Islet Amyloid in Whole Pancreas Transplants for Type 1 Diabetes Mellitus (DM): Possible Role of Type 2 DM for Graft Failure.
Long-term results with whole pancreas (WPTx) and islet transplantation (IT) continue to be suboptimal. Graft failure with undetectable C-peptide level is attributed to graft sclerosis (chronic rejection), recurrence of Type 1 diabetes mellitus (DM), or insufficient islet mass. In contrast, graft failure with measurable C-peptide has overlapping clinical features with Type 2 DM (suggesting persistent but insufficient β cell function), but is poorly understood. In general, the morphological substrate for islet failure is unclear because grafted islets are not routinely evaluated. We present two patients with graft failure at 5 and 8 years after successful WPTx for Type 1 DM, presenting with preserved C-peptide levels. On histopathology, the islets had preserved both α and β cell populations but also prominent accumulation of islet amyloid (IA), the morphological hallmark of Type 2 DM. IA previously reported in IT, represents fibrillary aggregates of islet amyloid polypeptide, a hormone normally cosecreted with insulin. Accumulation of IA correlates quantitatively with the development of hyperglycemia and is known to cause β cell dysfunction and loss. Accumulation of IA and development of Type 2 DM should be considered and studied as a potential cause of long-term islet failure in IT and WPTx.
Department of Pathology, Hospital Universitario Regional Carlos Haya, Malaga, Andalucia, Spain.
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León Fradejas
Department of Pathology, University of Massachusetts Medical School, Worcester, MA.
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Kandil
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD.
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Papadimitriou
Department of Pathology, Hospital Universitario Regional Carlos Haya, Malaga, Andalucia, Spain.
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del Pino Flórez Rial
Department of Pathology, Hospital Universitario Regional Carlos Haya, Malaga, Andalucia, Spain.
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Prieto Sánchez
Department of Pathology, University of Maryland School of Medicine, Baltimore, MD.
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Drachenberg
D000328:Adult; D002096:C-Peptide / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000601:surgery*; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D006084:Graft Rejection / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000378:metabolism*; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016035:Pancreas Transplantation / Q000009:adverse effects*; D011379:Prognosis; D012307:Risk Factors
D002096:C-Peptide; D058228:Islet Amyloid Polypeptide
biopsy; diabetes: new onset/posttransplant; diabetes: type 2; graft survival; islets of Langerhans