Effect of a Dietary Intervention on Intracellular Lipid Levels, Insulin Sensitivity, and Glycemic Control in Type 2 Diabetes

November 2, 2023 updated by: Physicians Committee for Responsible Medicine

Physicians Committee for Responsible Medicine, A Randomized, Crossover Trial of the Effect of a Dietary Intervention on Intracellular Lipid, Insulin Sensitivity, and Glycemic Control in Type 2 Diabetes

The purpose of this study is to compare the effects of a low-fat, plant-based dietary intervention and a portion-controlled dietary intervention (compliant with current American Diabetes Association (ADA) guidelines) on changes in intramyocellular and hepatocellular lipid content in adults with type 2 diabetes. Changes in insulin sensitivity and glycemic control will also be assessed in this study. The study duration is 44 weeks.

Study Overview

Status

Suspended

Conditions

Intervention / Treatment

Detailed Description

Type 2 diabetes is a disease characterized by discordance between the amount of insulin produced by pancreatic β-cells and the amount of insulin required to overcome insulin resistance in the liver and peripheral tissues. The development of insulin resistance has been strongly associated with the prolonged accumulation of lipids (fats) in the liver cells ("hepatocellular lipid") and muscle cells ("intramyocellular lipid"). Conventional pharmacologic therapeutics for type 2 diabetes, like metformin, are designed to reduce the accumulation of hepatocellular and intramyocellular lipids and, thereby, augment insulin sensitivity. Research has shown that a low-fat, plant-based diet, in which the consumption of lipids is limited, is a similarly effective therapeutic intervention for the reduction of hepatocellular and intramyocellular lipid content and the improvement of insulin sensitivity in type 2 diabetes.

The purpose of this study is to compare the effects of low-fat, plant-based dietary intervention and a portion-controlled dietary intervention (compliant with current American Diabetes Association (ADA) guidelines) on hepatocellular and intramyocellular lipid content in adults with type 2 diabetes. Using a cross-over design, participants with type 2 diabetes will be randomly assigned to start with a plant-based or a portion-controlled diet for 22 weeks. The two groups will then switch to the opposite diet regimen for an additional 22 weeks. Before and after each intervention period, the investigators will measure intramuscular and liver fat content. The investigators will also assess the relationship between these variables, insulin sensitivity, and glycemic control.

The investigators hypothesize that both dietary interventions will result in reductions in intramuscular and liver fat content, and that these changes will be associated with improvements in insulin sensitivity and glycemic control in individuals with type 2 diabetes. The investigators further hypothesize that the low-fat, plant-based dietary intervention will elicit greater changes in intracellular lipid concentration, compared with the portion-controlled dietary intervention.

Study Type

Interventional

Enrollment (Estimated)

60

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria are as follows:

  1. Men and women with type 2 diabetes treated by diet and/or oral hypoglycemic agents other that sulfonylureas
  2. Age ≥18 years
  3. Body mass index 26-40 kg/m2
  4. Medications (antidiabetic, antihypertensive, and lipid-lowering) have been stable for the past 3 months
  5. HbA1c between 6-10.5% (42-88 mmol/mol)

Exclusion criteria are as follows:

  1. Diabetes mellitus, type 1 and/or treatment with insulin or sulfonylureas
  2. Metal implants, such as a cardiac pacemaker or an aneurysm clip
  3. History of any endocrine condition that would affect body weight, such as thyroid disease, pituitary abnormality, or Cushing's syndrome
  4. Smoking during the past six months
  5. 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
  6. Use of recreational drugs in the past 6 months
  7. 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, MAOIs, SSRIs), antipsychotics, lithium, anticonvulsants, appetite suppressants or other weight-loss drugs, herbs for weight loss or mood, St. John's wort, ephedra, beta blockers
  8. Pregnancy or intention to become pregnant during the study period
  9. Unstable medical or psychiatric illness
  10. Evidence of an eating disorder
  11. Likely to be disruptive in group sessions
  12. Already following a low-fat, vegan diet
  13. Lack of English fluency
  14. Inability to maintain current medication regimen
  15. Inability or unwillingness to participate in all components of the study
  16. Intention to follow another weight-loss method during the trial

Participants will also review and complete the Yale MRI Safety Questionnaire to determine eligibility for the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Low-fat, vegan diet
For a 22-week period, participants will be asked to follow a low-fat vegan diet which consists of whole grains, vegetables, legumes, and fruits, with no restriction on energy intake. Animal products and added oils will be excluded. In choosing grain products and starchy vegetables (e.g., bread, potatoes), participants will be encouraged to select those retaining their natural fiber and having a glycemic index <70, using tables standardized to a value of 100 for glucose.
Behavioral: Dietary intervention
Low-fat, plant-based diet and a portion-controlled diet
Active Comparator: Portion-controlled diet
For a 22-week period, participants will be asked to follow a portion-controlled diet which will include individualized diet plans that reduce daily energy intake by 500 kcal for overweight participants, and keep carbohydrate intake reasonably stable over time. It will derive 50% of total energy from carbohydrates, 20% from protein, and less than 30% from fat (≤7% saturated fat), with less than 200 mg/day of cholesterol/day.
Behavioral: Dietary intervention
Low-fat, plant-based diet and a portion-controlled diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Intramyocellular lipid content
Time Frame: 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44
Proton magnetic resonance (MR) spectroscopy at 4T (Bruker) will be implemented to quantify intramyocellular lipid concentrations.
1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44
Hepatocellular lipid content
Time Frame: 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44
Proton magnetic resonance (MR) spectroscopy at 4T (Bruker) will be implemented to quantify intramyocellular lipid concentrations.
1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44
Insulin sensitivity
Time Frame: Change from baseline to 22 weeks and change from 22 weeks to 44 weeks
Insulin resistance will be assessed by the Homeostatic Model Assessment (HOMA) PREDIM indexes
Change from baseline to 22 weeks and change from 22 weeks to 44 weeks
Concentration of glucose
Time Frame: 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44
Concentration of glucose will be assessed during a standard meal test (Boost Plus, Nestle, Vevey, Switzerland; 720 kcal, 34% of energy from fat, 16% protein, 50% carbohydrate). Plasma concentrations of glucose will be measured at 0, 30, 60, 120, and 180 min.
1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44
Concentration of C-peptide
Time Frame: 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44
Concentration of C-peptide be assessed during a standard meal test (Boost Plus, Nestle, Vevey, Switzerland; 720 kcal, 34% of energy from fat, 16% protein, 50% carbohydrate). Concentration of C-peptide will be measured at 0, 30, 60, 120, and 180 min.
1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44
Rate of glycemic control
Time Frame: 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44
Rate of glycemic control will be assessed through HbA1C.
1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Resting energy expenditure
Time Frame: Change from baseline to 22 weeks and change from 22 weeks to 44 weeks
Resting energy expenditure REE (pulse, respiratory rate and body temperature) will be measured for 20 minutes through indirect calorimetry utilizing a ventilated hood system in fasting participants.
Change from baseline to 22 weeks and change from 22 weeks to 44 weeks
Postprandial metabolism
Time Frame: Change from Baseline to 22 weeks and change from 22 weeks to 44 weeks
Postprandial metabolism will be measured by indirect calorimetry. 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. Resting energy expenditure will be measured for 20 minutes through indirect calorimetry utilizing a ventilated hood system. Postprandial metabolism will be measured four times, 20 minutes each time, over the course of 3 hours after the standard breakfast.
Change from Baseline to 22 weeks and change from 22 weeks to 44 weeks
Body Composition
Time Frame: Change from baseline to 22 weeks and change from 22 weeks to 44 weeks
Body composition will be measured by dual energy x-ray absorptiometry (Lunar iDXA, GE Healthcare; Madison WI), assessing visceral adipose tissue volume and mass.
Change from baseline to 22 weeks and change from 22 weeks to 44 weeks
Gut microbiome composition
Time Frame: Change from baseline to 22 weeks and change from 22 weeks to 44 weeks
Quantitative determination of microorganisms and global analysis of microbial diversity from stool sample. The mean of the change between time points in bacteria counts.
Change from baseline to 22 weeks and change from 22 weeks to 44 weeks
Concentration of plasma lipids
Time Frame: Change from baseline to 22 weeks and change from 22 weeks to 44 weeks
Change in plasma cholesterol & triglycerides.
Change from baseline to 22 weeks and change from 22 weeks to 44 weeks
Body weight
Time Frame: Change from baseline to 22 weeks and change from 22 weeks to 44 weeks
Change in body weight measured on a calibrated scale.
Change from baseline to 22 weeks and change from 22 weeks to 44 weeks

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Advanced Glycation Endproducts (AGEs)
Time Frame: 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44
Advanced Glycation Endproducts (AGEs) will be measured using the AGE Reader mu by Diagnoptics.
1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44
Endothelial function
Time Frame: 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44
Endothelial function will be measured through use of the itamar EndoPAT, which quantifies the endothelium-mediated changes in vascular tone elicited by a 5-minute occlusion of the brachial artery.
1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Physicians Committee for Responsible Medicine

Collaborators

Yale University

Investigators

  • Principal Investigator: Hana Kahleova, MD, PhD, Physicians Committee for Responsible Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

July 1, 2024

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

July 1, 2025

Study Registration Dates

First Submitted

September 6, 2019

First Submitted That Met QC Criteria

September 11, 2019

First Posted (Actual)

September 13, 2019

Study Record Updates

Last Update Posted (Actual)

November 7, 2023

Last Update Submitted That Met QC Criteria

November 2, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Pro00037991

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Upon request individual participant data will be available to other researchers.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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