Hyperglycemia Suppresses Lactate Clearance During Exercise in Type 1 Diabetes

• Published in: The journal of clinical endocrinology and metabolism 2024-08, Vol.109 (9), p.e1720-e1731
• Main Authors: Romeres, Davide, Yadav, Yogesh, Ruchi, F N U, Carter, Rickey, Cobelli, Claudio, Basu, Rita, Basu, Ananda
• Format: Article
• Language: English
• Subjects: Adult; Blood Glucose - metabolism; Clinical; Diabetes; Diabetes mellitus (insulin dependent); Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - metabolism; Exercise - physiology; Exercise Tolerance - physiology; Female; Humans; Hyperglycemia; Hyperglycemia - etiology; Hyperglycemia - metabolism; Lactic acid; Lactic Acid - blood; Lactic Acid - metabolism; Male; Metabolism; Oxygen Consumption - physiology; Young Adult
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/clinem/dgae005

Abstract Context Circulating lactate concentration is an important determinant of exercise tolerance. Objective This work aimed to determine the role of hyperglycemia on lactate metabolism during exercise in individuals with type 1 diabetes (T1D). Methods The protocol at the University of Virginia compared 7 T1D participants and 7 participants without diabetes (ND) at euglycemia (5.5 mM) or hyperglycemia (9.2 mM) in random order in T1D and at euglycemia in ND. Intervention included [1-13C] lactate infusion, exercise at 65% maximal oxygen uptake (VO2max), euglycemia, and hyperglycemia visits. The main outcome measure was lactate turnover before, during, and after 60 minutes of exercise at 65% VO2max. Results A 2-compartment model with loss only from the peripheral compartment described lactate kinetics. Volume of distribution of the accessible compartment was similar between T1D and ND individuals (P = .76) and concordant with plasma volume (∼40 mL/kg). Circulating lactate concentrations were higher (P < .001) in T1D participants during exercise at hyperglycemia than euglycemia. Exercise-induced lactate appearance did not differ (P = .13) between hyperglycemia and euglycemia. However, lactate clearance (CL) was lower (P = .03) during hyperglycemia than euglycemia in T1D participants. There were no differences in any of the aforementioned parameters between T1D and ND participants during euglycemia. Conclusion Hyperglycemia modulates lactate metabolism during exercise by lowering CL, leading to higher circulating lactate concentrations in T1D individuals. This novel observation implies that exercise during hyperglycemia can lead to higher circulating lactate concentrations thus increasing the likelihood of reaching the lactate threshold sooner in T1D, and has high translational relevance both for providers and recreationally active people with T1D.