Metabolic Effects of Birth Weight on Overweight and Obese Chinese Adults and Their Responses to Weight Loss

Study Overview
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Brief Summary
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The overall objective of this study is to investigate in depth the impact of birth weight on the nature of metabolic physiology, body composition and epigenetic differences of the different phenotypes of overweight and obese individuals who are otherwise overtly healthy. We also aim to determine the efficacy of a weight loss intervention on the above mentioned metabolic parameters in these individuals.

Detailed Description
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There is an exponential rise in the prevalence of type 2 diabetes and obesity in Singapore coincident with rapid nutritional and socioeconomic transition. Differing birth weights, even in the normal ranges, predisposes individuals to the risk of type 2 diabetes and obesity. We aim to examine the causal pathways, developmental contribution and effects of a weight loss intervention to this differential by evaluating the hypothesis that genomic, birth weight, developmental, lifestyle and environmental factors contribute to the variation in phenotype observed in adults with obesity and metabolic syndrome. Although there are many large studies that examined the effect of birth weight on the expression of obesity and the metabolic syndrome phenotype, most of these studies usually lack in-depth physiological and epigenetic/genomic studies due to their large sample sizes. We therefore aim to explore such detailed aspects of physiological and epigenetic/genomic profiles on smaller but statistically powered samples, focusing on evaluating body composition, nutritional and metabolic phenotype in relationship to epigenetic/genetic markers and developmental history. In addition, we examine the effects of a weight loss intervention on these parameters. This will assist in weighing the importance of developmental and genetic pathways in contributing to individual risk and the response and efficacy to an intervention.

Official Title
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Developmental Pathways to Metabolic Diseases: To Investigate the Metabolic Effects of Birth Weight on Overweight and Obese Chinese Adults and Their Responses to Weight Loss Over 16 Weeks

Conditions
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Healthy, Overweight, Obesity

Intervention / Treatment
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* Procedure: Dietary and Exercise Intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to give informed consent Chinese males (aged 21-40) Body mass index between 23-30 kg/m2 Total body fat content >24% Sedentary adults < 1 episode of exercise > =30 min/week Birth weight between 5-95% percentiles Fasting glucose < 7 mmol/L Normotensive, defined as BP < 140/90 mmHg and not on any antihypertensive agents Exclusion Criteria: Recent changes in weight of >5% over the past 6 months Attempts to lose weight (weight not stable, exercises still changing and not in maintenance phase) over the past 6 months Significant changes in diet over the past 6 months Any use of weight reducing drugs in the past 6 months Previous abdominal surgery (and bariatric surgery) Any bleeding disorders which would preclude biopsies Any use of investigational drugs in the past 6 months Known allergy to insulin or local anaesthetics Known allergy to milk or milk products (eg. Ensure, liquid meal) Any serious illness requiring hospitalization or surgery in the past 6 months Treatment with medications for hypertension, diabetes mellitus or dyslipidemia, epilepsy, ischemic heart disease On anti-platelet agents, non-steroidal anti-inflammatory drugs (NSAIDs) or anticoagulants Use of any prescription medication that cannot be safely discontinued within 14 days prior to study entry Any use of corticosteroids in the past 6 months Any other medications that could alter insulin resistance History of surgery with metallic clips, staples or stents Presence of cardiac pacemaker or other foreign body in any part of the body including tattoos Mother no longer alive or unable to provide information on birth weight Born premature (ie. not full term baby < 37 weeks of gestation age)

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Higher Birth Weight<br>3447g to 3879g | Procedure: Dietary and Exercise Intervention<br>* Participants will be enrolled into a 16 weeks weight loss programme that consists of (a) dietary interventions and (b) structured exercise sessions and (c) physical activity to achieve 7 - 10% decrease (more than 8 kg) in initial body weight in 16 weeks. They will be subjected to a caloric deficit of 40% of the subject's energy expenditure or 1000kcal, which ever it is higher. (allowance given for dietary control and physical activity).<br>|
| Other: Lower Birth Weight<br>2624g to 2964g | Procedure: Dietary and Exercise Intervention<br>* Participants will be enrolled into a 16 weeks weight loss programme that consists of (a) dietary interventions and (b) structured exercise sessions and (c) physical activity to achieve 7 - 10% decrease (more than 8 kg) in initial body weight in 16 weeks. They will be subjected to a caloric deficit of 40% of the subject's energy expenditure or 1000kcal, which ever it is higher. (allowance given for dietary control and physical activity).<br>|
| Other: Normal Birth Weight<br>2965g to 3446g | Procedure: Dietary and Exercise Intervention<br>* Participants will be enrolled into a 16 weeks weight loss programme that consists of (a) dietary interventions and (b) structured exercise sessions and (c) physical activity to achieve 7 - 10% decrease (more than 8 kg) in initial body weight in 16 weeks. They will be subjected to a caloric deficit of 40% of the subject's energy expenditure or 1000kcal, which ever it is higher. (allowance given for dietary control and physical activity).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |