For the first 5 to 10 minutes of exercise, the main fuel used by a person without diabetes is stored muscle glycogen. But it can be used only to meet the energy needs of the muscle in which it’s contained. With prolonged exercise, the body uses glycogen from the liver, fat in the form of triglycerides and nonesterified fatty acids (NEFA).

As a person continues to exercise, muscle glycogen stores are depleted. Muscle glycogen depletion stimulates liver gluconeogenesis, which begins the replacement of glycogen stores. This happens in two stages. First, immediately after exercise, cell permeability to glucose increases, and muscle glycogen stores are restored rapidly with no need for insulin. In the second stage, muscle glycogen returns to near-normal levels, glucose uptake decreases, and insulin action increases.

In a person who has diabetes, the body’s use of muscle glycogen, triglycerides, liver glycogen, and NEFA differs. During short-term exercise, the rate of gluconeogenesis rises to two to three times above her baseline. Her liver’s response to brief exercise resembles the response to prolonged exercise in people without diabetes.

In people without diabetes and in those with diabetes who have mildly elevated blood glucose levels, an initial drop in NEFA concentration is followed by a gradual increase as exercise continues. In patients with diabetes who have severe hyperglycemia and ketosis, levels of NEFA are elevated, even at rest. For them, the increase in NEFA during exercise is even greater.

Normally, ketones aren’t a major source of fuel for the muscles. The body of a patient with diabetes who has mild ketosis, however, uses ketones for fuel during exercise.

A minimum amount of insulin is needed for glucose uptake by muscles and for the regulation of gluconeogenesis by the liver. An insulin deficiency triggers the abnormal secretion of counterregulatory hormones, which raise blood glucose levels. If exercise fails to lower high blood glucose levels, hyperglycemia results .

In patients with Type 1 diabetes, hypoglycemia rarely occurs during exercise but can occur up to a day later. Possible causes for late-onset hypoglycemia include glycogen depletion in the liver or muscles from intense or prolonged exercise, increases in insulin sensitivity, the use of glucose to replenish glycogen stores, counterregulatory response defect, and inappropriate adjustments of food intake or insulin therapy.