Diet, Insulin Sensitivity, and Postprandial Metabolism

Physicians Committee for Responsible Medicine220 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

220

Conditions

Overweight Obesity Insulin Resistance

Interventions

Plant-based dietOTHER

Weekly instructions will be given to the participants in the intervention group about following vegan diet.

Control DietOTHER

Participants will be asked to continue their usual diets for the 16-week study period.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Men and women age ≥18 years of age * Body mass index 28-40 kg/m2 Exclusion Criteria: 1. 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 2. Smoking during the past six months 3. 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 4. Use of recreational drugs in the past 6 months 5. 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 6. Pregnancy or intention to become pregnant during the study period 7. Unstable medical or psychiatric illness 8. Evidence of an eating disorder 9. Likely to be disruptive in group sessions 10. Already following a low-fat, vegan diet 11. Lack of English fluency 12. Inability to maintain current medication regimen 13. Inability or unwillingness to participate in all components of the study 14. Intention to follow another weight-loss method during the trial

Locations (1)

Physicians Committee for Responsible Medicine

Washington D.C., District of Columbia, United States

Outcomes

Primary Outcomes

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

Time frame: 16 weeks

Fat mass in grams

Anticipated weight-loss for intervention group compared with control group.

Time frame: 16 weeks

Visceral fat in cm^3

Anticipated weight-loss for intervention group compared with control group.

Time frame: 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.

Time frame: 16 Weeks

Insulin resistance

Insulin resistance will be assessed by the Homeostatic Model Assessment (HOMA) index.

Time frame: 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.

Data from ClinicalTrials.gov

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Secondary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 16 Weeks

Levels of Advanced Glycosylation Endproducts (AGEs)

An AGE reader will be used to measure the Levels of the AGEs in the skin

Time frame: 16 Weeks

Race Disparities

Compare the effectiveness of the vegan diet in Blacks vs. Whites in all the primary outcomes

Time frame: 16 weeks

Dietary Advanced Glycation End Products (AGEs)

Explore the effectiveness of a vegan diet in reducing dietary AGEs.

Time frame: 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.

Time frame: 16 weeks

PDI, hPDI, uPDI

Assess the total plant-based index (PDI), healthy PDI, and unhealthy PDI, and their relationship with weight loss

Time frame: 16 weeks

Ultraprocessed foods

The consumption of ultraprocessed foods will be assessed, using the NOVA classification, at baseline and 16 weeks.

Time frame: 16 weeks