Diet, Insulin Sensitivity, and Postprandial Metabolism (TEF)

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

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.

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight; Insulin Resistance
• Intervention / Treatment: Other: Plant-based diet; Other: Control Diet

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 Type: Interventional
• Enrollment (Actual): 220
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • District of Columbia
    • Washington, District of Columbia, United States, 20016
      • Physicians Committee for Responsible Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Physicians Committee for Responsible Medicine
• Collaborators: Yale University
• Investigators: Principal Investigator: Neal D Barnard, M.D., President

Publications and helpful links

General Publications

• Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. doi: 10.1249/01.MSS.0000078924.61453.FB.
• Barnard ND, Scialli AR, Turner-McGrievy G, Lanou AJ, Glass J. The effects of a low-fat, plant-based dietary intervention on body weight, metabolism, and insulin sensitivity. Am J Med. 2005 Sep;118(9):991-7. doi: 10.1016/j.amjmed.2005.03.039.
• Sparks LM, Xie H, Koza RA, Mynatt R, Hulver MW, Bray GA, Smith SR. A high-fat diet coordinately downregulates genes required for mitochondrial oxidative phosphorylation in skeletal muscle. Diabetes. 2005 Jul;54(7):1926-33. doi: 10.2337/diabetes.54.7.1926.
• Petersen KF, Dufour S, Morino K, Yoo PS, Cline GW, Shulman GI. Reversal of muscle insulin resistance by weight reduction in young, lean, insulin-resistant offspring of parents with type 2 diabetes. Proc Natl Acad Sci U S A. 2012 May 22;109(21):8236-40. doi: 10.1073/pnas.1205675109. Epub 2012 Apr 30.
• Tonstad S, Butler T, Yan R, Fraser GE. Type of vegetarian diet, body weight, and prevalence of type 2 diabetes. Diabetes Care. 2009 May;32(5):791-6. doi: 10.2337/dc08-1886. Epub 2009 Apr 7.
• Barnard ND, Levin SM, Yokoyama Y. A systematic review and meta-analysis of changes in body weight in clinical trials of vegetarian diets. J Acad Nutr Diet. 2015 Jun;115(6):954-69. doi: 10.1016/j.jand.2014.11.016. Epub 2015 Jan 22.
• American Dietetic Association; Dietitians of Canada. Position of the American Dietetic Association and Dietitians of Canada: Vegetarian diets. J Am Diet Assoc. 2003 Jun;103(6):748-65. doi: 10.1053/jada.2003.50142.
• Barnard ND, Gloede L, Cohen J, Jenkins DJ, Turner-McGrievy G, Green AA, Ferdowsian H. A low-fat vegan diet elicits greater macronutrient changes, but is comparable in adherence and acceptability, compared with a more conventional diabetes diet among individuals with type 2 diabetes. J Am Diet Assoc. 2009 Feb;109(2):263-72. doi: 10.1016/j.jada.2008.10.049.
• Barnard ND, Akhtar A, Nicholson A. Factors that facilitate compliance to lower fat intake. Arch Fam Med. 1995 Feb;4(2):153-8. doi: 10.1001/archfami.4.2.153.
• Shulman GI. Ectopic fat in insulin resistance, dyslipidemia, and cardiometabolic disease. N Engl J Med. 2014 Sep 18;371(12):1131-41. doi: 10.1056/NEJMra1011035. No abstract available. Erratum In: N Engl J Med. 2014 Dec 4;371(23):2241.
• Goff LM, Bell JD, So PW, Dornhorst A, Frost GS. Veganism and its relationship with insulin resistance and intramyocellular lipid. Eur J Clin Nutr. 2005 Feb;59(2):291-8. doi: 10.1038/sj.ejcn.1602076.
• Petersen KF, Dufour S, Feng J, Befroy D, Dziura J, Dalla Man C, Cobelli C, Shulman GI. Increased prevalence of insulin resistance and nonalcoholic fatty liver disease in Asian-Indian men. Proc Natl Acad Sci U S A. 2006 Nov 28;103(48):18273-7. doi: 10.1073/pnas.0608537103. Epub 2006 Nov 17.
• Gruetter R. Automatic, localized in vivo adjustment of all first- and second-order shim coils. Magn Reson Med. 1993 Jun;29(6):804-11. doi: 10.1002/mrm.1910290613.
• Rabol R, Petersen KF, Dufour S, Flannery C, Shulman GI. Reversal of muscle insulin resistance with exercise reduces postprandial hepatic de novo lipogenesis in insulin resistant individuals. Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13705-9. doi: 10.1073/pnas.1110105108. Epub 2011 Aug 1.
• Buzzard IM, Faucett CL, Jeffery RW, McBane L, McGovern P, Baxter JS, Shapiro AC, Blackburn GL, Chlebowski RT, Elashoff RM, Wynder EL. Monitoring dietary change in a low-fat diet intervention study: advantages of using 24-hour dietary recalls vs food records. J Am Diet Assoc. 1996 Jun;96(6):574-9. doi: 10.1016/S0002-8223(96)00158-7.
• Kahleova H, Rembert E, Nowak A, Holubkov R, Barnard ND. Effect of a diet intervention on cardiometabolic outcomes: Does race matter? A randomized clinical trial. Clin Nutr ESPEN. 2021 Feb;41:126-128. doi: 10.1016/j.clnesp.2020.12.012. Epub 2021 Jan 2.
• Kahleova H, Petersen KF, Shulman GI, Alwarith J, Rembert E, Tura A, Hill M, Holubkov R, Barnard ND. Effect of a Low-Fat Vegan Diet on Body Weight, Insulin Sensitivity, Postprandial Metabolism, and Intramyocellular and Hepatocellular Lipid Levels in Overweight Adults: A Randomized Clinical Trial. JAMA Netw Open. 2020 Nov 2;3(11):e2025454. doi: 10.1001/jamanetworkopen.2020.25454. Erratum In: JAMA Netw Open. 2021 Jan 4;4(1):e2035088. JAMA Netw Open. 2021 Feb 1;4(2):e210550. JAMA Netw Open. 2021 May 3;4(5):e2115510.

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): January 9, 2019

Study Registration Dates

• First Submitted: October 17, 2016
• First Submitted That Met QC Criteria: October 18, 2016
• First Posted (Estimated): October 20, 2016

Study Record Updates

• Last Update Posted (Actual): July 19, 2023
• Last Update Submitted That Met QC Criteria: July 17, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Obesity; Insulin sensitivity; Beta-cell function; Plant-based diet; Postprandial metabolism; Vegan diet; Intracellular lipid
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Hyperinsulinism; Hypersensitivity; Insulin Resistance; Overweight
• Other Study ID Numbers: Pro00018983

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED