Long-Term Improvement in Glucose Control and Counterregulation by Islet Transplantation for Type 1 Diabetes

J Clin Endocrinol Metab. 2016 Nov;101(11):4421-4430. doi: 10.1210/jc.2016-1649. Epub 2016 Aug 29.


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.

MeSH terms

  • Adult
  • Blood Glucose / analysis*
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / surgery*
  • Female
  • Humans
  • Islets of Langerhans Transplantation / methods*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care*


  • Blood Glucose