Impact of Impaired Awareness of Hypoglycemia on Glucose Changes During and After Exercise in Type 1 Diabetes-Results from the T1DEXI Study Cohort

Prior exposure to hypoglycemia and exercise may each dampen the sympathoadrenal response to subsequent hypoglycemia, leading to impaired awareness of hypoglycemia (IAH) and increased risk for experiencing clinically significant hypoglycemia. Whether glucose changes during exercise differ in those with IAH vs. intact awareness of hypoglycemia (Aware) has not been assessed in a large sample of ambulatory adults with type 1 diabetes, nor is the risk for hypoglycemia events in the next 24 hours known in such individuals. Using a case-control design, we compared participants with IAH (Clarke score ≥4 or ≥1 severe hypoglycemic event [SHE] within the past year) to Aware participants (Clarke score of ≤2 and no SHE within the past year), matching on sex, insulin modality, baseline HbA1c, and age. The analysis cohort included 95 adults with IAH matched to 95 Aware adults (in both groups, 74% female, mean ± SD age of 43 ± 14 yr, and HbA1c of 6.5 ± 0.7%) with a total of 4,236 exercise sessions and 1,794 post-exercise and 839 sedentary days available for analysis. IAH had a trend toward a greater but not clinically significant decline in glucose during exercise compared to Aware (−21 ± 44 vs. −19 ± 43 mg/dL, adjusted group difference of −4.2 [95% CI: −8.7 to 0.3] mg/dL, p=0.06). IAH had a higher proportion of hypoglycemic events (≥15 minutes <70 mg/dL) vs. Aware on both post-exercise days (51% vs. 43%, p=0.008) and sedentary days (48% vs. 30%, p=0.002). There was no evidence that the increased odds of hypoglycemia for IAH compared with Aware differed between post-exercise and sedentary days (interaction p=0.36). In summary, participants with IAH have an overall higher baseline risk of hypoglycemia than Aware participants. However, for those with IAH exercise itself does not appear to differentially increase the risk for hypoglycemia during the activity, or in the subsequent 24 hours compared to Aware individuals with type 1 diabetes. Disclosure J.L. Jo Kamimoto: None. Z. Li: None. R.L. Gal: None. J.R. Castle: Research Support; Dexcom, Inc. Advisory Panel; Novo Nordisk. Stock/Shareholder; Pacific Diabetes Technologies. Advisory Panel; Zealand Pharma A/S. F.J. Doyle: Stock/Shareholder; Mode AGC. Other Relationship; Insulet Corporation, Roche Diabetes Care, Dexcom, Inc. P.G. Jacobs: Other Relationship; Pacific Diabetes Technologies. Board Member; Pacific Diabetes Technologies. Research Support; Dexcom, Inc. C.K. Martin: Research Support; Pack Health, Evidation Health, Lilly. Board Member; EHE Health, Wondr Health. Other Relationship; ABGIL. Research Support; WW International, Inc. R. Beck: Research Support; Tandem Diabetes Care, Inc., Beta Bionics, Inc., Dexcom, Inc., Bigfoot Biomedical, Inc., Medtronic, Ascensia Diabetes Care, Roche Diabetes Care, Eli Lilly and Company. Consultant; Eli Lilly and Company. Research Support; Novo Nordisk. Consultant; Novo Nordisk, Diasome, Insulet Corporation. P. Calhoun: None. M. Riddell: Stock/Shareholder; Supersapiens. Advisory Panel; Zealand Pharma A/S. Speaker's Bureau; Dexcom, Inc. Consultant; Lilly Diabetes. Speaker's Bureau; Novo Nordisk, Sanofi. Stock/Shareholder; Zucara Therapeutics. Advisory Panel; Zucara Therapeutics, Indigo Diabetes. Consultant; Eli Lilly and Company, Jaeb Center for Health Research. M.R. Rickels: Consultant; Sernova, Corp., Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S. Research Support; Dompé. Funding The Leona M. and Harry B. Helmsley Charitable Trust; Verily Life Sciences; Dexcom, Inc.