During exercise, there is coordination between various hormonal systems to ensure glucoregulation. This study examined if hypoglycemia occurs during moderate-intensity exercise in non-obese and obese individuals with and without type 2 diabetes (T2D). Eighteen non-obese, 18 obese, and 10 obese with T2D completed 2 study days that included a meal at 1,800 h followed by rest (NOEX) or exercise (PMEX; 45 min/55% of VO2 max 2 h post meal). Glucose, insulin, and glucagon concentrations were measured throughout this 5.5 h period. Subjects with T2D had elevated glucose responses to the meal on both study days, compared to non-obese and obese subjects (P < 0.05). During evening exercise (PMEX), subjects with T2D had a greater drop in glucose concentration (−98.4 ± 13.3 mg/dL) compared to obese (−44.8 ± 7.1 mg/dL) and non-obese (−39.3 ± 6.1 mg/dL; P < 0.01) subjects. Glucose levels decreased more so in females than males in both conditions (P < 0.01). Nadir glucose levels <70 mg/dL were observed in 33 subjects during NOEX and 39 subjects during PMEX. Obese males had a larger exercise-induced insulin drop than obese females (P = 0.01). During PMEX, peak glucagon concentrations were elevated compared to NOEX (P < 0.001). Male participants with T2D had an increased glucagon response during NOEX and PMEX compared to females (P < 0.01). In conclusion, in individuals with varying glucose tolerance, there is a dramatic drop in glucose levels during moderate-intensity exercise, despite appropriate insulin concentrations prior to exercise, and glucagon levels rising during exercise. Moderate-intensity exercise can result in low glucose concentrations (<60 mg/dL), and yet many of these individuals will be asymptomatic.

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