Long-term improvement in glucose control and counterregulation by islet transplantation for type 1 diabetes.

Long-term improvement in glucose control and counterregulation by islet transplantation for type 1 diabetes.

J Clin Endocrinol Metab. 2016 Aug 29;:jc20161649

Authors: Rickels MR, Pelekis AJ, Markmann E, Dalton-Bakes C, Kong SM, Teff KL, Naji A

Abstract
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 ∼27 years were studied longitudinally before and 6 and 18 months post-transplant in the Clinical & Translational Research Center of the University of Pennsylvania, and 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-(2)H2-glucose.
RESULTS: Near-normal glycemia (HbA1c ≤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 and normalized at 18 months, and endogenous glucose production and symptoms, absent before, were normalized at 6 and 18 months post-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, physiologic effects that likely contribute to glycemic stability post-transplant.

PMID: 27571180 [PubMed - as supplied by publisher]

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