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Goals of Treatment for Type 2 Diabetes

β-Cell preservation for glycemic control

  1. Piero Marchetti, MD, PHD,
  2. Roberto Lupi, BS,
  3. Silvia Del Guerra, BS,
  4. Marco Bugliani, PHD,
  5. Valentina D'Aleo, BS,
  6. Margherita Occhipinti, MD,
  7. Ugo Boggi, MD,
  8. Lorella Marselli, MD and
  9. Matilde Masini, MD
  1. From the Department of Endocrinology and Metabolism, University of Pisa, Pisa, Italy.
  1. Corresponding author: Piero Marchetti, marchant{at}immr.med.unipi.it.

Type 2 diabetes is the most common form of diabetes in humans and results from a combination of genetic and acquired factors that impair β-cell function and tissue insulin sensitivity (1,2). However, there is growing evidence that β-cell dysfunction is crucial for the development and progression of this form of diabetes (3,4). Reduced β-cell functional mass in diabetes, and other categories of glucose intolerance, has been described by several authors, and decreased islet and/or β-cell volume in the pancreas of type 2 diabetic patients has been consistently reported. In addition, studies conducted in patients, and isolated islets, have shown both quantitative and qualitative defects of glucose-stimulated insulin secretion. Predictably, therefore, much interest is focused on the possibility of preserving the β-cell to prevent the onset of diabetes, or impede the progressive deterioration of glycemic control, observed after diagnosis and developing over the years. In this brief overview, several major features of β-cell dysfunction in different conditions (from normal glucose tolerance [NGT] to overt diabetes) will be described; thereafter, the possibility/feasibility of maintaining or restoring β-cell functional mass in type 2 diabetes, to prevent deterioration of glucose control, will be discussed.

β-CELL DYSFUNCTION AND TYPE 2 DIABETES: IN VIVO STUDIES

Several cross-sectional and prospective studies showed that β-cell dysfunction plays a major role in determining the onset and progression of type 2 diabetes. When insulin response to an oral glucose tolerance test and insulin sensitivity during euglycemic insulin clamp were measured in 388 individuals (138 with NGT; 49 with impaired glucose tolerance [IGT], and 201 with type 2 diabetes), a progressive decline of β-cell function (with insulin release corrected for glycemic stimulus and degree of insulin resistance) was observed; this decline commenced in normal glucose tolerant subjects (5). Furthermore, in 188 subjects, spanning the range from NGT to IGT or overt diabetes, it was found that …

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