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Kendall Moseley, M.D. and Todd T. Brown, M.D, Ph.D.
02-03-2011
- Estimated that 1 billion people worldwide have vitamin D deficiency or insufficiency (Holick).
- Studies ongoing to determine prevalence of hypovitaminosis D in type 1 diabetes (T1DM) and type 2 diabetes (T2DM); preliminary data suggests prevalence may be as high as 30% in T2DM (Targher).
- Vitamin D optimizes intestinal calcium and phosphorus absorption to maintain skeletal mineral content.
- Sources of vitamin D include sunlight exposure, dietary intake, dietary supplements.
- Vitamin D derived from sunlight or dietary sources metabolized in the liver to form 25-hydroxyvitamin D (25(OH)D)
- 25-hydroxyvitamin D metabolized by 1-alpha-hydroxylase in kidneys to active form, 1,25-dihydroxyvitamin D (1,25(OH)D)
- Vitamin D deficiency in adults can lead to development of osteopenia, osteoporosis, and/or osteomalacia; muscle weakness; and increased risk of fractures and falls (Holick).
- Vitamin D may have other roles in human health including modulation of immune function and reduction of inflammation.
- Gold standard: high-performance liquid chromatography , but expensive and cumbersome (Holick)
- Two assay types are in common use: immunoassay and liquid chromatography tandem mass spectroscopy (LC-MS). Immunoassays give a total 25(OH)D measurement, whereas LC-MS measures serum D2 and D3, the sum of which gives the total 25(OH)D concentration. Relative accuracy of these two methodologies is debated.
- Radioimmunoassays (RIA) used today in clinical practice measure both 1,25(OH)D2 and 1,25(OH)D3.
- Calcium and parathyroid hormone (PTH) tests may also be helpful if hypocalcemia suspected.
- No definite guidelines for screening for vitamin D deficiency or insufficiency in the otherwise-healthy population or in diabetes.
- 25(OH)D levels determine a person's vitamin D stores and thus status (Holick).
- Consider screening with 25(OH)D level in the elderly or those with limited sunlight exposure, excessive sunscreen use, minimal dairy intake, dark skin, obesity or malnutrition.
- Consider checking 25(OH)D level in workup for secondary causes of osteoporosis, persons with known or suspected celiac disease (CD), persons with other malabsorption conditions (ulcerative colitis, gastric bypass, etc.) (Taxel)
- Hypocalcemia on routine bloodwork or symptoms of tetany, paresthesias or muscle cramps.
- Symptoms such as fatigue, muscle weakness, and bony pain may be non-specific.
- Low 25(OH)D due to reduced synthesis: dark skin pigmentation, sunscreen use, older age, winter season, higher latitudes, liver disease (Holick).
- Low 25(OH)D due to decreased absorption: celiac disease, cystic fibrosis, Whipple's disease, gastric bypass, obesity (vitamin D sequestered in fat).
- Low 25(OH) due to decreased dietary intake.
- Low 25(OH)D due to increased catabolism: HIV therapy, anti-rejection medications, anti-seizure medications, steroids.
- Elevated 1,25(OH)D and low 25(OH)D: primary hyperparathyroidism, granulomatous disease, lymphoma.
- No definite consensus defining normal range of 25(OH)D or what defines vitamin D insufficiency versus deficiency (Holick).
- PTH plateaus at 25(OH)D levels between 30 and 40ng/mL, defining "normal" serum D levels as greater than 30 ng/mL
- Vitamin D insufficiency: 20-30 ng/mL
- Vitamin D deficiency: <20 ng/mL
- Vitamin D intoxication: 25(OH)D levels > 150 ng/mL in association with hypercalcemia, hypercalciuria, and hyperphosphatemia.
- Immunoassays and LC-MS assays are used most often, but discrepancies occur based on the assay used; efforts to standardize assays under way.
- 1,25(OH)D, though biologically active form of vitamin D, is not a good measure of vitamin D status due to short half-life (4-6 hours).
- Persons with vitamin D deficiency may have transient elevations in 1,25(OH)D due to elevated PTH in secondary hyperparathyroidism.
- Although 25(OH)D level of > 30 ng/mL may be considered "normal," each person has an individualized set-point for normal vitamin D, often appreciated with a concurrently normal PTH (no evident secondary hyperparathyroidism).
- A person may be within 25(OH)D range considered insufficient or deficient and still have normal PTH (no evident secondary hyperparathyroidism).
- Serum 25(OH)D level is the best indicator of vitamin D status.
- Prevalence of celiac disease in children and adolescents with T1DM may be as high as 10% (8% in adults); practitioners may screen for celiac antibodies (anti-tissue transglutaminase, anti-endomysial, anti-gliadin) and 25(OH)D levels in people with T1DM (Larsson).
- Supplementation of vitamin D in pregnancy and early childhood may reduce risk of T1DM via reduction of islet autoantibodies; this is controversial (Hyppönen)
- Low serum 25(OH)D levels associated with cardiovascular disease, obesity, beta cell dysfunction, insulin resistance, impaired glucose tolerance, metabolic syndrome, and T2DM in observational studies, although causality unclear (Cheng; Chiu; Pittas; Chonchol).
- Both T1DM and T2DM associated with increased risk of fracture; so vitamin D screening and appropriate supplementation is indicated in deficient and insufficient states to reduce fracture risk.
- Minimal adequate daily intake of vitamin D 400 IU, but may be as high as 1000 IU for older or post-menopausal adults.
- Diagnosis of vitamin D insufficiency or deficiency requires treatment with higher doses of vitamin D (e.g. ergocalciferol 50,000 IU orally once weekly for 8 weeks; repeat if vitamin D levels remain < 30 ng/mL).
- Adequate calcium intake is essential for vitamin D function and should also be optimized.
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