title: Intrahepatic islet transplantation in type 1 diabetic patients does not restore hypoglycemic hormonal counterregulation or symptom recognition after insulin independence.
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.
authors.affiliation: Clinical Islet Transplant Program, University of Alberta, 2000 College Plaza, 8215-112th Street, Edmonton, Alberta, Canada T6G 2C8. bpaty@cha.ab.ca
authors.forename: Breay W
authors.initials: BW
authors.lastname: Paty
authors.forename: Edmond A
authors.initials: EA
authors.lastname: Ryan
authors.forename: A M James
authors.initials: AM
authors.lastname: Shapiro
authors.forename: Jonathan R T
authors.initials: JR
authors.lastname: Lakey
authors.forename: R Paul
authors.initials: RP
authors.lastname: Robertson
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D002096:C-Peptide / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000601:surgery*; D004837:Epinephrine / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D006728:Hormones / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000378:metabolism*; D016381:Islets of Langerhans Transplantation; D008099:Liver / Q000601:surgery*; D008297:Male; D008875:Middle Aged
chemical_list: D001786:Blood Glucose; D002096:C-Peptide; D006728:Hormones; D007328:Insulin; D005934:Glucagon; D004837:Epinephrine