Meal Frequency/Composition Effects on Insulin Resistence in Obese Individuals

描述（由申请人提供）：葡萄糖水平的维持是通过全天胰岛素释放的精细调节振荡来完成的。2型糖尿病（T2D）患者失去了这种振荡反应模式，因此确定可以改变胰岛素释放的因素对于预防T2D非常重要。改变进餐频率和成分是已被证明可以改变胰岛素和肠促胰岛素反应的两个因素。我们对健康个体的初步数据表明，与每天吃3顿饭的模式相比，在12小时内吃6顿饭会增加全天的胰岛素反应，而葡萄糖水平保持不变。我们观察到类似的反应模式，但高蛋白餐（12小时6餐）的胰岛素水平略低。这些数据表明，进餐频率/成分可能会改变胰岛素的反应模式，这可能使个体易患糖尿病。本研究旨在阐明肥胖代谢综合征患者在不同膳食组成的频繁饮食中葡萄糖、胰岛素、GLP-1和胃饥饿素的反应差异，并确定运动训练是否可以减轻对这些饮食的任何不适当的葡萄糖/胰岛素反应。12名肥胖成人代谢综合征患者将在3餐条件下进行研究（混合餐- 3次喂食，混合餐- 6次喂食，高蛋白餐- 6次喂食）。由于已知运动会影响胰岛素敏感性，受试者将进行15天的运动训练，并对混合餐进行激素反应- 6次喂养重新测试。我们假设，为了维持葡萄糖水平，无论膳食成分如何，频繁进食都会导致胰岛素和GLP-1的增加，并减少对胃饥饿素反应的抑制；高蛋白餐的反应会稍微低一些。此外，我们假设运动训练将减少因频繁饮食而产生的胰岛素增加。这一试点数据可能为T2D的发展提供潜在的机制，这将在未来的研究中通过检查肌肉水平的潜在变化来追求。公共卫生相关性：确定导致胰岛素抵抗的因素至关重要。我们的初步数据表明，进食频繁会导致一天结束时胰岛素水平升高，这可能是导致胰岛素抵抗的一个因素。这个项目将调查是否同样的现象发生在肥胖的代谢综合征患者身上。此外，该项目将确定运动训练是否会减少因频繁饮食而产生的胰岛素增加。

DESCRIPTION (provided by applicant): Maintenance of glucose levels is accomplished by finely tuned oscillations of insulin release throughout the day. Individuals with type 2 diabetes (T2D) lose this oscillating pattern of response, and identifying factors that can alter insulin release is important in the prevention of T2D. Changing meal frequency and composition are 2 factors that have been shown to alter the insulin and incretin response. Our preliminary data in healthy individuals demonstrates eating 6-meals in 12-h increases the insulin response throughout the day, while glucose levels remain constant, compared to a 3 meal/day pattern. We observed a similar pattern of response but slightly lower insulin levels with a high-protein meal (6-meals in 12 h). This data suggests meal frequency/composition may alter the insulin pattern of response, which may predispose individuals to T2D. The study proposed herein will elucidate the differences in the glucose, insulin, GLP-1 and ghrelin responses to frequent meals of different dietary composition in obese individuals with metabolic syndrome, and establish if exercise training can attenuate any inappropriate glucose/insulin responses to these feedings. Twelve obese adults with metabolic syndrome will be studied under 3-meal conditions (mixed-meal - 3 feedings, mixed-meal - 6 feedings, high-protein- 6 feedings). Since exercise is known to impact insulin sensitivity, subjects will exercise train for 15 days, and have hormonal responses to the mixed meal- 6 feedings retested. We hypothesize that frequent feeding will result in increasing insulin and GLP-1 and reduced suppression of ghrelin responses in order to maintain glucose levels, regardless of meal composition; and slightly lower responses will be seen with the high protein meal. Further, we hypothesize that exercise training will minimize any increases in insulin that occurs with the frequent meals. This pilot data may offer a potential mechanism for the development of T2D, which will be pursued in future studies by examining potential changes at the muscle level. PUBLIC HEALTH RELEVANCE: Identifying the factors that lead to insulin resistance is critical. Our preliminary data has indicated that eating frequent meals results in higher insulin levels at the end of the day and this may be one factor that leads to insulin resistance. This project will investigate if this same phenomenon occurs in obese subjects with metabolic syndrome. Further this project will determine whether exercise training will minimize any increases in insulin that occurs with the frequent meals.