The impact of diabetes mellitus on vitamin D metabolism in predialysis patients

Bone. 2009 Nov;45(5):949-55. doi: 10.1016/j.bone.2009.07.016. Epub 2009 Jul 23.

Abstract

Although diabetes mellitus (DM) disturbs bone metabolism, little is known concerning its effects on laboratory abnormalities in chronic kidney disease-mineral and bone disorders (CKD-MBD). We extracted data for 602 patients from the Osaka Vitamin D Study in patients with CKD (OVIDS-CKD), an observational study enrolling predialysis outpatients. No enrolled patients received vitamin D, bisphosphonate, estrogen or raloxifene. We measured 1- 84 PTH, 25-hydroxyvitamin D (25D), calcitriol, fibroblast growth factor-23 (FGF-23), calcium (Ca), and phosphate (P). Since there were 112 DM patients (group D), we extracted 112 age-, sex-, and eGFR-matched non-DM counterparts (group N). We compared biochemical markers between groups, and then performed multiple regression analyses for all 602 subjects to confirm the results obtained. Group D had significantly higher corrected Ca and P than group N throughout all stages of CKD. In group D, 25D decreased as renal function declined, while in group N it remained constant (interaction P<0.05). Despite higher P and poorer vitamin D status in DM, there were no differences in 1- 84 PTH level between group D and group N stratified by stage of CKD, resulting in significantly lower calcitriol levels in group D in late CKD. Multiple regression analyses revealed that DM was significantly associated with low vitamin D status even with adjustment for urinary protein, and that this poorer vitamin D status in DM was responsible for lower calcitriol level associated with DM. Despite higher P, lower FGF-23 in early CKD (stages 1 + 2) and comparable level of FGF-23 in late stages of CKD (stages 3, 4, and 5) were observed in group D. We interpreted these results to indicate that inappropriate production of FGF-23 in DM might explain higher serum phosphate in DM. Multiple regression analysis with adjustment for covariates confirmed an independent relationship between DM and low FGF-23, implying the existence of dysfunction or decreased density of osteocytes in DM. Given the origin of these phosphaturic hormones, DM may thus have markedly deleterious effects on parathyroid and bone. Poorer vitamin D status and higher CaP product might be partly responsible for functional and structural changes of vasculature, respectively, in DM.

MeSH terms

  • Aged
  • Biomarkers / blood
  • Bone Density / physiology
  • Calcitriol / blood
  • Calcium / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / physiopathology
  • Demography
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / metabolism*
  • Diabetes Mellitus / physiopathology
  • Female
  • Fibroblast Growth Factors / blood
  • Humans
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / physiopathology
  • Kidney Function Tests
  • Male
  • Middle Aged
  • Parathyroid Hormone / blood
  • Phosphates / blood
  • Proteinuria / blood
  • Proteinuria / complications
  • Regression Analysis
  • Renal Dialysis*
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D / metabolism*

Substances

  • Biomarkers
  • Parathyroid Hormone
  • Phosphates
  • Vitamin D
  • Fibroblast Growth Factors
  • fibroblast growth factor 23
  • 25-hydroxyvitamin D
  • Calcitriol
  • Calcium