PMID- 16995860
OWN - NLM
STAT- MEDLINE
DCOM- 20070329
LR  - 20181201
IS  - 0306-5251 (Print)
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Linking)
VI  - 62
IP  - 4
DP  - 2006 Oct
TI  - Evaluation of proinflammatory cytokines and inflammation markers as biomarkers 
      for the action of thiazolidinediones in Type 2 diabetes mellitus patients and 
      healthy volunteers.
PG  - 391-402
AB  - 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.
FAU - van Doorn, Martijn
AU  - van Doorn M
AD  - Department of Molecular Biology, Leiden University, Leiden, the Netherlands. 
      mdoorn@chdr.nl
FAU - Kemme, Michiel
AU  - Kemme M
FAU - Ouwens, Margriet
AU  - Ouwens M
FAU - van Hoogdalem, Ewoud J
AU  - van Hoogdalem EJ
FAU - Jones, Richard
AU  - Jones R
FAU - Romijn, Hans
AU  - Romijn H
FAU - de Kam, Marieke
AU  - de Kam M
FAU - Schoemaker, Rik
AU  - Schoemaker R
FAU - Burggraaf, Koos
AU  - Burggraaf K
FAU - Cohen, Adam
AU  - Cohen A
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Cytokines)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Thiazolidinediones)
RN  - 05V02F2KDG (Rosiglitazone)
RN  - 9007-41-4 (C-Reactive Protein)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Biomarkers/metabolism
MH  - Blood Glucose/metabolism
MH  - C-Reactive Protein/metabolism
MH  - Cytokines/*metabolism
MH  - Diabetes Mellitus, Type 2/*drug therapy/metabolism
MH  - Double-Blind Method
MH  - Female
MH  - Humans
MH  - Hypoglycemic Agents/*administration & dosage/pharmacokinetics
MH  - Leukocyte Count
MH  - Male
MH  - Middle Aged
MH  - Patient Compliance
MH  - Rosiglitazone
MH  - Thiazolidinediones/*administration & dosage/pharmacokinetics
MH  - Treatment Outcome
PMC - PMC1885156
EDAT- 2006/09/26 09:00
MHDA- 2007/03/30 09:00
PMCR- 2007/10/01
CRDT- 2006/09/26 09:00
PHST- 2006/09/26 09:00 [pubmed]
PHST- 2007/03/30 09:00 [medline]
PHST- 2006/09/26 09:00 [entrez]
PHST- 2007/10/01 00:00 [pmc-release]
AID - BCP2532 [pii]
AID - 10.1111/j.1365-2125.2005.02532.x [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2006 Oct;62(4):391-402. doi: 
      10.1111/j.1365-2125.2005.02532.x.