Effects of Resistant Starch on Lipid and Glucose Metabolism in Insulin Resistance
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 4
- 主要终点
- Triglycerides
研究概览
简要总结
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.
详细描述
Clinic Visits:
Participants will visit the clinic a total of 11 times from screen to completion of the study. This will include weekly visits with a dietician and 7 visits requiring blood draws (screen and twice following each diet period). At each visit, participants will be weighed, waist and hip circumferences will be measured, and blood pressure will be monitored. The total amount of blood collected is 450ml.
Screening visit (V1: 1 hour):
Recruiters will initially determine eligibility through review of a screening questionnaire and a telephone or personal interview. If a potential subject is eligible and interested, an orientation package will be mailed that will include written information about the study requirements. Interested subjects will be scheduled for a screening visit to determine final eligibility by the Clinical staff. At the screening visit (V1), informed consent will be obtained, anthropometric measurements obtained (height, weight, waist circumference, blood pressure), and blood (30ml) will be drawn to assess laboratory criteria for enrollment (total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, glucose, and insulin for determination of HOMA-IR). Screening blood samples from individuals who are either not eligible or unwilling to proceed with the intervention will be destroyed. We will screen for pregnancy, and repeat pregnancy tests after all "A" visits (V2a, v3a, v4a). Menstruating women will be given a calendar to record their menstrual cycle for the duration of the study. Eligible individuals will be contacted within 2 weeks of this screen visit and invited to participate in the study. We are prepared to enroll up to 64 participants in this study to yield a target of 52 completed participants (20% dropout).
Dietitian Visits (Initial: 1 hr, Subsequent: 15 min):
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Men and women ≥ 20 years
- •Blood pressure less than 150/
- •If on three separate clinic visits blood pressure remains above this level, a subject will be referred to his or her physician for treatment.
- •Body mass index (BMI) ≥ 20 and ≤ 35 kg/m
- •Non-smoking and does not use nicotine products or recreational drugs.
- •Agrees to consume no alcohol or dietary supplements during the study.
- •Total cholesterol and LDL cholesterol <95th percentile for sex and age.
- •Fasting triglycerides <500mg/dl.
- •HOMA-IR ≥ 50th percentile for sex.
- •Fasting blood sugar (FBS) < 126 mg/dl.
- •Hematocrit ≥ 36%.
- •At least 3 months of a weight stable state. During the study, subjects will be required to maintain their body weight within ± 3% (up to a maximum change of 5 lbs) of their initial weight over the course of any consecutive two weeks.
- •For women of childbearing potential, two barrier methods of contraception must be used throughout the study and urine pregnancy B-hCG will be done at screen (v1) and at all "A" visits (v2a, 3a, 4a). Subjects who become pregnant will no longer be allowed to continue the study.
- •Women will be considered post-menopausal if ≥ 3 years since last menses or no menses for 1-3 years and plasma FSH elevated into postmenopausal range.
- •Subjects who cannot complete the requirements of the study for reasons determined by the investigator (i.e. non-accessible veins for blood drawing, inability to keep clinic appointments) will not be able to participate in the study.
排除标准
- •History of coronary heart disease, cerebrovascular disease, peripheral vascular disease, bleeding disorder, liver or renal disease, diabetes, lung disease, HIV, or cancer (other than skin cancer) in the last 5 years.
- •Taking drugs known to affect lipid metabolism, blood thinning agents or hormones
- •Abnormal thyroid stimulating hormone (TSH) levels
结局指标
主要结局
Triglycerides
时间窗: 2 weeks, 4 weeks, 8 weeks
LDL subfractions
时间窗: 2 weeks, 4 weeks, 8 weeks
次要结局
- apolipoproteins B, AI(2, 4, 8 weeks)
- HDL-cholesterol(2, 4, 8 weeks)
- Total cholesterol(2 weeks, 4 weeks, 8 weeks)