Diet, Insulin Sensitivity, and Postprandial Metabolism

Not Applicable

Completed

• Conditions: Insulin Resistance; Obesity; Overweight
• Interventions: Other: Plant-based diet; Other: Control Diet

• Registration Number: NCT02939638
• Lead Sponsor: Physicians Committee for Responsible Medicine

Brief Summary

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

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 Timeline

• Study Start: 2016-10
• Study First Submitted: 2016-10-17
• Study First Submitted QC: 2016-10-18
• Study First Posted: 2016-10-20
• Primary Completion: 2018-12
• Study Completion: 2019-01-09
• Status Verified: 2023-07
• Last Update Submitted: 2023-07-17
• Last Update Posted: 2023-07-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 220

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Plant-based diet	Plant-based diet	The diet group will be asked to follow a low-fat, vegan diet for 16 weeks
Control diet	Control Diet	Half of the participants will be asked to continue their usual diets for the 16-week study period.

Primary Outcome Measures

Name	Time	Method
Body weight in kg	16 weeks	Anticipated weight-loss for intervention group compared with control group. Weight and height will be combined to report BMI in kg/m\^2
Visceral fat in cm^3	16 weeks	Anticipated weight-loss for intervention group compared with control group.
Insulin resistance	16 weeks	Insulin resistance will be assessed by the Homeostatic Model Assessment (HOMA) index.
Resting Energy Expenditure (REE)	16 weeks	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.
Changes in intramyocellular and/or intrahepatocellular lipid	16 Weeks	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.
Postprandial metabolism	16 weeks	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.
Fat mass in grams	16 weeks	Anticipated weight-loss for intervention group compared with control group.

Secondary Outcome Measures

Name	Time	Method
Race Disparities	16 weeks	Compare the effectiveness of the vegan diet in Blacks vs. Whites in all the primary outcomes
Food costs	16 weeks	Food costs will be assessed, using the U.S. Department of Agriculture Thrifty Food Plan, 2021, at baseline and 16 weeks.
Endothelial function	16 weeks	Endothelial function will be measured using the EndoPAT, a proprietary diagnostic device for functional vascular health assessment, in a subset of participants.
Levels of Advanced Glycosylation Endproducts (AGEs)	16 Weeks	An AGE reader will be used to measure the Levels of the AGEs in the skin
Beta-cell function as measured by glucose (mmmol/L)	16 weeks	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.
Beta-cell function as measured by insulin (pmol/L)	16 weeks	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.
Beta-cell function as measured by C-peptide (ng/mL)	16 weeks	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.
Dietary Advanced Glycation End Products (AGEs)	16 weeks	Explore the effectiveness of a vegan diet in reducing dietary AGEs.
PDI, hPDI, uPDI	16 weeks	Assess the total plant-based index (PDI), healthy PDI, and unhealthy PDI, and their relationship with weight loss
The Effect of Carbohydrate Quantity & Quality on Body Composition & Insulin Resistance	16 Weeks	Regression Analysis will be used to assess The Effect of Carbohydrate Quantity \& Quality on Body Composition \& Insulin Resistance
Microbiome Analysis	16 weeks	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.
Diet Assessment Recall Questionnaire	16 weeks	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.
The Effect of Fat Quantity & Quality on Body Composition, Insulin Resistance, & Insulin Secretion	16 Weeks	Regression Analysis will be used to assess The Effect of Fat Quantity \& Quality on Body Composition, Insulin Resistance, \& Insulin Secretion
The Effect of Protein Quantity & Quality on Body Composition, Insulin Resistance, & Insulin Secretion	16 Weeks	Regression Analysis will be used to assess The Effect of Protein Quantity \& Quality on Body Composition, Insulin Resistance, \& Insulin Secretion
Ultraprocessed foods	16 weeks	The consumption of ultraprocessed foods will be assessed, using the NOVA classification, at baseline and 16 weeks.

Trial Locations

Locations (1)

Physicians Committee for Responsible Medicine; 🇺🇸 Washington, District of Columbia, United States