Olfactory Dysfunction Mediates Adiposity in Cognitive Impairment of Type 2 Diabetes: Insights From Clinical and Functional Neuroimaging Studies
Olfactory Dysfunction Mediates Adiposity in Cognitive Impairment of Type 2 Diabetes: Insights From Clinical and Functional Neuroimaging Studies
复制标题
嗅觉功能障碍介导 2 型糖尿病认知障碍中的肥胖：来自临床和功能神经影像学研究的见解
DOI：
10.2337/dc18-2584
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发表时间：
2019-07-01
期刊：
影响因子：
16.2
通讯作者：
Bi, Yan
中科院分区：
文献类型：
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作者：
Zhang, Zhou;Zhang, Bing;Bi, Yan
目标 大量 2 型糖尿病患者患有肥胖症。然而，肥胖糖尿病患者的认知和相关脑功能的变化尚未得到表征。在这里，我们研究了这些患者的认知、嗅觉功能和气味引起的大脑改变，以及胰高血糖素样肽 1 受体激动剂 (GLP-1Ras) 对他们心理行为和嗅觉网络的治疗效果。研究设计和方法 对 35 名肥胖 2 型糖尿病患者和 35 名非肥胖 2 型糖尿病患者以及 35 名年龄、性别和教育程度相匹配的对照受试者进行认知、嗅觉和气味诱导的大脑激活评估。其中，20 名血糖控制不足且接受二甲双胍单药治疗的肥胖糖尿病患者接受了 3 个月的 GLP-1Ra 治疗，并重新评估了代谢、认知、嗅觉和神经影像学变化。结果 与非肥胖糖尿病受试者相比，肥胖糖尿病受试者表现出较低的一般认知和嗅觉阈值评分、左侧海马激活减少以及与右侧岛叶基于种子的功能连接中断。研究发现肥胖与情景记忆之间以及糖尿病患者的空腹胰岛素与处理速度测试时间之间存在负相关。中介分析表明嗅觉功能和左侧海马体激活介导了这些相关性。经过 3 个月的 GLP-1Ra 治疗，患有糖尿病的肥胖受试者表现出蒙特利尔认知评估 (MoCA) 评分、嗅觉测试总分的改善，以及气味诱导的右侧海马旁回激活的增强。结论 患有 2 型糖尿病的肥胖受试者表现出认知受损以及嗅觉和大脑网络功能障碍，后者介导了糖尿病认知障碍中的肥胖。 GLP-1Ras 改善了肥胖糖尿病患者的认知和嗅觉异常，为这些患者认知衰退的早期诊断和治疗方法提供了新的视角。
OBJECTIVE Large numbers of people with type 2 diabetes are obese. However, changes in cognition and related brain function in obese people with diabetes have not been characterized. Here, we investigated cognition, olfactory function, and odor-induced brain alterations in these patients and therapeutic effects of glucagon-like peptide 1 receptor agonists (GLP-1Ras) on their psychological behavior and olfactory networks. RESEARCH DESIGN AND METHODS Cognitive, olfactory, and odor-induced brain activation assessments were administered to 35 obese and 35 nonobese people with type 2 diabetes and 35 control subjects matched for age, sex, and education. Among them, 20 obese individuals with diabetes with inadequate glycemic control and metformin monotherapy received GLP-1Ra treatment for 3 months and were reassessed for metabolic, cognitive, olfactory, and neuroimaging changes. RESULTS Obese subjects with diabetes demonstrated lower general cognition and olfactory threshold scores, decreased left hippocampal activation, and disrupted seed-based functional connectivity with right insula compared with nonobese subjects with diabetes. Negative associations were found between adiposity and episodic memory and between fasting insulin and processing speed test time in diabetes. Mediation analyses showed that olfactory function and left hippocampus activation mediated these correlations. With 3-month GLP-1Ra treatment, obese subjects with diabetes exhibited improved Montreal Cognitive Assessment (MoCA) score, olfactory test total score, and enhanced odor-induced right parahippocampus activation. CONCLUSIONS Obese subjects with type 2 diabetes showed impaired cognition and dysfunctional olfaction and brain networks, the latter of which mediated adiposity in cognitive impairment of diabetes. GLP-1Ras ameliorated cognitive and olfactory abnormalities in obese subjects with diabetes, providing new perspectives for early diagnosis and therapeutic approaches for cognitive decrements in these patients.