Pancreatic β-Cell Function Is Associated with Augmented Counterregulation to In-Exercise Hypoglycemia in Type 1 Diabetes

Purpose: This study aimed to investigate the influence of residual beta-cell function on counterregulatory hormonal responses to hypoglycemia during acute physical exercise in people with type 1 diabetes (T1D). A secondary aim was to explore relationships between biomarkers of pancreatic beta-cell function and indices of glycemia following acute exercise including the nocturnal period. Methods: This study involved an exploratory, secondary analysis of data fromindividuals with T1D who partook in a four-peroid, randomized, cross-over trial involving a bout of evening exercise followed by an overnight stay in a clinical laboratory facility. Participants were split into two groups: (i) a stimulated C-peptide level of >= 30 pmol.L-1 (low-level secretors [LLS], n = 6) or ( ii) <30 pmol.L-1 (microsecretors [MS], n = 10). Pancreatic hormones (C-peptide, proinsulin, and glucagon), catecholamines (epinephrine [EPI] and norepinephrine [NE]), and metabolic biomarkers (blood glucose, blood lactate, and beta-hydroxybutyrate) were measured at rest, during exercise with and without a hypoglycemic (blood glucose <= 3.9 mmol.L-1) episode, and throughout a 13-h postexercise period. Interstitial glucose monitoring was used to assess indices of glycemic variability. Results: During in-exercise hypoglycemia, LLS presented with greater sympathoadrenal (EPI and NE P <= 0.05) and ketone (P < 0.01) concentrations. Glucagon remained similar (P = 0.09). Over exercise, LLS experienced larger drops in C-peptide and proinsulin (both P < 0.01) as well as greater increases in EPI (P < 0.01) and beta-hydroxybutyrate (P = 0.03). LLS spent less time in the interstitial-derived hypoglycemic range acutely postexercise and had lower glucose variability throughout the nocturnal period. Conclusion: Higher residual beta-cell function was associated with greater sympathoadrenal and ketonic responses to exercise-induced hypoglycemia as well as improved glycemia leading into and throughout the nocturnal hours. Even a minimal amount of residual beta-cell function confers a beneficial effect on glycemic outcomes during and after exercise in people with T1D.