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Glycemic Thresholds for Activation of Counterregulatory Hormone and Symptom Responses in Islet Transplant Recipients

Department of Medicine, Divisions of Endocrinology, Diabetes, and Metabolism (M.R.R., M.H.S., R.M., K.L.T.) and Nephrology (S.K.), Department of Surgery, Division of Transplantation (J.F.M., A.N.), and the Monell Chemical Senses Center (K.L.T.), University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6149

Address all correspondence and requests for reprints to: Michael R. Rickels, M.D., University of Pennsylvania School of Medicine, Division of Endocrinology, Diabetes, and Metabolism, 778 Clinical Research Building, 415 Curie Boulevard, Philadelphia, Pennsylvania 19104-6149. E-mail: rickels{at}mail.med.upenn.edu.

Context: In patients with type 1 diabetes and reduced awareness of hypoglycemia, the glycemic thresholds for activation of counterregulatory hormone and symptom responses to hypoglycemia are impaired, in part due to recurrent episodes of hypoglycemia. Islet transplantation can ameliorate occurrences of hypoglycemia in these patients.

Objective: The objective of the study was to determine whether the avoidance of hypoglycemia achieved through islet transplantation results in improved glycemic thresholds for counterregulatory responses.

Setting: The study was conducted at a general clinical research center.

Participants: Seven islet transplant recipients, six type 1 diabetic, and eight nondiabetic control subjects participated in the study.

Intervention: We performed a stepped hyperinsulinemic hypoglycemic clamp and, in 12 subjects, a paired hyperinsulinemic euglycemic clamp to calculate the glycemic thresholds for and magnitude of counterregulatory responses.

Results: The glycemic thresholds for all counterregulatory hormone and symptom responses in the islet transplant group were comparable with normal and higher than in the type 1 diabetes group (P < 0.01 for glucagon; P < 0.05 for epinephrine). The magnitude of the glucagon and epinephrine responses in the islet transplant group, although greater than in the type 1 diabetes group (P < 0.05 for both), remained less than normal (P < 0.01 for glucagon; P < 0.05 for epinephrine). The magnitude of GH secretion in the islet transplant group was comparable with normal and greater than in the type 1 diabetes group (P < 0.05).

Conclusions: The glycemic thresholds for activation of counterregulatory hormone and symptom responses appear normal after islet transplantation; however, the magnitudes of the glucagon and epinephrine responses remain impaired.

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