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	James L. Holly, M.D.

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EPM Tools - Progression to Diabetes - Beta Cell Rest

The following is from Dr. Thomas A. Buchanan's presentation at the Ist International Congress on Prediabetes and the Metabolic Syndrome. April, 2005, Berlin, Germany

What is Pre-Diabetes? His definition:

"Rising glucose levels and
falling B-cell function
Occurring on a background of insulin resistance."

General concepts:

IGT and IFG are not synonymous with Prediabetes.
People with normal glucose tolerance can have pre-diabetes.
Rising glucose is the important clinical phenotype.

What are the effects of thiazolidinediones (TZD) on progression to Diabetes?

TRIPOD (TRoglitazone in Prevention of Diabetes) used Rezulin (has been withdrawn from the market).
PIPOD used Pioglitazone (Actos)

PIPOD: Main Messages

Actos treatment was associated with a relatively low incidence rate of diabetes
Actos stabilized falling B-cell function in women who had been losing function on placebo and maintained relatively stable b-cell function in women who had already been stabilized on Rezulin.
B-cell rest (for definition see below) was associated with protection from diabetes inn PIPOD, as it was in TRIPOD.

Beta Cell Rest -- reduction in secretory demands imposed on B-cells by chronic insulin resistance

Did Pioglitazone (Actos) alter the course of b-cell function compared to the pattern observed in TRIPOD (Rezulin)? Yes

TRIPOD: Main Messages

Rezulin treatment reduced the incidence of type 2 diabetes by 55% in high-risk Hispanic women.
The mechanism for protection appeared to be a reduction in secretory demands imposed on B-cells by chronic insulin resistance (B-cell "rest")
It is impossible to stop progression toward and to type 2 diabetes (true prevention)

Role of Pharmacology in Diabetes Prevention


Step One	Screening
Step Two	Insulin Resistance
Step Three	Measure Glucose

Diabetic	Treat Diabetes

Impaired	Higher Risk

	Diet and Exercise Intervention
	Rising Glycemia -- Pharmacological treatment with TZD
	Stable Glycemia -- Continue Diet and Exercise

Normal	Lower Risk

	Diet and Exercise Advice -- Annual follow-up

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