Can thiazolidinediones delay disease progression in type 2 diabetes?

ABSTRACT

Background: Type 2 diabetes results from increasing insulin resistance coupled with progressive loss of β-cell function. Further deterioration of β-cell function is associated with progression of diabetes and the potential development of microvascular and macrovascular complications.

Scope: This review examines current knowledge of β-cell function and uses this information to assess how the results of ongoing trials could increase our understanding of disease progression and potential interventions. Data were derived from a Medline search using the search terms ‘β-cell dysfunction’, ‘IGT’, ‘thiazolidinediones’, ‘metformin’, and ‘sulfonylurea’.

Results: The mechanisms that underlie β-cell dysfunction are complex and most likely involve the interplay of a range of factors that reduce both β-cell mass and secretory function. These include detrimental effects associated with hyperglycemia itself, elevated free fatty acids, and inflammatory responses linked to adipocyte-derived cytokines, with apoptosis a key underlying mechanism. Early intervention with treatments that address these defects, and preserve β-cell function while improving insulin sensitivity, may delay disease progression in patients with type 2 diabetes and also prevent the development of diabetes in ‘at-risk’ individuals. Two of the studies examining the effects of interventions on development and progression of diabetes that are due to report shortly are ADOPT (A Diabetes Outcome Progression Trial), comparing a thiazolidinedione, metformin and a sulfonylurea in patients with type 2 diabetes not previously treated with oral hypoglycemic agents, and DREAM (Diabetes REduction Assessment with ramipril and rosiglitazone Medication), assessing the effects of a thiazolidinedione and an angiotensin-converting enzyme inhibitor in subjects with impaired glucose tolerance and/or impaired fasting glucose.

Conclusions: Although we do not have a full understanding of the mechanisms driving progression of type 2 diabetes, there is growing evidence that we may be able to modulate them and thereby improve patient outcomes.

Key words: :

• β-cell function
• Glycemic control
• Impaired glucose tolerance
• Insulin resistance
• Prevention
• Thiazolidinedione
• Type 2 diabetes