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. 2012 Aug;35(8):1757-62.
doi: 10.2337/dc11-2010. Epub 2012 Jun 14.

Early loss of the glucagon response to hypoglycemia in adolescents with type 1 diabetes

Aris Siafarikas  1 , Robert J Johnston, Max K Bulsara, Peter O'Leary, Timothy W Jones, Elizabeth A Davis
Affiliations

Early loss of the glucagon response to hypoglycemia in adolescents with type 1 diabetes

Aris Siafarikas et al. Diabetes Care. 2012 Aug.

Abstract

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 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.

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Figures

Figure 1
Figure 1
A and B: Glucagon response to hypoglycemia and arginine. The line diagrams show glucagon levels from clamp studies as mean and SEM during euglycemia and in response to hypoglycemia and arginine infusion, respectively. n = 28 for type 1 diabetes and n = 12 for control subjects. A linear mixed model was used for analysis.
See this image and copyright information in PMC

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