Improving Autonomic Function and Balance in Diabetic Neuropathy

描述(由申请人提供)： 目的：糖调节受损(IGR)与自主神经病变和平衡障碍的发展有关，可能使患者丧失能力。糖尿病退伍军人遭受与自主神经病变和平衡控制受损相关的残疾的比例不成比例。自主神经症状和自主神经功能缺陷在糖调节受损(IGR)患者中很常见，即使受试者只有糖耐量受损(IGT)。在非对照试验中，改善饮食和锻炼可以显著改善甚至逆转与IGR相关的神经病变，但需要进行盲法对照试验，以确定强烈的量身定制的生活方式改变计划在减缓进展或逆转糖尿病自主神经病变和平衡障碍方面的作用。IGR包括轻度2型糖尿病(DM2)、糖耐量减低(IGT)和空腹血糖受损(IFG)的患者，这些患者是根据ADA诊断DM2的标准化标准得出的。我们假设，与IGR参与者被建议遵循当前关于饮食和运动的标准护理建议(Standard Care或“SC”)相比，IGR参与者接受仔细监控的、量身定制的高强度饮食、体力活动和平衡增强计划(DPAEP)，将显示出自主神经功能和平衡控制的更大改善。此外，我们将检验这样一种假设，即自主神经功能、平衡控制和活动能力的改善将与代谢功能、自主神经功能的临床测量和生活质量的改善密切相关。在研究结束时，我们应该能够确定一个单独定制的12个月的DPAEP计划是否可以(1)逆转或延缓IGR受试者自主神经病变的进展，(2)改善和维持平衡控制的改善，(3)评估与自主神经功能和平衡受损相关的因素，以及这些因素的改善是否与研究中主要、次要和其他疗效指标的改善平行。研究计划：这是一项单盲、平行组、意向治疗研究，比较了仔细监测的、量身定制的强化DPAEP干预和SC组。在这项研究中，将比较两组患者自主神经病变进展、平衡性、活动度、代谢功能和生活质量的具体指标。试点数据显示，改善饮食和增加流动性的生活方式干预计划也可以改善糖尿病神经病变患者的自主神经功能和平衡，这为这一建议的可行性提供了证据。这项新提议将与糖尿病退伍军人的康复高度相关，这些退伍军人患有自主神经和平衡障碍，有摔倒增加的风险。方法：80例明确的IGR和自主神经病变患者，年龄30-80岁，随机分为两组(DPAEP组和SC组)。参与者将被招募超过32人，并在12个月内接受跟踪。DPAEP组将参加高强度的饮食、有氧运动和平衡计划。他们将每周接受三次评估。SC参与者将得到一般的饮食和锻炼建议，并将得到后续跟进。主要的疗效衡量标准是12个月时的呼气与吸气(E：I)比率。次要疗效指标为6个月时测量的躯干定位误差(TrE)。其他结果将评估持续平衡控制、皮肤汗腺神经支配、代谢参数、临床反应和生活质量。研究的具体目的是确定IGR和自主神经病变患者在12个月内：(1)DPAEP干预对自主神经功能的影响；(2)DPAEP干预对平衡控制的影响；(3)自主神经功能或平衡控制与(A)活动能力、(B)葡萄糖、胰岛素或脂肪代谢的变化和体重减轻以及(C)临床结果和生活质量的关系。

DESCRIPTION (provided by applicant): Objectives: Impaired glucose regulation (IGR) is associated with development of autonomic neuropathy and balance impairment that may be disabling for the patient. Diabetic Veterans suffer disproportionately from disability related to autonomic neuropathy and impaired balance control. Autonomic symptoms and defects in autonomic function are common in patients with impaired glucose regulation (IGR) even when the subject only has impaired glucose tolerance (IGT). In uncontrolled trials, improved diet and exercise can significantly improve and even reverse neuropathy associated with IGR, however blinded controlled trials are needed to establish the role of an intense tailored lifestyle modification program in slowing progression or reversing diabetic autonomic neuropathy and balance impairment. IGR includes patients with mild type 2 diabetes mellitus (DM2), IGT, and impaired fasting glucose (IFG) based on standardized ADA criteria for the diagnosis of DM2. We hypothesize that, compared to IGR participants advised to follow the current standard care recommendations on diet and exercise (Standard Care or "SC"), IGR participants undergoing a carefully monitored, tailored intensive diet, physical activity and balance enhancement program (DPAEP), will show greater improvement in autonomic function and balance control. Furthermore, we will test the hypothesis that improvement in autonomic function, balance control and mobility will correlate strongly with each other and with improvement in metabolic function, clinical measures of autonomic function and quality of life. At the end of the study we should be able to determine if an individually tailored 12 month DPAEP program can (1) reverse or delay the progression of autonomic neuropathy in subjects with IGR, (2) improve and sustain improvement in balance control, (3) evaluate factors that are associated with impaired autonomic function and balance and if improvement in these factors parallels improvement in the primary, secondary and other efficacy measures in the study. Research Plan: This is a single blinded, parallel group, intention-to-treat study comparing a carefully monitored, tailored intensive DPAEP intervention with an SC group. In the study, specific measures of autonomic neuropathy progression, balance, mobility, metabolic function, and quality of life will be compared between the two groups. Evidence for the feasibility of this proposal is provided by pilot data showing that a lifestyle intervention program that improves diet and increases mobility can also improve autonomic function and balance in patients with diabetic neuropathy. This new proposal will be highly relevant to the rehabilitation of diabetic veterans with autonomic and balance impairment that are at risk of increased falls. Methods: 80 participants with defined IGR and autonomic neuropathy, age 30-80 years, will be randomized into one of two groups (DPAEP and SC). Participants will be recruited over 32 and followed over 12 months. The DPAEP group will participate in an intense dietary, aerobic exercise and balance program. They will be assessed three times a week. SC participants will receive general dietary and exercise advice and will receive follow up. The primary efficacy measure is the expiration:inspiration (E:I) ratio at 12 months. The secondary efficacy measure is the trunk repositioning error (TRE) measured at 6 months. Other outcomes will assess sustained balance control, skin sweat gland innervation, metabolic parameters, clinical response, and quality of life. The Specific Aims are to determine in subjects with IGR and autonomic neuropathy over 12 months: (1) The effect of a DPAEP intervention on autonomic function; (2) The effect of a DPAEP intervention on balance control; (3) The relationships between autonomic function or balance control to (a) mobility, (b) changes in glucose, insulin, or lipid metabolism and weight loss, and (c) clinical outcomes and quality of life.