Diet, Insulin Sensitivity, and Postprandial Metabolism

NCT02939638 | Completed DMC

• 1 other identifier: Pro00018983
• Study Type: interventional
• Target: 220
• Locations: 1 country
• Sites: 1

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.

Conditions

Overweight; Obesity; Insulin Resistance

Keywords

Plant-based diet; Obesity; Insulin sensitivity; Intracellular lipid; Postprandial metabolism; Vegan diet; Beta-cell function

Outcome Measures

Primary Outcomes (7)

• 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 Outcomes (15)

• Beta-cell function as measured by glucose (mmmol/L)

  16 weeks

• Beta-cell function as measured by insulin (pmol/L)

  16 weeks

• Beta-cell function as measured by C-peptide (ng/mL)

  16 weeks

• Microbiome Analysis

  16 weeks

• Endothelial function

  16 weeks

Study Arms (2)

Plant-based diet

ACTIVE COMPARATOR

The diet group will be asked to follow a low-fat, vegan diet for 16 weeks

Other: Plant-based diet

Control diet

ACTIVE COMPARATOR

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

Other: Control Diet

Interventions

Plant-based diet OTHER

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

Also known as: Vegan diet

Plant-based diet

Control Diet OTHER

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

Control diet

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and women age ≥18 years of age
• Body mass index 28-40 kg/m2

You may not qualify if:

• 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

Sponsors & Collaborators

• Physicians Committee for Responsible Medicine: lead
• Yale University: collaborator

Study Sites (1)

Physicians Committee for Responsible Medicine

Washington D.C., District of Columbia, 20016, United States

Location

Related Publications (20)

• 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.

  PMID: 19351712 BACKGROUND

• 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.

  PMID: 25620754 BACKGROUND

• 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.

  PMID: 16164885 BACKGROUND

• 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.

  PMID: 25229917 BACKGROUND

• 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.

  PMID: 22547801 BACKGROUND

• 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.

  PMID: 15983191 BACKGROUND

• 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.

  PMID: 15523486 BACKGROUND

• 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.

  PMID: 19167953 BACKGROUND

• 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.

  PMID: 12900694 BACKGROUND

• 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.

  PMID: 17114290 BACKGROUND

• 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.

  PMID: 8350724 BACKGROUND

• 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.

  PMID: 21808028 BACKGROUND

• 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.

  PMID: 12778049 BACKGROUND

• 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.

  PMID: 7842153 BACKGROUND

• 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.

  PMID: 8655904 BACKGROUND

• Kahleova H, Brennan H, Znayenko-Miller T, Holubkov R, Barnard ND. Does diet quality matter? A secondary analysis of a randomized clinical trial. Eur J Clin Nutr. 2024 Mar;78(3):270-273. doi: 10.1038/s41430-023-01371-y. Epub 2023 Nov 28.

  PMID: 38012413 DERIVED

• Kahleova H, Sutton M, Maracine C, Nichols D, Monsivais P, Holubkov R, Barnard ND. Vegan Diet and Food Costs Among Adults With Overweight: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2023 Sep 5;6(9):e2332106. doi: 10.1001/jamanetworkopen.2023.32106.

  PMID: 37669055 DERIVED

• Kahleova H, Znayenko-Miller T, Uribarri J, Holubkov R, Barnard ND. Dietary advanced glycation products and their associations with insulin sensitivity and body weight: A 16-week randomized clinical trial. Obes Sci Pract. 2022 Oct 21;9(3):235-242. doi: 10.1002/osp4.646. eCollection 2023 Jun.

  PMID: 37287522 DERIVED

• 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.

  PMID: 33487254 DERIVED

• 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.

  PMID: 33252690 DERIVED

MeSH Terms

Conditions

Overweight; Obesity; Insulin Resistance

Interventions

Diet, Plant-Based; Diet, Vegan

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Diet, Vegetarian

Study Officials

• Neal D Barnard, M.D.

  President

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 17, 2016
• First Posted: October 20, 2016
• Study Start: October 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: January 9, 2019
• Last Updated: July 19, 2023

Record last verified: 2023-07

Locations

US (1)