Memory advancement by intranasal insulin in type 2 diabetes (MemAID) randomized controlled clinical trial: Design, methods and rationale
Memory advancement by intranasal insulin in type 2 diabetes (MemAID) randomized controlled clinical trial: Design, methods and rationale
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DOI：
10.1016/j.cct.2020.105934
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发表时间：
2020-02-01
影响因子：
2.2
通讯作者：
Novak, V
中科院分区：
文献类型：
--
作者：
Galindo-Mendez, B.;Trevino, J. A.;Novak, V
背景：2型糖尿病(T2 DM)加速脑老化，增加痴呆风险。胰岛素是大脑中一种关键的神经营养因子，它调节能量代谢、神经血管偶联和再生。胰岛素介导的脑信号转导受损和中枢胰岛素抵抗可能是T2 DM认知和功能下降的原因之一。方法/设计：从2015年开始，一项前瞻性、双中心、随机、双盲、安慰剂对照试验将210名受试者(120名T2 DM和90名非糖尿病老年人)随机分成4组(60名T2 DM-INI、60名T2 DM-安慰剂、45名对照-INI和45名对照-安慰剂)，评估每天鼻腔注射40国际单位(IU)人胰岛素的长期效果，并与安慰剂(无菌生理盐水)进行比较。研究结果是：1)INI对认知、日常功能和步态速度的长期影响；2)确定INI治疗反应的临床相关表型；3)长期安全性。结论：本研究解决了鼻用胰岛素对老年T2 DM和非糖尿病对照组记忆和认知的长期影响的重要知识空白，并可能为预防和治疗认知和功能衰退以及痴呆提供新的治疗靶点。
Background: Type 2 diabetes mellitus (T2DM) accelerates brain aging and increases the risk for dementia. Insulin is a key neurotrophic factor in the brain, where it modulates energy metabolism, neurovascular coupling, and regeneration. Impaired insulin-mediated brain signaling and central insulin resistance may contribute to cognitive and functional decline in T2DM. Intranasal insulin (INI) has emerged as a potential therapy for treating T2DM-related cognitive impairment.Methods/design: Ongoing from 2015, a prospective, two-center, randomized, double-blind, placebo-controlled trial of 210 subjects (120 T2DM and 90 non-diabetic older adults) randomized into four treatment arms (60 T2DM-INI, 60 T2DM-Placebo, 45 Control-INI, and 45 Control-Placebo) evaluating the long-term effects of daily intranasal administration of 40 International Units (IU) of human insulin, as compared to placebo (sterile saline) over 24 weeks and 24 weeks of post-treatment follow-up. Study outcomes are: 1) long-term INI effects on cognition, daily functionality, and gait speed; 2) identifying a clinically relevant phenotype that predicts response to INI therapy; 3) long-term safety.Conclusion: This study addresses an important knowledge gap about the long-term effects of intranasal insulin on memory and cognition in older people with T2DM and non-diabetic controls, and may provide a novel therapeutic target for prevention and treatment of cognitive and functional decline and dementia.