Separating insulin-mediated and non-insulin-mediated glucose uptake during and after aerobic exercise in type 1 diabetes

Aerobic exercise in type 1 diabetes (T1D) causes rapid increase in glucose utilization due to muscle work during exercise, followed by increased insulin sensitivity after exercise. Better understanding of these changes is necessary for models of exercise in T1D. Twenty-six individuals with T1D underwent three sessions at three insulin rates (100%, 150%, 300% of basal). After 3-h run-in, participants performed 45 min aerobic exercise (moderate or intense). We determined area under the curve for endogenous glucose production (AUC_EGP) and rate of glucose disappearance (AUC_Rd) over 45 min from exercise start. A novel application of linear regression of R_d across the three insulin sessions allowed separation of insulin-mediated from non-insulin-mediated glucose uptake before, during, and after exercise. AUC_Rd increased 12.45 mmol/L (CI = 10.33–14.58, P < 0.001) and 13.13 mmol/L (CI = 11.01–15.26, P < 0.001) whereas AUC_EGP increased 1.66 mmol/L (CI = 1.01–2.31, P < 0.001) and 3.46 mmol/L (CI = 2.81–4.11, P < 0.001) above baseline during moderate and intense exercise, respectively. AUC_EGP increased during intense exercise by 2.14 mmol/L (CI = 0.91–3.37, P < 0.001) compared with moderate exercise. There was significant effect of insulin infusion rate on AUC_Rd equal to 0.06 mmol/L per % above basal rate (CI = 0.05–0.07, P < 0.001). Insulin-mediated glucose uptake rose during exercise and persisted hours afterward, whereas non-insulin-mediated effect was limited to the exercise period. To our knowledge, this method of isolating dynamic insulin- and non-insulin-mediated uptake has not been previously employed during exercise. These results will be useful in informing glucoregulatory models of T1D. The study has been registered at www.clinicaltrials.gov as NCT03090451.