| Autonomic neuropathy predisposes to rosiglitazone-induced vascular leakage in insulin-treated patients with type 2 diabetes: a randomised, controlled trial on thiazolidinedione-induced vascular leakage. | |
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MedLine Citation:
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PMID: 20499046 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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AIMS/HYPOTHESIS: The mechanism of fluid-related complications caused by thiazolidinedione derivatives is unclear. One potential mechanism is thiazolidinedione-induced arterial vasodilatation, which results in vascular leakage and a fall in blood pressure, normally counterbalanced by sympathetic activation and subsequent renal fluid retention. We hypothesised that thiazolidinedione-induced vascular leakage will be particularly prominent in patients with autonomic neuropathy. METHODS: We conducted a randomised, double-blind, placebo-controlled, parallel study in 40 patients with type 2 diabetes on insulin treatment recruited from a university medical centre. The randomisation was performed by a central office using a randomisation schedule. Both treatment groups, placebo (n = 21) and rosiglitazone (n = 19), were stratified for sex and level of autonomic neuropathy as assessed by Ewing score (<2.5 or >or=2.5). We investigated the effects of 16 weeks of treatment with rosiglitazone 4 mg twice daily on vascular leakage (transcapillary escape rate of albumin, TERalb), body weight, extracellular volume and plasma volume. RESULTS: Thirty-nine patients were included in the analysis. In patients with high Ewing scores (n = 16), rosiglitazone increased TERalb significantly (DeltaTERalb: rosiglitazone +2.43 +/- 0.45%/h, placebo -0.11 +/- 0.15%/h, p = 0.002), while rosiglitazone had no effect in the patients with low Ewing scores (n = 23). Rosiglitazone-induced increases in TERalb and Ewing score at baseline were correlated (r = 0.65, p = 0.02). There was no correlation between Ewing score and rosiglitazone-induced changes in fluid variables. One subject was withdrawn from the study because of atrial fibrillation. CONCLUSIONS/INTERPRETATION: Rosiglitazone may increase vascular leakage in insulin-treated patients with type 2 diabetes with autonomic neuropathy. Autonomic neuropathy did not exaggerate rosiglitazone-induced fluid retention. Therefore, autonomic neuropathy should be considered as a risk factor for thiazolidinedione-induced oedema, not for thiazolidinedione-induced fluid retention. TRIAL REGISTRATION: ClinicalTrials.gov NCT00422955. FUNDING: GlaxoSmithKline. |
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Authors:
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A J Rennings; P Smits; M W Stewart; C J Tack |
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Publication Detail:
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Type: Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't Date: 2010-05-25 |
Journal Detail:
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Title: Diabetologia Volume: 53 ISSN: 1432-0428 ISO Abbreviation: Diabetologia Publication Date: 2010 Sep |
Date Detail:
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Created Date: 2010-07-28 Completed Date: 2010-11-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0006777 Medline TA: Diabetologia Country: Germany |
Other Details:
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Languages: eng Pagination: 1856-66 Citation Subset: IM |
Affiliation:
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Department of Pharmacology-Toxicology 149, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands. A.Rennings@pharmtox.umcn.nl |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged Capillary Permeability / drug effects* Diabetes Mellitus, Type 2 / drug therapy* Diabetic Neuropathies / complications* Double-Blind Method Female Humans Hypoglycemic Agents / adverse effects*, therapeutic use* Insulin / therapeutic use* Male Middle Aged Thiazolidinediones / adverse effects*, therapeutic use Vasodilation / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Hypoglycemic Agents; 0/Thiazolidinediones; 11061-68-0/Insulin; 122320-73-4/rosiglitazone |
| Comments/Corrections | |
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