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- May 12, 2008 |
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"Could Glitazones Have Unique Properties in Early Diabetes Therapy?"Prof. Bernard Zinman (biography)
English - 2006-09-13 - 32 minutes
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Summary :
It is now well established that type 2 diabetes mellitus (T2DM) is a progressive disease characterized by beta-cell failure in the milieu of insulin resistance.The glitazones or thiazolidinediones (TZD) have been documented to have a robust effect on improving glucose control when used as monotherapy or in combination with other glucose lowering medications. In addition, accumulating evidence suggests that TZDs may have additional properties as it relates to beta-cell function and cardiovascular risk factors. In the context of beta-cell function, pre-clinical studies in various animal models of progressive glucose intolerance have demonstrated that TZDs can have unique effects on beta-cell preservation. In addition, Buchanan has demonstrated that in patients previously diagnosed with gestational diabetes mellitus (GDM), treatment with TZDs can significantly delay the development of T2DM principally as a consequence of improved beta-cell function.
The number of therapies for T2DM has increased substantially over the last few years. Although, there are many studies demonstrating improved glycaemic control with these therapies, there are remarkably few head-to-head studies comparing the various therapeutic options. In this context, ADOPT (A Diabetes Outcome Progression Trial) is designed to determine whether TZDs have unique properties as compared to metformin and sulphonylureas in the early management of T2DM. Specifically, ADOPT will compare the effects of monotherapy treatment with rosiglitazone, metformin and/or glyburide/glibenclamide on the improvement and maintenance of glycaemic control in patients recently diagnosed with T2DM. The primary outcome of this large (4,356 participants) North American and European study is the time to monotherapy failure defined as a fasting plasma glucose (FPG) greater than 10 mmol/l (180 mg/dl).Other outcomes for this double-blind, randomized controlled trial focus on measures of beta-cell function, insulin sensitivity, HbA1c, markers of cardiovascular risk, quality of life, and pharmaco-economic measures. Results of the ADOPT study will be reported at the International Diabetes Federation (IDF) meeting in Cape Town, SA in December of 2006.
It is well recognized that there is a metabolic continuum starting with obesity and insulin resistance, pre-diabetes (impaired fasting glucose, impaired glucose tolerance), early diabetes, and long-term diabetes with micro- and macrovascular complications. Current studies are evaluating the role of TZDs at various points in this continuum and the results will help establish whether there is a unique role for TZDs in the context of early diabetes intervention.
Learning objectives :
After viewing this presentation the participant will be able to discuss:
- Guidelines for management of hyperglycaemia in T2DM.
- Mechanisms of action of glitazones.
- The ADOPT trial: study design, baseline characteristics of
participants including characteristics by GAD antibody
status.
- Outcome studies in IGT/IFG/T2DM.
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