Resistant Starch Insulin Sensitivity Trial

NCT01027325 | Completed DMC

• 1 other identifier: 1RC1DK086472-01
• Study Type: interventional
• Target: 52
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Healthy; Cardiovascular Disease; Atherogenic Dyslipidemia; Insulin Resistance

Keywords

Resistant Starch; Amylose; Amylopectin; LDL subclasses; Dietary carbohydrate; Postprandial insulinemia

Outcome Measures

Primary Outcomes (2)

• Triglycerides

  2 weeks, 4 weeks, 8 weeks

• LDL subfractions

  2 weeks, 4 weeks, 8 weeks

Secondary Outcomes (3)

• Total cholesterol

  2 weeks, 4 weeks, 8 weeks

• HDL-cholesterol

  2, 4, 8 weeks

• apolipoproteins B, AI

  2, 4, 8 weeks

Study Arms (5)

High CHO/Low Amylose

EXPERIMENTAL

55% Carbohydrate (11.2% Amylose, 26.3% Amylopectin) 20% Protein 25% Fat

Other: Dietary Intervention

Low Carbohydrate/Hi Amylose

EXPERIMENTAL

40% Carbohydrate (26.3% Amylose, 11.2% Amylopectin) 20% Protein 40% Fat

Other: Dietary Intervention

High CHO/High Amylose

EXPERIMENTAL

55% Carbohydrate (26.3% Amylose, 11.2% Amylopectin) 20% Protein 25% Fat

Other: Dietary Intervention

Low Carbohydrate/Low Amylose

EXPERIMENTAL

40% Carbohydrate (11.2% Amylose, 26.3% Amylopectin) 20% Protein 40% Fat

Other: Dietary Intervention

Baseline

ACTIVE COMPARATOR

40% Carbohydrate 20% Protein 40% Fat

Other: Dietary Intervention

Interventions

Dietary Intervention OTHER

Starch digestibility and carbohydrate quantity

Also known as: Dietary carbohydrate, Resistant starch, Amylose, Amylopectin, Lipids

Baseline; High CHO/High Amylose; High CHO/Low Amylose; Low Carbohydrate/Hi Amylose; Low Carbohydrate/Low Amylose

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women ≥ 20 years
• Blood pressure less than 150/90. 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/m2.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• UCSF Benioff Children's Hospital Oakland: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (2)

Cholesterol Research Center

Berkeley, California, 94705, United States

Location

Children's Hospital Oakland Research Institute

Oakland, California, 94609, United States

Location

MeSH Terms

Conditions

Cardiovascular Diseases; Insulin Resistance

Interventions

Diet Therapy; Dietary Carbohydrates; Resistant Starch; Amylose; Amylopectin; Lipids

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Nutrition Therapy; Therapeutics; Carbohydrates; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Starch; Glucans; Biopolymers; Polymers; Macromolecular Substances; Dietary Fiber; Polysaccharides

Study Officials

• Ronald M Krauss, MD

  UCSF Benioff Children's Hospital Oakland

  PRINCIPAL INVESTIGATOR

• Nathalie Bergeron, PhD

  Children's Hospital Oakland Research Institiute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2009
• First Posted: December 7, 2009
• Study Start: June 1, 2010
• Primary Completion: August 1, 2011
• Study Completion: November 1, 2012
• Last Updated: January 14, 2013

Record last verified: 2013-01

Locations

US (2)