Metabolically Normal and Metabolically Abnormal Obesity

NCT01184170 | Completed DMC

• 1 other identifier: 10-0708
• Study Type: interventional
• Target: 71
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to learn more about why some obese persons are resistant to developing obesity-related metabolic diseases (such as diabetes and cardiovascular disease), while others are prone to developing these conditions. We will do this by studying obese persons before and after a 5% body weight gain. Subjects will be asked to increase their current diet for a period of 8-12 weeks in order to increase their current body weight by 5%. Each will then be asked to maintain this weight increase for 3 weeks. We will monitor subjects throughout this time period with weekly medical evaluations. At the completion of the study, we will provide each subject with a 6-month weight loss program.

Conditions

Obesity; Metabolic Syndrome

Keywords

obesity; metabolism; cardiovascular metabolic syndrome

Outcome Measures

Primary Outcomes (5)

• Change in Intrahepatic Triglyceride

  an average of three months, from baseline to 5% weight gain

• Change in de novo lipogenesis

  an average of three months, from baseline to 5% weight gain

• Change in VLDL kinetics

  an average of three months, from baseline to 5% weight gain

• Change in hepatic insulin sensitivity

  an average of three months, from baseline to 5% weight gain

• Change in skeletal muscle insulin sensitivity

  an average of three months, from baseline to 5% weight gain

Secondary Outcomes (4)

• Change in adipose tissue insulin sensitivity

  an average of three months, from baseline to 5% weight gain

• Change in CD36 concentration in skeletal muscle

  an average of three months, from baseline to 5% weight gain

• change in CD36 concentration in adipose tissue

  an average of three months, from baseline to 5% weight gain

• Change in cell proliferation (growth) rates in the colon

  an average of three months, from baseline to 5% weight gain

Study Arms (2)

Metabolically Normal

EXPERIMENTAL

Subjects in this group are metabolically normal. They have low liver fat defined as less than five percent as determined by magnetic resonance spectroscopy. Intervention: Subjects will begin an 8-12 week high-calorie diet intervention. They will eat an additional 1000 kcal/day for two to three months, until a moderate, approximately 5% weight gain is achieved. The recommended dietary energy intake will be 1000 kcal/d more than the subject's baseline resting energy expenditure. An individualized diet plan will be developed for each subject by the study dietitian based on estimated energy requirements, and the subject's food preferences and dietary habits.

Behavioral: overfeeding

Metabolically Abnormal

EXPERIMENTAL

Subjects in this group are metabolically abnormal. They have high liver fat defined as at least ten percent as determined by magnetic resonance spectroscopy. Intervention: Subjects will begin an 8-12 week high-calorie diet intervention. They will eat an additional 1000 kcal/day for two to three months, until a moderate, approximately 5% weight gain is achieved. The recommended dietary energy intake will be 1000 kcal/d more than the subject's baseline resting energy expenditure. An individualized diet plan will be developed for each subject by the study dietitian based on estimated energy requirements, and the subject's food preferences and dietary habits.

Behavioral: overfeeding

Interventions

overfeeding BEHAVIORAL

Subjects will begin an 8-12 week high-calorie diet intervention. They will eat an additional 1000 kcal/day for two to three months, until a moderate, approximately 5% weight gain is achieved. The recommended dietary energy intake will be 1000 kcal/d more than the subject's baseline resting energy expenditure. An individualized diet plan will be developed for each subject by the study dietitian based on estimated energy requirements, and the subject's food preferences and dietary habits.

Also known as: directed weight gain

Metabolically Abnormal; Metabolically Normal

Eligibility Criteria

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

You may qualify if:

• Obese subjects (BMI 30.0 - 39.9 kg/m2)
• Sedentary subjects (exercise less than 1 hr/wk)

You may not qualify if:

• Pregnant or lactating women
• Michigan Alcohol Screening Test score ≥4
• Active or previous history of liver disease
• Active or previous history of diabetes
• history of alcohol abuse, or currently consuming ≥20 g alcohol/day
• Severe hypertriglyceridemia (\>300 mg/dL)
• Smoke tobacco
• Take medication that might confound the study results

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Publications (3)

• Yoshino J, Patterson BW, Klein S. Adipose Tissue CTGF Expression is Associated with Adiposity and Insulin Resistance in Humans. Obesity (Silver Spring). 2019 Jun;27(6):957-962. doi: 10.1002/oby.22463. Epub 2019 Apr 19.

  PMID: 31004409 DERIVED

• Fabbrini E, Tiemann Luecking C, Love-Gregory L, Okunade AL, Yoshino M, Fraterrigo G, Patterson BW, Klein S. Physiological Mechanisms of Weight Gain-Induced Steatosis in People With Obesity. Gastroenterology. 2016 Jan;150(1):79-81.e2. doi: 10.1053/j.gastro.2015.09.003. Epub 2015 Sep 12.

  PMID: 26376348 DERIVED

• Fabbrini E, Yoshino J, Yoshino M, Magkos F, Tiemann Luecking C, Samovski D, Fraterrigo G, Okunade AL, Patterson BW, Klein S. Metabolically normal obese people are protected from adverse effects following weight gain. J Clin Invest. 2015 Feb;125(2):787-95. doi: 10.1172/JCI78425. Epub 2015 Jan 2.

  PMID: 25555214 DERIVED

MeSH Terms

Conditions

Obesity; Metabolic Syndrome

Condition Hierarchy (Ancestors)

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

Study Officials

• Samuel Klein, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: August 12, 2010
• First Posted: August 18, 2010
• Study Start: August 1, 2010
• Primary Completion: August 1, 2014
• Study Completion: February 1, 2015
• Last Updated: July 2, 2017

Record last verified: 2017-06

Locations

US (1)