Clinical approaches to preserving β-cell function in diabetes

Abstract

In type 2 diabetes (DM2) there is progressive deterioration of β-cell function and mass. It was found that islet function was about 50% of normal at the time of diagnosis and there was a reduction of β-cell mass of about 60% at necropsy (accelerated apoptosis). Among the interventions to preserve the β-cells, those that lead to short-term improvement of β-cell secretion are weight loss, metformin, sulfonylureas, and insulin. Long-term improvement was demonstrated with short-term insulin therapy of newly diagnosed DM2. Besides, long-term intensive insulin therapy plus metformin or triple oral therapy (metformin + glyburide + pioglitazone) for 3.5 years enabled β-cell function to be preserved for at least that period of time. Furthermore, long-term improvement was also shown with the isolated use of anti-apoptotic drugs such as glitazones, and the use of glucagon-like peptide-1 receptor agonists (GLP-1 mimetics), not inactivated by the enzyme dipeptidyl peptidase-4, and/or to inhibit that enzyme (GLP-1 enhancers). The incretin hormones are released from the gastrointestinal tract in response to nutrient ingestion to enhance glucose-dependent insulin secretion from the pancreas and overall maintenance of glucose homeostasis. Of the incretins, only GLP-1 mimetics or enhancers can be used for the treatment of DM2. Although incretin-based medications maintain β-cell function, there is no evidence that they increase β-cell mass.