PracticeUpdate: Conference Series | ADC 2018

Clinical Islet Transplantation in Australia BY TOBY COATES MBBS, PhD, FRACP

Dr. Toby Coates Dr. Coates is Professor of Medicine and Director of Kidney and Pancreatic Islet Transplantation at the University of Adelaide, Royal Adelaide Hospital in Adelaide, South Australia. I slet transplantation is an effective therapy for selected patients with type 1 diabetes who suffer from hypoglycemic unawareness and severe metabolic instability, who have failed other technologies and therapeutic interventions. In Australia, islet transplantation is offered through the Australian Islet Consortium at three centres: Westmead Hospital in Sydney, St Vincent’s Hospital in Melbourne, and the Royal Adelaide Hospital in Adelaide. Outcomes for clinical islet transplantation have significantly improved, with 60% of recipients becoming insulin independent and some patients remaining insulin independent for up to 9 years. All patients transplanted for hypoglycemic unawareness experience a dramatic resolution of this symptom, which persists for as long as the transplanted islets produce insulin even without insulin independence. Complications of islet transplantation are min- imal and mainly relate to the side effects of immunosuppression, required to prevent trans- plant rejection and recurrence of autoimmune diabetes. An important new clinical trial to induce toler- ance for islet transplantation is now recruiting at all three sites, supported by grant funding from JDRF Australia. Practitioners can refer patients for islet transplantation by contacting the islet coordinators at each of the hospitals. Wait-listed patients are generally transplanted within a few months. Nationally Funded Centre status for the program ensures that the costs of patients travelling interstate to access islet transplantation are covered.

Comment BY JOSEPHINE FORBES PhD

Professor Forbes is Program Leader in Chronic Disease at Mater Research Institute–The University of Queensland in Brisbane, Australia. C hronic complications in people with T1D begin much earlier than previously thought. In adolescents with T1D, high-risk stratifica- tion for future kidney and CVD is possible using the highest tertile of the urinary excretion of the protein albumin (uACR), even with values within a "normal" range.

Professor Josephine Forbes

My colleagues and I showed that early kidney damage in young adults with T1D (using uACR and glomerular filtration rate), was accompanied by defects in cellular power stations, the mitochondria. The mitochondria produce energy as ATP from oxygen and substrates derived from our food, including glucose, free fatty acids, ketones, and amino acids. Interestingly, sites affected by the chronic complications of diabetes, such as kidney, nerves, and the heart, seem most reliant on the generation of high concentrations of ATP by mitochondria for their normal function. In young T1D patients at high risk of DKD and CVD, studies using typically "adult" DKD treatments have failed. Good control of blood glucose is also notoriously difficult to achieve in childhood to early adulthood. This early evidence of mitochondrial dysfunction and early kidney damage in "at risk" 15- to 25-year-olds with T1Dmay provide a novel target for therapies to prevent progression to overt DKD and lower risk for future CVD.

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11 ADC 2018 • PRACTICEUPDATE CONFERENCE SERIES