Category: Formulation and Quality
Purpose: Type 1 diabetes (T1D) is a chronic disease that requires constant care for successful glucose control. Continuous glucose monitoring (CGM) is being used to guide accurate insulin dosing [1, 2]. However, glucose levels vary as a result of multiple natural perturbations such as meal consumption, exercise and stress [3-5]. In this study, using a rat exercise model, the combination of glucose, lactate, glycerol and tissue acidity were investigated as potential biomarkers to provide useful metabolic information to facilitate accurate insulin dosing.
Methods: 24 Sprague Dawley rats were divided into four groups with six rats per group: normal rats with aerobic exercise; normal rats with anaerobic exercise; diabetic rats with aerobic exercise; and diabetic rats with anaerobic exercise. The diabetic rats were obtained by inducing the normal rats with streptozocin (STZ) (60 mg/kg, IP) . The samples were collected using microdialysis techniques. Briefly, on experimental day, microdialysis probes were inserted into the rat subcutaneous tissue and subjected to 1 h equilibrium, followed by 1 h exercise (aerobic, running on a treadmill; or anaerobic, ladder climbing on a treadmill) and then a 1 h recovery period after exercise. The samples were continuously collected through the microdialysis probes every 10 minutes. The pH values of the samples were measured with a pH meter. Glucose and lactate were measured using a YSI biochemical analyzer. Glycerol was measured using a commercial glycerol assay kit.
Results: A microdialysis technique has been used to monitor analyte trends in the interstitial fluid of normal and diabetic rats during aerobic and anaerobic exercise and the results are shown in Figure 1A and 1B. Aerobic and anaerobic exercise altered analyte levels differently. Importantly, lactate and glycerol levels showed large differences during aerobic and anaerobic exercise for both normal and diabetic rats, possibly due to the fact that glycerol and lactate are metabolic by-products for lipolysis and anaerobic glycolysis, respectively. Typically, there was a significant increase in glycerol levels in normal rats subjected to aerobic exercise, while lactate levels increased significantly in normal rats subjected to anaerobic exercise. In the case of diabetic rats, significant increase in glycerol levels was observed in rats subjected to aerobic exercise, while there was significant increase in both glycerol and lactate levels in diabetic rats subjected to anaerobic exercise. In the case of normal rats, there was no significant change in the glucose levels, except a small initial change due to the stress produced by the forced running and climbing activities. In the case of diabetic rats, the glucose levels increased initially and did not recover during the exercise as these animals do not have insulin to control their glucose levels. This effect was more pronounced with the anaerobic exercise. There was no significant change in the pH, for either normal or diabetic rats under aerobic or anaerobic exercise, as measured by microdialysis. However the dilution effect of microdialysis may have contributed to this finding.
Conclusion: These results suggested that monitoring the trends of multi-analytes are useful to validate the type, onset and duration of exercise and may provide useful information to facilitate accurate insulin dosing.