Early loss of the glucagon response to hypoglycemia in adolescents with type 1 diabetes.
OBJECTIVE
To assess the glucagon response to hypoglycemia and identify influencing factors in patients with type 1 diabetes compared with nondiabetic control subjects.


METHODS
Hyperinsulinemic hypoglycemic clamp studies were performed in all participants. The glucagon response to both hypoglycemia and arginine was measured, as well as epinephrine, cortisol, and growth hormone responses to hypoglycemia. Residual β-cell function was assessed using fasting and stimulated C-peptide.


RESULTS
Twenty-eight nonobese adolescents with type 1 diabetes (14 female, mean age 14.9 years [range 11.2-19.8]) and 12 healthy control subjects (6 female, 15.3 years [12.8-18.7]) participated in the study. Median duration of type 1 diabetes was 0.66 years (range 0.01-9.9). The glucagon peak to arginine stimulation was similar between groups (P = 0.27). In contrast, the glucagon peak to hypoglycemia was reduced in the group with diabetes (95% CI): 68 (62-74) vs. 96 (87-115) pg/mL (P < 0.001). This response was greater than 3 SDs from baseline for only 7% of subjects with type 1 diabetes in comparison with 83% of control subjects and was lost at a median duration of diabetes of 8 months and as early as 1 month after diagnosis (R = -0.41, P < 0.01). There was no correlation in response with height, weight, BMI, and HbA(1c). Epinephrine, cortisol, and growth hormone responses to hypoglycemia were present in both groups.


CONCLUSIONS
The glucagon response to hypoglycemia in adolescents with type 1 diabetes is influenced by the duration of diabetes and can be lost early in the course of the disease.
Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, Western Australia, Australia.
Aris
A
Siafarikas
Robert J
RJ
Johnston
Max K
MK
Bulsara
Peter
P
O'Leary
Timothy W
TW
Jones
Elizabeth A
EA
Davis
D000293:Adolescent; D001120:Arginine / Q000494:pharmacology; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004837:Epinephrine / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood*; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007003:Hypoglycemia / Q000097:blood*; D008297:Male
D013006:Growth Hormone; D005934:Glucagon; D001120:Arginine; D006854:Hydrocortisone; D004837:Epinephrine