minimal model), as modified by Finegood et al64 to quantify glucose tolerance, insulin response, insulin sensitivity, and glucose effectiveness; and stepped hypoglycemic clamp tests, to measure hormonal glucose counterregulation, autonomic, and neuroglycopenic symptoms in response to hypoglycemia.32

Key to any analysis of the benefits of islet transplants are the assessments of the development, progression, and reversal of microvascular and macrovascular complications; health-related quality of life; cost-utility; and life expectancy. The first pilot study to address health-related quality of life in islet recipients used telephone interviews; the survey instruments were the Health Utilities Index Mark 3, SF-32 version 2, Hypoglycemia Fear Survey, and Audit of Diabetes Dependent Quality of Life Survey65 and showed a marked improvement in studied parameters.

Immunosuppression. Shapiro et al developed a glucocorticoid-free immunosuppressive protocol, which markedly improved islet transplant outcomes. Their protocol consisted of the IL-2 receptor blocker daclizumab for induction, then sirolimus and low-dose tacrolimus for maintenance immunosuppression.26 Daclizumab induction therapy was given intravenously at a dose of 1 mg/kg every 14 days for a total of 5 doses over a 10-week period, thus allowing an extended period for a supplemental islet transplant procedure. If the second islet transplant procedure occurred more than 10 weeks after the first, the course of daclizumab was repeated. No glucocorticoids were given at any time. Sirolimus was dosed to achieve and maintain trough levels of 12 to 15 ng/mL for the first 3 months and of 7 to 10 ng/mL thereafter. Tacrolimus was administered at an initial dose of 1 mg twice daily, then adjusted to maintain a trough concentration at 12 hours of 3 to 6 ng/mL. Type 1 diabetic islet allograft recipients reliably achieved and maintained freedom from the need of exogenous insulin after transplantation of an adequate mass of islets prepared from 2 to 4 donor organs, suggesting that the protocol by Shapiro et al protected against alloimmune and autoimmune reactivity.26,66

The success reported by the Edmonton group using glucocorticoid-free immunosuppression involving sirolimus has been confirmed by other institutions.45,67-69 Immunosuppression with daclizumab, sirolimus, and reduced-dose tacrolimus has evolved as the gold standard for type 1 diabetic islet transplant recipients. A multicenter trial (with 9 participating islet transplant centers in North America and Europe) is currently underway to evaluate, in more detail, the safety and efficacy of the Edmonton immunosuppressive protocol.

The acute, and in particular, long-term risks associated with novel immuno-suppressive regimens are unknown. The preliminary results on about 300 islet recipients since 1995 provide only incomplete information as to the risks of immunosuppression. Since publication of the Edmonton trial, most islet transplants are performed as solitary islet transplants in nonuremic recipients whose diabetes is complicated by hypoglycemia unawareness. Invasive CMV disease, opportunistic infections, post-transplant lymphoproliferative disorders, and other malignancies have not been reported in this recipient category. These encouraging results are presumably related to the small CMV viral load transferred with islet products,70 the exclusion at most institutions of EBV-negative patients from participation in

Supplements For Diabetics

Supplements For Diabetics

All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.

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