Evidence for a vicious cycle of exercise and hypoglycemia in type 1 diabetes mellitus

Abstract

Exercise is a cornerstone of diabetes management as it aids in glycemic control, weight management, reducing blood pressure, and improving the quality of life of patients. Unfortunately, owing to the complexity and difficulties of regulating exogenous insulin in a physiologic manner during exercise, physical activity often results in hypoglycemia in patients with type 1 diabetes mellitus (type 1 DM). When glucose levels fall below threshold glycemic levels, neuroendocrine, autonomic nervous system (ANS), and metabolic glucose counterregulatory mechanisms are activated. These hypoglycemic counterregulatory mechanisms in type 1 DM can be blunted irreversibly by disease duration or by acute episodes of prior stress. These reduced (or absent) counterregulatory responses result in a threefold increase in severe hypoglycemia when intensive glycemic control is implemented in type 1 DM. Much recent work has been focused on determining the in vivo mechanisms responsible for causing the increased incidence of severe hypoglycemia in type 1 DM. Studies from several laboratories have demonstrated the role played by episodes of antecedent hypoglycemia in producing blunted glucose counterregulatory responses during subsequent exposures of hypoglycemia. Until recently, the mechanisms responsible for exercise related hypoglycemia in type 1 DM have been attributed to relative or absolute increases of insulin levels or incomplete glycogen repletion after physical activity. Owing to the qualitative similarity of neuroendocrine, ANS, and metabolic responses to hypoglycemia and exercise, we have hypothesized that neuroendocrine and ANS counterregulatory dysfunction may also play an important role in the pathogenesis of exercise-related hypoglycemia in type 1 DM. Vicious cycles can be created in type 1 DM, where an episode of hypoglycemia or exercise can feed forward to downregulate neuroendocrine and ANS responses to a subsequent episode of either stress, thereby creating further hypoglycemia. This article will review the recent work that has studied the contribution of counterregulatory dysfunction to exercise-induced hypoglycemia in type 1 DM.