With Type 1 Diabetes Mellitus

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At the turn of the century a patient diagnosed with Type 1 diabetes mellitus had average life expectancy of only two years. The development of insulin as a therapeutic agent revolutionized the treatment of diabetes mellitus by changing it from a rapidly fatal disease into a chronic illness. Unfortunately this increased longevity brought to the fore serious secondary complications including nephropathy, neuropathy, retinopathy and macro- and microvascular complications in survivors 10 to 20 years after disease onset. The annual national direct and indirect costs of Type 1 and 2 diabetes in 2002 - including hospital and physician care, laboratory tests, pharmaceutical products, and patient workdays lost because of disability and premature death - exceeded $130 billion.1

Currently, the prevalence of Type 1 diabetes in the United States is estimated to be 1,000,000 individuals, and 30,000 new cases are diagnosed each year. Presently there is no practical mechanical insulin-delivery method coupled with an effective glucose-sensory device that could replace the function of the impaired cells to administer insulin with a degree of control to produce a near constant euglycemic state without risk of hypoglycemia. Therefore, persons with Type 1 diabetes are resigned to manually regulate blood glucose levels by subcutaneous insulin injection, and as a consequence, typically exhibit wide deviations of plasma glucose levels from hour to hour and from day to day. Since hypoglycemia is intolerable, glucose control must error on the high side and patients live with relative chronic hyperglycemia as evidenced by elevated HgbA1c levels. Hyperglycemia is the most important factor in the development and progression of the secondary complications of diabetes. These observations and the known fact that conventional exogenous insulin therapy cannot prevent the development of the secondary complications of Type 1 diabetes, has lead to a search for alternative methods of treatment designed to achieve better glycemic control to the extent that the progression of long-term complications can be altered.

The only treatments that have been demonstrated to influence the progression of secondary complications normalize or near normalize glycosylated hemoglobin levels - beta cell replacement therapy with pancreas or islet transplantation and intensive insulin therapy. Islet transplantation is discussed in Chapter 8. Pancreas transplantation is superior to that and intensive insulin therapy with regard to the efficacy of achieving glycemic control, and its beneficial effects on diabetic

Organ Transplantation, 2nd edition, edited by Frank P. Stuart, Michael M. Abecassis and Dixon B. Kaufman. ©2003 Landes Bioscience.

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