Intrahepatic Islet Transplantation in Type 1 Diabetic Patients Does Not Restore Hypoglycemic Hormonal Counterregulation or Symptom Recognition After Insulin Independence

  1. Breay W. Paty12,
  2. Edmond A. Ryan1,
  3. A.M. James Shapiro1,
  4. Jonathan R.T. Lakey1 and
  5. R. Paul Robertson2
  1. 1Clinical Islet Transplant Program, University of Alberta, Edmonton, Alberta, Canada
  2. 2Pacific Northwest Research Institute, Seattle, Washington

    Abstract

    Islet allotransplantation can provide prolonged insulin independence in selected individuals with type 1 diabetes. Whether islet transplantation also restores hypoglycemic counterregulation is unclear. To determine if hypoglycemic counterregulation is restored by islet transplantation, we studied hormone responses and hypoglycemic symptom recognition in seven insulin-independent islet transplant recipients using a 3-h stepped hypoglycemic clamp, and compared their responses to those of nontransplanted type 1 diabetic subjects and nondiabetic control subjects. Glucagon responses of islet transplant recipients to hypoglycemia were significantly less than that observed in control subjects (incremental glucagon [mean ± SE]: −12 ± 12 vs. 64 ± 22 pg/ml, respectively; P < 0.05), and not significantly different from that of nontransplanted type 1 diabetic subjects (−17 ± 10 pg/ml). Epinephrine responses and symptom recognition were also not restored by islet transplantation (incremental epinephrine [mean ± SE]: 195 ± 128 [islet transplant recipients] vs. 238 ± 73 [type 1 diabetic subjects] vs. 633 ± 139 pg/ml [nondiabetic control subjects], P < 0.05 vs. control; peak symptom scores: 3.3 ± 0.9 [islet transplant recipients] vs. 3.1 ± 1.1 [type 1 diabetic subjects] vs. 6.7 ± 0.8 [nondiabetic control subjects]). Thus the results indicate that despite providing prolonged insulin independence and near-normal glycemic control in these patients with long-standing type 1 diabetes, hypoglycemic hormonal counterregulation and symptom recognition were not restored by intrahepatic islet transplantation.

    Footnotes

    • Address correspondence and reprint requests to Breay W. Paty, MD, Clinical Islet Transplant Program, University of Alberta, 2000 College Plaza, 8215–112th St., Edmonton, AB Canada T6G 2C8. E-mail: bpaty{at}cha.ab.ca.

      Received for publication 9 May 2002 and accepted in revised form 6 September 2002.

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