148-OR: CGM Time Below Range Predicts Epinephrine Response to Hypoglycemia in Patients with Type 1 Diabetes

Abstract

Identifying T1D patients with impaired awareness of hypoglycemia (IAH) is essential, as these patients are at ~10-fold risk of severe hypoglycemia. Defining IAH has relied on questionnaires such as Clarke score that are rarely used in clinical practice. Additional tools are needed to stratify hypoglycemia risk in patients with T1D. Here we show that CGM metrics correlate with physiologic response to hypoglycemia. We measured serum epinephrine levels in 22 subjects with T1D (ages 28-52, A1c 6.1-7.2, median Clarke score 3) during a hyperinsulinemic-hypoglycemic clamp. Baseline CGM data was collected for 2 weeks prior to clamp. These data show a novel, inverse relationship between CGM time below range (TBR, <70 mg/dL) and epinephrine response (EpiR, pg/mL/min) FIGURE. CGM TBR (ρ = -0.562, p = 0.006), Clarke score (ρ = -0.592, p = 0.03), and older age (ρ = -0.500, p = 0.015) were inversely associated with EpiR. Higher average glucose was associated with increased EpiR while time in range, coefficient of variation, BMI, and duration of T1D showed no significant association with EpiR. Our study suggests that CGM TBR predicts counterregulatory dysfunction in T1D. CGM TBR demonstrated a robust, inverse correlation with EpiR similar to the validated Clarke survey. CGM is now the gold standard for glycemic monitoring in T1D, and the percentage TBR may help identify patients at highest risk for severe hypoglycemia outcomes. Disclosure R.L.Thomas: None. J.M.Gregory: Advisory Panel; Eli Lilly and Company, vTv Therapeutics, Other Relationship; Medtronic. E.R.Giovannetti: None. S.C.Boeder: Consultant; Cecelia Health, Research Support; Dexcom, Inc., REMD Biotherapeutics, Eli Lilly and Company. J.Pettus: Advisory Panel; Sanofi, Novo Nordisk, Lilly, MannKind Corporation, Consultant; Carmot Therapeutics, Inc., Diasome. Funding JDRF (2-SRA-2018-606-M-B, 5-ECR-2020-950-A-N); National Institute of Diabetes and Digestive and Kidney Diseases (K23DK123392)