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Diabetes Mellitus, Type 2NCT04088981

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

A study testing Dietary intervention in people with Diabetes Mellitus, Type 2, run by Physicians Committee for Responsible Medicine at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
Dietary intervention
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Jul 2025to Jul 2026
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

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

Who cannot join

  • Diabetes mellitus, type 1 and/or treatment with insulin or sulfonylureas
  • Metal implants, such as a cardiac pacemaker or an aneurysm clip
  • History 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
Show all 17Show fewer
  • 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
  • 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
  • Participants will also review and complete the Yale MRI Safety Questionnaire to determine eligibility for the study.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Physicians Committee for Responsible Medicine

    Washington D.C., District of Columbia, 20016

Other trials in United States

About this study

Official title: 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.

Read the 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.

Keywords
insulin sensitivity, glycemic control, intramyocellular, nutrition, hepatocellular
Medical subject headings
Diabetes Mellitus, Type 2, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT04088981
Study groupRoleWhat they receive
Low-fat, vegan dietActive comparatorFor 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.
Receives: Behavioral: Dietary intervention
Portion-controlled dietActive comparatorFor 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.
Receives: Behavioral: Dietary intervention

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Intramyocellular lipid content

    Proton magnetic resonance (MR) spectroscopy at 4T (Bruker) will be implemented to quantify intramyocellular lipid concentrations.

    Measured: 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44

  2. Hepatocellular lipid content

    Proton magnetic resonance (MR) spectroscopy at 4T (Bruker) will be implemented to quantify intramyocellular lipid concentrations.

    Measured: 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44

  3. Insulin sensitivity

    Insulin resistance will be assessed by the Homeostatic Model Assessment (HOMA) PREDIM indexes

    Measured: Change from baseline to 22 weeks and change from 22 weeks to 44 weeks

  4. Concentration of glucose

    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.

    Measured: 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44

  5. Concentration of C-peptide

    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.

    Measured: 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44

  6. Rate of glycemic control

    Rate of glycemic control will be assessed through HbA1C.

    Measured: 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44

Secondary outcomes (6)

  1. Resting energy expenditure

    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.

    Measured: Change from baseline to 22 weeks and change from 22 weeks to 44 weeks

  2. Postprandial metabolism

    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.

    Measured: Change from Baseline to 22 weeks and change from 22 weeks to 44 weeks

  3. Body Composition

    Body composition will be measured by dual energy x-ray absorptiometry (Lunar iDXA, GE Healthcare; Madison WI), assessing visceral adipose tissue volume and mass.

    Measured: Change from baseline to 22 weeks and change from 22 weeks to 44 weeks

  4. Gut microbiome composition

    Quantitative determination of microorganisms and global analysis of microbial diversity from stool sample. The mean of the change between time points in bacteria counts.

    Measured: Change from baseline to 22 weeks and change from 22 weeks to 44 weeks

  5. Concentration of plasma lipids

    Change in plasma cholesterol \& triglycerides.

    Measured: Change from baseline to 22 weeks and change from 22 weeks to 44 weeks

  6. Body weight

    Change in body weight measured on a calibrated scale.

    Measured: Change from baseline to 22 weeks and change from 22 weeks to 44 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Sep 2019
  2. Study startJul 2025 (estimated)
  3. Primary completionJul 2026 (estimated)
  4. Study completionJul 2026 (estimated)

Why it stopped: The study was not initiated due to COVID-19 restrictions during the original study start date. After the restrictions were lifted, the study was redesigned and entered as a different study.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Model description
randomized, cross-over
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04088981
Sponsor's protocol ID
Pro00037991
Status last verified
Jun 2025
First submitted
6 Sep 2019
Last updated
27 Jun 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: Upon request individual participant data will be available to other researchers.

Publications

  • Ferrannini E, Gastaldelli A, Miyazaki Y, Matsuda M, Pettiti M, Natali A, Mari A, DeFronzo RA. Predominant role of reduced beta-cell sensitivity to glucose over insulin resistance in impaired glucose tolerance. Diabetologia. 2003 Sep;46(9):1211-9. doi: 10.1007/s00125-003-1169-6. Epub 2003 Jul 23.

    PubMed 12879253

  • Krssak M, Falk Petersen K, Dresner A, DiPietro L, Vogel SM, Rothman DL, Roden M, Shulman GI. Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia. 1999 Jan;42(1):113-6. doi: 10.1007/s001250051123.

    PubMed 10027589

  • Perseghin G, Scifo P, De Cobelli F, Pagliato E, Battezzati A, Arcelloni C, Vanzulli A, Testolin G, Pozza G, Del Maschio A, Luzi L. Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Diabetes. 1999 Aug;48(8):1600-6. doi: 10.2337/diabetes.48.8.1600.

    PubMed 10426379

  • 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.

    PubMed 25229917

  • Goodpaster BH, Theriault R, Watkins SC, Kelley DE. Intramuscular lipid content is increased in obesity and decreased by weight loss. Metabolism. 2000 Apr;49(4):467-72. doi: 10.1016/s0026-0495(00)80010-4.

    PubMed 10778870

  • Sinha R, Dufour S, Petersen KF, LeBon V, Enoksson S, Ma YZ, Savoye M, Rothman DL, Shulman GI, Caprio S. Assessment of skeletal muscle triglyceride content by (1)H nuclear magnetic resonance spectroscopy in lean and obese adolescents: relationships to insulin sensitivity, total body fat, and central adiposity. Diabetes. 2002 Apr;51(4):1022-7. doi: 10.2337/diabetes.51.4.1022.

    PubMed 11916921

  • Thamer C, Machann J, Bachmann O, Haap M, Dahl D, Wietek B, Tschritter O, Niess A, Brechtel K, Fritsche A, Claussen C, Jacob S, Schick F, Haring HU, Stumvoll M. Intramyocellular lipids: anthropometric determinants and relationships with maximal aerobic capacity and insulin sensitivity. J Clin Endocrinol Metab. 2003 Apr;88(4):1785-91. doi: 10.1210/jc.2002-021674.

    PubMed 12679474

  • Machado MV, Ferreira DM, Castro RE, Silvestre AR, Evangelista T, Coutinho J, Carepa F, Costa A, Rodrigues CM, Cortez-Pinto H. Liver and muscle in morbid obesity: the interplay of fatty liver and insulin resistance. PLoS One. 2012;7(2):e31738. doi: 10.1371/journal.pone.0031738. Epub 2012 Feb 16.

    PubMed 22359625

  • Larson-Meyer DE, Newcomer BR, Ravussin E, Volaufova J, Bennett B, Chalew S, Cefalu WT, Sothern M. Intrahepatic and intramyocellular lipids are determinants of insulin resistance in prepubertal children. Diabetologia. 2011 Apr;54(4):869-75. doi: 10.1007/s00125-010-2022-3. Epub 2010 Dec 23.

    PubMed 21181394

  • Wang C, Liu F, Yuan Y, Wu J, Wang H, Zhang L, Hu P, Li Z, Li Q, Ye J. Metformin suppresses lipid accumulation in skeletal muscle by promoting fatty acid oxidation. Clin Lab. 2014;60(6):887-96. doi: 10.7754/clin.lab.2013.130531.

    PubMed 25016691

  • Sanchez-Munoz V, Salas-Romero R, Del Villar-Morales A, Martinez-Coria E, Pegueros-Perez A, Franco-Sanchez JG. [Decrease of liver fat content by aerobic exercise or metformin therapy in overweight or obese women]. Rev Invest Clin. 2013 Jul-Aug;65(4):307-17. Spanish.

    PubMed 24304731

  • Bajaj M, Baig R, Suraamornkul S, Hardies LJ, Coletta DK, Cline GW, Monroy A, Koul S, Sriwijitkamol A, Musi N, Shulman GI, DeFronzo RA. Effects of pioglitazone on intramyocellular fat metabolism in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab. 2010 Apr;95(4):1916-23. doi: 10.1210/jc.2009-0911. Epub 2010 Feb 15.

    PubMed 20157197

  • Phielix E, Brehm A, Bernroider E, Krssak M, Anderwald CH, Krebs M, Schmid AI, Nowotny P, Roden M. Effects of pioglitazone versus glimepiride exposure on hepatocellular fat content in type 2 diabetes. Diabetes Obes Metab. 2013 Oct;15(10):915-22. doi: 10.1111/dom.12112. Epub 2013 May 1.

    PubMed 23574533

  • Marchesini G, Petta S, Dalle Grave R. Diet, weight loss, and liver health in nonalcoholic fatty liver disease: Pathophysiology, evidence, and practice. Hepatology. 2016 Jun;63(6):2032-43. doi: 10.1002/hep.28392. Epub 2016 Jan 22.

    PubMed 26663351

  • Greco AV, Mingrone G, Giancaterini A, Manco M, Morroni M, Cinti S, Granzotto M, Vettor R, Camastra S, Ferrannini E. Insulin resistance in morbid obesity: reversal with intramyocellular fat depletion. Diabetes. 2002 Jan;51(1):144-51. doi: 10.2337/diabetes.51.1.144.

    PubMed 11756334

Questions about this trial

What is this clinical trial studying?

A study testing Dietary intervention in people with Diabetes Mellitus, Type 2, run by Physicians Committee for Responsible Medicine at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 27 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Intramyocellular lipid content (time frame: 1.) Change from week 0 to week 22; 2.) Change from week 22 to week 44). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04088981, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jun 2025.

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