Longitudinal Changes in Auditory Function Among Veterans with Diabetes

患有糖尿病的退伍军人听觉功能的纵向变化

• 批准号: 8868522
• 负责人: Marilyn F. Dille
• 金额: --
• 依托单位: PORTLAND VA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8868522
• 关键词: Acoustic Nerve; Acoustics; Address; Adverse effects; Affect; Age; Age of Onset; Aging; Aging-Related Process; Animal Model; Auditory; Auditory system; Behavioral; Benchmarking; Biological; Blindness; Brain; Brain Stem; Caring; Characteristics; Clinical Trials; Cochlea; Cognition; Cognitive; Cohort Studies; Communication impairment; Comorbidity; Complex; Comprehension; Cross-Sectional Studies; Cues; Data; Deterioration; Diabetes Mellitus; Diagnosis; Diet; Disease; Economics; Emotional; Exhibits; Eye; Fatty acid glycerol esters; Functional disorder; Future; Glycosylated hemoglobin A; Goals; Health; Hearing; Human; Hyperglycemia; Hyperlipidemia; Hypertension; Impaired cognition; Impairment; Individual; Insulin; Intervention; Kidney; Kidney Diseases; Knowledge; Laboratories; Labyrinth; Link; Longitudinal Studies; Measures; Metabolic Control; Metabolic Diseases; Metabolic syndrome; Mission; Modeling; Molecular; Morbidity - disease rate; Mus; Nature; Neurologic; Neurons; Neuropathy; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Output; Patients; Peripheral; Personal Satisfaction; Phenotype; Physiological; Population; Presbycusis; Prevention; Procedures; Process; Publishing; Quality of life; Relative (related person); Research; Retinal; Risk; Risk Factors; Sensory; Severities; Severity of illness; Speech; Staging; Statistical Models; Surveys; Testing; Time; Veterans; Work; age related; auditory pathway; auditory stimulus; base; behavior measurement; clinical Diagnosis; clinically significant; cognitive change; cognitive function; cognitive process; cohort; disability; feeding; glycemic control; hearing impairment; improved; knowledge base; macrovascular disease; mouse model; non-diabetic; normal aging; premature; prevent; programs; prospective; public health relevance; relating to nervous system; senescence; social; speech processing; trend

 DESCRIPTION (provided by applicant): Diabetes Mellitus (DM) is a metabolic disease that causes microvascular and neurologic complications and affects 20-30% of Veterans. Evidence supports a link between DM and hearing loss. A growing body of evidence-including from our own laboratory-suggests that DM-related harmful effects alter the cochlea, auditory nerve, and brain, impacting auditory processing at peripheral, central, and cognitive levels. Because ofthe documented adverse effects of hearing loss on an individual's social, emotional and economic well-being, the insidious nature of even a mild peripheral hearing loss when combined with central and cognitive declines,and the potential for dual sensory loss of vision and hearing in this population, it is important that the pathophysiologic and histopathologic mechanisms of DM-related auditory senescence be revealed. Like most previous studies considering hearing loss and DM, initial findings originating from the NCRAR were established in cross-sectional studies. Our published results support the notion that DM effects are more notable in a younger population, reminiscent of changes from presbycusis among non-diabetics who are much older, and among Veterans with more severe disease, requiring insulin (Austin et al 2009; Konrad-Martin et al., 2010). However, historically, we did not address progression in auditory dysfunction over time, or how these hearing changes impact speech understanding or quality of life. We are currently in the last year of a 4-year longitudinal study of auditory function among Veterans with and without DM, some of whom were first seen in our DM studies 5-17 years ago, thereby providing additional longitudinal contrasts. Like many cohort studies, this longitudinal study becomes more valuable the longer the observation is continued. We propose to continue longitudinal surveillance in this valuable cohort of Veterans with DM-related auditory and cognitive changes and to augment findings with a longitudinal assessment of DM-related auditory senescence in a mouse model of type 2 DM. Proposed research aims to more precisely determine the longitudinal changes from DM compared to changes from aging alone in humans and mice, including estimating effect sizes and the age of onset of key measures of auditory and cognitive dysfunction. We introduce measures of temporal processing in both species because of its importance for speech understanding in humans and because, in animal models, impaired temporal processing at neural and behavioral levels has been linked to peripheral-auditory changes that may occur prematurely with DM. Specific Aim (1) Benchmark longitudinal changes in auditory function among Veterans with type 2 DM and estimate the differences from normal aging. Specific Aim (2) Determine the extent to which type 2 DM exacerbates presbycusis in the mouse cochlea. Specific Aim (3) Determine the DM characteristics and comorbidities that are risk factors for auditory dysfunction in Veterans. We expect results to demonstrate that DM precedes and contributes to declines over time in peripheral, central-auditory and cognitive processing among Veterans, although the temporal trajectory of the DM effects will vary across individuals. Since some DM comorbidities can be mitigated by strict metabolic control, if premature deterioration of the auditory pathway can be shown to associate strongly with DM severity, there exists a potential mechanism for prevention that can be tested in a future clinical trial. By studying longitudinal changes in auditory function in humans and mice together with longitudinal trends in DM, we will be better able to determine the biological causes of auditory dysfunction in this complex disease, and thus ways to prevent or delay the damage. Results will include prediction models that identify the likely longitudinal trajectory of key auditory measures for an individual given their DM risk factor profile. Appropriate intervention could potentially mitigate impairments of hearing and cognition, leading to improved quality of life for those with DM. Therefore, this study indisputably promotes the VA mission of improved health and well-being of our nation's Veterans.

 描述（由申请人提供）： 糖尿病（DM）是一种代谢疾病，会导致微血管和神经系统并发症，并影响20-30％的退伍军人。证据支持DM与听力损失之间的联系。越来越多的证据体现在我们自己的实验室探测中，这些探索与DM相关的有害影响改变了耳蜗，听觉神经和大脑，从而影响外围，中央和认知水平的听觉处理。由于听力丧失对个人的社会，情感和经济福祉的不利影响，因此当与中心和认知能力下降结合时，即使是轻度的外周听力损失的阴险性质，以及在这种人群中双重感觉丧失和听力的潜力，重要的是，重要的是，病理学和组织病理学机制的听觉声音机制很重要。 就像大多数考虑听力损失和DM的研究一样，跨截面研究中建立了源自NCRAR的初步发现。我们发表的结果支持了以下观点：在年轻人口中，DM效应更为明显，让人联想到年龄较大的非糖尿病的变化，以及在患有更严重疾病的退伍军人中，需要胰岛素（Austin等人，2009年； Konrad-Martin等人，2010年）。但是，从历史上看，随着时间的流逝，我们没有解决听觉功能障碍的进展，或者这些听力如何改变了语音理解或生活质量。目前，我们正处于有或没有DM的退伍军人中对听觉功能的4年纵向研究的最后一年，其中一些人在5 - 7年前首次在我们的DM研究中出现，从而提供了其他纵向对比。像许多队列研究一样，这项纵向研究变得更加有价值，观察的时间越长。 我们建议在与DM相关的这位有价值的退伍军人队列中继续进行纵向监视 在2型DM的小鼠模型中，通过对DM相关听觉的纵向评估，通过纵向评估了听觉和认知变化，并增加了发现。拟议的研究旨在与人类和小鼠单独的衰老变化相比，更精确地确定DM的纵向变化，包括估计效果大小以及关键听觉和认知功能障碍的关键测量的年龄。我们介绍了这两个物种临时处理的测量，因为它对于人类中的语音理解的重要性，并且在动物模型中，在神经和行为层面上暂时处理受损与外围审计剂的变化有关，而DM可能会过早发生。 具体目的（1）2型DM的退伍军人之间听觉功能的基准纵向变化，并估计与正常衰老的差异。具体目的（2）确定2型DM在小鼠耳蜗中加剧的多样性。具体目的（3）确定DM特征和合并症是退伍军人听觉功能障碍的风险因素。 我们预计结果将证明DM先前是在外围时间随着时间的流逝而造成的， 尽管DM效应的暂时轨迹在个人之间会有所不同，但在退伍军人中进行了中央审计和认知处理。由于某些DM合并症可以通过严格的代谢控制来减轻，因此，如果可以证明对听觉途径的过早定义可以与DM严重程度密切相关，则存在一种潜在的预防机制，可以在未来的临床试验中进行测试。通过研究人类和小鼠的听觉功能的纵向变化以及DM中的纵向趋势，我们将能够更好地确定这种复杂疾病中听觉功能障碍的生物学原因，从而防止或延迟损害。结果将包括预测模型，这些模型可以识别个人DM风险因素概况的关键听觉度量的可能纵向轨迹。适当的干预可能会减轻听力和认知的损害，从而改善DM患者的生活质量。因此，这项研究无疑促进了改善国家退伍军人健康和福祉的VA使命。