CHILDREN'S HOSPITAL & RESEARCH CENTER AT OAKLAND
Grant: $529,746 - National Institutes of Health - Sep. 28, 2009
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Award Description: 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 and 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. Overall, this project will 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 quantit
Project Description: Resistant starches, so designated because of their resistance to digestion by alpha-amylases, have been shown to improve glycemic control, but their influence on blood lipids is not well understood. We hypothesize that a diet consisting primarily of resistant vs. rapidly digested starch will improve components of the atherogenic lipoprotein phenotype (high triglycerides, low HDL-cholesterol, increased small dense LDL). We further hypothesize that substituting resistant for digestible starch will improve insulin responses to meals containing these starches. Ultimately, understanding the mechanisms by which resistant vs. rapidly digested starches improve insulinemic and lipid control may facilitate the formulation of dietary recommendations aimed at the prevention and treatment of insulin resistance and its associated dyslipidemia. In this dietary intervention study, participants will be provided with most of the food for the baseline and test diet periods. To date, most of our activities have therefore focused on planning and developing these diets. We have had several meetings with research dietitians from the Bionutrition Unit of the University of California, San Francisco-based CTSI. They have begun developing 4-day rotating menus for the baseline diet and will soon be testing the use of high-amylose cornstarch in various recipes. We have also been in contact with our collaborator, Dr. Ratnayake, an expert in starch chemistry and functionality from the University of Nebraska-Lincoln, who will quantify the resistant starch content and measure the in vitro digestibility of our high- and low-amylose cornstarches. Finally we have had meetings to discuss start up activities including implementation of clinical protocols, logistical considerations, database creation, and compliance with all IRB regulations. The development of advertising materials for the recruitment of study participants is also under way.
Jobs Summary: As of 9/30/09, Individuals were identified to work on the project and would be hired in October 2009. (Total jobs reported: 0)
Project Status: Not Started
This award's data was last updated on Sep. 28, 2009. Help expand these official descriptions using the wiki below.
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