Abstract:
AIMS:Thiazolidinediones (TZDs) not only enhance cellular glucose transport but are reported to have potent anti-inflammatory effects. These effects may play an important role in the insulin sensitizing mechanism, and possibly precede the effects on parameters of glucoregulation. We sought to investigate whether these anti-inflammatory effects could yield early responding biomarkers for TZD action in Type 2 diabetes mellitus (T2DM) patients and healthy volunteers (HV) to expedite early clinical development of novel compounds. METHODS:We investigated the timing of treatment effects on several proinflammatory cytokines and markers of inflammation in comparison with effects on typical measures of glucoregulation in T2DM patients and HV receiving rosiglitazone 4 mg or placebo twice daily for 6 weeks. RESULTS:We found a significant reduction in interleukin (IL)-6 [-39.4%, confidence interval (CI) - 60.0, - 8.2] and white blood cell count (-18.4%, CI - 30.2, - 4.5) after 4 weeks of treatment in the T2DM group. These anti-inflammatory effects did not precede the effects on typical parameters of glucoregulation in the T2DM group and there was no significant anti-inflammatory response in the HV group. CONCLUSION:We could not identify biomarkers that precede the effects of rosiglitazone on parameters of glucoregulation in T2DM or that have a significant response in HV. However, the IL-6 response observed in this study indicates a potential role for this cytokine as complementary biomarker in clinical 'proof of concept' studies with novel TZDs.
journal_name
Br J Clin Pharmacoljournal_title
British journal of clinical pharmacologyauthors
van Doorn M,Kemme M,Ouwens M,van Hoogdalem EJ,Jones R,Romijn H,de Kam M,Schoemaker R,Burggraaf K,Cohen Adoi
10.1111/j.1365-2125.2005.02532.xsubject
Has Abstractpub_date
2006-10-01 00:00:00pages
391-402issue
4eissn
0306-5251issn
1365-2125pii
BCP2532journal_volume
62pub_type
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