Table 1.
Summary of studies of vitamin D administration in type 1 and type 2 diabetes.
| Reference | Type of Study | Intervention | Participants | Results (Intervention) |
|---|---|---|---|---|
| Type 1 Diabetes | ||||
| Studies examining effects on immune modulation | ||||
| [25] | 18-month randomized controlled trial (RCT) | 2000 IUs vitamin D3 daily or placebo | 38 participants; 35 completers; 7–30 years old |
Increase in regulatory T-cell (T-reg) percentage; lower cumulative incidence of progression to undetectable C-peptide; no difference in HbA1C, insulin requirement or BMI |
| [26] | 12-month RCT | 70 IUs/kg/day vitamin D3 vs. placebo | 29 Participants; >6 years old; <3 months duration of T1D |
Increase in suppressive capacity of T-regs |
| Studies of prevention of islet autoimmunity or T1D | ||||
| [27] | Meta-analysis of four case-control and one cohort study | Vitamin D supplementation (variable doses) | Infants | Four case control studies: risk of T1D decreased; similar findings in cohort study; some evidence of a dose-response effect |
| [28] | Population impact number of eliminating a risk factor (PIN-ER-t) Statistical method | Vitamin D supplementation (variable doses) |
Babies born in 2012 | For a population of 729,674 babies born in England and Wales in 2012, 374 cases of T1D (out of 1357 total predicted cases) could be prevented over 18 years if all were supplemented with vitamin D |
| [31] | Cohort study; assessment every 3 months between 3–48 months, and then every 6 months | Maternal vitamin D supplementation during pregnancy (based on recall); cumulative intake of vitamin D supplements and n-3 FAs analyzed | 8676 children with increased genetic risk for T1D in Finland, Germany, Sweden and the US | Vitamin D supplementation during pregnancy was not associated with risk for development of islet autoantibodies (any/none and cumulative intake) |
| Studies examining course or complications of T1D | ||||
| [29] | 6-month RCT | 0.25 mcg twice daily of alfacalcidol vs. placebo | 61 participants; 54 completers; 8–15 years old; <8 weeks duration of T1D |
Higher fasting C-peptide; lower daily insulin dose |
| [30] | 12–24 weeks single arm intervention study | 1000–2000 IUs of vitamin D3 daily | 271 adolescents with T1D with 25(OH)D <15 ng/mL | Improved endothelial function; decreased urinary inflammatory cytokines/chemokines; no change in systolic or diastolic blood pressure, lipids, HbA1C and albumin/creatinine ratio |
| [32] | 2-year RCT | 0.25 mcg daily of calcitriol or placebo | 34 participants 11–35 years old with recent onset T1D and high basal C-peptide | No effect on beta cell function |
| [33] | Single dose single arm intervention study | Vitamin D3: 100,000 IUs for those 2–10 years old; 160,000 IUs for those >10 years |
40 children <19 years with T1D and vitamin D deficiency (<20 ng/mL) included in ITT analysis | No difference in HbA1C levels at 3 months or at 1 year |
| [34] | 6-month RCT | Vitamin D3 60,000 IUs once a month for 6 months | 52 children with T1D 1–18 years old | Higher mean C-peptide level; no difference in HbA1C or insulin requirement |
| Obesity, Prediabetes or Type 2 Diabetes | ||||
| Adults | ||||
| [35] | Single arm intervention study | Vitamin D3 two doses of 100,000 IUs at 2-week intervals | 33 adults with vitamin D deficiency (25(OH)D < 20 ng/mL) and without T2D | No change in mean blood glucose or insulin, or insulin sensitivity (assessed using an OGTT) |
| [36] | 6-month RCT | Vitamin D3 4000 IUs daily or placebo | 82 insulin resistant, vitamin D deficient (25(OH)D < 20 ng/mL) South Asian women in New Zealand without T2D | HOMA-IR improved when 25(OH)D level rose to >32 ng/mL; no differences in insulin secretion, CRP, BMI or lipid levels |
| [37] | 6-month intervention study | Vitamin D3 20,000 IUs or placebo given twice weekly over 6 months | 104 adults with vitamin D deficiency; 94 completers | No difference in insulin secretion, insulin sensitivity (using a hyperglycemic clamp) or lipids |
| [38] | 4-month RCT | Vitamin D3 2500 IUs or placebo daily | 114 post-menopausal women with 25(OH)D between 10–60 ng/mL | No improvement in blood pressure, endothelial function, arterial stiffness, inflammation and CRP |
| [39] | 16-week RCT | Vitamin D3 supplementation 200 IUs or placebo daily | 165 healthy women 18–35 years | No change in lipids; modest change in systolic and diastolic blood pressure |
| [40] | 5-year RCT | Vitamin D3 20,000 IUs/week or placebo; followed every 6 months | 556 adults 25–80 years old with prediabetes; 503 completers | 25(OH)D increased from ~24 ng/mL to 48 ng/mL with supplementation; no effect on progression to T2D, measures of glucose metabolism, serum lipids or blood pressure in the group as a whole, or in those with vitamin D deficiency |
| [41] | Pooled meta-analysis of 28 RCTs | Vitamin D3 supplementation, variable doses | Adults at risk for T2D (no T2D) | No effect on controlling fasting plasma glucose levels, improving insulin resistance, or preventing T2D; stratified analysis suggested a possible beneficial effect in those without obesity, those with prediabetes, when 25(OH)D levels were ≥20 ng/mL, and when the supplemental dose was >2000 IUs per day and given without calcium supplementation |
| [42] | RCT | Vitamin D3 4000 IUs or placebo regardless of vitamin D status | 2423 adult participants meeting criteria for prediabetes (2382 randomized) | No differences in baseline 25(OH)D; supplemented group had 25(OH)D levels about twice that in the placebo group; no difference in progression to T2D (9.4 vs. 10.7 events per 100 person-years respectively at a median follow-up of 2.5 years) |
| Children | ||||
| [43] | 6-month RCT | Vitamin D3 4000 IUs daily or placebo | 35 adolescents with obesity 9–19 years old | Improved HOMA-IR and QUICKI (but not fasting glucose, HbA1C, CRP, IL-6 or TNF-alpha) in those who received vitamin D |
| [44] | 1-year open label parallel arm prospective study | Vitamin D3 5000 IUs weekly for 8 weeks vs. no intervention | 70 indigenous Argentinean children vs. 20 non-supplemented children | Improved HDL |
| [45] | 12-week RCT | Vitamin D3 300,000 IUs weekly or placebo | 50 children with obesity 10–16 years old | Improved serum insulin and HOMA-IR with no effect on lipids, fasting blood sugar or blood pressure |
| [46] | Retrospective study | Vitamin D supplementation | 43 children 3–18 years old with T2D for >12 months and a diagnosis of vitamin D deficiency (25(OH)D < 20 ng/mL) | Decrease in BMI-SDS, HbA1C and ALT in supplemented group |
| [47] | 12-week RCT | Vitamin D3 2000 IUs daily or placebo | 58 adolescents with obesity 12–18 years old | No change in fasting glucose, insulin, HOMA-IR, lipids or CRP |
| [48] | 12-week RCT | Vitamin D3 two doses (400 IU/day and 2000 IU/day) for 12 weeks | 51 Caucasian adolescents with obesity 12–18 years old; 46 completers | No change in 25(OH)D levels in the in 400 IU/day group and a modest increase in the 2000 IU/day group. No change in fasting HOMA-IR, insulin, glucose or lipid levels post-supplementation |
| [49] | 2-year prospective study | Vitamin D3 100,00 IUs/year to both groups | 104 children in Group A (treated in 2014) and 86 in Group B (treated in 2013) | Changes in 25(OH)D levels were significantly associated with lower LDL-C and Apo-B levels. |
| [50] | 3-month open label, prospective study | Vitamin D3 100,000 IUs monthly for 3 months | 19 children with obesity and vitamin D deficiency 13–18 years old | No change in endothelial function, fasting lipids, glucose, insulin and CRP values |
| [51] | 12-week RCT | Vitamin D3 at either 0, 400, 1000, 2000 or 4000 IU/day for 12 weeks | 323 early pubertal children At baseline, 15% had 25(OH)D levels that were insufficient <25 ng/mL, 6% had levels <16 ng/mL and 1% had levels lower than 12 ng/mL |
At baseline, 25(OH)D levels were inversely associated with insulin and HOMA-IR. However, glucose, insulin and insulin resistance increased over 12 weeks in all dosage groups |
| [52] | 12-week RCT | Vitamin D3 50,000 IUs per week vs. placebo | 29 African American children with obesity 13–17 years old | No impact on insulin secretion or sensitivity |