Diet, Insulin Sensitivity, and Postprandial Metabolism

Study Overview
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Brief Summary
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This randomized, controlled trial aims to elucidate the mechanisms by which a plant-based dietary intervention causes weight loss. Using a low-fat, plant-based diet for 16 weeks, along with an untreated control for comparison, the study will measure changes in body weight, body composition, intramyocellular and/or intrahepatocellular lipid, and changes in association to body weight.

Detailed Description
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In a 16-week trial, overweight adults will be randomly assigned to two groups. Changes in body weight, body composition, intramyocellular and/or intrahepatocellular lipid, and changes in association to body weight will be measured among other outcomes. The Intervention Group will follow a low-fat, vegan diet and will receive weekly classes and support. The Control Group will be asked to follow a conventional control diet. This study conducts a pilot sub-study to test the hypothesis that changes in insulin sensitivity and beta-cell function observed in response to a diet intervention correlate with changes in intramyocellular and/or intrahepatocellular lipid. Another sub-study assesses the association between metabolic outcomes and gut microbiome. One additional sub-study is looking for associations between metabolic outcomes and endothelial function.

Official Title
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A Randomized, Controlled Trial on Diet, Insulin Sensitivity, and Postprandial Metabolism

Conditions
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Overweight, Obesity, Insulin Resistance

Intervention / Treatment
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* Other: Plant-based diet
* Other: Control Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women age ≥18 years of age Body mass index 28-40 kg/m2 Exclusion Criteria: Diabetes mellitus, type 1 or 2, history of diabetes mellitus or of any endocrine condition that would affect body weight, such as thyroid disease, pituitary abnormality, or Cushing's syndrome Smoking during the past six months Alcohol consumption of more than 2 drinks per day or the equivalent, episodic increased drinking (e.g., more than 2 drinks per day on weekends), or a history of alcohol abuse or dependency followed by any current use Use of recreational drugs in the past 6 months Use within the preceding six months of medications that affect appetite or body weight, such as estrogens or other hormones, thyroid medications, systemic steroids, antidepressants (tricyclics, monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), antipsychotics, lithium, anticonvulsants, appetite suppressants or other weight-loss drugs, herbs for weight loss or mood, St. John's wort, ephedra, beta blockers Pregnancy or intention to become pregnant during the study period Unstable medical or psychiatric illness Evidence of an eating disorder Likely to be disruptive in group sessions Already following a low-fat, vegan diet Lack of English fluency Inability to maintain current medication regimen Inability or unwillingness to participate in all components of the study Intention to follow another weight-loss method during the trial

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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Plant-based diet<br>The diet group will be asked to follow a low-fat, vegan diet for 16 weeks | Other: Plant-based diet<br>* Weekly instructions will be given to the participants in the intervention group about following vegan diet.<br>* Other names: Vegan diet;|
| Active Comparator: Control diet<br>Half of the participants will be asked to continue their usual diets for the 16-week study period. | Other: Control Diet<br>* Participants will be asked to continue their usual diets for the 16-week study period.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body weight in kg | Anticipated weight-loss for intervention group compared with control group. Weight and height will be combined to report BMI in kg/m^2 | 16 weeks | 
| Fat mass in grams | Anticipated weight-loss for intervention group compared with control group. | 16 weeks | 
| Visceral fat in cm^3 | Anticipated weight-loss for intervention group compared with control group. | 16 weeks | 
| Changes in intramyocellular and/or intrahepatocellular lipid | A subset of participants will be selected for magnetic resonance (MR) spectroscopy studies quantifying hepatic lipid and/or intramyocellular and/or contents in order to provide data regarding possible causal relationships between dietary changes, ectopic lipid, and insulin sensitivity. Selected individuals with varying degrees of insulin-resistance in both groups will be assessed before and after the intervention period. These magnetic resonance spectroscopy (MRS) studies will take place at the Magnetic Research Center at Yale University School of Medicine, New Haven, CT. | 16 Weeks | 
| Insulin resistance | Insulin resistance will be assessed by the Homeostatic Model Assessment (HOMA) index. | 16 weeks | 
| Resting Energy Expenditure (REE) | Participants will be asked to report to the laboratory within 60 minutes of waking and after a 12-hour fast. Following 30 minutes of quiet rest in a dimly lit room, pulse, respiratory rate, and body temperature will be measured. REE will be measured for 20 minutes through indirect calorimetry (COSMED Metabolic Company Quark Resting Metabolic Rate (RMR), Chicago, IL) utilizing a ventilated hood system. The laboratory temperature will be maintained at 23 degrees C throughout, and precautions will be taken to minimize any disturbances that could affect the metabolic rate. For premenopausal women, measures will be timed so as to occur in the luteal phase of the menstrual cycle. | 16 weeks | 
| Postprandial metabolism | Participants will be asked to report to the laboratory within 60 minutes of waking and after a 12-hour fast. Postprandial metabolism will be measured for three hours after the standard meal. For premenopausal women, measures will be timed so as to occur in the luteal phase of the menstrual cycle. | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Beta-cell function as measured by glucose (mmmol/L) | A standard meal test will be performed after an overnight fast. Plasma glucose, will be measured at 0, 30, 60, 120, and 180 min for a total of 3-hours over a 16-week period. Glucose, insulin and C-peptide will combined and analyzed to report Beta-cell function. | 16 weeks | 
| Beta-cell function as measured by insulin (pmol/L) | A standard meal test will be performed after an overnight fast. Plasma insulin will be measured at 0, 30, 60, 120, and 180 min for a total of 3-hours over a 16-week period. Glucose, insulin and C-peptide will combined and analyzed to report Beta-cell function. | 16 weeks | 
| Beta-cell function as measured by C-peptide (ng/mL) | A standard meal test will be performed after an overnight fast. Plasma C-peptide will be measured at 0, 30, 60, 120, and 180 min for a total of 3-hours over a 16-week period. Glucose, insulin and C-peptide will combined and analyzed to report Beta-cell function. | 16 weeks | 
| Microbiome Analysis | Microbiome analysis from participant-provided stool sample. Analysis from uBiome Biotechnology company in a subset of participants. Anticipated changes in the dietary intervention group include changes in the microbiome composition that correlate with changes in insulin sensitivity. | 16 weeks | 
| Endothelial function | Endothelial function will be measured using the EndoPAT, a proprietary diagnostic device for functional vascular health assessment, in a subset of participants. | 16 weeks | 
| Diet Assessment Recall Questionnaire | 24-hour multi-pass dietary recalls will be used to assess dietary adherence to assist study personnel in working with individuals who need additional teaching or support. | 16 weeks | 
| The Effect of Fat Quantity & Quality on Body Composition, Insulin Resistance, & Insulin Secretion | Regression Analysis will be used to assess The Effect of Fat Quantity & Quality on Body Composition, Insulin Resistance, & Insulin Secretion | 16 Weeks | 
| The Effect of Carbohydrate Quantity & Quality on Body Composition & Insulin Resistance | Regression Analysis will be used to assess The Effect of Carbohydrate Quantity & Quality on Body Composition & Insulin Resistance | 16 Weeks | 
| The Effect of Protein Quantity & Quality on Body Composition, Insulin Resistance, & Insulin Secretion | Regression Analysis will be used to assess The Effect of Protein Quantity & Quality on Body Composition, Insulin Resistance, & Insulin Secretion | 16 Weeks | 
| Levels of Advanced Glycosylation Endproducts (AGEs) | An AGE reader will be used to measure the Levels of the AGEs in the skin | 16 Weeks | 
| Race Disparities | Compare the effectiveness of the vegan diet in Blacks vs. Whites in all the primary outcomes | 16 weeks | 
| Dietary Advanced Glycation End Products (AGEs) | Explore the effectiveness of a vegan diet in reducing dietary AGEs. | 16 weeks | 
| Food costs | Food costs will be assessed, using the U.S. Department of Agriculture Thrifty Food Plan, 2021, at baseline and 16 weeks. | 16 weeks | 
| PDI, hPDI, uPDI | Assess the total plant-based index (PDI), healthy PDI, and unhealthy PDI, and their relationship with weight loss | 16 weeks | 
| Ultraprocessed foods | The consumption of ultraprocessed foods will be assessed, using the NOVA classification, at baseline and 16 weeks. | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Plant-based diet, Obesity, Insulin sensitivity, Intracellular lipid, Postprandial metabolism, Vegan diet, Beta-cell function