et al. (2011) U.S. 23/24 M/F Multiethnic ≥25 (≥23 if Asian) Prediabetes (IGT, IFG, HbA1c ≥5.8%) T 59.9 ± 2.7,§ P 60.4 ± 2.7§ T 15.7 ± 3.7§ (change from baseline), P −20.5 ± 3.5§ Vitamin D3; oral; 2,000 LC-MS 4 Insulin sensitivity index (FIVGTT), 2-h glucose (OGTT) Harris et al. (2012) U.S. 43/46 M/F African American 25–39.9 Prediabetes or early T2D (HbA1c 6.7–7%), baseline 25(OH)D <50 nmol/L T 39.6 ± 12.9, P 38.2 ± 15.5 T 41.6 ± 3.1§ (change from baseline), P 0.9 ± 2.9§ Vitamin D3; oral; 4,000 RIA 3 Matsuda index, 2-h glucose (OGTT) Iraj et al. (2012) Iran 20/20 M/F Middle Eastern ≥25 First-degree relatives with T2D, 25(OH)D <75 nmol/L, prediabetes T 27.5 ± 15.0, P 28.2 ± 15.0 T 87.4 ± 49.9, P 38.7 ± 54.9 Vitamin D3; injection; 10,000 CLIA 2 Matsuda index, AUCglucose (OGTT) Davidson et al. (2013) U.S. 56/53 M/F Multiethnic (Hispanic and African American) ≥25 Prediabetes, 25(OH)D <75 nmol/L T 54.9 ± 12.5, P 54.9 ± 12.5 T 169.6 ± 37.4, P 54.9 ± 17.4 Vitamin D3; oral; 12,695 LC-MS 3 Matsuda index, 2-h glucose Oosterwerff et al. (2014) Netherlands 53/57 M/F Multiethnic (Morocco, Suriname, Turkey) ≥25 IFG or IGT, 25(OH)D <50 nmol/L T 25.0 ± 10.8, P 22.0 ± 11.0 T 60.0 ± 16.0, P 23.0 ± 15.0 Vitamin D3; oral; 1,200 LC-MS 4 Insulin sensitivity index, 2-h glucose Gagnon et al. (2014) Australia 35/45 M/F Multiethnic 25–40 25(OH)D <50 nmol/L, prediabetes T 47.0 ± 13.0, P 43.2 ± 13.0 T 89.1 ± 16.5, P 41.4 ± 16.3 Vitamin D3; oral; 2,000 CLIA 6 Matsuda index Kampmann et al. (2014) Denmark 7/8 M/F NR ≥25 T2D, 25(OH)D <50 nmol/L T 31.0 ± 4.9,§ P 34.8 ± 3.8§ T 104.9 ± 19.0,§ P 32.1 ± 3.8§ Vitamin D3; oral; 6,400 ELISA 3 M value derived from clamp Mitchell et al. (2015) U.S. 40/50 M/F Multiethnic Median 25 25(OH)D <50 nmol/L T 44.9 ± 17.5, P 44.9 ± 17.5 T 107.3 ± 29.9, P 49.9 ± 24.9 Vitamin D2; oral; 7,142 LC-MS 3 Insulin sensitivity index (FIVGTT) Tuomainen et al. (2015) Finland T1/T2/P (24/21/21) M/F NR ≥25 Prediabetes, 25(OH)D <75 nmol/L Mean baseline T + P 57.0 ± 11.0 T1 27.7 ± 17.2 (change from baseline) (T1) Vitamin D3; oral; 1,600 HPLC-CEAD 5 Matsuda index T2 45.0 ± 23.4 (change from baseline), P 4.1 ± 17.3 (T2) Vitamin D3; oral; 3,200 Wagner et al. (2016) Sweden 21/22 M/F NR ≤32 Prediabetes or drug-naive diabetes, HbA1c ≤7.9%, FPG <9 mmol/L, 25(OH)D <75 nmol/L T median 43.0 (IQR 36.0–50.0), P 43.0 (37.0–54.0) Median change T 42.0 (IQR 32.0–50.0), P 0.0 (−7.0 to 11.0) Vitamin D3; oral; 4,285 CLIA 2 GIR derived from clamp Yeow et al. (2015) Malaysia 13/13 F Asian 23–31 History of GDM during last pregnancy 6–48 months postpartum; hypovitaminosis (25(OH)D 15–50 nmol/L) T median 35.6 (IQR 25.6–43.9), P 35.1 (21.6–40.7) Median change T 51.1 (IQR 39.9–76.1), P −0.2 (−10.18 to 11.8) Vitamin D3; oral; 4,000 ECLIA 6 Insulin sensitivity index, 2-h glucose Barengolts et al. (2015) U.S. 87/86 M African American 28–39 Fasting glucose 5.3–6.9 mmol/L, HbA1c 5.7–6.4%, 25(OH)D 12.5–75 nmol/L T 36.7 ± 11.7, P 34.9 ± 12.0 T 120.1 ± 45.9, P 49.7 ± 18.2 Vitamin D2; oral; 7,142 CLIA 12 Matsuda index Garg et al. (2015) India 15/17 F Asian ≥23 PCOS, 25(OH)D <50 nmol/L P 16.9 ± 6.1 T 78.6 ± 34.6, P 16.7 ± 5.8 Vitamin D3; oral; 4,000 CLIA 6 Matsuda index, AUCglucose Mousa et al. (2017) Australia 28/26 M/F Multiethnic ≥25 25(OH)D <50 nmol/L T 31.4 ± 12.6, P 34.2 ± 10.0 T 88.4 ± 21.0, P 36.1 ± 15.3 Vitamin D3; oral; 4,000 CLIA 4 M value derived from clamp Gulseth et al. (2017) Norway 33/29 M/F Multiethnic (Nordic and South Asian) <45 T2D, 25(OH)D <50 nmol/L T 38.0 ± 11.9, P 36.8 ± 12.6 T 53.7 ± 9.2, P 38.2 ± 12.9 Vitamin D3; injection and oral; 3,333 RIA 6 GIR derived from clamp Lerchbaum et al. (2017) Austria 49/49 M NR Median 25 25(OH)D <75 nmol/L T median 52.0 (IQR 42.0–65.0), P 51.0 (43.0–68.0) Median T 107.0 (IQR 89.0–119.0), P 69.0 (46.0–79.0) Vitamin D3; oral; 2,857 LC-MS 3 Matsuda index, AUCglucose Moreira-Lucas et al. (2017) Canada 36/35 M/F Multiethnic <40 25(OH)D ≤65 nmol/L, HbA1c 5.4%–6.4% T 48.1 ± 14.3, P 47.6 ± 14.3 Mean change T 50.6 (95% CI 36.7, 64.6), P −2.11 (−6.11, 1.89) Vitamin D3; oral; 4,000 LC-MS 6 Matsuda index, AUCglucose Cefalo et al. (2018) Italy 9/9 M/F NR >25 BMI ≥30 kg/m2, 25(OH)D <75 nmol/L T 36.7 ± 13.2, P 34.7 ± 21.1 T 74.8 ± 18.7, P 41.7 ± 7.7 Vitamin D3; oral; 3,571 NR 3 Insulin-mediated glucose uptake, AUCglucose (from OGTT) CLIA, chemiluminescence immunoassay; ECLIA, electrochemiluminescence immunoassay; FPG, fasting plasma glucose; FIVGTT, frequently sampled intravenous glucose tolerance test; HPLC-CEAD, high-performance liquid chromatography-coulometric electrode array detector; IFG, impaired fasting glucose; IGT, impaired glucose tolerance; IQR, interquartile range; LC-MS, liquid chromatography–mass spectrophotometry; M, male; F, female; NR, not reported; P, placebo; RIA, radioimmunoassay; Tx/Px, treatment/placebo group; T, treatment; T2D, type 2 diabetes.
↵§ Data are means ± SE.
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