Modulatory Properties of Vitamin D in Type 2 Diabetic Patients: A Focus on Inflammation and Dyslipidemia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Study Design and Registration
2.2. Adapted Search Strategy and Information Sources
2.3. Study Selection Procedure
2.4. Data Extraction, Quality, and Certainty of Evidence Assessment
2.5. Subgroup, Sensitivity Analysis, and Publication Bias
2.6. Data Synthesis and Statistical Analysis
3. Results
3.1. Comprehensive Search and Information Sources
3.2. General Characteristics of Included Randomized Controlled Trials
Author, Year | Study Design, Country | Population and Sample Size | Intervention Group, n. Male, n (%) | Mean Age of Intervention Group (Years) | Vitamin D, Dosage, and Duration of Intervention | Effect on Lipids and Inflammatory Markers |
---|---|---|---|---|---|---|
Hu et al., 2022 [68] | Randomized controlled trial (RCT); China | T2D patients, 220 | 115; 32 (27.8) | 66.05 ± 9.35 | Oral dose of 800 IU (two capsules) of vitamin D3 for 30 months. | Vitamin D supplementation significantly decreased total cholesterol (TC) and CRP. |
Hoseini et al., 2022 [57] | Randomized, single-blinded, placebo-controlled clinical trial; Iran | T2D patients, 20 | 10; 10 (100) | 49.10 ± 1.23 | 50,000 IU of Vitamin D capsules per week for eight weeks. | Vitamin D supplementation significantly reduced tumor necrosis factor-alpha (TNF-α) and CRP. |
Limonte et al., 2021 [58] | Randomized double-blinded placebo-controlled trial; USA | T2D patients, 1312 | 703; 376 (53.5) | 67.4 ± 7.0 | 2000 IU vitamin D3 per day for five years. | Vitamin D supplementation showed no significant changes in interleukin (IL)-6 and CRP compared to the placebo group. |
Barale et al., 2020 [65] | Open-label randomized-controlled pilot study; Italy | T2D patients, 30 | 16; 11 (68.8) | 71.6 ± 3.5 | 500 IU oral cholecalciferol once a week for one year. | Vitamin D supplementation showed no significant difference in lipid profiles compared to the placebo group. |
Hajj et al., 2020 [76] | Randomized controlled double-blind study; Lebanon | T2D patients, 88 | 45; 23 (51) | 66.9 ± 4.1 | 10,000 IU cholecalciferol three times per week for six months. | Vitamin D supplementation significantly reduced CRP and TNF-α levels compared to baseline data. No significant changes were observed in terms of IL-6 when compared to baseline data. |
Imanparast et al., 2020 [56] | Randomized placebo-controlled trial; Iran | T2D patients, 92 | 23; 11 (47.8) | 53.63 ± 12.29 | 50,000 IU of vitamin D3 per week for four months | Vitamin D supplementation significantly decreased TC and TNF-α levels, with no significant changes in LDL, HDL, and triglyceride (TG) levels compared to the placebo group. |
Meng et al., 2020 [59] | Double-blinded randomized placebo-controlled trial USA | T2D patients, 127 | 56; 43 (76.8) | 65 ± 8.0 | 4000 IU per day of vitamin D3 for 24 weeks. | Vitamin D supplementation showed no significant difference in serum LDL and HDL-c compared to the placebo. |
Mirzavandi et al., 2020 [55] | Randomized, controlled clinical trial; Iran | T2D patients, 50 | 25; 5 (20) | 46 ± 1.0 | Two intramuscular injections of a 200,000 IU vitamin D supplement at 0 and 4 weeks. | Vitamin D supplementation led to a significant decrease in the levels of CRP and TG in comparison to baseline data. |
Dadrass et al., 2019 [54] | Randomized, placebo-controlled, double-blinded clinical trial; Iran | T2D patients, 24 | 12; 12 (100) | 53.83 ± 6.61 | 50,000 IU per 2 weeks for three months | Vitamin D supplementation significantly decreased IL-6 and TNF-α without change in CRP compared to placebo. |
Omidian et al., 2019 a [52] | Randomized double-blinded placebo-controlled trial; Iran | T2D patients, 66 | 32; 19 (59.4) | 49.7 ± 6.5 | 4000 IU vitamin D daily for 12 weeks. | Vitamin D supplementation significantly increased TG levels compared to baseline data. |
Omidian et al., 2019 b [53] | Parallel randomized double-blind placebo-controlled clin- ical trial; Iran | T2D patients, 47 | 24; 10 (41.6) | 51.3 ± 4.7 | 4000 IU vitamin D daily for 12 weeks. | Vitamin D supplementation significantly decreased IL-6 and MCP-1 levels compared to baseline data. |
Wenclewska et al., 2019 [77] | Randomized controlled trial; Poland | T2D patients, 92 | 48; 14 (29) | 63.43 ±1.57 | 2000 IU of vitamin D3 per day for three months. | Vitamin D supplementation increased HDL compared to baseline data. |
Angellotti et al., 2019 [60] | Randomized, double-blind, placebo-controlled clinical trial; USA | T2D patients, 114 | 66; 49 (71) | 60.1 ± 8.4 | 4000 units of vitamin D3 for 48 weeks. | Vitamin D supplementation revealed no significant in CRP, with a significant reduction in TG levels. |
Fazelian et al., 2018 [51] | Randomized double-blind placebo-controlled clinical trial; Iran | T2D patients, 51 | 26; 0 (0) | 48.5 ± 7.58 | one oral pearl of 50,000 IU vitamin D3 for 16 weeks. | Vitamin D supplementation significantly reduced CRP and increased IL-10 levels. |
Upreti et al., 2018 [70] | Parallel randomized, placebo-controlled trial; India | T2D patients, 60 | 30; 15 (50) | 48.3 ± 9.8 | 60,000 IU weekly for six weeks, followed by once every four weeks for 24 weeks. | Vitamin D supplementation led to a significant difference in total cholesterol compared to the placebo group. |
Barchetta et al., 2016 [64] | Randomized, double-blind, placebo-controlled trial; Italy | T2D patients, 65 | 26; 18 (50) | 57.4 ± 10.7 | 2000 IU cholecalciferol per day for 24 weeks. | Vitamin D supplementation showed a significant difference in LDL, HDL, and TG without any significant difference in CRP levels. |
Dalan et al., 2016 [74] | Parallel randomized, double-blind, placebo-con- trolled trial; Singapore | T2D patients, 61 | 31; 14 (45) | 52.2 ± 8.2 | 4000 IU vitamin D (oral cholecalciferol) and 2000 IU for 16 weeks. | Vitamin D supplementation showed no significant effect on lipid profiles and CRP in comparison to baseline data. |
Sadiya et al., 2015 [47] | Randomized, double-blind clinical trial; United Arab Emirates | T2D patients with obesity, 82. | 43; 9 (20.9) | 49 ± 8.0 | Vitamin D (6000 IU) per day, followed by 3000 IU vitamin D3 daily for six months. | Vitamin D supplementation showed no significant differences in lipids and CRP compared to placebo groups. |
Muñoz-Aguirre et al., 2014 [73] | Randomized, double-blind, placebo- controlled trial; Mexico | T2D patients, 104. | 52; 0 (0) | 56.1 ± 5.1 | 4000 IU of vitamin D daily for six months. | Vitamin D supplementation revealed no significant changes in LDL, and TC levels significantly decreased TG compared to the placebo. |
Gagnon et al., 2014 [67] | Randomized, double-blinded, placebo-controlled trial; Australia | T2D patients, 80. | 35; 10 (28.6) | 53.8 ± 11.9 | 2000 IU of vitamin D3 for six months. | Vitamin D supplementation showed no difference in inflammatory markers compared to placebo. |
Jehle et al., 2014 [75] | Prospective, randomized, double-blind, placebo-con- trolled pilot; Switzerland | T2D patients, 55. | 29; 10 (34.5) | 66.9 ± 3.1 | A single 300,000 IU intramuscular injection of vitamin D3 for six months. | Vitamin D supplementation revealed no significant difference in levels of CRP compared to placebo groups. |
Kampmann et al., 2014 [69] | Randomized, double-blind, placebo-controlled trial; Denmark | T2D patients, 16. | 8; 6 (75) | 61.6 ± 4.4 | 11,200 IU cholecalciferol per day for ten weeks | Vitamin D supplementation resulted in no significant difference in HDL, LDL, TC, TG, CRP, TNF-α, IL-6, and IL-8 compared to placebo groups. |
Maggi et al., 2014 [66] | Randomized, double-blind, placebo-controlled clinical trial; Italy | T2D patients, 30 | 14; 9 (64) | 69 ± 4.5 | Single oral dose of 300,000 IU of Vitamin D3 for 24 weeks. | Vitamin D supplementation led to no significant difference in TNF-α levels compared to the group on placebo. |
Ryu et al., 2014 [72] | Prospective, randomized, double-blind- ed, placebo-controlled trial; Korea | T2D patients, 158 | 79; NR | 54.8 ± 7.6 | 1000 IU of vitamin D3 with a combined 100 mg of calcium twice daily for 24 weeks. | Vitamin D supplementation showed no significant difference in lipid profiles and inflammatory markers compared to placebo groups. |
Tabesh et al., 2014 [50] | Parallel- randomized placebo- controlled clinical trial; Iran | T2D patients, 118 | 29; 15 (51.7) | 50.2 ± 6.6 | 50,000 IU vitamin D3 per week for eight weeks. | Vitamin D supplementation showed no significant effect on serum levels of HDL, LDL, and TG compared to a placebo group. |
Akbarzadeh et al., 2013 [49] | Randomized double-blind placebo-controlled trial; Iran | T2D patients, 70 | 35; 35 (100) | 53.8 ± 8.9 | Two tablets of Calcitriol (0.25 μg 1,25-dihydroxy cholecalciferol) (≈10 IU) per day for 12 weeks. | Vitamin D supplementation showed no significant effect on the marker of inflammation, including CRP, IL-6, and IL-18 levels, compared to baseline data. |
Breslavsky et al., 2013 [71] | Randomized, double-blind, placebo-controlled trial; Israel | T2D patients, 47 | 24; 11 (45.8) | 66.8 ± 9.2 | 1000 IU Vitamin D daily for 12 months. | Vitamin D supplementation had no significant effect on lipid profile and CRP compared to the placebo group. |
Neyestani et al., 2012 [48] | Randomized, double-blinded controlled trial; Iran | T2D Patients, 60 | 30; NR. | 51.5 ± 5.4 | 500 IU vitamin D3 and 150 calcium for 12 weeks. | Vitamin D supplementation significantly decreased CRP, IL-1β, and IL-6 compared to placebo. |
Punthakee et al., 2012 [62] | Randomized, double-blind placebo-controlled trial; Canada | T2D patients, 1332 | 607; 362 (59.6) | 66.7 ± 6.7 | 1000 IU daily for five and a half years. | Vitamin D supplementation showed no significant effect on HDL, LDL, TG, and TC in comparison to placebo. |
Witham et al., 2010 [61] | Parallel, randomized, placebo- controlled trial; Canada | T2D patients, 95 | 37; 13 (35) | 64.27 ± 10.27 | A single dose of 100,000 IU vitamin D3 or 200,000 IU vitamin D3 for 16 weeks. | There was no significant difference in TC levels between the vitamin D and placebo groups. |
3.3. The Methodological Quality of Included RCTs
3.4. Effect of Vitamin D on Markers of Inflammation
3.4.1. Effect of Vitamin D on High Sensitivity-C-Reactive Protein (hs-CRP) in T2D Patients
3.4.2. Effect of Vitamin D on Interleukin-6 (IL-6)
3.4.3. Effect of Vitamin D on Tumor Necrosis Factor-Alpha (TNF-α)
3.5. Effect of Vitamin D on Lipid Profiles (Triglycerides and Total Cholesterol)
3.6. Effect of Vitamin D on Lipid Profiles (HDL and LDL)
3.7. Subgroup Analysis
3.8. Sensitivity Analysis
3.9. Publication Bias
3.10. Certainty of Evidence
4. Discussion
5. Conclusions and Future Perspectives
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
CI | Confidence intervals. |
CRP | C-reactive protein. |
CVD | Cardiovascular disease. |
GRADE | Grading of Recommendation Assessment, Development, and Evaluation. |
HDL | High-density lipoprotein. |
IDF | International Diabetes Federation. |
IFγ | Interferon-gamma. |
IL-6 | Interleukin-6. |
IQR | Interquartile Range. |
IU | International Unit. |
LDL | Low-density lipoprotein. |
MCP-1 | Monocyte-Chemoattractant Protein-1. |
MD | Mean difference. |
NF-kβ | Nuclear Factor kappa beta. |
NO | Nitric oxide. |
NR | Not Reported. |
oxLDL | Oxidised Low-density lipoprotein. |
PRISMA | Preferred Reporting Items for Systematic Review and Meta-analysis. |
RM | Randomized Model. |
SD | Standard deviation. |
SEM | Standard Error of Mean. |
SMD | Standard mean difference. |
T2D | Type 2 diabetes. |
TNF-α | Tumor necrosis factor-alpha. |
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MacGirlley, R.; Phoswa, W.N.; Mokgalaboni, K. Modulatory Properties of Vitamin D in Type 2 Diabetic Patients: A Focus on Inflammation and Dyslipidemia. Nutrients 2023, 15, 4575. https://doi.org/10.3390/nu15214575
MacGirlley R, Phoswa WN, Mokgalaboni K. Modulatory Properties of Vitamin D in Type 2 Diabetic Patients: A Focus on Inflammation and Dyslipidemia. Nutrients. 2023; 15(21):4575. https://doi.org/10.3390/nu15214575
Chicago/Turabian StyleMacGirlley, Rizqah, Wendy N. Phoswa, and Kabelo Mokgalaboni. 2023. "Modulatory Properties of Vitamin D in Type 2 Diabetic Patients: A Focus on Inflammation and Dyslipidemia" Nutrients 15, no. 21: 4575. https://doi.org/10.3390/nu15214575
APA StyleMacGirlley, R., Phoswa, W. N., & Mokgalaboni, K. (2023). Modulatory Properties of Vitamin D in Type 2 Diabetic Patients: A Focus on Inflammation and Dyslipidemia. Nutrients, 15(21), 4575. https://doi.org/10.3390/nu15214575