Autonomic function and insulin resistance in a multiethnic population

描述（由申请人提供）：自主神经系统对心跳变异性的调节在糖尿病患者中经常中断。此外，在糖尿病和非糖尿病人群中，心率变异性的降低与心血管疾病（CVD）死亡率的增加有关。心血管疾病死亡率在许多种族群体之间差别很大。在夏威夷，夏威夷原住民的心血管疾病死亡率比亚洲人和高加索人高得多。夏威夷土著健康研究项目的初步数据表明，与动脉粥样硬化相关的传统风险因素可能不能完全解释夏威夷心脏病和中风死亡率的种族差异。胰岛素抵抗与心血管疾病发病率和死亡率增加有关，也与心率变异性降低有关。本研究将探讨多民族人群中胰岛素抵抗与心功能自主调节之间的关系。拟议的研究还将为未来的纵向研究提供基线数据，这些研究将调查这些新的风险因素在多大程度上解释夏威夷心血管疾病死亡率的种族差异。这项研究的发现可能对胰岛素抵抗作为独立心血管疾病危险因素的治疗具有重要意义。

DESCRIPTION (provided by the applicant): Autonomic nervous system regulation of heartbeat variability is often disrupted among patients with diabetes. Moreover, reduced heart rate variability has been associated with increased Cardiovascular Disease (CVD) mortality among diabetic and non-diabetic populations. CVD mortality rates differ greatly among many ethnic groups. In Hawaii, Native Hawaiians have been shown to have disproportionately higher CVD mortality than Asian and Caucasian groups. Preliminary data from the Native Hawaiian Health Research Project suggest that conventional risk factors associated with Atherosclerosis may not fully account for ethnic disparities in heart disease and stroke mortality rates in Hawaii. Insulin resistance has been associated with increased CVD incidence and mortality, and has also been associated with reduced heart rate variability. The proposed study will investigate the relationship between insulin resistance and autonomic regulation of cardiac function in a multi-ethnic population. The proposed research will also provide baseline data for future longitudinal studies that will investigate the extent to which these novel risk factors explain ethnic disparities in CVD mortality in Hawaii. The findings of the proposed study may have important implications with regards to the treatment of insulin resistance as an independent CVD risk factor. Specific Aims: Collaborator component (Aim #1). Establish a collaborative laboratory in Hawaii for the evaluation of autonomic function in a multiethnic population. Principal Investigator component (Aim #2). Investigate the relationship between insulin resistance, body-fat distribution, and autonomic function. (Aim #3) Establish a cohort with baseline measures of autonomic function and insulin resistance that will serve as a study population for R01-supported longitudinal studies. Hypotheses: By fulfilling these specific aims, we propose to test the following specific research hypotheses: (1.) Autonomic function will differ significantly by ethnicity, after adjustment for age, gender, body-mass index, and central obesity. (2.) Insulin resistance is independently associated with autonomic function, after an adjustment for age, gender, body-mass index, and central obesity. Secondary Questions: Does insulin resistance and plasma glucose interact, in their effects on autonomic function? What role do plasma lipids, blood pressure, diet, and physical activity have in explaining any observed ethnic disparities in autonomic function? Is the questionnaire-derived Composite Autonomic Symptom Scale (COMPASS) correlated with autonomic function in Hawaii's multiethnic population?