Towards Prevention of Nonsevere Hypoglycemia in Type 1 Diabetes with Oral Glucose at a Higher Blood Glucose Threshold-The REVERSIBLE Trial

Background: Current guidelines recommend initiating the treatment of non-severe (NS) hypoglycemia with 15g of carbohydrates (CHO) at 15 minutes intervals when blood glucose (BG) reaches <72 mg/dl. Despite this recommendation, NS hypoglycemia management remains challenging for people living with type 1 diabetes (pwT1D) and more optimal treatment strategies are required. We aim to assess the efficacy of 15g of CHO at higher treatment thresholds. Methods: The REVERSIBLE Trial is an open-label, randomized, three interventions x three periods cross-over study. Following inpatient insulin-induced decrease in BG, 16g of oral carbohydrates is administered at a plasma glucose threshold of <72 mg/dl, ≤81 mg/dl or ≤90 mg/dl. The primary outcome is the time (in minutes) spent in hypoglycemia (<72 mg/dl) after the initial correction. Results: Participants (n=29) characteristics are 52% male, 46.8±16.3 years old, BMI of 26.4±3.9 kg/m2, diabetes duration of 26.2±15.9 years, A1c of 53.4±15.5 mmol/mol and 62% insulin pump users. When comparing <72 mg/dl (control) to ≤81 mg/dl and ≤90 mg/dl treatment thresholds, 100% vs. 86% (p=0.1201) vs. 34% (p<0.0001) of participants had hypoglycemia. These hypoglycemic events lasted 26.0±12.6 vs. 17.9±14.7 (p=0.026) vs. 7.1±11.8 (p=0.002) minutes, with a blood glucose nadir of 56.5±9.9 vs. 63.5±7.9 (p=0.008) vs. 73.4±9.7 mg/dl (p=0.002) respectively. In the control group, 69% of participants required more than one treatment to reach or maintain normoglycemia (≥ 72 mg/dl) compared to 52% in the ≤81 mg/dl group and 31% in the ≤90 mg/dl group with no significant rebound hyperglycemia (>180mg/dl) within the first hour. Conclusion: Compared with <72 mg/dl, consuming 16g of oral carbohydrates at ≤81 mg/dl and ≤90 mg/dl shortened the time spent in hypoglycemia, lessened the glucose nadir and reduced the need for repetitive treatments. For some NS episodes, pwT1D could benefit from CHO intake at a higher BG threshold. Disclosure R.Cheng: None. N.Taleb: Consultant; Viatris Inc. Z.Wu: Other Relationship; Eli Lilly and Company. V.Messier: None. R.Rabasa-lhoret: Consultant; Dexcom, Inc., Abbott, Janssen Pharmaceuticals, Inc., Novo Nordisk Canada Inc., Sanofi, Lilly, Tandem Diabetes Care, Inc., Insulet Corporation. Funding JDRF (4-SRA-2018-651-Q-R); Canadian Institutes of Health Research (JT1-157204)