Oyer David S
Department of Medicine, Division of Endocrinology, Metabolism, and Molecular Medicine, Feinberg School of Medicine, Northwestern University, 211 E. Chicago Avenue, Suite 1050, Chicago IL 60611, USA.
Curr Diabetes Rev. 2013 May;9(3):195-208. doi: 10.2174/15733998113099990059.
The risk of hypoglycemia with anti-hyperglycemic agents is an important limiting factor in the management of type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. While hypoglycemia is more common in T1DM, the incidence is high in T2DM patients who use insulin or secretagogues, particularly patients with longer duration of diabetes. The underlying cause of hypoglycemia in diabetes is a complex interaction between hyperinsulinemia and compromised physiologic and behavioral responses to falling glucose levels. Pancreatic dysfunction also causes loss of normal therapeutic response to hypoglycemia--a reduction in circulating insulin (in T2DM only) and an increase in glucagon secretion. In T1DM and advanced T2DM, the third defense against hypoglycemia is increase in adrenomedullary sympathoadrenal epinephrine secretion, which is also compromised, causing the syndrome of defective glucose counterregulation. Diminished increase in epinephrine, also called hypoglycemia-associated autonomic failure (HAAF), is largely responsible for defective glucose counterregulation. HAAF can result in recurrent hypoglycemia and lowering of glycemic threshold that typically triggers sympathoadrenal response to hypoglycemia. This results in hypoglycemia without warning symptoms, or "hypoglycemia unawareness," which increases the risk of severe hypoglycemia associated with substantial morbidity and mortality. Long-term effects of severe hypoglycemia, aside from causing accidents, may include adverse cardiovascular outcomes and cognitive impairment. To reduce the impact of hypoglycemia, it is important to identify patients at risk and use careful consideration when choosing antidiabetes medications. Newer insulin analogs that more accurately replicate endogenous insulin secretion and incretin therapies that cause glucose-sensitive insulin secretion may ultimately reduce the risk of hypoglycemia.
使用抗高血糖药物时发生低血糖的风险是1型糖尿病（T1DM）和2型糖尿病（T2DM）管理中的一个重要限制因素。虽然低血糖在T1DM中更常见，但在使用胰岛素或促分泌剂的T2DM患者中发生率也很高，尤其是糖尿病病程较长的患者。糖尿病患者发生低血糖的根本原因是高胰岛素血症与对血糖水平下降的生理和行为反应受损之间的复杂相互作用。胰腺功能障碍也会导致对低血糖的正常治疗反应丧失——循环胰岛素减少（仅在T2DM中）和胰高血糖素分泌增加。在T1DM和晚期T2DM中，对抗低血糖的第三种防御机制是肾上腺髓质交感肾上腺肾上腺素分泌增加，而这一机制也受到损害，导致葡萄糖反调节缺陷综合征。肾上腺素增加减弱，也称为低血糖相关自主神经功能衰竭（HAAF），在很大程度上导致了葡萄糖反调节缺陷。HAAF可导致反复低血糖和血糖阈值降低，而血糖阈值通常会触发交感肾上腺对低血糖的反应。这会导致无警告症状的低血糖，即“低血糖无意识”，从而增加了与严重发病率和死亡率相关的严重低血糖风险。严重低血糖的长期影响，除了导致事故外，可能还包括不良心血管结局和认知障碍。为了降低低血糖的影响，识别有风险的患者并在选择抗糖尿病药物时仔细考虑非常重要。能够更准确模拟内源性胰岛素分泌的新型胰岛素类似物以及能引起葡萄糖敏感型胰岛素分泌的肠促胰岛素疗法最终可能会降低低血糖风险。
