Galassetti Pietro, Tate Donna, Neill Ray A, Morrey Sachiko, Wasserman David H, Davis Stephen N
Departments of Medicine and Molecular Physiology and Biophysics, Vanderbilt University School of Medicine and Nashville Veteran Affairs Medical Center, Nashville, Tennessee 37232-6303, USA.
Diabetes. 2003 Jul;52(7):1761-9. doi: 10.2337/diabetes.52.7.1761.
Exercise-related hypoglycemia is common in intensively treated patients with type 1 diabetes. The underlying mechanisms are not clearly defined. In nondiabetic subjects, hypoglycemia blunts counterregulatory responses to subsequent exercise. It is unknown whether this also occurs in type 1 diabetes. Therefore, the goal of this study was to test the hypothesis that prior hypoglycemia could result in acute counterregulatory failure during subsequent exercise in type 1 diabetes. A total of 16 type 1 diabetic patients (8 men and 8 women, HbA(1c) 7.8 +/- 0.3%) were investigated during 90 min of euglycemic cycling exercise, following either two 2-h periods of previous-day hypoglycemia (2.9 mmol/l) or previous-day euglycemia. Patients' counterregulatory responses (circulating levels of counterregulatory hormones, intermediary metabolites, substrate flux via indirect calorimetry, tracer-determined glucose kinetics, and cardiovascular measurements) were comprehensively assessed during exercise. Identical euglycemia and basal insulin levels were successfully maintained during all exercise studies, regardless of blood glucose levels during the previous day. After resting euglycemia, patients displayed normal counterregulatory responses to exercise. Conversely, when identical exercise was repeated after hypoglycemia, the glucagon response to exercise was abolished, and the epinephrine, norepinephrine, cortisol, endogenous glucose production, and lipolytic responses were reduced by 40-80%. This resulted in a threefold increase in the amount of exogenous glucose needed to maintain euglycemia during exercise. Our results demonstrate that antecedent hypoglycemia, in type 1 diabetes, can produce acute counterregulatory failure during a subsequent episode of prolonged moderate-intensity exercise. The metabolic consequence of the blunted neuroendocrine and autonomic nervous system counterregulatory responses was an acute failure of endogenous glucose production to match the increased glucose requirements during exercise. These data indicate that counterregulatory failure may be a significant in vivo mechanism responsible for exercise-associated hypoglycemia in type 1 diabetes.
运动相关低血糖在强化治疗的1型糖尿病患者中很常见。其潜在机制尚未明确。在非糖尿病受试者中，低血糖会减弱对随后运动的反调节反应。在1型糖尿病患者中是否也会发生这种情况尚不清楚。因此，本研究的目的是检验以下假设：先前的低血糖会导致1型糖尿病患者在随后的运动中出现急性反调节功能衰竭。共有16名1型糖尿病患者（8名男性和8名女性，糖化血红蛋白7.8±0.3%）在进行90分钟的血糖正常的循环运动期间接受了调查，此前经历了两天2小时的前一天低血糖（2.9 mmol/l）或前一天血糖正常。在运动期间全面评估了患者的反调节反应（反调节激素的循环水平、中间代谢产物、通过间接测热法测定的底物通量、示踪剂测定的葡萄糖动力学以及心血管测量）。在所有运动研究中，无论前一天的血糖水平如何，均成功维持了相同的血糖正常水平和基础胰岛素水平。在静息血糖正常后，患者对运动表现出正常的反调节反应。相反，在低血糖后重复相同运动时，对运动的胰高血糖素反应消失，肾上腺素、去甲肾上腺素、皮质醇、内源性葡萄糖生成和脂解反应降低了40 - 80%。这导致在运动期间维持血糖正常所需的外源性葡萄糖量增加了两倍。我们的结果表明，在1型糖尿病中，先前的低血糖会在随后的长时间中等强度运动期间导致急性反调节功能衰竭。神经内分泌和自主神经系统反调节反应减弱的代谢后果是内源性葡萄糖生成无法满足运动期间增加的葡萄糖需求，从而导致急性功能衰竭。这些数据表明，反调节功能衰竭可能是1型糖尿病中运动相关低血糖的一个重要体内机制。
