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J Clin Endocrinol Metab. 2016 Nov;101(11):4421-4430. Epub 2016 Aug 29.

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

Author information

1
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.

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 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.

PMID:
27571180
PMCID:
PMC5426339
DOI:
10.1210/jc.2016-1649
[Indexed for MEDLINE]
Free PMC Article

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