The Impact of Vitamin D Supplementation on Fasting Plasma Glucose, Insulin Sensitivity, and Inflammation in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Design and Registration
2.2. Eligibility Criteria
2.3. Data Search and Selection
2.4. Data Extraction
2.5. Risk of Bias Assessment
2.6. Statistical Analysis
3. Results
3.1. Study Selection
3.2. Risk of Bias in Studies
3.3. Study Result Summaries
3.4. Fasting Plasma Glucose (FPG)
3.5. Insulin Level
3.6. HOMA-IR
3.7. HOMA-B
3.8. HbA1c Level
3.9. Hs-CRP
3.10. Level Change in Serum Vitamin D from Baseline
3.11. GRADE Analysis
3.12. Leave-One-Out Sensitivity Analysis
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Database | Combined Keywords with Boolean Operators | Filter Applies |
---|---|---|
PubMed | (“Vitamin D” OR Calcitriol) AND (adult OR obesity) AND “Diabetes Mellitus Type 2” | - Publication date: Last 10 years - Article type: Randomized Controlled Trial (RCT) and Clinical Trial (CT) |
Scopus | TITLE-ABS-KEY (“Vitamin D” OR Calcitriol) AND (adult OR obesity) AND “Diabetes Mellitus Type 2” | - Publication date: Last 10 years - Document type: Article (Research Article) |
Cochrane Library | (“Vitamin D” OR Calcitriol) AND (adult OR obesity) AND “Diabetes Mellitus Type 2”: ti, ab, kw | - Publication date: Last 10 years - Study type: Randomized Controlled Trial (RCT) and Clinical Trial (CT) |
Epistemonikos | (“Vitamin D” OR Calcitriol) AND (adult OR obesity) AND “Diabetes Mellitus Type 2” | - Publication date: Last 10 years - Study type: Randomized Controlled Trial (RCT) and Clinical Trial (CT) |
ScienceDirect | TITLE-ABSTR-KEY (“Vitamin D” OR Calcitriol) AND (adult OR obesity) AND “Diabetes Mellitus Type 2”) | - Publication date: Last 10 years - Document type: Research Article |
Author; Year | Country/ Place | Study Design | Vitamin D Level Before Treatment (Intervention/Control) | Vitamin D Level Before Treatment (Intervention/Control) | Supplementation | Population | Functional Outcome (Intervention/Control) (Mean ± SD) | |||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Sample Size (n) | Supplementation/Placebo | Mean Age (Years) (Mean ± SD) | Follow-Up (Weeks) | FPG | Insulin | HOMA-IR | HOMA-B | HbA1c | Hs-CRP | TNF-a | ||||||
Muñoz, et al.; 2014 [26] | Mexico | Randomized Clinical Trial | Not Reported | Not Reported | vit D3 4000 IU/day | 104 | 52/52 | Supplementation: 56.1 ± 5.1; Placebo: 57.4 ± 5.0 | 24 weeks | 146 ± 40/154 ± 42 | 19.0 ± 9.0/20.8 ± 11.0 | 6.7 ± 3.7/7.5 ± 4.0 | No Result | 9.0 ± 1.6/9.0 ± 1.8 | No Result | No Result |
Jafari., et al.; 2015 [27] | Iran | Randomized Clinical Trial | 62.23 ± 4.52/62.72 ± 4.27 | 86.83 ± 4.87/56.13 ± 2.89 | 2000 IU vitamin D3 in 100 g/day | 59 | 30/29 | Supplementation: 57.8 ± 5.5; Placebo: 56.8 ± 5.7 | 12 | No Result | 5.17 ± 0.46/11.20 ± 1.04 | 2.13 ± 0.20/4.72 ± 0.44 | 64.27 ± 5.98/135.02 ± 13.08 | 7.24 ± 0.22/7.58 ± 0.23 | 9.8 ± 0.4/12.1 ± 1.0 | No Result |
Krul., et al.; 2015 [28] | Netherlands | Randomized Clinical Trial | 60.6 ± 23.3/59.1 ± 23.2 | 90.3 ± 22.2/48.4 ± 26.2 | vit D3 50,000 IU/month | 261 | 129/132 | Supplementation: 67 ± 8; Placebo: 67 ± 9 | 24 | 8.1 ± 1.4/7.8 ± 1.2 | 16.3 (11.1)/16.3 (9.8) | 4.99 (3.29–6.98)/4.83 (3.37–7.24) | 64.8 (46.1–93.8)/67.4 (42.5–102.7) | 6.86 (0.6)/6.86 (0.6) | No Result | No Result |
Asemi., et al.; 2016 [29] | Iran | Randomized Clinical Trial | Not Reported | Not Reported | 5 μg vit D3, 90 μg vit K plus 500 mg Ca | 66 | 33/33 | Supplementation: 65.9 (11.4); Placebo: 65.0 (11.1) | 12 | 140.7 (56.2)/145·5 (70.4) | 12.7 (7.2)/20.1 (10.5) | 4.0 (2.4)/6.0 (3.9) | 36.6 (30.1)/64.5 (47.2) | No Result | 2.7 (2.3)/6.3 (5.8) | No Result |
Mousa., et al.; 2017 [30] | Australia | Randomized Clinical Trial | 31.4 ± 12.6/34.2 ± 10.0 | 88.4 ± 21.0/36.1 ± 10.0 | vit D3 100,000 IU bolus followed by 4000 IU/day | 54 | 28/26 | Supplementation: 30.5 (25–35); Placebo: 29.5 (25–41) | 16 | 4.6 ± 0.5/4.7 ± 0.3 | 10.2 (6.9–18.2)/7.9 (5.8–13.6) | No Result | No Result | No Result | No Result | No Result |
Bhatt., et al.; 2020 [31] | India | Randomized Clinical Trial | 29.9 ± 5.9/32.1 ± 5.2 | 56.6 ± 12.6/49.1 ± 12.1 | vit D3 60,000 IU/week | 121 | 61/60 | Not stated | 26 | 110.9 ± 8.5/111.8 ± 7.9 | 12.3 ± 7.3/11.5 ± 8.7 | 1.39 ± 0.08/1.81 ± 0.09 | No Result | No Result | No Result | No Result |
52 | 108.4 ± 21.0/105.5 ± 17.5 | 10.7 ± 5.6/10.3 ± 4.8 | 1.42 ± 0.09/1.38 ± 0.07 | No Result | No Result | No Result | No Result | |||||||||
78 | 101.8 ± 11.9/106.9 ± 26.9 | 10.6 ± 4.8/10.1 ± 4.7 | 1.20 ± 0.06/1.24 ± 0.04 | No Result | No Result | No Result | No Result | |||||||||
Hajj., et al.; 2020 [20] | Lebanon | Randomized Clinical Trial | 14.8 ± 4.5/15.02 ± 4.2 | 34.9 ± 4.7/14.5 ± 3.9 | vit D3 30,000 IU/week | 88 | 45/43 | Supplementation: 66.9 ± 4.1; Placebo: 65.7 ± 4.5 | 24 | No Result | No Result | 2.51 ± 2.46/2.41± 1.92 | No Result | 6.53 ± 0.63/6.64 ± 1.31 | 5.3 ± 2.31/5.19 ± 2.23 | 2.61 ± 1.04/3.01 ± 0.83 |
Cojic., et al.; 2021 [32] | Serbia | Randomized Clinical Trial | 48.79 ± 31.63/58.02 ± 32.32 | 92.24 ± 20.25/51.77 ± 23.99 | vit D3 14,000 IU/week | 130 | 65/65 | Supplementation: 60.41 (8.5); Placebo: 63.65 (8.2) | 12 | 7.28 (1.16)/7.97 (1.74) | 9.81 (7.04)/12.62 (8.30) | 3.63 (3.02)/3.42 (2.64) | No Result | 6.32 (0.69)/6.66 (0.85) | No Result | No Result |
24 | 7.23 (1.26)/7.74 (1.49) | 11.26 (6.68)/11.92 (7.86) | 3.44 (2.89)/3.39 (3.37) | No Result | 6.48 (0.70)/6.87 (0.92) | No Result | No Result | |||||||||
Sun., et al.; 2023 [33] | China | Randomized Clinical Trial | Not Reported | Not Reported | Vit D3 1000 IU/day | 30 | 15/15 | Not stated | 12 | 6.5 ± 0.8/7.1 ± 1.3 | 11.0 ± 8.9/15.1 ± 11.0 | 3.2 ± 2.7/5.1 ± 4.9 | No Result | 6.6 ± 0.8/6.7 ± 0.8 | No Result | No Result |
Outcome | Effect Size (MD, 95% CI) | No. of Studies | Risk of Bias | Certainty | Key Justification(s) |
---|---|---|---|---|---|
Fasting Plasma Glucose (FPG) | −2.61 [−5.53 to 0.32]; p = 0.08 | Multiple | Moderate | ⬤⬤◯◯ Low | Downgraded for inconsistency (I2 = 73%) and imprecision (non-significant, CI crosses 0); 3/9 studies had unclear randomization. |
Insulin Level | −2.09 [−4.75 to 0.56]; p = 0.12 | Multiple | Moderate | ⬤⬤◯◯ Low | Downgraded for inconsistency (I2 = 91%) and imprecision; risk of bias due to unclear randomization in several studies. |
HOMA-IR | −0.74 [−1.75 to 0.27]; p = 0.15 | Multiple | Moderate | ⬤⬤◯◯ Low | Downgraded for imprecision (CI crosses 0) and moderate inconsistency (I2 = 59%); some studies with unclear randomization. |
HOMA-B | −33.97 [−83.42 to 15.48]; p = 0.18 | Multiple | Moderate | ⬤◯◯◯ Very Low | Downgraded for inconsistency (I2 = 99%), imprecision (wide CI), and subgroup inconsistency (p = 0.03); moderate RoB due to unclear randomization. |
HbA1c Level | −0.17 [−0.35 to 0.00]; p = 0.05 | Multiple | Low–Moderate | ⬤⬤⬤◯ Moderate | Downgraded for imprecision (borderline p and CI), but heterogeneity was acceptable (I2 = 44%); most studies low risk, some concerns in 3/9 studies. |
Hs-CRP | −1.79 [−3.70 to 0.13]; p = 0.07 | Multiple | Moderate | ⬤⬤◯◯ Low | Downgraded for inconsistency (I2 = 91%), imprecision, and significant subgroup inconsistency (p = 0.0001); 3 studies had randomization issues. |
Serum Vitamin D Change | +33.88 [23.24 to 44.52]; p < 0.00001 | Multiple | Low–Moderate | ⬤⬤⬤◯ Moderate | Downgraded for inconsistency (I2 = 97%) but retained moderate certainty due to consistent large effect and direction despite some RoB concerns. |
Outcome | Leave-One-Out | Estimate | SE | Z-Value | p-Value | CI Lower | CI Upper | Q | Qp | Tau2 | I2 (%) | H2 |
---|---|---|---|---|---|---|---|---|---|---|---|---|
FPG | −1 | 6.867 | 2.068 | −1.979 | 0.304 | 2.359 | 5.212 | 5.638 | 0.912 | 8.413 | 90.926 | 5.629 |
−2 | 7.895 | 1.935 | 4.247 | 0.05 | −3.033 | 9.945 | 18.72 | 0.317 | 6.322 | 88.636 | 7.969 | |
−3 | 9.817 | 2.595 | 0.679 | 0.005 | 2.17 | 14.966 | 1.162 | 0.2 | 5.852 | 20.305 | 4.857 | |
−4 | 4.199 | 1.267 | −2.145 | 0.231 | −0.436 | 11.977 | 7.795 | 0.717 | 9.27 | 46.479 | 4.551 | |
−5 | 7.814 | 1.412 | −1.684 | 0.071 | −1.755 | 6.209 | 1.35 | 0.231 | 8.277 | 76.697 | 6.229 | |
−6 | 4.584 | 0.978 | 2.348 | 0.763 | 4.319 | 10.332 | 17.03 | 0.376 | 5.789 | 75.2 | 8.259 | |
−7 | 8.265 | 2.725 | 0.398 | 0.565 | −2.31 | 6.406 | 12.79 | 0.511 | 7.468 | 45.921 | 3.479 | |
−8 | −0.421 | 2.354 | −0.238 | 0.025 | −3.871 | 11.242 | 2.871 | 0.138 | 3.745 | 63.509 | 9.057 | |
Insulin | −1 | 9.43 | 1.695 | 1.836 | 0.589 | 2.31 | 9.904 | 8.948 | 0.21 | 1.728 | 74.026 | 5.277 |
−2 | 8.679 | 2.101 | −1.812 | 0.285 | 4.101 | 10.692 | 10.87 | 0.35 | 9.945 | 88.868 | 6.705 | |
−3 | 8.833 | 2.238 | −0.409 | 0.135 | 2.425 | 5.672 | 8.345 | 0.637 | 2.751 | 74.423 | 7.825 | |
−4 | 7.029 | 2.028 | −0.259 | 0.271 | 1.782 | 5.36 | 16.77 | 0.913 | 8.861 | 10.761 | 7.827 | |
−5 | −1.348 | 1.947 | 4.826 | 0.864 | 1.021 | 12.628 | 0.842 | 0.433 | 2.936 | 76.555 | 3.903 | |
−6 | 6.251 | 2.966 | 0.188 | 0.882 | −2.605 | 9.518 | 19.01 | 0.031 | 8.053 | 74.418 | 1.281 | |
−7 | 4.498 | 0.867 | 4.576 | 0.632 | 2.771 | 5.619 | 12.94 | 0.451 | 3.922 | 30.152 | 8.383 | |
−8 | 0.405 | 2.904 | 2.965 | 0.745 | 1.097 | 5.185 | 6.329 | 0.273 | 7.27 | 29.534 | 8.056 | |
−9 | 3.272 | 0.627 | −2.857 | 0.374 | −1.144 | 6.785 | 19.51 | 0.456 | 8.888 | 20.875 | 8.239 | |
HOMA-IR | −1 | −1.036 | 1.91 | −1.502 | 0.009 | 2.614 | 11.05 | 0.769 | 0.553 | 1.371 | 96.687 | 3.014 |
−2 | 6.221 | 2.305 | 1.37 | 0.185 | −2.339 | 10.231 | 6.836 | 0.599 | 4.722 | 11.999 | 3.602 | |
−3 | 8.707 | 2.124 | −1.577 | 0.047 | 0.849 | 8.338 | 15.18 | 0.937 | 6.653 | 17.846 | 7.337 | |
−4 | 5.04 | 1.37 | 2.066 | 0.352 | −4.814 | 9.897 | 1.309 | 0.015 | 6.615 | 45.765 | 4.763 | |
−5 | 0.164 | 2.633 | 1.504 | 0.275 | −4.673 | 12.593 | 11.6 | 0.407 | 0.734 | 76.639 | 6.544 | |
−6 | −1.884 | 0.971 | 1.925 | 0.849 | 4.62 | 12.151 | 4.656 | 0.667 | 8.549 | 20.304 | 4.699 | |
−7 | 2.995 | 0.578 | −0.001 | 0.155 | 4.412 | 5.049 | 14.4 | 0.603 | 0.076 | 9.449 | 1.762 | |
−8 | 8.784 | 1.85 | −2.758 | 0.049 | 2.173 | 5.831 | 10.33 | 0.042 | 6.437 | 15.698 | 9.872 | |
−9 | 7.155 | 1.255 | 3.718 | 0.387 | −4.307 | 7.97 | 5.383 | 0.043 | 9.656 | 39.821 | 8.742 | |
HOMA-B | −1 | 7.731 | 0.678 | −0.314 | 0.788 | −1.317 | 10.31 | 8.014 | 0.162 | 2.391 | 53.44 | 3.075 |
−2 | 4.054 | 2.768 | −1.709 | 0.361 | −0.459 | 10.042 | 10.09 | 0.525 | 5.2 | 89.3 | 5.257 | |
−3 | 9.409 | 0.964 | −1.253 | 0.53 | −4.039 | 7.094 | 19.98 | 0.34 | 9.803 | 26.724 | 5.961 | |
HbA1c | −1 | 0.973 | 1.136 | 4.334 | 0.611 | 3.479 | 8.843 | 14.33 | 0.412 | 3.406 | 38.956 | 1.582 |
−2 | 2.527 | 2.295 | 0.158 | 0.68 | 2.541 | 12.752 | 9.894 | 0.999 | 1.562 | 99.006 | 5.555 | |
−3 | 5.142 | 0.65 | −0.44 | 0.876 | −4.328 | 10.953 | 5.21 | 0.494 | 7.379 | 88.052 | 3.918 | |
−4 | −1.688 | 2.689 | −0.027 | 0.341 | 2.776 | 12.274 | 17.9 | 0.605 | 1.15 | 73.74 | 6.813 | |
−5 | 5.952 | 1.659 | 3.82 | 0.429 | 3.718 | 11.247 | 17.73 | 0.493 | 9.091 | 55.075 | 3.081 | |
−6 | 1.218 | 1.254 | −2.535 | 0.507 | 1.473 | 9.716 | 0.513 | 0.714 | 5.382 | 23.323 | 1.856 | |
hs-CRP | −1 | 2.349 | 0.826 | −1.345 | 0.218 | −3.81 | 10.12 | 8.679 | 0.579 | 9.793 | 82.216 | 4.494 |
−2 | 4.179 | 2.733 | 1.915 | 0.447 | −1.445 | 13.693 | 6.918 | 0.859 | 5.061 | 17.348 | 3.277 | |
−3 | −1.612 | 0.759 | 0.603 | 0.132 | −1.792 | 13.262 | 13.88 | 0.818 | 6.027 | 29.9 | 4.152 | |
Vitamin D | −1 | 4.048 | 0.724 | −0.985 | 0.604 | 2.84 | 13.706 | 14.1 | 0.816 | 4.49 | 62.115 | 6.158 |
−2 | 8.781 | 2.666 | −1.18 | 0.208 | 0.56 | 8.886 | 4.445 | 0.69 | 6.638 | 79.21 | 5.533 | |
−3 | 3.285 | 2.569 | −1.709 | 0.303 | 1.48 | 9.355 | 14.12 | 0.085 | 3.186 | 87.486 | 1.038 | |
−4 | 3.479 | 1.634 | 2.203 | 0.197 | −2.116 | 9.983 | 11.58 | 0.868 | 9.388 | 71.056 | 8.379 | |
−5 | −0.021 | 2.059 | −2.096 | 0.05 | 4.012 | 5.333 | 11.82 | 0.253 | 4.188 | 5.06 | 4.221 | |
−6 | 0.712 | 2.991 | −1.793 | 0.591 | −3.136 | 9.245 | 19.24 | 0.299 | 1.389 | 22.088 | 6.045 |
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Probosari, E.; Subagio, H.W.; Heri-Nugroho; Rachmawati, B.; Muis, S.F.; Tjandra, K.C.; Adiningsih, D.; Winarni, T.I. The Impact of Vitamin D Supplementation on Fasting Plasma Glucose, Insulin Sensitivity, and Inflammation in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Nutrients 2025, 17, 2489. https://doi.org/10.3390/nu17152489
Probosari E, Subagio HW, Heri-Nugroho, Rachmawati B, Muis SF, Tjandra KC, Adiningsih D, Winarni TI. The Impact of Vitamin D Supplementation on Fasting Plasma Glucose, Insulin Sensitivity, and Inflammation in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Nutrients. 2025; 17(15):2489. https://doi.org/10.3390/nu17152489
Chicago/Turabian StyleProbosari, Enny, Hertanto W. Subagio, Heri-Nugroho, Banundari Rachmawati, Siti F. Muis, Kevin C. Tjandra, Dwi Adiningsih, and Tri I. Winarni. 2025. "The Impact of Vitamin D Supplementation on Fasting Plasma Glucose, Insulin Sensitivity, and Inflammation in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis" Nutrients 17, no. 15: 2489. https://doi.org/10.3390/nu17152489
APA StyleProbosari, E., Subagio, H. W., Heri-Nugroho, Rachmawati, B., Muis, S. F., Tjandra, K. C., Adiningsih, D., & Winarni, T. I. (2025). The Impact of Vitamin D Supplementation on Fasting Plasma Glucose, Insulin Sensitivity, and Inflammation in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. Nutrients, 17(15), 2489. https://doi.org/10.3390/nu17152489