Dietary Protein and Insulin Sensitivity Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Effects of Increased Dietary Protein Intake on Insulin Sensitivity in Stable Weight Individuals, Independent of Dietary Content of Carbohydrate and Saturated Fat

Conditions
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Insulin Resistance, Type 2 Diabetes, Metabolic Syndrome, Cardiovascular Disease, Dyslipidemia

Intervention / Treatment
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* Other: Diet
* Other: Diet
* Other: Diet
* Other: Diet
* Other: Diet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br> | Other: Diet<br>* 15% protein, 55% carbohydrate, 30% fat (7% saturated, 7% polyunsaturated)<br>|
| Experimental: 2<br> | Other: Diet<br>* 20% protein, 35% carbohydrate, 45% fat (7% saturated, 7% polyunsaturated)<br>|
| Experimental: 3<br> | Other: Diet<br>* 20% protein, 35% carbohydrate, 45% fat (15% saturated, 7% polyunsaturated)<br>|
| Experimental: 4<br> | Other: Diet<br>* 30% protein, 35% carbohydrate, 35% fat (7% saturated, 7% polyunsaturated)<br>|
| Experimental: 5<br> | Other: Diet<br>* 30% protein, 35% carbohydrate, 35% fat (15% saturated, 7% polyunsaturated)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin Sensitivity by Frequently Sampled Intravenous Glucose Tolerance test |  | 4wks and 8wks | 
| Total Cholesterol |  | 4wks and 8wks | 
| LDL Cholesterol |  | 4wks and 8wks | 
| HDL Cholesterol |  | 4wks and 8wks | 
| Triglycerides |  | 4wks and 8wks | 
| LDL peak particle size |  | 4wks and 8wks | 
| LDL subclasses |  | 4wks and 8wks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apolipoprotein B |  | 4wks and 8wks | 
| Apolipoprotein A1 |  | 4wks and 8wks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diet, Protein, Glucose, Insulin, Cholesterol, Triglycerides, LDL subclasses