CLINICAL ISLET TRANSPLANTATION

D.M. Thompson¹, Z. Ao², M. Meloche³, J. Shapiro³, P.A. Keown⁴, B. Paty³, M. Fung³, S. Ho⁵, D. Worsley⁶, I. Begg³, M. Al mehthel³, J. Kondi³, G. Meneilly¹, C. Harris¹, S.E. Kozak¹, S. Tong¹, M. Trinh³, G. Warnock^7
1Medicine, Vancouver General Hospital, Vancouver/CANADA, ²Department Of Surgery, University Of British Columbia, Human Islet Transplant Laboratory, Vancouver/CANADA, ³, Vancouver General Hospital, Vancouver/CANADA, ⁴Medicine, University of British Columbia, Vancouver/CANADA, ⁵Radiology, Vancouver General Hospital, Vancouver/CANADA, ⁶Nuclear Medicine, Vancouver General Hospital, Vancouver/CANADA, ⁷Surgery, Vancouver General Hospital, Vancouver/CANADA

Body: Introduction: The effect of islet transplantation on diabetic microvascular complicaitons is unknown. Methods: The British Columbia Islet Transplant program is conducting a single-centre, prospective, cross-over study comparing the effects of intensive medical therapy and islet transplantation on the progression of microvascular complications in type 1 diabetes. Eligible subjects were 20 – 65 years of age with > 5yrs diabetes duration were c-peptide negative and with evidence of retinopathy and mild nephropathy (urine ACR > 2.0 and GFR > 70 ml/min). Forty-four subjects were enrolled between January 2002 – January 2005 and followed at least 12 months. All subjects began medical therapy upon enrollment, consisting of intensive glucose management, angiotensin blockade and control of lipids and blood pressure to recommended levels. When a donor becomes available, the best matched subject from the group receives the islet transplant. The first transplant was in March 2003 and by February 2010, 32 subjects had received 81 islet infusions. A subject crosses over and becomes analyzed in the transplanted group at the time of their first islet infusion. All subjects are included although only 36 are currently followed (3 ICT, 5 medical have withdrawn). Analysis is by intention to treat. The primary renal endpoint is the rate of change in GFR as measured by the blood clearance of ^99mTc-DTPA performed every 6 months with the secondary endpoint GFR estimated by the MDRD equation. Retinopathy is assessed by annual seven-field fundus photography. Progression was defined as advancing by more than one level using the international scale, requirement for laser therapy or the development of clinically significant macular edema. Neuropathy was assessed by annual nerve conduction studies of seven peripheral nerves. Results: The median follow-up is 35 months for the medical group and 60 months post islet transplant, the discrepancy caused by the one way cross-over nature of the study. Progression has occurred in 10/82 eyes in the medical group and 0/64 eyes after islet transplantation (p < .01). The rate of decline in GFR is less after transplant than with medical treatment: – 2.3 ml/min/yr post transplant and – 4.1 ml/min/yr for medical patients as measured by ^99mTc-DTPA and – 0.8 ml/min/yr post transplant, – 1.4 ml/min/yr estimated by MDRD (p <0.01 for each). There has been no worsening of nerve conduction in either group. Possible reasons for the better results in the post transplant group include better glucose control (median A1c post-transplant 6.7, medical 7.6 p < 0.05) or possibly the presence of c-peptide. Conclusion: In conclusion, we present evidence that islet transplantation results in a reduction of progression of diabetic retinopathy and nephropathy compared to patients treated with intensive medical therapy. We believe that this should be further studied in randomized, controlled trials.

Disclosure: All authors have declared no conflicts of interest.