Meal Frequency/Composition Effects on Insulin Resistence in Obese Individuals

描述(申请人提供)：血糖水平的维持是通过一天中胰岛素释放的微调振荡来完成的。2型糖尿病(T2D)患者失去了这种振荡的反应模式，识别能够改变胰岛素释放的因素在预防T2D方面很重要。改变饮食频率和组成是两个已被证明会改变胰岛素和胰岛素反应的因素。我们在健康人身上的初步数据显示，12小时内吃6顿饭会增加全天的胰岛素反应，而血糖水平保持不变，而不是每天吃3顿饭。我们观察到了类似的反应模式，但高蛋白膳食(12小时内6餐)的胰岛素水平略低。这一数据表明，膳食频率/组成可能会改变胰岛素的反应模式，这可能使个人容易患上T2D。这项研究将阐明患有代谢综合征的肥胖者对不同饮食组成的频繁膳食的葡萄糖、胰岛素、GLP-1和Ghrelin反应的差异，并确定运动训练是否可以减弱对这些饮食的任何不适当的葡萄糖/胰岛素反应。12名患有代谢综合征的肥胖成年人将在三餐条件下进行研究(混合餐-3餐，混合餐-6餐，高蛋白-6餐)。由于运动已知会影响胰岛素敏感性，受试者将进行为期15天的运动训练，并对混合膳食的荷尔蒙反应进行重新测试。我们假设，频繁喂食会导致胰岛素和GLP-1的增加，并减少对Ghrelin反应的抑制，以保持血糖水平，而无论膳食成分如何；而高蛋白膳食的反应将略低。此外，我们假设运动训练将使因频繁进餐而产生的胰岛素增加降至最低。这一先导数据可能为T2D的发展提供了一种潜在的机制，这将在未来的研究中通过检测肌肉水平的潜在变化来进行。与公共卫生相关：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，频繁进餐会导致一天结束时胰岛素水平较高，这可能是导致胰岛素抵抗的一个因素。该项目将调查患有代谢综合征的肥胖受试者是否会出现同样的现象。此外，该项目将确定运动训练是否会将频繁进餐引起的胰岛素增加降至最低。

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.