Long-term improvement in glucose control and counterregulation by islet transplantation for type 1 diabetes
MR Rickels, AJ Peleckis, E Markmann… - The Journal of …, 2016 - academic.oup.com
MR Rickels, AJ Peleckis, E Markmann, C Dalton-Bakes, SM Kong, KL Teff, A Naji
The Journal of Clinical Endocrinology & Metabolism, 2016•academic.oup.comContext: 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 …
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 …
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 6,6-2H2-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 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.
Oxford University Press