title: Long-Term Improvement in Glucose Control and Counterregulation by Islet Transplantation for Type 1 Diabetes.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  All 10 patients underwent intrahepatic islet transplantation according to the CIT07 protocol at the Hospital of the University of Pennsylvania.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors: Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism (M.R.R., A.J.P., C.D.-B., S.M.K., K.L.T.) and Department of Surgery, Division of Transplantation (E.M., A.N.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and the Monell Chemical Senses Center (K.L.T.), Philadelphia, Pennsylvania 19104.
authors: Michael R
authors: MR
authors: Rickels
authors: Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism (M.R.R., A.J.P., C.D.-B., S.M.K., K.L.T.) and Department of Surgery, Division of Transplantation (E.M., A.N.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and the Monell Chemical Senses Center (K.L.T.), Philadelphia, Pennsylvania 19104.
authors: Amy J
authors: AJ
authors: Peleckis
authors: Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism (M.R.R., A.J.P., C.D.-B., S.M.K., K.L.T.) and Department of Surgery, Division of Transplantation (E.M., A.N.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and the Monell Chemical Senses Center (K.L.T.), Philadelphia, Pennsylvania 19104.
authors: Eileen
authors: E
authors: Markmann
authors: Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism (M.R.R., A.J.P., C.D.-B., S.M.K., K.L.T.) and Department of Surgery, Division of Transplantation (E.M., A.N.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and the Monell Chemical Senses Center (K.L.T.), Philadelphia, Pennsylvania 19104.
authors: Cornelia
authors: C
authors: Dalton-Bakes
authors: Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism (M.R.R., A.J.P., C.D.-B., S.M.K., K.L.T.) and Department of Surgery, Division of Transplantation (E.M., A.N.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and the Monell Chemical Senses Center (K.L.T.), Philadelphia, Pennsylvania 19104.
authors: Stephanie M
authors: SM
authors: Kong
authors: Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism (M.R.R., A.J.P., C.D.-B., S.M.K., K.L.T.) and Department of Surgery, Division of Transplantation (E.M., A.N.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and the Monell Chemical Senses Center (K.L.T.), Philadelphia, Pennsylvania 19104.
authors: Karen L
authors: KL
authors: Teff
authors: Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism (M.R.R., A.J.P., C.D.-B., S.M.K., K.L.T.) and Department of Surgery, Division of Transplantation (E.M., A.N.), Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104; and the Monell Chemical Senses Center (K.L.T.), Philadelphia, Pennsylvania 19104.
authors: Ali
authors: A
authors: Naji
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis*; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000601:surgery*; D005260:Female; D006801:Humans; D016381:Islets of Langerhans Transplantation / Q000379:methods*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care
chemical_list: D001786:Blood Glucose