The role of 25-hydroxyvitamin D deficiency in promoting insulin resistance and inflammation in patients with Chronic Kidney Disease: a randomised controlled trial

Petchey, William, Hickman, Ingrid J., Duncan, Emma, Prins, Johannes B., Hawley, Carmel M., Johnson, David W., Barraclough, Katherine and Isbel, Nicole M. (2009) The role of 25-hydroxyvitamin D deficiency in promoting insulin resistance and inflammation in patients with Chronic Kidney Disease: a randomised controlled trial. BMC Nephrology, 10 41: x-x. doi:10.1186/1471-2369-10-41


Author Petchey, William
Hickman, Ingrid J.
Duncan, Emma
Prins, Johannes B.
Hawley, Carmel M.
Johnson, David W.
Barraclough, Katherine
Isbel, Nicole M.
Title The role of 25-hydroxyvitamin D deficiency in promoting insulin resistance and inflammation in patients with Chronic Kidney Disease: a randomised controlled trial
Journal name BMC Nephrology   Check publisher's open access policy
ISSN 1471-2369
Publication date 2009-12-10
Year available 2009
Sub-type Article (original research)
DOI 10.1186/1471-2369-10-41
Open Access Status DOI
Volume 10
Issue 41
Start page x
End page x
Total pages 6
Editor Norton, Melissa
Place of publication UK
Publisher BioMed Central Ltd
Collection year 2010
Language eng
Subject C1
920199 Clinical Health (Organs, Diseases and Abnormal Conditions) not elsewhere classified
110312 Nephrology and Urology
Abstract Approximately 50% of patients with stage 3 Chronic Kidney Disease are 25-hydroxyvitamin D insufficient, and this prevalence increases with falling glomerular filtration rate. Vitamin D is now recognised as having pleiotropic roles beyond bone and mineral homeostasis, with the vitamin D receptor and metabolising machinery identified in multiple tissues. Worryingly, recent observational data has highlighted an association between hypovitaminosis D and increased cardiovascular mortality, possibly mediated via vitamin D effects on insulin resistance and inflammation. The main hypothesis of this study is that oral Vitamin D supplementation will ameliorate insulin resistance in patients with Chronic Kidney Disease stage 3 when compared to placebo. Secondary hypotheses will test whether this is associated with decreased inflammation and bone/adipocyte-endocrine dysregulation. Methods/Design This study is a single-centre, double-blinded, randomised, placebo-controlled trial. Inclusion criteria include; estimated glomerular filtration rate 30-59 ml/min/1.73 m2; aged ≥18 on entry to study; and serum 25-hydroxyvitamin D levels <75 nmol/L. Patients will be randomised 1:1 to receive either oral cholecalciferol 2000IU/day or placebo for 6 months. The primary outcome will be an improvement in insulin sensitivity, measured by hyperinsulinaemic euglycaemic clamp. Secondary outcome measures will include serum parathyroid hormone, cytokines (Interleukin-1β, Interleukin-6, Tumour Necrosis Factor alpha), adiponectin (total and High Molecular Weight), osteocalcin (carboxylated and under-carboxylated), peripheral blood mononuclear cell Nuclear Factor Kappa-B p65 binding activity, brachial artery reactivity, aortic pulse wave velocity and waveform analysis, and indirect calorimetry. All outcome measures will be performed at baseline and end of study. Discussion To date, no randomised controlled trial has been performed in pre-dialysis CKD patients to study the correlation between vitamin D status with supplementation, insulin resistance and markers of adverse cardiovascular risk. We remain hopeful that cholecalciferol may be a safe intervention, with health benefits beyond those related to bone-mineral homeostasis. Trial registration Australian and New Zealand Clinical Trials Registry ACTRN12609000246280
Q-Index Code C1
Q-Index Status Confirmed Code

Document type: Journal Article
Sub-type: Article (original research)
Collections: 2010 Higher Education Research Data Collection
School of Medicine Publications
 
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Created: Fri, 26 Mar 2010, 12:14:08 EST by Denise Wilson on behalf of Medicine - Princess Alexandra Hospital