Effect of Moderate Weight Loss in Metabolically Abnormal Lean Subjects (MAL)

The Washington University

Status

Withdrawn

Conditions

Weight Loss

Treatments

Other: Moderate (8-10%) diet-induced weight loss

Study type

Interventional

Funder types

Other

Identifiers

NCT02452567

201501010

Details and patient eligibility

About

Obesity is associated with a constellation of cardiometabolic abnormalities (including insulin resistance, elevated blood pressure and dyslipidemia) that are risk factors for diabetes and cardiovascular disease. Weight loss can improve all of the cardiometabolic abnormalities associated with obesity. Up to ~25% of lean people (Body Mass Index [BMI] 18.5-24.9 kg/m²) have many of the cardiometabolic abnormalities associated with obesity and are referred to as metabolically abnormal lean (MAL) people. However, the MAL phenotype is not well characterized, and it is unclear whether weight loss has beneficial metabolic effects in already lean people. Accordingly, the goal of this study is to: 1) carefully phenotype MAL people and 2) evaluate the effect of moderate (8-10%) diet-induced weight loss in MAL people. This will be investigated in 15 MAL (defined as having 2 or more of the following: intrahepatic triglyceride (IHTG) content ≥5.6%, glycated hemoglobin ≥5.7%, fasting plasma glucose concentration ≥100 mg/dl, 2-hr oral glucose tolerance test (OGTT) plasma glucose concentration ≥140 mg/dl, homeostatic model assessment of insulin resistance (HOMA-IR) ≥ 2.5) men and women. Only lean people who have a BMI ≥21.0 but <25.0 kg/m² will be asked to lose weight to avoid the risk that participants become underweight (BMI <18.5 kg/m²) during weight loss therapy.

Sex

All

Ages

18 to 55 years old

Volunteers

Accepts Healthy Volunteers

Inclusion criteria

BMI 21.0-24.9 kg/m²
Weight stable (+/- 2% for at least 3 months before enrollment)
Two or more of the following: IHTG content ≥5.6%, HOMA- IR index ≥ 2.5, HbA1C ≥ 5.7%, 2-hr OGTT plasma glucose concentration ≥ 140 mg/dl, fasting plasma glucose concentration ≥ 100 mg/dl.

Exclusion criteria

Women who are pregnant or breastfeeding
Evidence of significant organ system dysfunction or disease (e.g., diabetes, chronic kidney disease, advanced heart disease, etc.)
Men who consume >21 units (e.g., glass of wine or bottle of beer) of alcohol per week and women who consume >14 units of alcohol per week
Use of dietary supplements or medications known to affect metabolism
Eating disorder (assessed by using the Eating Disorder Examination Questionnaire [EDE-Q])
Participation in structured endurance or resistance exercise program >150 min/week
Use of tobacco products
Unable or unwilling to follow the study protocol or the research team believes that for any reason the volunteer is not an appropriate candidate for this study, including non-compliance with screening appointments or previous appointments/contact arrangements
Individuals that take Coumadin or similar anticoagulants
Use of antibiotics in last 60 days
Previous bariatric surgery
Cancer or cancer that has been in remission for <5 years
Major psychiatric illness