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.
DM2 is a growing problem among older adults, particularly Veterans and disproportionately affects several minority Veteran populations. Among Veterans with diabetes, 87% are in poor physical health, and are significantly more impaired if they have neuropathy. At the current time, there is no effective therapy to completely prevent, or reverse diabetic neuropathy. The proposed research is thus highly relevant to the VA patient care mission. An intervention that can prevent and/or treat disability associated with autonomic or balance impairment will potentially have major effects on health outcomes important to all older adults with diabetes, including prevention of catastrophic diabetes complications, maintenance of personal independence, improved quality of life and in the long run, decreased costs for medical and personal care. This practical intervention is designed to decrease progression of autonomic neuropathy, improve balance, and is appropriate for use within the integrated VA Health System.
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