Clinical trial NCT00508937: Dietary Protein and Insulin Sensitivity Study
Official title: The Effects of Increased Dietary Protein Intake on Insulin Sensitivity in Stable Weight Individuals, Independent of Dietary Content of Carbohydrate and Saturated Fat
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insulin Resistance
Type 2 Diabetes
Metabolic Syndrome
Cardiovascular Disease
Dyslipidemia
Keywords: Diet
Protein
Glucose
Insulin
Cholesterol
Triglycerides
LDL subclasses
Lead sponsor: UCSF Benioff Children's Hospital Oakland
Sponsor class: OTHER
Collaborators: name: Dairy Management Inc.
First posted: 2007-07-30
Enrollment: 660
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The overall objective of the Dietary Protein and Insulin Sensitivity Study is to test the hypothesis that increased protein in a diet with reduced carbohydrate (35% energy) can ameliorate insulin resistance in the absence of weight loss, and that this effect is independent of saturated fat content. Moreover, we will test whether such diets result in beneficial changes in total LDL cholesterol, small, dense LDL, and HDL cholesterol that are also independent of saturated fat intake.

Detailed description: Insulin resistance is a major metabolic disturbance associated with excess adiposity that contributes to atherogenic dyslipidemia and predisposes to both cardiovascular disease and type 2 diabetes mellitus. The effects on insulin resistance of changes in dietary macronutrient composition in the absence of weight loss are poorly understood. To better understand these effects, we will study men and women with insulin resistance after 4 weeks on a basal diet (15% protein, 55% carbohydrate, 30% fat) and 4 weeks after random assignment to the basal diet or one of 4 diets with 35% carbohydrate and either 20% or 30% protein, and either 7% or 15% saturated fat. At the end of each dietary period (4 weeks and 8 weeks), we will draw a blood sample for detailed metabolic measurements and measure insulin sensitivity by the frequently sampled intravenous glucose tolerance test (FSIGT) method. In addition to insulin resistance, we will assess the effect of dietary composition on parameters of atherogenic dyslipidemia.

Eligibility criteria: Inclusion Criteria:

* Body mass index (BMI) ≥ 27 and ≤ 40 kg/m2
* HOMA-IR ≥ 2.5
* Non-smoking
* Total cholesterol and LDL cholesterol \<95th percentile for sex and age
* Fasting triglycerides \< 500mg/dl
* Fasting blood sugar \< 126
* Urinary microalbumin \< 30 mg/L
* Normal thyroid stimulating hormone levels
* Hematocrit ≥ 36%
* Blood pressure \< 150/90
* At least 3 months of a weight-stable state (± 5 lbs) prior to the study. 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 after the second week of baseline diet or during the last week of each diet phase

Exclusion Criteria:

* 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
* Use of drugs known to affect lipid metabolism or insulin resistance, hormones, or the blood thinning agent, warfarin
* Use of alcohol or dietary supplements during the study
* Pregnancy

Primary outcomes:
measure: Insulin Sensitivity by Frequently Sampled Intravenous Glucose Tolerance test
timeFrame: 4wks and 8wks
measure: Total Cholesterol
timeFrame: 4wks and 8wks
measure: LDL Cholesterol
timeFrame: 4wks and 8wks
measure: HDL Cholesterol
timeFrame: 4wks and 8wks
measure: Triglycerides
timeFrame: 4wks and 8wks
measure: LDL peak particle size
timeFrame: 4wks and 8wks
measure: LDL subclasses
timeFrame: 4wks and 8wks
Secondary outcomes:
measure: Apolipoprotein B
timeFrame: 4wks and 8wks
measure: Apolipoprotein A1
timeFrame: 4wks and 8wks
Other outcomes:
Locations:
city: Berkeley
country: United States
facility: Cholesterol Research Center
state: California
city: San Francisco
country: United States
facility: San Francisco General Hospital
state: California
Study officials:
affiliation: UCSF Benioff Children's Hospital Oakland
name: Ronald M Krauss, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Chiu S, Williams PT, Dawson T, Bergman RN, Stefanovski D, Watkins SM, Krauss RM. Diets high in protein or saturated fat do not affect insulin sensitivity or plasma concentrations of lipids and lipoproteins in overweight and obese adults. J Nutr. 2014 Nov;144(11):1753-9. doi: 10.3945/jn.114.197624. Epub 2014 Sep 3.