1. Early Loss of the Glucagon Response to Hypoglycemia in Adolescents With Type 1 Diabetes Featured Article: Aris Siafarikas, F.R.A.C.P., M.D., Robert J. Johnston, M.R.C.P., Max K. Bulsara, Ph.D., Peter O’Leary, Ph.D., Timothy W. Jones, M.B.B.S., F.R.A.C.P., M.D., Elizabeth A. Davis, M.B.B.S., F.R.A.C.P., Ph.D. Diabetes Care Volume 35: 1757-1762 August, 2012

2. Study Objective To assess the glucagon response to hypoglycemia and identify influencing factors in patients with type 1 diabetes compared with nondiabetic control subjects Siafarikas A et al. Diabetes Care 2012;35:1757-1762

3. Study Design Hyperinsulinemic hypoglycemic clamp studies performed in 28 adolescents with type 1 diabetes and 12 healthy control participants Measured: Glucagon response to both hypoglycemia and arginine Epinephrine, cortisol, and growth hormone responses to hypoglycemia Residual β-cell function using fasting and stimulated C-peptide Siafarikas A et al. Diabetes Care 2012;35:1757-1762

4. Results Type 1 diabetes participants: 50% female, mean age 14.9 years (range 11.2–19.8), Median duration of type 1 diabetes 0.66 years (range 0.01–9.9) Healthy control subjects: 50% female, mean age 15.3 years (12.8– 18.7) Glucagon peak to arginine stimulation was similar between groups (P = 0.27) 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) 3 SDs from baseline for 7% of subjects with type 1 diabetes vs. 83% of controls Lost at median duration of diabetes of 8 months and as early as 1 month after diagnosis (R =20.41, P < 0.01). Not correlated with height, weight, BMI, and HbA1c Epinephrine, cortisol, and growth hormone responses to hypoglycemia were present in both groups Siafarikas A et al. Diabetes Care 2012;35:1757-1762

10. 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 Siafarikas A et al. Diabetes Care 2012;35:1757-1762