<br>当前和未来治疗低血糖意识受损的疗法,Frontiers in Pharmacology

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当前和未来治疗低血糖意识受损的疗法
Frontiers in Pharmacology ( IF 4.4 ) Pub Date : 2023-10-24 , DOI: 10.3389/fphar.2023.1271814
Erica L Macon ₁ , Micah H Devore ₁ , Yu Kuei Lin ₂ , Megan B Music ₁ , Mason Wooten ₁ , Colleen A McMullen ₁ , Andrea M Woodcox ₁ , Ashlee R Marksbury ₁ , Zachary Beckner ₁ , Bansi V Patel ₁ , Lily A Schoeder ₁ , Ashley N Iles ₁ , Simon J Fisher ₁

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为了实现最佳血糖控制，1 型糖尿病 (T1D) 和胰岛素依赖型 2 型糖尿病 (T2D) 患者需要强化胰岛素治疗。不幸的是，强化血糖控制常常导致胰岛素引起的低血糖。此外，低血糖的反复发作导致与低血糖相关的特征性警告症状的消失以及反调节激素反应的减弱。警告症状的减弱被称为低血糖意识受损（IAH）。 IAH 和激素反应丧失一起被称为低血糖相关自主神经衰竭 (HAAF)。 IAH 在 1 型糖尿病患者中的患病率高达 25%，在 2 型糖尿病患者中的患病率高达 10%。 IAH 和 HAAF 分别使严重低血糖的风险增加 6 倍和 25 倍。为了降低严重低血糖的风险，正在探索多种不同的治疗方法，以提高对低血糖的认识。目前提高低血糖意识的疗法包括患者教育和心理教育、使用新型血糖控制技术、胰腺/胰岛移植和药物治疗。本综述检查了现有疗法和处于临床前测试中的潜在疗法。通过改善反调节激素反应或改善低血糖症状识别来提高低血糖意识的新疗法也将揭示导致 IAH 发生的可能神经机制。为了降低糖尿病患者发生严重低血糖的风险，阐明 IAH 背后的机制并开发靶向治疗方法是 IAH 患者目前尚未满足的需求。

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Current and future therapies to treat impaired awareness of hypoglycemia

In order to achieve optimal glycemic control, intensive insulin regimes are needed for individuals with Type 1 Diabetes (T1D) and insulin-dependent Type 2 Diabetes (T2D). Unfortunately, intensive glycemic control often results in insulin-induced hypoglycemia. Moreover, recurrent episodes of hypoglycemia result in both the loss of the characteristic warning symptoms associated with hypoglycemia and an attenuated counterregulatory hormone responses. The blunting of warning symptoms is known as impaired awareness of hypoglycemia (IAH). Together, IAH and the loss of the hormonal response is termed hypoglycemia associated autonomic failure (HAAF). IAH is prevalent in up to 25% in people with T1D and up to 10% in people with T2D. IAH and HAAF increase the risk of severe hypoglycemia 6-fold and 25-fold, respectively. To reduce this risk for severe hypoglycemia, multiple different therapeutic approaches are being explored that could improve awareness of hypoglycemia. Current therapies to improve awareness of hypoglycemia include patient education and psychoeducation, the use of novel glycemic control technology, pancreas/islet transplantation, and drug therapy. This review examines both existing therapies and potential therapies that are in pre-clinical testing. Novel treatments that improve awareness of hypoglycemia, via improving the counterregulatory hormone responses or improving hypoglycemic symptom recognition, would also shed light on the possible neurological mechanisms that lead to the development of IAH. To reduce the risk of severe hypoglycemia in people with diabetes, elucidating the mechanism behind IAH, as well as developing targeted therapies is currently an unmet need for those that suffer from IAH.

更新日期：2023-10-24

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