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 Presentation

"Insulin Resistance and Disease Progression in Diabetes: An Endocrine Perspective"

Dr. Ehud Ur (biography)
English - 2002-11-23 - 45 minutes
(45 slides)

Summary :
It is estimated that by the year 2020 there will be approximately 250 million people affected by Type 2 diabetes (DM2) worldwide. In Canada, the current prevalence is expected to double by that date.
Although the underlying cause of diabetes is unknown, it is clear that insulin resistance (IR) plays a major role in the development and progression of the disease. Progressively worsening insensitivity to the action of insulin leads to compensatory hyperinsulinemia, achieved through increased b-cell secretion. As long as the hyperinsulinemia is adequate to overcome the IR, glucose tolerance remains normal. Once insulin secretion cannot keep pace with the underlying resistance, glucose intolerance and overt DM2 develop. Evidence is accumulating that IR has an important role in this progressive deterioration in b-cell function.
What are evident from this model is that the natural history of the disease is prolonged and that many key features predate the onset of hyperglycemia and clinically evident disease. The years of exposure to the burdens of metabolic dysregulation represent a significant risk even before diagnosis, and explain why so many patients (up to 50%) have complication at the time of presentation. Thus, diabetes prevention is emerging as an important therapeutic strategy. A number of recent studies suggest that in patients with impaired glucose tolerance (IGT) diabetes can be deferred or perhaps even prevented, by interventions that have included lifestyle change, metformin, acarbose or xenical.
The advent of the thiazolidinedione (TZD) insulin-sensitizing group of drugs has had a huge impact on our understanding of IR. These agents enhance insulin action and are now in widespread use as therapeutic agents for the treatment of DM2. Unpublished data from the TRIPOD study, in women who had gestational diabetes, and from the Diabetes Prevention Program in an IGT population, suggest that impressive reduction in progression to diabetes can be found with the use of the TZD troglitazone (no longer available due to hepatotoxic effects). This, together with animal data showing the effect of the TZD rosiglitazone on b-cell function, and preliminary clinical trial data showing sustained glycemic control over 3 years with this agent, suggest that TZD therapy may prove to be the most effective approach for preventing disease progression both in the pre-diabetes and the diabetes phases of the disease. Major clinical trials are currently underway to test the hypotheses in greater detail.


Learning objectives :
The participant will gain some new insights into diabetes progression and treatment:

- Treatment gaps in diabetes would be helped by targeting microvascular and macrovascular complications
- Our knowledge of the progression of diabetes is evolving and now includes the role of insulin resistance
- Several clinical trials are now underway to study diabetes prevention


Bibliographic references :
Almind K, Kulkarni RN, Lannon SM, Kahn CR. 2003. Identification of interactive Loci linked to insulin and leptin in mice with genetic insulin resistance. Diabetes 52(6):1535-43.
http://www.ncbi.nlm.nih.gov/entrez

   


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