Pathogenesis of Type 2 Diabetes Mellitus

Pathogenesis of Type 1 Diabetes Mellitus Type 1 diabetes mellitus results from a cellular-mediated autoimmune destruction of the insuhn-secreting cells of pancreatic p-cells. In the vast majority of patients, the destruction is mediated by T cells. This is termed type lA or immune-mediated diabetes (Box 25-2). The a-, 8-, and other islet cells are preserved. The islet cells have a chronic mononuclear cell infiltrate, called insulitis. The autoimmune process leading to type 1 diabetes begins months or years before the clinical presentation, and an 80% to 90% reduction in the volume of the j3-cells is required to induce symptomatic type 1 diabetes. The rate of islet cell destruction is variable and is usually more rapid in children than in adults. 

The most practical markers of P cell autoimmunity are circulating antibodies, which can be detected in the serum years before the onset of hyperglycemia. The best characterized antibodies 

Insulin autoantibodies (lAAs) are present in more than 90% of children who develop type 1 diabetes before age 5, but in fewer than 40% of individuals developing dia-betes after age 12. Their frequency in healthy people is similar to tliat of ICA. A radioisotopic method that calculates the displaceable insulin radiohgand binding after the addition of excess nonradiolabeled insulin is recommended for lAA. Results are positive when concentrations exceed the mean +2 (or 3) standard deviations (SD) of healthy controls. An important caveat is that insulin antibodies develop after insrdin therapy, even in those persons who use human insulin. 

Insulinoma-associated antigens (IA-2A and lA-2jiA), directed against two tyrosine phosphatases, have been detected in more than 50% of newly diagnosed type 1 diabetes patients. A widely used method to measure IA-2A uses S-labeled recombinant IA-2 in a dual micromethod and RIA. The concurrent analysis of IA-2 and GADgg in a single assay has been reported.  

Although antibodies to bovine serum albumin have been reported m patients with newly diagnosed type 1 diabetes, this model is contentious, and conflicting data exist. 

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