Journal
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
Volume 101, Issue 11, Pages 4421-4430Publisher
ENDOCRINE SOC
DOI: 10.1210/jc.2016-1649
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Funding
- U.S. Public Health Services Research [R01 DK091331, U01 DK070430, UL1 TR000003, P30 DK19525]
- W.W. Smith Charitable Trust
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Context: Islet transplantation has been shown to improve glucose counterregulation and hypoglycemia symptom recognition in patients with type 1 diabetes (T1D) complicated by severe hypoglycemia episodes and symptom unawareness, but long-term data are lacking. Objective: To assess the long-term durability of glucose counterregulation and hypoglycemia symptom responses 18 months after intrahepatic islet transplantation and associated measures of glycemic control during a 24-month follow-up period. Design, Setting, and Participants: Ten patients with T1D disease duration of approximately 27 years were studied longitudinally before and 6 and 18 months after transplant in the Clinical & Translational Research Center of the University of Pennsylvania and were compared to 10 nondiabetic control subjects. Intervention: All 10 patients underwent intrahepatic islet transplantation according to the CIT07 protocol at the Hospital of the University of Pennsylvania. Main Outcome Measures: Counterregulatory hormone, endogenous glucose production, and autonomic symptom responses derived from stepped hyperinsulinemic-hypoglycemic and paired hyperinsulinemic-euglycemic clamps with infusion of 6,6-H-2(2)-glucose. Results: Near-normal glycemia (HbA(1c) <= 6.5%; time 70-180 mg/dL 95%) was maintained for 24 months in all patients, with one returning to low-dose insulin therapy. In response to insulin induced hypoglycemia, glucagon secretion was incompletely restored at 6 and 18 months, epinephrine was improved at 6 months and normalized at 18 months, and endogenous glucose production and symptoms, absent before, were normalized at 6 and 18 months after transplant. Conclusions: In patients with T1D experiencing problematic hypoglycemia, intrahepatic islet transplantation can lead to long-term improvement of glucose counterregulation and hypoglycemia symptom recognition, physiological effects that likely contribute to glycemic stability after transplant.
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