Resistant Starch Insulin Sensitivity Trial (RESIST)

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 stearoyl 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.