BACKGROUND: Pancreas transplantation (PTx) represents the method of choice in type 1 diabetic patients with conservatively intractable hypoglycemia unawareness syndrome. In 2005, the Institute for Clinical and Experimental Medicine (IKEM) launched a program to investigate the safety potential of islet transplantation (ITx) in comparison to PTx. AIM: This study aims to compare the results of PTx and ITx regarding severe hypoglycemia elimination, metabolic control, and complication rate. METHODS: We analyzed the results of 30 patients undergoing ITx and 49 patients treated with PTx. All patients were C-peptide-negative and suffered from hypoglycemia unawareness syndrome. Patients in the ITx group received a mean number of 12,349 (6,387-15,331) IEQ/kg/person administered percutaneously into the portal vein under local anesthesia and radiological control. The islet number was reached by 1-3 applications, as needed. In both groups, we evaluated glycated hemoglobin, insulin dose, fasting and stimulated C-peptide, frequency of severe hypoglycemia, and complications. We used the Mann Whitney test, Wilcoxon signed-rank test, and paired t-test for analysis. We also individually assessed the ITx outcomes for each patient according to recently suggested criteria established at the EPITA meeting in Igls. RESULTS: Most of the recipients showed a significant improvement in metabolic control one and two years after ITx, with a significant decrease in HbA1c, significant elevation of fasting and stimulated C-peptide, and a markedly significant reduction in insulin dose and the frequency of severe hypoglycemia. Seventeen percent of ITx recipients were temporarily insulin-independent. The results in the PTx group were comparable to those in the ITx group, with 73% graft survival and insulin independence in year 1, 68% 2 years and 55% 5 years after transplantation. There was a higher rate of complications related to the procedure in the PTx group. Severe hypoglycemia was eliminated in the majority of both ITx and PTx recipients. CONCLUSION: This report proves the successful initiation of pancreatic islet transplantation in a center with a well-established PTx program. ITx has been shown to be the method of choice for hypoglycemia unawareness syndrome, and may be considered for application in clinical practice if conservative options are exhausted.

• MeSH
• C-Peptide blood   MeSH
• Diabetes Mellitus, Type 1 epidemiology   etiology   therapy   MeSH
• Adult MeSH
• Risk Assessment MeSH
• Hypoglycemia epidemiology   therapy   MeSH
• Blood Glucose metabolism   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Follow-Up Studies MeSH
• Graft Survival MeSH
• Retrospective Studies MeSH
• Syndrome MeSH
• Islets of Langerhans Transplantation * adverse effects   methods   MeSH
• Pancreas Transplantation * adverse effects   methods   MeSH
• Choice Behavior MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Transplantace Langerhansových ostrůvků (TxLO) byla v roce 2005 zavedena v Institutu klinické a experimentální medicíny (IKEM) jako potenciálně bezpečnější alternativa transplantace pankreatu (TxP), jež dosud představovala metodu volby u diabetiků 1. typu s konzervativně nezvládnutelným syndromem porušeného vnímání hypoglykemie. Cílem práce je porovnat schopnost obou metod eliminovat závažné hypoglykemie a další komplikace. Transplantaci Langerhansových ostrůvků od zavedení metody v roce 2005 do listopadu 2015 podstoupilo celkem 48 pacientů. Výsledky jsme hodnotili u 22 z nich, u kterých byl přítomen syndrom porušeného vnímání hypoglykemie. Počet transplantovaných ostrůvkových ekvivalentů činil 12 096 (6933−16 705) IEQ/kg, byly podány v místním znecitlivění perkutánně pod radiologickou kontrolou do portální žíly. TxP podstoupilo od roku 1996 44 pacientů. Hodnotili jsme glykovaný hemoglobin (HbA1c), dávky inzulinu, C-peptid lačný a stimulovaný, frekvenci těžkých hypoglykemií a komplikace. Mediány (interquartile range) jsme porovnávali pomocí Wilcoxonova rank testu. Po 1 i 2 letech od TxLO významně klesl HbA1c, byl měřitelný C-peptid, snížila se dávka inzulinu i frekvence hypoglykemií, 18 % příjemců bylo přechodně (maximálně 6 měsíců) bez potřeby inzulinu. Nejčastější komplikací bylo krvácení u 41 % pacientů. Jeden rok po TxP bylo 73 % pacientů bez potřeby inzulinu a hypoglykemií, 2 roky poté pak 68 % pacientů bez inzulinu a hypoglykemií, graftektomie proběhla u 20 % pacientů. Transplantace Langerhansových ostrůvků i transplantace pankreatu vedly k obnově sekrece inzulinu a eliminovaly těžké hypoglykemie. TxP vedla častěji k nezávislosti na inzulinu za cenu závažnějších komplikací. TxLO je méně invazivní metoda, kterou je potřeba dále rozvíjet.

Islet transplantation (ITx) started in 2005 in IKEM as a potentially safer alternative to pancreas transplantation (PTx), which so far had represented the method of choice in type-1 diabetic patients with conservatively intractable hypoglycemia unawareness syndrome. The aim of the study was to compare these two methods with regard to severe hypoglycemia elimination and to frequency of complications. Up to November 2015 a total number of 48 patients underwent ITx. The results from 22 patients with hypoglycemia unawareness were statistically analyzed. The mean number of transplanted islet equivalents was 12,096 (6,933−16,705) IEQ/kg administered percutaneously in local anesthesia under radiological control to the portal vein. 44 patients underwent PTx from 1996. We evaluated glycated hemoglobin(HbA1c), insulin dose, fasting and stimulated C-peptide, frequency of severe hypoglycemia and complications. Medians (interquartile range) were analyzed using the Wilcoxon signed-rank test. One and two years after ITx, HbA1c decreased, C-peptide became significantly positive, insulin dose and frequency of severe hypoglycemia decreased and 18 % of ITx recipients were temporarily insulin-independent. Bleeding was present in 41 % of patients. One year after PTx, 73 % of patients were insulin and hypoglycemia-free, after two years 68 % of patients were insulin and hypoglycemia-free; graftectomy occurred in 20 % of recipients. Both methods led to restoration of insulin secretion and severe hypoglycemia elimination. PTx made more recipients insulin-independent at the cost of serious complications.

• Keywords
• syndrom porušeného vnímání hypoglykemie,
• MeSH
• C-Peptide metabolism   MeSH
• Diabetes Mellitus, Type 1 * surgery   MeSH
• Adult MeSH
• Glycated Hemoglobin analysis   MeSH
• Hypoglycemia diagnosis   epidemiology   prevention & control   MeSH
• Insulin therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Tissue and Organ Harvesting MeSH
• Pilot Projects MeSH
• Postoperative Complications MeSH
• Prospective Studies MeSH
• Syndrome MeSH
• Islets of Langerhans Transplantation * methods   MeSH
• Pancreas Transplantation * methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH

Variability of pancreatic donors may significantly impact the success of islet isolation. The aim of this study was to evaluate donor factors associated with isolation failure and to investigate whether immunohistology could contribute to organ selection. Donor characteristics were evaluated for both successful (n = 61) and failed (n = 98) islet isolations. Samples of donor pancreatic tissue (n = 78) were taken for immunohistochemical examination. Islet isolations with 250000 islet equivalents were considered successful. We confirmed that BMI of less than 25 kg/m(2) (P < 0.001), cold ischemia time more than 8 hours (P < 0.01), hospitalization longer than 96 hours (P < 0.05), higher catecholamine doses (P < 0.05), and edematous pancreases (P < 0.01) all unfavorably affected isolation outcome. Subsequent immunohistochemical examination of donor pancreases confirmed significant differences in insulin-positive areas (P < 0.001). ROC analyses then established that the insulin-positive area in the pancreas could be used to predict the likely success of islet isolation (P < 0.001). At the optimal cutoff point (>1.02%), sensitivity and specificity were 89% and 76%, respectively. To conclude, while the insulin-positive area, determined preislet isolation, as a single variable, is sufficient to predict isolation outcome and helps to improve the success of this procedure, its combination with the established donor scoring system might further improve organ selection.

• MeSH
• Tissue Donors statistics & numerical data   MeSH
• Length of Stay statistics & numerical data   MeSH
• Diabetes Mellitus, Type 1 surgery   MeSH
• Edema epidemiology   MeSH
• Hospitalization MeSH
• Immunohistochemistry MeSH
• Body Mass Index MeSH
• Insulin metabolism   MeSH
• Islets of Langerhans metabolism   surgery   MeSH
• Humans MeSH
• Pancreas MeSH
• Retrospective Studies MeSH
• Cold Ischemia statistics & numerical data   MeSH
• Islets of Langerhans Transplantation methods   MeSH
• Vasoconstrictor Agents therapeutic use   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH

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