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: 9503635
• 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 2019-09-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9503635
• 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; Disease; Economics; Emotional; Exhibits; Eye; Functional disorder; Future; Glycosylated hemoglobin A; Goals; Health; Hearing; High Fat Diet; Human; Hyperglycemia; Hyperlipidemia; Hypertension; Impaired cognition; Impairment; Individual; Insulin; Intervention; Kidney; Kidney Diseases; Knowledge; Laboratories; Labyrinth; Link; Longitudinal Studies; Longitudinal trends; Measures; Metabolic Control; Metabolic Diseases; Metabolic syndrome; Mission; Molecular; Morbidity - disease rate; Mus; Nature; Neurologic; Neurons; Neuropathy; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Output; Patients; Peripheral; Personal Satisfaction; Phenotype; Physiological; Population; Predictive Factor; Presbycusis; Prevention; Procedures; Process; Publishing; Quality of life; Research; Retinal; Risk; Risk Factors; Sensory; Severities; Severity of illness; Speech; Statistical Models; Surveys; Testing; Time; Veterans; Work; age related; auditory pathway; auditory processing; auditory stimulus; austin; base; behavior measurement; clinical Diagnosis; clinically significant; cognitive change; cognitive function; cohort; disability; glycemic control; hearing impairment; improved; knowledge base; macrovascular disease; mouse model; non-diabetic; normal aging; predictive modeling; premature; prevent; programs; prospective; public health relevance; relating to nervous system; senescence; social

 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，可引起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（包括来自我们自己实验室的证据）表明，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。由于听力损失对个体的社会、情感和经济健康的不良影响，即使是轻微的外周听力损失，当与中枢和认知能力下降相结合时，也具有潜在的潜在性，以及该人群中视觉和听力双重感觉丧失的可能性，因此揭示DM相关听觉衰老的病理生理学和组织病理学机制是很重要的。 与大多数考虑听力损失和糖尿病的先前研究一样，NCRAR的初步发现是在横断面研究中建立的。我们发表的结果支持这样的观点，即DM效应在年轻人群中更显著，这让人想起年龄大得多的非糖尿病患者和患有更严重疾病的退伍军人中的老年性耳聋的变化，需要胰岛素（Austin et al 2009; Konrad-Martin et al.，2010年）。然而，从历史上看，我们没有解决听觉功能障碍随时间的进展，或者这些听力变化如何影响言语理解或生活质量。我们目前正在进行一项为期4年的纵向研究，对患有和不患有糖尿病的退伍军人的听觉功能进行研究，其中一些人在5-17年前首次出现在我们的糖尿病研究中，从而提供了额外的纵向对比。像许多队列研究一样，这种纵向研究的观察持续时间越长，就越有价值。 我们建议继续纵向监测这一有价值的退伍军人与DM相关的队列。 听觉和认知变化，并在2型糖尿病小鼠模型中通过对糖尿病相关听觉衰老的纵向评估来增强研究结果。拟议的研究旨在更精确地确定与人类和小鼠单独老化的变化相比，DM的纵向变化，包括估计效应大小和听觉和认知功能障碍关键指标的发病年龄。我们介绍的时间处理的措施，在这两个物种，因为它的重要性，在人类的语音理解，因为在动物模型中，受损的时间处理在神经和行为水平已被链接到周围听觉的变化，可能会过早地发生与DM。 具体目的（1）对退伍军人2型糖尿病患者听觉功能的纵向变化进行研究，并估计其与正常老年人的差异。具体目标（2）确定2型DM加剧小鼠耳蜗老年性聋的程度。明确糖尿病的特征和合并症是退伍军人听觉功能障碍的危险因素。 我们希望结果能证明DM先于外周血， 虽然DM效应的时间轨迹在个体之间会有所不同，但退伍军人的中枢听觉和认知处理。由于一些糖尿病合并症可以通过严格的代谢控制来减轻，如果听觉通路的过早恶化与糖尿病的严重程度密切相关，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，从而预防或延迟损害的方法。结果将包括预测模型，确定可能的纵向轨迹的关键听觉措施的个人给予他们的糖尿病风险因素概况。适当的干预可能会减轻听力和认知障碍，从而改善DM患者的生活质量。因此，这项研究无可争议地促进了VA改善我国退伍军人健康和福祉的使命。