Evaluation of proinflammatory cytokines and inflammation markers as biomarkers for the action of thiazolidinediones in Type 2 diabetes mellitus patients and healthy volunteers
| Autor: | Adam F. Cohen, Margriet Ouwens, Marieke de Kam, Rik C. Schoemaker, Michiel J. B. Kemme, Hans Romijn, Martijn B A van Doorn, Ewoud J. van Hoogdalem, Richard Jones, K. Burggraaf |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Blood Glucose Male medicine.medical_specialty endocrine system diseases medicine.medical_treatment Type 2 diabetes Proinflammatory cytokine Rosiglitazone Leukocyte Count Double-Blind Method Internal medicine Diabetes mellitus medicine Humans Hypoglycemic Agents Pharmacology (medical) Aged Pharmacology biology business.industry Insulin C-reactive protein Type 2 Diabetes Mellitus Original Articles Middle Aged medicine.disease C-Reactive Protein Treatment Outcome Endocrinology Diabetes Mellitus Type 2 biology.protein Cytokines Patient Compliance Biomarker (medicine) Female Thiazolidinediones business Biomarkers medicine.drug |
| Zdroj: | British Journal of Clinical Pharmacology. 62:391-402 |
| ISSN: | 1365-2125 0306-5251 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text