Ertl A C, Davis S N
Division of Diabetes, Endocrinology, and Metabolism, Vanderbilt University Medical Center, Preston Research Building, Nashville, TN 37232-6303, USA.
Diabetes Metab Res Rev. 2004 Mar-Apr;20(2):124-30. doi: 10.1002/dmrr.450.
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.
运动是糖尿病管理的基石，因为它有助于血糖控制、体重管理、降低血压并改善患者的生活质量。不幸的是，由于在运动期间以生理方式调节外源性胰岛素存在复杂性和困难，体力活动常常导致1型糖尿病（T1DM）患者发生低血糖。当血糖水平降至阈值血糖水平以下时，神经内分泌、自主神经系统（ANS）和代谢性葡萄糖对抗调节机制被激活。T1DM中的这些低血糖对抗调节机制可能会因病程或先前应激的急性发作而不可逆转地减弱。当在T1DM中实施强化血糖控制时，这些减弱（或缺失）的对抗调节反应会导致严重低血糖的发生率增加两倍。最近的许多工作都集中在确定导致T1DM中严重低血糖发生率增加的体内机制。几个实验室的研究已经证明了先前低血糖发作在随后低血糖暴露期间产生减弱的葡萄糖对抗调节反应中所起的作用。直到最近，T1DM中与运动相关的低血糖的机制一直被归因于胰岛素水平的相对或绝对增加或体力活动后糖原补充不完全。由于神经内分泌、ANS和对低血糖和运动的代谢反应在性质上相似，我们推测神经内分泌和ANS对抗调节功能障碍也可能在T1DM中与运动相关的低血糖的发病机制中起重要作用。在T1DM中可能会形成恶性循环，即一次低血糖或运动发作可引发后续应激发作时神经内分泌和ANS反应的下调，从而导致进一步的低血糖。本文将综述最近研究对抗调节功能障碍对T1DM中运动诱发低血糖的影响的工作。
