Vitamin D Deficiency, Insulin Resistance and FGF-23
Information source: Massachusetts General Hospital
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Vitamin D Deficiency
Intervention: Ergocalciferol (Drug)
Phase: N/A
Status: Completed
Sponsored by: Massachusetts General Hospital Official(s) and/or principal investigator(s):
Sherri-Ann M Burnett-Bowie, MD, MPH, Principal Investigator, Affiliation: Massachusetts General Hospital
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.
Clinical Details
Official title: Impact of Vitamin D Deficiency on Insulin Resistance and the Regulation of FGF-23
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Efficacy Study
Primary outcome: Change in insulin resistance, insulin secretion, and FGF-23
Secondary outcome: Change in BMI, blood pressure, waist circumference, waist to hip ratio, lipids, 1,25 dihydroxyvitamin D, and fractional excretion of phosphate
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 45 Years.
Gender(s): Both.
Criteria:
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)
Locations and Contacts
Massachusetts General Hospital, Boston, Massachusetts 02114, United States
Additional Information
Related publications: Burnett SM, Gunawardene SC, Bringhurst FR, Juppner H, Lee H, Finkelstein JS. Regulation of C-terminal and intact FGF-23 by dietary phosphate in men and women. J Bone Miner Res. 2006 Aug;21(8):1187-96. Burnett-Bowie SM, Mendoza N, Leder BZ. Effects of gonadal steroid withdrawal on serum phosphate and FGF-23 levels in men. Bone. 2007 Apr;40(4):913-8. Epub 2006 Dec 8.
Starting date: May 2006
Ending date: February 2008
Last updated: March 26, 2008
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