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) 是一种代谢性疾病，会导致微血管和神经系统并发症，影响 20-30% 的退伍军人。有证据支持糖尿病和听力损失之间的联系。越来越多的证据（包括来自我们自己的实验室的证据）表明，与 DM 相关的有害影响会改变耳蜗、听觉神经和大脑，影响外周、中枢和认知水平的听觉处理。由于已记录的听力损失对个人的社会、情感和经济福祉产生不利影响，即使是轻微的周围性听力损失与中枢和认知能力下降相结合时也具有潜在的潜在性，以及该人群中视力和听力双重感觉丧失的可能性，因此揭示与 DM 相关的听觉衰老的病理生理学和组织病理学机制非常重要。 与之前大多数考虑听力损失和糖尿病的研究一样，NCRAR 的初步研究结果是在横断面研究中得出的。我们发表的结果支持这样的观点，即糖尿病的影响在较年轻的人群中更为显着，这让人想起年龄大得多的非糖尿病患者以及患有更严重疾病、需要胰岛素的退伍军人中老年性耳聋的变化（Austin 等人，2009 年；Konrad-Martin 等人，2010 年）。然而，从历史上看，我们并没有解决听觉功能障碍随着时间的推移而进展的问题，也没有解决这些听力变化如何影响言语理解或生活质量。目前，我们正处于对患有和不患有 DM 的退伍军人进行为期 4 年的听觉功能纵向研究的最后一年，其中一些人在 5-17 年前首次出现在我们的 DM 研究中，从而提供了额外的纵向对比。与许多队列研究一样，观察持续的时间越长，这项纵向研究就变得更有价值。 我们建议继续对这一有价值的患有糖尿病相关退伍军人群体进行纵向监测 听觉和认知变化，并通过对 2 型糖尿病小鼠模型中与糖尿病相关的听觉衰老进行纵向评估来增强研究结果。拟议的研究旨在更准确地确定人类和小鼠中与单独衰老引起的变化相比，糖尿病引起的纵向变化，包括估计听觉和认知功能障碍关键指标的效应大小和发病年龄。我们在这两个物种中引入了时间处理的测量方法，因为它对于人类的言语理解很重要，而且因为在动物模型中，神经和行为水平上的时间处理受损与 DM 可能过早发生的外周听觉变化有关。 具体目标 (1) 对患有 2 型糖尿病的退伍军人听觉功能的纵向变化进行基准测试，并估计与正常衰老的差异。具体目标 (2) 确定 2 型 DM 加剧小鼠耳蜗老年性耳聋的程度。具体目标 (3) 确定作为退伍军人听觉功能障碍危险因素的 DM 特征和合并症。 我们期望结果能够证明，随着时间的推移，DM 会先于并导致外周、 退伍军人的中枢听觉和认知处理，尽管 DM 效应的时间轨迹因人而异。由于一些糖尿病合并症可以通过严格的代谢控制来缓解，如果可以证明听觉通路的过早恶化与糖尿病的严重程度密切相关，那么就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听觉功能的纵向变化以及 DM 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，从而找到预防或延缓损害的方法。结果将包括预测模型，根据个人的 DM 风险因素特征，识别关键听觉测量的可能纵向轨迹。适当的干预可能会减轻听力和认知损伤，从而提高糖尿病患者的生活质量。因此，这项研究无疑促进了退伍军人管理局改善我国退伍军人健康和福祉的使命。