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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Normal protein diet | Experimental | Animal based protein. 60% carbohydrates, 10% proteins and 30% lipids (i.e. 0.8g of protein/kg of body weight/day) |
|
| Animal based high protein meal | Experimental | 40% carbohydrates, 30% proteins and 30% lipids (i.e. 2.4g of protein/kg of body weight/day) |
|
| Plant based high protein meal | Experimental | 40% carbohydrates, 30% proteins and 30% lipids (i.e. 2.4g of protein/kg of body weight/day) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Normal protein diet | Other | Animal-based protein meal plan consisted of 60% carbohydrates, 10% proteins and 30% lipids |
|
| 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
• Smoker or currently on nicotine therapy
Males and females
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Nutrition Research Centre | Singapore | Singapore | 117599 | Singapore |
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Randomized, controlled
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| Animal protein diet | Other | Animal based high protein meal consisting of 40% carbohydrates, 30% proteins and 30% lipids |
|
| Plant based diet | Other | Plant based high protein meal consisting of 40% carbohydrates, 30% proteins and 30% lipids |
|
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. |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D056128 | Obesity, Abdominal |
| D009765 | Obesity |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006946 | Hyperinsulinism |
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| ID | Term |
|---|---|
| D000095500 | Diet, Plant-Based |
| ID | Term |
|---|---|
| D004035 | Diet Therapy |
| D044623 | Nutrition Therapy |
| D013812 | Therapeutics |
| D004032 | Diet |
| D009747 | Nutritional Physiological Phenomena |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
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