Wang Ya-Rong, Gao Yang, Liu Yan-Chao, Xu Zhi-Peng, Wang Yu-Ying, Xu Hai-Bo, Wang Jian-Zhi, Zhang Yao
Department of Endocrinology, Li-Yuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430077, Hubei Province, China.
Department of Radiology, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, Hubei Province, China.
World J Diabetes. 2025 Aug 15;16(8):106664. doi: 10.4239/wjd.v16.i8.106664.
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.
To investigate the role of HbA1c in APOE4-associated cognitive and olfactory dysfunction in patients with T2DM.
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.
APOE4 was associated with increased risks of cognitive impairment [odds ratios (OR) = 1.815, = 0.021] and olfactory dysfunction (OR = 2.588, < 0.001). Higher HbA1c levels were also related to worse cognitive (OR = 1.189, < 0.001) and olfactory performance (OR = 1.149, = 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, < 0.001) and olfactory dysfunction (OR = 1.440, = 0.027).
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.
载脂蛋白Eε4（APOE4）被认为是2型糖尿病（T2DM）和阿尔茨海默病认知功能下降和神经退行性变的遗传危险因素，而糖化血红蛋白（HbA1c）反映持续高血糖，是T2DM长期血糖控制的关键指标。虽然这两个因素都与神经行为缺陷单独相关，但HbA1c是否会导致T2DM患者出现与APOE4相关的认知和嗅觉损害仍不确定。
探讨HbA1c在T2DM患者APOE4相关认知和嗅觉功能障碍中的作用。
从中国湖北省武汉市的五个医疗中心招募了636例T2DM患者。采用杰拉德法通过聚合酶链反应评估APOE基因分型。分别通过简易精神状态检查和康涅狄格化学感觉临床研究中心测试评估认知和嗅觉功能。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作用。
APOE4与认知障碍风险增加相关[比值比（OR）=1.815，P=0.021]和嗅觉功能障碍（OR=2.588，P<0.001）。较高的HbA1c水平也与较差的认知（OR=1.189，P<0.001）和嗅觉表现（OR=1.149，P=0.011）相关。HbA1c在APOE4及其对认知和嗅觉的影响之间起调节作用，但不起中介作用。具体而言，较高水平的HbA1c加剧了APOE4的损害作用，对认知障碍（OR=2.687，P<0.001）和嗅觉功能障碍（OR=1.440，P=0.027）均有显著交互作用。
HbA1c水平升高与T2DM患者认知和嗅觉障碍风险增加相关，可能会加剧APOE4的有害影响。这些发现强调了针对血糖控制不佳和携带APOE4的个体制定早期预防策略以降低神经退行性变风险的必要性。
