Exercise-related hypoglycemia in diabetes mellitus

Abstract

Current recommendations are that people with Type 1 and Type 2 diabetes mellitus exercise regularly. However, in cases in which insulin or insulin secretagogues are used to manage diabetes, patients have an increased risk of developing hypoglycemia, which is amplified during and after exercise. Repeated episodes of hypoglycemia blunt autonomic nervous system, neuroendocrine and metabolic defenses (counter-regulatory responses) against subsequent episodes of falling blood glucose levels during exercise. Likewise, antecedent exercise blunts counter-regulatory responses to subsequent hypoglycemia. This can lead to a vicious cycle, by which each episode of either exercise or hypoglycemia further blunts counter-regulatory responses. Although contemporary insulin therapies cannot fully mimic physiologic changes in insulin secretion, people with diabetes have several management options to avoid hypoglycemia during and after exercise, including regularly monitoring blood glucose, reducing basal and/or bolus insulin, and consuming supplemental carbohydrates.

Figure 1. Glucose metabolism at rest in nondiabetic individuals

This diagram depicts the interplay between insulin secretion and substrate metabolism under resting conditions. Under post-prandial conditions, insulin levels are elevated, inhibiting endogenous glucose production and NEFA release from adipose tissue. NEFA oxidation decreases and insulin-stimulated muscle glucose uptake increases, providing a major sink for disposal of excess blood glucose. Under post-absorptive conditions, insulin levels decrease, allowing endogenous glucose production to increase to maintain an adequate supply of glucose to the brain. NEFA release from adipose tissue is increased and becomes the primary energy substrate for skeletal muscle metabolism. Gray arrows show hormone signaling pathways, and black arrows show substrate production and uptake. NEFA: Nonesterified fatty acid.

Figure 2. Glucose metabolism during exercise in nondiabetic individuals

This diagram depicts the interplay between metabolic hormone (i.e., insulin, glucagon, epinephrine, norepinephrine) release and substrate metabolism under exercise conditions, during which energy needs drastically increase. Insulin secretion is suppressed and glucagon secretion is increased, which stimulates an increase in endogenous glucose production sufficient to maintain euglycemia. Release of NEFA from adipose tissue is increased, although the contribution of NEFA to skeletal muscle metabolism becomes proportionally smaller. Although insulin levels decrease, muscle glucose uptake increases substantially in response to contraction. High intensity exercise stimulates large increases in epinephrine, which in turn stimulates additional increases in hepatic glucose production and skeletal muscle glycogenolysis to ensure maintenance of euglycemia. Gray dotted lines show nervous system signaling pathways; gray arrows show hormone signaling pathways; and black arrows show substrate production and uptake. NEFA: Nonesterified fatty acid.