During the initial phase of physical exercise muscle glycogen is the primary source of fuel for contracting muscle in normal man. When exercise continues beyond the first 5–10 min blood glucose and free fatty acids (FFA) become increasingly important substrates. Glucose utilization may account for 25–35 of the total substrate supply during mild to moderately heavy exercise. The augmented glucose utilization by working muscle is balanced by a rise in hepatic glucose production. The latter is achieved primarily by hepatic glycogenolysis during brief work, but during prolonged exercise gluconeogenesis may account for as much as 40–50 of the hepatic glucose output. Muscle uptake of FFA is determined primarily by its availability to the working muscle, and it may account for 30–60 of the total fuel supply. Ketone bodies are not utilized by working muscle in normal man. In patients with diabetes mellitus the metabolic effects of physical exercise are to a large extent determined by the time interval between insulin administration and the onset of exercise. Thus, in insulin treated patients with mild hyperglycaemia and no or minimal ketonaemia the utilization of glycogen, blood glucose and FFA by working muscle is similar to that of healthy subjects, and exercise is accompanied by a fall in blood glucose levels. In contrast, patients with more marked hyperglycaemia and hyperketonaemia may respond to exercise with a further rise in both blood glucose and ketone body levels, reflecting augmented rates of hepatic gluconeogenesis as well as ketogenesis. The repletion of muscle and liver glycogen, which takes place for 24–48 h after exercise, requires — besides carbohydrate feeding — a minimum concentration of insulin. Glycogen resynthesis probably accounts for a major part of the empirically well established beneficial effect of physical exercise in diabetic patients. The above considerations underscore the importance of adequate insulin administration in connection with exercise in diab
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