Early Loss of the Glucagon Response to Hypoglycemia in Adolescents With Type 1 Diabetes
- Aris Siafarikas, FRACP, MD1,2,3,
- Robert J. Johnston, MRCP1,
- Max K. Bulsara, PHD3,4,
- Peter O’Leary, PHD5,6,
- Timothy W. Jones, MBBS, FRACP, MD1,2,7 and
- Elizabeth A. Davis, MBBS, FRACP, PHD1,2,7⇓
- 1Department of Endocrinology and Diabetes, Princess Margaret Hospital for Children, Perth, Western Australia, Australia
- 2School of Pediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia
- 3Institute of Health and Rehabilitation Research, University of Notre Dame Fremantle, Fremantle, Western Australia, Australia
- 4School of Population Health, The University of Western Australia, Perth, Western Australia, Australia
- 5Department of Biochemistry, Princess Margaret Hospital for Children, Perth, Western Australia, Australia
- 6Centre for Population Health Research, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia
- 7Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia, Australia
- Corresponding author: Elizabeth A. Davis, .
OBJECTIVE To assess the glucagon response to hypoglycemia and identify influencing factors in patients with type 1 diabetes compared with nondiabetic control subjects.
RESEARCH DESIGN AND 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 HbA1c. 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.
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- Received October 14, 2011.
- Accepted March 22, 2012.
- © 2012 by the American Diabetes Association.
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