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The "Metabolically-obese Normal-weight" Phenotype and Its Reversal by Calorie Restriction

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ClinicalTrials.gov Identifier: NCT03239782
Recruitment Status : Completed
First Posted : August 4, 2017
Last Update Posted : March 13, 2018
Sponsor:
Information provided by (Responsible Party):
Faidon Magkos, Clinical Nutrition Research Centre, Singapore

Brief Summary:

The prevalence of overweight and obesity in Singapore is approximately half of that in the United States, yet the incidence of type 2 diabetes is similar, and is expected to double in the near future. This indicates that metabolic dysfunction, particularly insulin resistance, is widely prevalent even among individuals who are considered normal-weight or lean by conventional measures, i.e. body mass index (BMI) and percent body fat. These individuals are often referred to as "metabolically-obese normal-weight" (MONW), and have increased risk for cardiometabolic disease despite their normal BMI and total body fat values. The prevalence of the MONW phenotype varies across populations and differs markedly among different ethnicities. However, our understanding of the complex interactions between ethnicity, body composition, and metabolic dysfunction and its reversal remains rudimentary. Previous attempts to characterize the MONW phenotype are confounded by the small but significant differences in BMI or percent body fat between groups (even if all subjects were lean, within the "normal" range), with MONW subjects being always "fatter" than the corresponding control subjects. There are no published studies that prospectively recruited groups of metabolically healthy and unhealthy lean individuals matched on BMI and percent body fat. Furthermore, although weight loss improves body composition and many of the cardiometabolic abnormalities in most obese patients, little is known about the possible therapeutic effects of calorie restriction in MONW subjects.

Accordingly, a better understanding of the MONW phenotype and the evaluation of therapeutic approaches for its reversal will have important implications for public health. By facilitating earlier identification of these subjects, who are more likely to go undiagnosed and thus less likely to be treated before clinically overt cardiometabolic disease develops, results from this study will allow for earlier and effective intervention.


Condition or disease Intervention/treatment Phase
Glucose Metabolism Disorders Obesity, Visceral Obesity; Endocrine Insulin Sensitivity/Resistance Behavioral: Calorie restriction Not Applicable

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 77 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The "Metabolically-obese Normal-weight" Phenotype in Two Asian Ethnic Groups and Its Reversal by Calorie Restriction
Actual Study Start Date : March 29, 2016
Actual Primary Completion Date : October 7, 2017
Actual Study Completion Date : October 7, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Body Weight

Arm Intervention/treatment
Experimental: Metabolically unhealthy

Subjects classified as metabolically unhealthy (MONW) go on to participate in a calorie restriction intervention.

MONW subjects will participate in a supervised weight loss program to help ensure they are under a similar weekly energy deficit and achieve a 5 % weight loss at approximately the same time. Participants will be prescribed a reduced-calorie diet (~500 kcal/d below their needs for weight maintenance), and will be instructed not to change their physical activity habits, in order to achieve a weekly weight loss of ~0.5 kg.

The macronutrient composition of the diet will be the same for all groups (55-60 % of energy from carbohydrate, 15-20 % from protein, and 20-30 % from fat); no vitamins or other nutritional supplements will be given.

Behavioral: Calorie restriction
Calorie restriction with behavioral modification and provision of one catered, reduced calorie meal a day




Primary Outcome Measures :
  1. Whole-body insulin sensitivity [ Time Frame: 3 hours ]
    Our primary endpoint is whole-body insulin sensitivity (i.e. the major metabolic correlate of the MONW phenotype), determined by using the hyperinsulinemic-euglycemic clamp.



Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy male or female
  • Chinese or Indian descent
  • Between 21-65 years old (inclusive)
  • BMI from >=19 to <25 kg/m2

Exclusion Criteria:

  • BMI ≥25 kg/m2
  • BMI <19 kg/m2 (to avoid the risk of subjects becoming seriously underweight (i.e. BMI ≤18 kg/m2) after 5 % weight loss)
  • Age <21 and >65 yrs
  • Use of medications that can affect metabolic function (including oral contraceptives and hormone replacement therapy)
  • Regular use of tobacco products
  • Regular consumption of alcohol
  • Pregnant or breastfeeding women
  • Evidence of significant organ system dysfunction or disease
  • Recent weight loss (≥5 % over the past 6 months)
  • Severe asthma and respiratory problems that prevent subjects from exercising

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03239782


Sponsors and Collaborators
Clinical Nutrition Research Centre, Singapore
Investigators
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Principal Investigator: Faidon Magkos, PhD Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research
  Study Documents (Full-Text)

Documents provided by Faidon Magkos, Clinical Nutrition Research Centre, Singapore:
Informed Consent Form  [PDF] March 22, 2016

Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Faidon Magkos, Principal Investigator, Clinical Nutrition Research Centre, Singapore
ClinicalTrials.gov Identifier: NCT03239782    
Other Study ID Numbers: MONW
First Posted: August 4, 2017    Key Record Dates
Last Update Posted: March 13, 2018
Last Verified: March 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Obesity
Insulin Resistance
Metabolic Diseases
Glucose Metabolism Disorders
Obesity, Abdominal
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Hyperinsulinism