Diets for Obesity

Overseen By Brittney Mason

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: Washington University School of Medicine

Must not be taking: Steroids, Non-statin lipid-lowering, Anticoagulants, others

Disqualifiers: Diabetes, Cancer, Psychiatric illness, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

The purpose of this research study is to 1) understand how some, but not all people with obesity develop obesity related conditions such as type 2 diabetes and cardiovascular disease, and 2) compare the effects of 3 popular weight loss diets (Mediterranean, low-carbohydrate, or a very-low-fat plant-based diet) in people with obesity.

Will I have to stop taking my current medications?

The trial requires that you stop taking medications that could affect the study's results, like steroids or certain cholesterol-lowering drugs, if they can't be temporarily stopped for the study.

What data supports the effectiveness of the treatment for metabolically abnormal obese individuals?

Research suggests that adjusting the macronutrient content of diets can help improve insulin sensitivity in overweight or obese individuals who are insulin resistant. This approach may help reduce the risk of developing related health issues, such as type 2 diabetes, by managing insulin resistance and hyperinsulinemia (high levels of insulin in the blood). ^{1 2 3 4 5}

Is the diet treatment for obesity safe for humans?

Research on Very Low Calorie Diets (VLCD) in obese patients has evaluated their safety, suggesting that they can be safe when properly managed, although individual responses may vary. ^{4 6 7 8 9}

How does the treatment for metabolically abnormal obesity differ from other treatments?

This treatment focuses on lifestyle interventions, such as diet and exercise, to improve metabolic health in obese individuals who are insulin-resistant, aiming to achieve similar metabolic outcomes as those seen in metabolically healthy obese individuals. Unlike some treatments that may focus solely on weight loss, this approach emphasizes improving insulin sensitivity and overall metabolic function. ^{6 7 8 10 11}

Research Team

Samuel Klein, MD

Principal Investigator

Washington University School of Medicine

Eligibility Criteria

This trial is for obese individuals with specific metabolic abnormalities, such as high intrahepatic triglyceride levels or abnormal glucose readings. Participants should have a BMI between 30.0 and 50.0 kg/m2 and not be heavy smokers, drug users, or have conditions that interfere with the study. Pregnant women, those on certain medications, or with severe diseases are excluded.

Inclusion Criteria

My liver fat, blood sugar, and cholesterol levels are within normal ranges.

My BMI is either between 18.5-24.9 or 30.0-50.0.

I am obese with high liver fat, blood sugar, or HbA1C levels.

Exclusion Criteria

I have gone through menopause naturally or due to medical reasons.

I can complete all tests without issues from severe mobility problems, missing limbs, or metal implants.

I have had weight loss surgery that changed my digestive system.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Testing

Cross-sectional comparison of metabolically normal lean, metabolically normal obese, and metabolically abnormal obese subjects

4 weeks

1 visit (in-person)

Dietary Intervention

Metabolically abnormal obese participants are randomized to follow a Mediterranean, low-carbohydrate ketogenic, or plant-based very-low-fat diet

6-7 months

Monthly visits (in-person)

Weight Maintenance

Participants maintain weight loss achieved during the dietary intervention

4-8 weeks

Follow-up

Participants are monitored for changes in metabolic health and other outcomes after weight loss

12 months

Treatment Details

Interventions

• Metabolically abnormal obese (Other)

Trial Overview The study aims to understand why some obese individuals develop diabetes and heart disease while others don't. It compares three diets: Mediterranean, low-carbohydrate ketogenic, and very-low-fat plant-based in metabolically abnormal obese participants to see which diet might be most effective for weight loss and health improvement.

Participant Groups

Group I: Metabolically abnormal obese - Plant-based very-low-fat diet Experimental Treatment 1 Intervention

Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver. Dietary intervention - A plant-based diet high in complex carbohydrates and low in fat, protein, and sodium, with approximately 70% of daily calories from carbohydrates, 15% from fat, and 15% from protein.

Group II: Metabolically abnormal obese - Mediterranean diet Experimental Treatment 1 Intervention

Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver. Dietary intervention - A nutritionally balanced diet that includes fruits, vegetables, fish, beans, whole grains, and olive oil with approximately 50% of daily calories coming from complex carbohydrates, 30% of calories from fat, and 20% of calories from protein.

Group III: Metabolically abnormal obese - Low carbohydrate ketogenic diet Experimental Treatment 1 Intervention

Metabolically abnormal obese - Persons with obesity with glucose levels higher than recommended and a moderate to high amount of fat in the liver. Dietary intervention - A very-low-carbohydrate, adequate protein, high-fat diet containing 20 grams of carbohydrate or less per day (about 5% of calories), derived mainly from vegetables.

Group IV: Metabolically normal obese - Baseline testing only Active Control 1 Intervention

Metabolically normal obese - Persons with obesity that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content. Dietary intervention - None.

Group V: Metabolically normal lean - Baseline testing only Active Control 1 Intervention

Metabolically normal lean - Lean individuals that have good glucose (sugar) control, normal plasma triglyceride (fat) levels and a low liver fat content. Dietary intervention - None.

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Pershing Square Foundation

Collaborator

Trials

1

Recruited

180+

Findings from Research

Capella's gastroplasty surgery leads to significant metabolic and inflammatory changes in patients, as indicated by alterations in blood parameters such as increased C-reactive protein and glucose levels post-surgery.

The study found no technical advantage of using bilateral arciform incisions over supra-umbilical midline incisions, suggesting that both surgical approaches are equally effective in terms of patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Capella's gastroplasty: metabolites and acute phase proteins changes in midline and bilateral arciform approaches. de Moura, LG., Guimarães, SB., de Castro-Filho, HF., et al.[2019]

Insulin resistance varies significantly among healthy individuals, with about one-third at high risk for serious health issues, including type 2 diabetes, when their insulin production can't keep up with their body's needs.

Dietary interventions, such as weight loss and adjusting macronutrient intake, can help improve insulin sensitivity and reduce the negative effects associated with insulin resistance syndrome (IRS).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The insulin resistance syndrome: definition and dietary approaches to treatment. Reaven, GM.[2022]

In a study of 46 very obese individuals (11 inpatients and 35 outpatients), it was found that their caloric intake was directly related to their level of obesity, with both groups consuming high-calorie density foods and engaging in occasional binge eating.

By replacing high-calorie density foods with lower-calorie options, participants could potentially reduce their caloric intake by 20%, which could significantly aid in weight loss efforts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food intake of very obese persons: quantitative and qualitative aspects. Strain, GW., Hershcopf, RJ., Zumoff, B.[2007]

A 16-week calorie-restricted diet in 57 obese, insulin-resistant individuals showed that both moderate carbohydrate (60%) and lower carbohydrate (40%) diets resulted in similar weight loss, averaging around 6 kg.

The lower carbohydrate diet (40%) led to greater improvements in cardiovascular risk markers, including reduced insulin and triacylglycerol levels, increased HDL-cholesterol, and improved LDL particle size, suggesting it may be more beneficial for heart health compared to a higher carbohydrate diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of moderate variations in macronutrient composition on weight loss and reduction in cardiovascular disease risk in obese, insulin-resistant adults. McLaughlin, T., Carter, S., Lamendola, C., et al.[2023]

Current dietary guidelines suggest a variety of dietary patterns for weight loss, but emerging evidence indicates that specific diets may be more effective for certain groups of overweight or obese individuals based on their metabolic characteristics.

Insulin dynamics, including insulin sensitivity and secretion, may play a crucial role in how different macronutrient compositions in diets affect weight loss outcomes in individuals on a hypocaloric diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary composition and weight loss: can we individualize dietary prescriptions according to insulin sensitivity or secretion status? Pittas, AG., Roberts, SB.[2019]

Metabolically healthy obese (MHO) individuals exhibit a postprandial metabolic response similar to lean healthy (LH) individuals, showing preserved insulin sensitivity compared to metabolically unhealthy obese (MUO) individuals after consuming a high-calorie meal.

MHO individuals demonstrate a greater ability to adapt to caloric challenges, with minor differences in amino acid responses and lower changes in certain polyunsaturated fatty acids compared to MUO individuals, indicating a distinct metabolic profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge. Badoud, F., Lam, KP., Perreault, M., et al.[2022]

A subgroup of obese individuals, known as 'metabolically healthy obese,' appears to be protected from common obesity-related health issues like type 2 diabetes and cardiovascular diseases, despite having excess body weight.

The article explores potential mechanisms that contribute to this healthy phenotype, such as reduced liver fat accumulation and lower inflammation in fat tissue, highlighting the clinical importance of understanding this group within the broader obesity epidemic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolically healthy obese individuals -- mechanisms and clinical relevance. Hrasko, T., Bendlová, B., Hainer, V., et al.[2018]

In a study of 12 obese subjects, a hypo-energetic diet significantly improved insulin sensitivity by 353% and 147% during two separate 6-week periods, indicating that weight loss through negative energy balance is crucial for improving metabolic health.

The study found that maintaining weight on an iso-energetic diet led to a 43.5% decrease in insulin sensitivity, suggesting that simply keeping weight stable is less effective than actively losing weight for managing insulin resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insulin resistance in obesity: body-weight or energy balance? Assali, AR., Ganor, A., Beigel, Y., et al.[2019]

In a study of 44 patients with obesity, a Very Low Calorie Diet (VLCD) resulted in an average weight loss of 7 kg and a weight loss rate of 1.2 kg per week, indicating its effectiveness for weight management.

While 33% of participants reported mild side effects, such as constipation and dizziness, the majority (84%) adhered to the VLCD, suggesting that with proper support, adherence can be maintained.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of Very Low Calory Diets in obese patients]. Sáez Belló, M., Segarra Villalba, C., Gras Colomer, E., et al.[2018]

A 9-month lifestyle intervention for 262 non-diabetic obese individuals led to significant reductions in visceral fat and improved insulin sensitivity (IS) in those with obese insulin-resistant (OIR) profiles, but their IS remained much lower than that of metabolically healthy obese (MHO) individuals.

Despite improvements in the OIR group, their insulin sensitivity did not reach levels that would adequately protect against type 2 diabetes and cardiovascular disease, highlighting the need for early pharmacological treatment alongside lifestyle changes for certain obese individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a lifestyle intervention in metabolically benign and malign obesity. Kantartzis, K., Machann, J., Schick, F., et al.[2021]

The prevalence of metabolically healthy obesity (MHO) varies widely based on different definitions, ranging from 2.2% to 36.6% among obese individuals, highlighting the need for a standardized definition of MHO.

Higher dietary quality and compliance with food pyramid recommendations, along with moderate to high levels of physical activity, are associated with a greater likelihood of being metabolically healthy, regardless of obesity status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Defining metabolically healthy obesity: role of dietary and lifestyle factors. Phillips, CM., Dillon, C., Harrington, JM., et al.[2022]

References

1. Brazil pubmed.ncbi.nlm.nih.gov

Capella's gastroplasty: metabolites and acute phase proteins changes in midline and bilateral arciform approaches. [2019]

2. United States pubmed.ncbi.nlm.nih.gov

The insulin resistance syndrome: definition and dietary approaches to treatment. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Food intake of very obese persons: quantitative and qualitative aspects. [2007]

4. United States pubmed.ncbi.nlm.nih.gov

Effects of moderate variations in macronutrient composition on weight loss and reduction in cardiovascular disease risk in obese, insulin-resistant adults. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Dietary composition and weight loss: can we individualize dietary prescriptions according to insulin sensitivity or secretion status? [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Metabolomics Reveals Metabolically Healthy and Unhealthy Obese Individuals Differ in their Response to a Caloric Challenge. [2022]

7. Czech Republic pubmed.ncbi.nlm.nih.gov

Metabolically healthy obese individuals -- mechanisms and clinical relevance. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Insulin resistance in obesity: body-weight or energy balance? [2019]

9. Spain pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of Very Low Calory Diets in obese patients]. [2018]

10. Germany pubmed.ncbi.nlm.nih.gov

Effects of a lifestyle intervention in metabolically benign and malign obesity. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

Defining metabolically healthy obesity: role of dietary and lifestyle factors. [2022]