title: Impact of activated vitamin D on insulin resistance in nondiabetic chronic kidney disease patients.
abstract: Although vitamin D deficiency has been associated with increased insulin resistance, a causal link has not been established. Interpreting the relationship has been confounded by a close correlation between vitamin D deficiency and obesity. The current clinical approach of assessing endogenous 25-hydroxyvitamin D (25(OH)D) concentrations in patients with chronic kidney disease (CKD), and independently administering activated vitamin D (AD), allows a unique opportunity to clarify cause and effect in the relationship of vitamin D, obesity and insulin resistance.
  
  
  METHODS
  We assessed how 25(OH)D and body mass index (BMI) related to fasting insulin concentrations in 120 nondiabetic patients with CKD. In addition, we described how treatment with AD modified these relationships.
  
  
  RESULTS
  In the full cohort, fasting insulin concentrations varied inversely with both 25(OH)D (r = -0·22, P = 0·02) and BMI (r = -0·36, P < 0·0001). The administration of AD altered these relationships. In individuals treated with AD, there was no association between 25(OH)D and fasting insulin, and the mean fasting insulin concentrations were significantly lower than in those not receiving AD (40·5 ± 22·0 vs 54·1 ± 30·9 pm, P = 0·01). In a multivariate analysis, both AD treatment and BMI were independent predictors of fasting insulin. Furthermore, obese patients treated with AD had insulin concentrations similar to nonobese patients (46·1 ± 24·9 vs 40·2 ± 21·5 pm), whereas untreated obese patients had markedly higher fasting insulin concentrations (74·4 ± 33·4 pm, P = 0·003).
  
  
  CONCLUSIONS
  25(OH)D deficiency is associated with insulin resistance in CKD. Replacement with pharmacologic doses of AD is associated with lower fasting insulin concentrations, especially in obese patients.
authors.affiliation: Division of Nephrology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Friedman
authors.forename: Nisha
authors.initials: N
authors.lastname: Bhatt
authors.forename: Najwah S
authors.initials: NS
authors.lastname: Hayman
authors.forename: Brendan J
authors.initials: BJ
authors.lastname: Nichols
authors.forename: Mark
authors.initials: M
authors.lastname: Herman
authors.forename: Nikolay
authors.initials: N
authors.lastname: Nikolaev
authors.forename: John
authors.initials: J
authors.lastname: Danziger
mesh_terms: D000328:Adult; D000368:Aged; D001823:Body Composition / Q000502:physiology; D015992:Body Mass Index; D015331:Cohort Studies; D005215:Fasting / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications / Q000453:epidemiology / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000097:blood / Q000502:physiology; D014808:Vitamin D Deficiency / Q000097:blood / Q000150:complications / Q000453:epidemiology / Q000378:metabolism
chemical_list: D007328:Insulin; D014807:Vitamin D; C104450:25-hydroxyvitamin D