Energy Metabolism and Acute Effects of Protein Diets in Metabolically Obese Normal Weight Individuals (MONW)

Energy Metabolism and Acute Effects of Protein Diets in Metabolically Obese Normal Weight (MONW) Individuals

Asians tend to develop type 2 diabetes (T2D) at lower body mass index (BMI) levels and younger ages compared to other populations. This leads to a longer duration of suffering from long-term complications associated with the disease, ultimately resulting in shorter life expectancy. Notably, approximately 40% of newly diagnosed T2D cases in Asians occur in individuals considered lean, with a BMI reported to be less than 22 kg/m2. This phenomenon is termed the "Metabolically Obese Normal Weight" (MONW) phenotype. MONW individuals are characterized as having a normal body weight but exhibiting obesity-related metabolic disturbances, including excess body fat with ectopic fat deposition, insulin resistance, and dyslipidemia.

Study Overview

• Status: Active, not recruiting
• Conditions: Glucose Metabolism Disorders; Healthy; Insulin Resistance; Insulin Sensitivity; Obesity; Endocrine; Obesity, Visceral
• Intervention / Treatment: Other: Normal protein diet; Other: Animal protein diet; Other: Plant based diet

Detailed Description

Asian populations have higher prevalence of abdominal obesity, accounting for ~60% of the global diabetic population. Type 2 diabetes (T2D) developing at lower BMI levels and younger ages compared to Western populations, suggest underlying metabolic issues in Asian. A cluster of metabolically obese, normal weight (MONW) individuals are identified in 40% of newly diagnosed Asian T2D.

MONW individuals have normal body weight but exhibit obesity-related metabolic disturbances, such as excess body fat, insulin resistance, and dyslipidemia, predisposing them to develop metabolic symptoms such as T2D and cardiovascular disease. They also show reduced physical activity, lower aerobic capacity, low muscle quality and impaired thermogenesis. Elevated plasma amino acids are associated with insulin resistance, resembling obesity, diabetes and sarcopenia. Given the complex nature of MONW, further examination is needed for early diagnosis and effective prevention strategies. Increased protein intake is known to improve satiety, thermogenesis and muscle health, while enhancing insulin sensitivity and fat oxidation. High-protein diets can aid in weight loss and are often preferred over traditional calorie restriction for combating obesity. In our previous study, a 5% weight loss from calorie restriction improved body composition and metabolism in MONW individuals. Hence, this study aims to 1) better understand the physiology and energy balance of MONW individuals; 2) identify biomarkers for early diagnosis; and 3) examine the effects of high-protein diets on the metabolism of MONW individuals. The study will involve participants of Chinese descent, evaluating metabolic biomarkers in energy balance and the impact of different protein sources on their acute metabolic effects.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 117599
    • Clinical Nutrition Research Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body mass index between 18.5 - 24.9 kg/m2
• Non-diabetic
• Blood pressure (≤140/90 mmHg)
• <5% weight change in the past 6 months
• Fasting triglyceride < 90 mg/dl and HOMA-IR ≤ 1.0 will be defined as healthy subjects
• Fasting triglyceride ≥ 90 mg/dl and HOMA-IR > 1.0 will be defined as MONW subjects

Exclusion Criteria:

• • Smoker or currently on nicotine therapy

  • Regularly consume alcohol >1 unit per day
  • On hypocaloric/hypercaloric diet aiming for weight loss/gain
  • An athlete or sportive person with regular exercising >3 times per week and >45 minutes per section.
  • Currently receiving therapy (e.g. insulin) or any medication/ treatment (including supplements) that may affect glucose and lipid metabolism, energy metabolism or body composition
  • Currently on steroids, protease inhibitors, or antipsychotics therapies
  • Has symptomatic Irritable Bowel Syndrome
  • Has glucose-6-phosphate dehydrogenase (G6PD) deficiency
  • Had major medical or surgical event requiring hospitalization within the preceding 3 months
  • Participated in drug trials within 3 months before the start of the study
  • Donated blood within 3 months before the start of the study
  • Has intolerances or allergies to any of the study foods (eg. anaphylaxis to glutens)
  • Pregnant (pregnancy test will be done), lactating, or planning to be become pregnant during the study period
  • Has active Tuberculosis (TB) or currently receiving treatment for TB
  • Has chronic infection or is known to suffer from or has previously suffered from or is a carrier of Hepatitis B Virus (HBV), Hepatitis C Virus (HCV), Human Immunodeficiency Virus (HIV)
  • Has claustrophobia, trypanophobia, or hemophobia
  • Unwilling to consume study foods
  • Inadequate fluency in the English language
  • Unable to understand the study procedures and signs forms providing written informed consent to participate in the study.
  • Is a member of the research team or their immediate family members. Immediate family member is defined as a spouse, parent, child, or sibling, whether biological or legally adopted

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal protein diet; Animal based protein. 60% carbohydrates, 10% proteins and 30% lipids (i.e. 0.8g of protein/kg of body weight/day)	Other: Normal protein diet; Animal-based protein meal plan consisted of 60% carbohydrates, 10% proteins and 30% lipids
Experimental: Animal based high protein meal; 40% carbohydrates, 30% proteins and 30% lipids (i.e. 2.4g of protein/kg of body weight/day)	Other: Animal protein diet; Animal based high protein meal consisting of 40% carbohydrates, 30% proteins and 30% lipids
Experimental: Plant based high protein meal; 40% carbohydrates, 30% proteins and 30% lipids (i.e. 2.4g of protein/kg of body weight/day)	Other: Plant based diet; Plant based high protein meal consisting of 40% carbohydrates, 30% proteins and 30% lipids

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gycaemic control	The primary outcome in this study is the effect on glycaemic control (fasting glucose, insulin, insulin sensitivity).	Blood will be sampled at timepoints, t = 0minute(fasting), following the meal test,for 4 hours (t = 15, 30, 60, 90, 120, 150, 180 and 240 minutes),and pre- and post-exercise
Energy expenditure and fuel utilization	Metabolism will be assessed in the whole body calorimeter (WBC). Only one subject alone in the WBC room during the test. The subject can move around freely. O2 consumption and CO2 production will be detailed energy metabolism in different parameters, such as RMR, DIT, PAEE and NEAT.measured to calculate energy expenditure using Weir formulae Urine samples collected across 4 different sessions throughout the WBC stay to assess protein utilisation	Assessed for 9 hours in the whole body calorimeter room on visits 3, 4 and 5. 30 minute-RMR,3hour-DIT, 30minute-exercise-induced EE (or PAEE)); urine samples collected on 4 different sessions throughout the WBC
Postprandial amino acids and proteomics profiles	To identify novel biomarkers and gain insights to investigate phenotypic differences of MONW individuals.	Blood will be sampled at timepoints, t = 0 minute (Baseline) and at t=60 minutes.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postprandial profiles of lipid and inflammation	Effects on fasting lipids and inflammatory markers	Blood will be sampled at timepoints, t = 0 minute (fasting), following the meal test, for 4 hours (t = 15, 30, 60, 90, 120, 150, 180 and 240 minutes), and pre- and post-exercise.
Measure of appetite regulation and postprandial gut hormones	A visual analogue scale incorporating a 100-point rating scale will be used to assess each appetitive sensation, e.g. hunger, fullness, desire to eat, induced by each intervention. Gut hormones will also be measured from blood samples.	Rate hunger and satiety immediately before (t=0 minute) and after meal (t=15, 30, 60, 120, 180, and 240 minutes)
Measure of muscle and inflammation biomarkers after exercise bout	Measure of muscle and inflammation biomarkers after exercise to evaluating metabolic biomarkers in energy balance	Blood samples were taken prior to the exercise and immediately after the 30-minute exercise
Baseline gut microbial populations and functions and relationship to the host's diet	Subjects will be instructed to pass stool onto a provided dry clean stool catcher and transfer 1-5 grams stool specimen using a spatula attached to the tube lid into the stool collection leak prof tube containing preservatives.	1 stool sample collected during study,taken at baseline (between baseline visit and before first intervention visit). Can be collected in centre or at home using a stool kit. Kit contained stabilising reagents to stabilize DNA and RNA.

Collaborators and Investigators

• Sponsor: Singapore Institute of Food and Biotechnology Innovation

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2022
• Primary Completion (Estimated): February 1, 2025
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: January 17, 2025
• First Submitted That Met QC Criteria: January 24, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 24, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Glycaemic control
• Additional Relevant MeSH Terms: Nutrition Disorders; Overnutrition; Body Weight; Hyperinsulinism; Overweight; Obesity; Insulin Resistance; Metabolic Diseases; Glucose Metabolism Disorders; Obesity, Abdominal
• Other Study ID Numbers: 2021-192

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No