Effects of resistant starch on lipid and glucose metabolism in insulin resistance

描述(由申请人提供)：本申请涉及广泛的挑战领域(15)转化科学，以及具体的挑战主题15-DK-101：确定饮食中影响代谢状态的生物活性微量营养素。肥胖患病率的惊人增长令人非常关切，因为它与许多不利的健康状况有关，包括胰岛素抵抗和2型糖尿病，这些疾病与心血管疾病(CVD)风险增加有关。该项目的主要目标是确定有效的饮食策略，重点关注碳水化合物数量和淀粉消化率，以改善表现致动脉粥样硬化脂蛋白表型(ALP)组分的胰岛素抵抗个体与心血管疾病风险相关的结果变量。目前的饮食指南强调用碳水化合物卡路里代替总脂肪卡路里和饱和脂肪卡路里来预防和管理慢性病。然而，我们和其他人已经表明，高碳水化合物饮食增加了碱性磷酸酶的表达，其特征是血浆甘油三酯增加，高密度脂蛋白胆固醇降低，小而致密的低密度脂蛋白颗粒水平增加，这种表型被适度的碳水化合物限制逆转。我们还发现，糖类限制会减少参与甘油三酯合成的酯酰辅酶A去饱和酶(SCD)的表达，并且这种变化与血浆甘油三酯的反应有关。虽然限制碳水化合物对ALP的管理是有效的，但淀粉质量的作用尚未得到解决。此外，还没有关于高碳水化合物饮食和低碳水化合物饮食中添加抗性淀粉和可消化淀粉的影响的研究。由于个别报告表明增加抗性淀粉的摄入可以降低血浆甘油三酯和餐后胰岛素血症，我们推测淀粉质量是碱性磷酸酶组成的一个重要决定因素，这可能部分是通过减少脂肪组织SCD的表达来调节的。这项建议的目的1将通过对52名胰岛素抵抗男性和女性进行受控饮食干预来解决这一假设，在高碳水化合物饮食和低碳水化合物饮食中，用抗性淀粉取代可消化淀粉后，将确定血浆血脂、脂蛋白和造脂基因表达的变化。在目标2中，将测量抵抗与可消化淀粉粉对空腹和餐后血糖和胰岛素的反应，以检验淀粉可消化性通过与饮食诱导的血脂和脂蛋白变化有关的方式改善血糖和胰岛素控制的假设。最终，了解抵抗淀粉和快速消化淀粉改善胰岛素和血脂控制的机制可能有助于制定更具体的饮食建议，旨在预防和治疗胰岛素抵抗及其相关的致动脉粥样硬化性血脂异常和心血管疾病风险。 公共卫生相关性：该项目的总体目标是测试一种特定的饮食成分--抗性淀粉的能力，以改善因胰岛素敏感性降低而易患2型糖尿病的人的心血管疾病风险的代谢生物标记物。从这项研究中获得的信息有助于制定注重碳水化合物质量和数量的心血管疾病预防和管理饮食建议。

DESCRIPTION (provided by applicant): This application addresses the broad Challenge Area (15) Translational Science, and specific Challenge Topic 15-DK-101: Identification of bioactive macronutrients in the diet that impact metabolic state. The alarming increase in the prevalence of obesity is a cause of great concern given its association with many adverse health conditions, including insulin resistance and type 2 diabetes, which are associated with increased cardiovascular disease (CVD) risk. The primary objective of this project is to identify effective dietary strategies, focused on carbohydrate quantity and starch digestibility, to improve outcome variables associated with CVD risk in insulin resistant individuals who express components of the atherogenic lipoprotein phenotype (ALP). Current dietary guidelines emphasize substitution of carbohydrate calories for total and saturated fat calories for prevention and management of chronic disease. Yet, we and others have shown that high-carbohydrate diets increase the expression of the ALP, characterized by increased plasma triglycerides, reduced HDL cholesterol, and increased levels of small, dense LDL particles, and that this phenotype is reversed by moderate carbohydrate restriction. We have also shown that expression of steroyl coenzymeA desaturase (SCD), an enzyme involved in triglyceride synthesis, is reduced with carbohydrate restriction and that this change is correlated with plasma triglyceride response. While carbohydrate restriction is effective for management of ALP, the role of starch quality has not been addressed. Furthermore, there has been no study of the effects of resistant vs. digestible starches incorporated into high- vs. lower carbohydrate diets. Since isolated reports suggest that increased intake of resistant starch lowers plasma triglycerides and postprandial insulinemia, we hypothesize that starch quality is an important determinant of components of ALP, and that this may be mediated in part by reduced adipose tissue SCD expression. Aim 1 of this proposal will address this hypothesis by a controlled dietary intervention in 52 insulin resistant men and women in which changes in plasma lipids, lipoproteins and lipogenic gene expression will be determined after substituting resistant starch for digestible starch in a high- vs. lower-carbohydrate diet. In Aim 2, the fasting and postprandial glucose and insulin responses to a resistant vs. digestible starch meal will be measured to test the hypothesis that starch digestibility improves glycemic and insulinemic control in a way that relates to diet-induced changes in plasma lipids and lipoproteins. Ultimately, understanding the mechanisms by which resistant vs. rapidly digested starches improve insulinemic and lipid control may facilitate the formulation of more specific dietary recommendations aimed at prevention and treatment of insulin resistance, and its associated atherogenic dyslipidemia and CVD risk. PUBLIC HEALTH RELEVANCE: The overall objective of this project is to test the capacity of a specific dietary component, resistant starch, to improve metabolic biomarkers of CVD risk in individuals who are predisposed to type 2 diabetes by virtue of reduced insulin sensitivity. The information gained from this study could facilitate formulation of dietary recommendations for CVD prevention and management that focus on carbohydrate quality as well as quantity