Ya-Rong Wang, Yang Gao, Yan-Chao Liu, Zhi-Peng Xu, Yu-Ying Wang, Hai-Bo Xu, Jian-Zhi Wang, Yao Zhang
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Although both factors have been individually linked to neurobehavioral deficits, it remains uncertain whether HbA1c contributes to APOE4-related cognitive and olfactory impairment in individuals with T2DM.</p><p><strong>Aim: </strong>To investigate the role of HbA1c in APOE4-associated cognitive and olfactory dysfunction in patients with T2DM.</p><p><strong>Methods: </strong>Of 636 T2DM patients were recruited from five medical centers in Wuhan, Hubei Province, China. APOE genotyping was evaluated by polymerase chain reaction using Gerard's method. Cognitive and olfactory functions were assessed by mini-mental state examination and Connecticut chemosensory clinical research center test, respectively. Regression analysis was employed to assess the independent and interactive effects of HbA1c on APOE4-associated cognitive and olfactory function.</p><p><strong>Results: </strong>APOE4 was associated with increased risks of cognitive impairment [odds ratios (OR) = 1.815, <i>P</i> = 0.021] and olfactory dysfunction (OR = 2.588, <i>P</i> < 0.001). Higher HbA1c levels were also related to worse cognitive (OR = 1.189, <i>P</i> < 0.001) and olfactory performance (OR = 1.149, <i>P</i> = 0.011). HbA1c exerted a moderating effect, yet not a mediating effect, between APOE4 and its impacts on cognition and olfaction. Specifically, a higher level of HbA1c exacerbated the damaging effect of APOE4, as shown by significant interaction effects on both cognitive impairment (OR = 2.687, <i>P</i> < 0.001) and olfactory dysfunction (OR = 1.440, <i>P</i> = 0.027).</p><p><strong>Conclusion: </strong>Elevated HbA1c levels are associated with increased risks of cognitive and olfactory impairments in patients with T2DM and may exacerbate the detrimental effects of APOE4. These findings underscore the need for early preventive strategies targeting individuals with both poor glycemic control and APOE4 carriage to mitigate neurodegenerative risk.</p>","PeriodicalId":48607,"journal":{"name":"World Journal of Diabetes","volume":"16 8","pages":"106664"},"PeriodicalIF":4.6000,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12432546/pdf/","citationCount":"0","resultStr":"{\"title\":\"Higher glycated hemoglobin amplifies the effect of apolipoprotein E epsilon 4-related cognition and olfaction impairments in type 2 diabetes.\",\"authors\":\"Ya-Rong Wang, Yang Gao, Yan-Chao Liu, Zhi-Peng Xu, Yu-Ying Wang, Hai-Bo Xu, Jian-Zhi Wang, Yao Zhang\",\"doi\":\"10.4239/wjd.v16.i8.106664\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Apolipoprotein E epsilon 4 (APOE4) is recognized as a genetic risk factor for cognitive decline and neurodegeneration in both type 2 diabetes mellitus (T2DM) and Alzheimer's disease, while glycated hemoglobin (HbA1c) reflects persistent hyperglycemia and serves as a key indicator of long-term glycemic control in T2DM. Although both factors have been individually linked to neurobehavioral deficits, it remains uncertain whether HbA1c contributes to APOE4-related cognitive and olfactory impairment in individuals with T2DM.</p><p><strong>Aim: </strong>To investigate the role of HbA1c in APOE4-associated cognitive and olfactory dysfunction in patients with T2DM.</p><p><strong>Methods: </strong>Of 636 T2DM patients were recruited from five medical centers in Wuhan, Hubei Province, China. APOE genotyping was evaluated by polymerase chain reaction using Gerard's method. Cognitive and olfactory functions were assessed by mini-mental state examination and Connecticut chemosensory clinical research center test, respectively. Regression analysis was employed to assess the independent and interactive effects of HbA1c on APOE4-associated cognitive and olfactory function.</p><p><strong>Results: </strong>APOE4 was associated with increased risks of cognitive impairment [odds ratios (OR) = 1.815, <i>P</i> = 0.021] and olfactory dysfunction (OR = 2.588, <i>P</i> < 0.001). Higher HbA1c levels were also related to worse cognitive (OR = 1.189, <i>P</i> < 0.001) and olfactory performance (OR = 1.149, <i>P</i> = 0.011). HbA1c exerted a moderating effect, yet not a mediating effect, between APOE4 and its impacts on cognition and olfaction. Specifically, a higher level of HbA1c exacerbated the damaging effect of APOE4, as shown by significant interaction effects on both cognitive impairment (OR = 2.687, <i>P</i> < 0.001) and olfactory dysfunction (OR = 1.440, <i>P</i> = 0.027).</p><p><strong>Conclusion: </strong>Elevated HbA1c levels are associated with increased risks of cognitive and olfactory impairments in patients with T2DM and may exacerbate the detrimental effects of APOE4. 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引用次数: 0
摘要
背景：载脂蛋白E ε 4 （APOE4）被认为是2型糖尿病（T2DM）和阿尔茨海默病认知能力下降和神经退行性变的遗传危险因素，而糖化血红蛋白（HbA1c）反映持续性高血糖，是T2DM患者长期血糖控制的关键指标。尽管这两个因素都与神经行为缺陷有关，但HbA1c是否与apoe4相关的T2DM患者认知和嗅觉障碍有关仍不确定。目的：探讨HbA1c在T2DM患者apoe4相关认知和嗅觉功能障碍中的作用。方法：从中国湖北省武汉市的5个医疗中心招募636例T2DM患者。采用聚合酶链反应法测定APOE基因分型。认知功能和嗅觉功能分别通过迷你精神状态检查和康涅狄格化学感觉临床研究中心测试进行评估。采用回归分析评估HbA1c对apoe4相关认知和嗅觉功能的独立和交互影响。结果：APOE4与认知功能障碍[比值比(OR) = 1.815, P = 0.021]和嗅觉功能障碍（OR = 2.588, P < 0.001）的风险增加相关。较高的HbA1c水平也与较差的认知能力（OR = 1.189, P < 0.001）和嗅觉能力（OR = 1.149, P = 0.011）有关。在APOE4及其对认知和嗅觉的影响之间，HbA1c发挥了调节作用，而不是中介作用。具体而言，较高的HbA1c水平加重了APOE4的损伤作用，对认知功能障碍（OR = 2.687, P < 0.001）和嗅觉功能障碍（OR = 1.440, P = 0.027）均有显著的交互作用。结论：HbA1c水平升高与T2DM患者认知和嗅觉障碍的风险增加有关，并可能加剧APOE4的有害影响。这些发现强调了针对血糖控制不良和携带APOE4的个体采取早期预防策略以减轻神经退行性风险的必要性。
Higher glycated hemoglobin amplifies the effect of apolipoprotein E epsilon 4-related cognition and olfaction impairments in type 2 diabetes.
Background: Apolipoprotein E epsilon 4 (APOE4) is recognized as a genetic risk factor for cognitive decline and neurodegeneration in both type 2 diabetes mellitus (T2DM) and Alzheimer's disease, while glycated hemoglobin (HbA1c) reflects persistent hyperglycemia and serves as a key indicator of long-term glycemic control in T2DM. Although both factors have been individually linked to neurobehavioral deficits, it remains uncertain whether HbA1c contributes to APOE4-related cognitive and olfactory impairment in individuals with T2DM.
Aim: To investigate the role of HbA1c in APOE4-associated cognitive and olfactory dysfunction in patients with T2DM.
Methods: Of 636 T2DM patients were recruited from five medical centers in Wuhan, Hubei Province, China. APOE genotyping was evaluated by polymerase chain reaction using Gerard's method. Cognitive and olfactory functions were assessed by mini-mental state examination and Connecticut chemosensory clinical research center test, respectively. Regression analysis was employed to assess the independent and interactive effects of HbA1c on APOE4-associated cognitive and olfactory function.
Results: APOE4 was associated with increased risks of cognitive impairment [odds ratios (OR) = 1.815, P = 0.021] and olfactory dysfunction (OR = 2.588, P < 0.001). Higher HbA1c levels were also related to worse cognitive (OR = 1.189, P < 0.001) and olfactory performance (OR = 1.149, P = 0.011). HbA1c exerted a moderating effect, yet not a mediating effect, between APOE4 and its impacts on cognition and olfaction. Specifically, a higher level of HbA1c exacerbated the damaging effect of APOE4, as shown by significant interaction effects on both cognitive impairment (OR = 2.687, P < 0.001) and olfactory dysfunction (OR = 1.440, P = 0.027).
Conclusion: Elevated HbA1c levels are associated with increased risks of cognitive and olfactory impairments in patients with T2DM and may exacerbate the detrimental effects of APOE4. These findings underscore the need for early preventive strategies targeting individuals with both poor glycemic control and APOE4 carriage to mitigate neurodegenerative risk.
期刊介绍：
The WJD is a high-quality, peer reviewed, open-access journal. The primary task of WJD is to rapidly publish high-quality original articles, reviews, editorials, and case reports in the field of diabetes. In order to promote productive academic communication, the peer review process for the WJD is transparent; to this end, all published manuscripts are accompanied by the anonymized reviewers’ comments as well as the authors’ responses. The primary aims of the WJD are to improve diagnostic, therapeutic and preventive modalities and the skills of clinicians and to guide clinical practice in diabetes. Scope: Diabetes Complications, Experimental Diabetes Mellitus, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Diabetes, Gestational, Diabetic Angiopathies, Diabetic Cardiomyopathies, Diabetic Coma, Diabetic Ketoacidosis, Diabetic Nephropathies, Diabetic Neuropathies, Donohue Syndrome, Fetal Macrosomia, and Prediabetic State.
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