Cryer P E
Division of Endocrinology, Diabetes and Metabolism, and General Clinical Research Center, Washington University School of Medicine, St. Louis, Missouri, USA.
Horm Metab Res. 1997 Mar;29(3):92-6. doi: 10.1055/s-2007-978997.
Hypoglycemia elicits a characteristic sequence of responses in healthy humans. These responses (and their arterialized venous glycemic thresholds) include: 1) Decreased insulin secretion (approximately 4.5 mmol/L). 2) Increased glucose counterregulatory hormone (glucagon, epinephrine, growth hormone and cortisol) secretion (approximately 3.6-3.8 mmol/L). 3) Symptoms of hypoglycemia (approximately 3.0 mmol/L). 4) Cognitive dysfunction (approximately 2.6 mmol/L). Thus, insulin secretion decreases as plasma glucose levels fall within the physiological range, and counterregulatory hormone secretion increases as plasma glucose levels fall just below the physiological range at substantially higher glucose levels than those required to produce symptoms and impair cognitive function. These data are entirely consistent with the body of evidence that insulin, glucagon and epinephrine stand high in the hierarchy of redundant glucoregulatory factors that prevent, as well as correct, hypoglycemia. When the same methods are used, these thresholds are remarkably reproducible from laboratory to laboratory. Nonetheless, the glycemic thresholds are dynamic rather than static. They vary in relation to recent antecedent glycemia. For example, lower plasma glucose concentrations are required to elicit autonomic, including epinephrine, and symptomatic responses in patients with well controlled IDDM, a phenomenon best attributed to recent antecedent iatrogenic hypoglycemia. This is the basis of the clinical syndrome of hypoglycemia unawareness, which is now known to be reversible with scrupulous avoidance of iatrogenic hypoglycemia. The latter also at least partially reverses reduced epinephrine responses to hypoglycemia, a key component (in the setting of absent glucagon responses) of the syndrome of defective glucose counterregulation. While perhaps seemingly adaptive, these threshold shifts appear to be maladaptive since both defective glucose counterregulation and hypoglycemia unawareness are associated with substantially increased rates of severe iatrogenic hypoglycemia in people with IDDM.
低血糖会在健康人体内引发一系列特征性反应。这些反应（及其动脉化静脉血糖阈值）包括：1）胰岛素分泌减少（约4.5毫摩尔/升）。2）葡萄糖反向调节激素（胰高血糖素、肾上腺素、生长激素和皮质醇）分泌增加（约3.6 - 3.8毫摩尔/升）。3）低血糖症状（约3.0毫摩尔/升）。4）认知功能障碍（约2.6毫摩尔/升）。因此，随着血浆葡萄糖水平在生理范围内下降，胰岛素分泌减少；而当血浆葡萄糖水平略低于生理范围时，反向调节激素分泌增加，此时的血糖水平远高于产生症状和损害认知功能所需的水平。这些数据与大量证据完全一致，即胰岛素、胰高血糖素和肾上腺素在预防和纠正低血糖的冗余葡萄糖调节因子层级中处于高位。当使用相同方法时，这些阈值在不同实验室之间具有显著的可重复性。尽管如此，血糖阈值是动态的而非静态的。它们会因近期的血糖情况而变化。例如，在血糖控制良好的1型糖尿病患者中，引发自主神经反应（包括肾上腺素）和症状性反应所需的血浆葡萄糖浓度较低，这一现象最可能归因于近期医源性低血糖。这就是低血糖无意识临床综合征的基础，现在已知通过严格避免医源性低血糖，该综合征是可逆的。后者至少部分逆转了对低血糖的肾上腺素反应降低，这是葡萄糖反向调节缺陷综合征（在胰高血糖素反应缺失的情况下）的一个关键组成部分。虽然这些阈值变化看似具有适应性，但实际上似乎是适应不良的，因为葡萄糖反向调节缺陷和低血糖无意识都与1型糖尿病患者严重医源性低血糖的发生率大幅增加有关。
