Stopping Type 1 Diabetes: Attempts to Prevent or Cure Type 1 Diabetes in Man
- From the Diabetes Research Institute, University of Miami Miller School of Medicine, Miami, Florida.
- Corresponding author: Jay S. Skyler, .
Type 1 diabetes—or, more accurately, type 1A diabetes—is thought to arise from selective immunologically mediated destruction of the insulin-producing β-cells in the pancreatic islets of Langerhans with consequent insulin deficiency (1). This occurs in individuals in whom genetic susceptibility outweighs genetic protection and is probably initiated by environmental factors not yet clearly defined. The disease arises via a cellular-mediated immune process, presumably a specific reaction to one or more β-cell proteins (autoantigens). There is consequent progressive impairment of β-cell function and apparent decline in β-cell mass. A secondary humoral immune response is characterized by the appearance of autoantibodies that serve as markers of the immune damage to β-cells. This insidious type 1 diabetes disease process generally evolves over a variable period of years (Fig. 1). The decline in β-cell function—and presumably in mass—is evidenced metabolically by loss of first-phase insulin response to an intravenous glucose challenge and later by the appearance of impairment in glycemic regulation, which is manifested as dysglycemia either as impaired glucose tolerance, impaired fasting glucose, or “indeterminate” glucose levels (values >200 mg/dl [11.1 mmol/l] at 30, 60, or 90 min during an oral glucose tolerance test). Ultimately, the clinical syndrome of type 1 diabetes becomes evident when the majority of β-cell function has been lost and presumably most β-cells have been destroyed; at this juncture, frank hyperglycemia supervenes. Although that broad sequence can be articulated, there are still gaps in many of the details. Further understanding of the nature of the disease process will facilitate the design of intervention strategies aimed at abrogating β-cell destruction and ultimately at prophylaxis of type 1 diabetes.