Vitamin D Deficiency
Conditions
Keywords
Vitamin D, Vitamin D deficiency, Insulin resistance, Diabetes, Diabetes mellitus, FGF-23, FGF23, Phosphate
Brief summary
The purpose of this project is to determine if treating vitamin D deficiency decreases insulin resistance and improves insulin secretion in healthy volunteers. Additionally, this project will investigate if treating vitamin D deficiency affects a new phosphate-regulating hormone called FGF-23.
Detailed description
Vitamin D deficiency or hypovitaminosis D, defined as serum 25 hydroxyvitamin D \< or = 20 ng/mL, is prevalent in several populations in the United States, specifically minorities and the elderly. Causes of vitamin D deficiency include lack of exposure to sunlight, malnutrition, and drugs that alter vitamin D metabolism and absorption. Vitamin D is an essential factor for many organ systems. Data suggest that vitamin D is required for normal insulin secretion by the pancreas. Specifically, animal studies demonstrate that treatment of vitamin D deficiency improves insulin secretion. In humans, there is less consensus about the impact of vitamin D deficiency on insulin resistance. In one study of middle-aged patients with Type 2 diabetes mellitus, no association was seen between serum 25 hydroxyvitamin D levels and a measure of insulin resistance. However, in a larger study of younger glucose tolerant subjects, serum 25 hydroxyvitamin D levels were associated with both insulin secretion and insulin resistance. These data suggest that treatment of vitamin D deficiency may delay or prevent the development of insulin resistance, and thus diabetes mellitus type 2. Repletion of this common vitamin deficiency could therefore have major public health implications for the prevention of diabetes mellitus. Fibroblast growth factor 23 (FGF-23) is a newly discovered phosphaturic hormone that is regulated by both dietary and serum phosphate. Hormonal regulation of FGF-23, however, is largely unknown. Recent data suggest that vitamin D plays an important role in the regulation of FGF-23. Some groups have shown that inactivation of the vitamin D receptor gene decreases serum FGF-23 levels in mice; administration of 1,25 dihydroxyvitamin D stimulates the transcription of the FGF-23 gene in vitro. Little is known, however, about the regulation of FGF-23 by vitamin D in humans. Phosphate is critical for bone mineralization, muscle function, signal transduction, and the creation and utilization of energy. Vitamin D deficiency can result in phosphate malabsorption, osteomalacia and increased risk of fractures. Enhanced understanding of the regulation of this new phosphate-regulating hormone, FGF-23, will advance the field of phosphate metabolism.
Interventions
DIETARY_SUPPLEMENTErgocalciferol
Ergocalciferol 50000 international units once a week for 12 weeks
DIETARY_SUPPLEMENTErgocalciferol placebo
Ergocalciferol placebo once a week for 12 weeks
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 18 to 45 yrs * Serum 25-OHD \< or = 20 ng/mL * At least 1 menses in the last 3 months (females) and normal serum testosterone (males)
Exclusion criteria
* Significant cardiac, hepatic, oncologic, or psychiatric disease * History of diabetes mellitus, malabsorption, kidney stones, or recent alcohol excess/abuse (15 drinks per week in the last month) * Fasting glucose \> 126 mg/dl or 2 hour OGTT \> 200 mg/dl * Use of medications known to affect serum phosphate levels including phosphate-binding antacids, sodium etidronate, calcitonin, excessive doses of vitamin D (\> 1000 units per day), excessive doses of vitamin A (\> 20,000 units/day), calcitriol, growth hormone, or anti-convulsants * Use of metformin or insulin sensitizing agents * Serum calcium \< 8 or \> 11 mg/dL, creatinine \> 1.5 mg/dL, or Hgb \< 11 gm/dL * Liver function tests \> 2 times the upper limit of normal * TSH \< 0.1 or \> 7 uU/mL * WBC \< 2,000 or \> 15,000/cmm * Platelet count \< 100,000 or \> 500,000/cum * Hormone replacement therapy or testosterone use * Urine uhCG positive (females), testosterone \< 270 ng/dL (males)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fibroblast Growth Factor 23 (FGF23) After 12 Weeks of Weekly Ergocalciferol 50000 Units | 12 weeks | Fibroblast growth factor 23 (FGF23) is a phosphate and vitamin D regulating hormone. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled from 2006-2008. Subjects were healthy volunteers recruited from the community
Participants by arm
| Arm | Count |
|---|---|
| Ergocalciferol Group Ergocalciferol 50000 international units once a week for 12 weeks | 40 |
| Placebo Group Matching placebo once a week for 12 weeks | 50 |
| Total | 90 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Pregnancy | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
Baseline characteristics
| Characteristic | Placebo Group | Ergocalciferol Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 50 Participants | 40 Participants | 90 Participants |
| Age, Continuous | 29 years STANDARD_DEVIATION 9 | 28 years STANDARD_DEVIATION 7 | 28 years STANDARD_DEVIATION 8 |
| Region of Enrollment United States | 50 participants | 40 participants | 90 participants |
| Sex: Female, Male Female | 31 Participants | 24 Participants | 55 Participants |
| Sex: Female, Male Male | 19 Participants | 16 Participants | 35 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 40 | 1 / 50 |
| serious Total, serious adverse events | 0 / 40 | 0 / 50 |
Outcome results
Primary
Fibroblast Growth Factor 23 (FGF23) After 12 Weeks of Weekly Ergocalciferol 50000 Units
Fibroblast growth factor 23 (FGF23) is a phosphate and vitamin D regulating hormone.
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ergocalciferol Group | Fibroblast Growth Factor 23 (FGF23) After 12 Weeks of Weekly Ergocalciferol 50000 Units | 74 pg/mL | Standard Deviation 42 |
| Ergocalciferol Placebo Group | Fibroblast Growth Factor 23 (FGF23) After 12 Weeks of Weekly Ergocalciferol 50000 Units | 39 pg/mL | Standard Deviation 29 |
p-value: <0.05ANOVA