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）转化科学和特定的挑战主题15-DK-101：鉴定饮食中影响代谢状态的生物活性常量营养素。肥胖症流行率的惊人增加是一个令人严重关切的问题，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，这与心血管疾病（CVD）风险增加有关。该项目的主要目的是确定有效的饮食策略，重点是碳水化合物的数量和淀粉消化率，以改善与表达致动脉粥样硬化脂蛋白表型（ALP）组分的胰岛素抵抗个体的CVD风险相关的结果变量。目前的饮食指南强调用碳水化合物热量替代总热量和饱和脂肪热量，以预防和管理慢性疾病。然而，我们和其他人已经表明，高碳水化合物饮食增加了ALP的表达，其特征是血浆甘油三酯增加，HDL胆固醇降低，小而致密的LDL颗粒水平增加，并且这种表型可以通过适度的碳水化合物限制来逆转。我们还表明，表达的甾醇辅酶A去饱和酶（SCD），参与甘油三酯合成的酶，减少与碳水化合物限制，这种变化与血浆甘油三酯反应。虽然碳水化合物限制是有效的管理ALP，淀粉质量的作用尚未得到解决。此外，还没有研究将抗性淀粉与可消化淀粉结合到高碳水化合物饮食与低碳水化合物饮食中的影响。由于孤立的报告表明，抗性淀粉的摄入量增加降低血浆甘油三酯和餐后胰岛素血症，我们假设淀粉质量是ALP成分的一个重要决定因素，这可能是介导的部分脂肪组织SCD表达减少。本提案的目的1将通过对52名胰岛素抵抗男性和女性进行控制性饮食干预来解决这一假设，其中在高碳水化合物饮食与低碳水化合物饮食中用抗性淀粉替代可消化淀粉后，将测定血浆脂质、脂蛋白和脂肪生成基因表达的变化。在目标2中，将测量对抗性淀粉餐与可消化淀粉餐的空腹和餐后葡萄糖和胰岛素反应，以检验淀粉消化率以与膳食诱导的血浆脂质和脂蛋白变化相关的方式改善血糖和胰岛素控制的假设。最终，了解抗性淀粉与快速消化淀粉改善胰岛素和脂质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CVD风险。 公共卫生相关性：该项目的总体目标是测试特定饮食成分抗性淀粉改善因胰岛素敏感性降低而易患2型糖尿病的个体的CVD风险的代谢生物标志物的能力。从这项研究中获得的信息可以促进制定心血管疾病预防和管理的饮食建议，重点是碳水化合物的质量和数量

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