Healthy, Overweight and Obese Adults
Conditions
Keywords
caloric restriction, low calorie diet, menopause, overweight, obesity, weigh loss, ageing, energy expenditure, body composition
Brief summary
Obesity increases the risk of type 2 diabetes, cardiovascular disease, and certain cancers, primarily due to elevated abdominal fat storage. With nearly two-thirds of the UK population living with overweight or obesity, there is an urgent necessity for evidence-based public health guidance to promote healthy weight. Calorie deficit can facilitate weight loss and body fat reduction, leading to health benefits, such as improved blood glucose control. Current weight management advice centres on lifestyle modification, incorporating changes to diet and physical activity to support a calorie deficit. However, existing dieting recommendations fail to consider gender or age. This is a surprising oversight, as it is well established that health outcomes vary significantly between men and women across the lifespan. Further, the menopause may have an impact on fat storage linked to changes in sex hormones. Our recent research, involving both mice and humans, has indicated that females are less responsive to weight loss and fat reduction during dieting. This study aims to understand endocrine and metabolic sex-based differences in obesity and calorie restriction, with a particular focus on women's health. We plan to conduct a diet study with 75 participants, encompassing both younger and older men and women, to monitor changes in energy expenditure and body composition using gold-standard techniques, such as doubly-labelled water. Blood and abdominal fat tissue samples will be collected to investigate how sex hormones might elucidate these differences. The aim of the study is to enhance our understanding of diet and women's health to combat obesity and promote healthy ageing.
Interventions
OTHERPhase 1 - Maintenance Diet
3d maintenance diet (MT, fixed macronutrient composition of 15% protein, 30% fat and 55% CHO), fed to energy requirements (1.3 X RMR)
OTHERPhase 2 - Weight loss diet
6 week calorie restricted high protein diet (CR, fixed macronutrient composition as 30% protein, 35% fat and 35% CHO) fed to energy requirements \[0.8 X Resting Metabolic Rate (RMR)\], with stepwise reduction of 100kcal/d at week 3 and 5
Sponsors
University of Edinburgh
University of Aberdeen
Study design
Allocation
NON_RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* Adults (aged over 18years) who are healthy but overweight/obese (BMI 27-45kg/m2) males and females as: * 15 women (age 40 or less years) * 15 men (age 40 or less years) * 15 women (age 55-65 years) in menopause\*; not taking Hormone Replacement Therapy (HRT) * 15 men (age 55-65 years) * 15 women (age 55-65 years) in menopause; taking HRT\*\* * menopause definition is no menstrual period for 12 months \*\*HRT inclusion criteria - women will have continuously taken oestrogen HRT for 24 months
Exclusion criteria
Potential volunteers will be asked to fill in a health questionnaire at the screening visit to assess their suitability for the study. This information will allow us to exclude participants. Medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in body mass expressed as weight in kilograms (kg) | From baseline (day 1) to end of intervention (day 53); additional measurements taken three times a week throughout the intervention duration | Measured using digital scale |
| Change in energy expenditure expressed in kilocalories per day (kcal/day) | From day 11 (start of the calorie-restricted diet) to the end of the intervention (day 52); with additional doses consumed on day 25 and 39 | Measured using stable isotope method - doubly labelled water (DLW) - with urine sample collection |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in total body density expressed in litres (l) | From day 8 (start of the maintenance diet) to end of the intervention (day 53) | Measured using BodPod air displacement plethysmography |
| Change in non-esterified fatty acids (NEFA) concentration in fasted blood sample | From day 8 (start of the maintenance diet) to end of the intervention (day 53); also measured at midpoint of calorie-restricted diet (day 32) | Analysed by KONE |
| Change in concentration of caloric-restriction (CR) related hormones in fasted blood sample | From day 8 (start of the maintenance diet) to end of the intervention (day 53); also measured at midpoint of calorie restricted diet (day 32) | Includes: leptin, adiponectin, cortisol; analysed by ELISA |
| Change in sex hormones concentration in fasted blood sample | From day 8 (start of the maintenance diet) to end of the intervention (day 53); also measured at midpoint of calorie restricted diet (day 32) | Includes: oestrogens, progesterone, androgens; analysed by high -sensitivity liquid chromatography-mass spectrometry (LC-MS) |
| Body height measured in meters (m) | Only at baseline | Measured using stadiometer |
| Change in Body Mass Index (BMI) expressed as kg/m^2 | From baseline (day 1) to end of intervention (day 53); additional measurements taken three times a week throughout the intervention duration | BMI will be calculated using weight and height measures |
| Change in adipose tissue metabolism assessed by adipocite size | From day 8 (start of the maintenance diet) to end of the intervention (day 53) | Measured via abdominal subcutaneous fat biopsy using fine needle aspiration and histomorphometry method |
| Change in adipose tissue metabolism assessed by phosphorylation of hormone-sensitive lipase (HSL) | From day 8 (start of the maintenance diet) to end of the intervention (day 53) | Measured via abdominal subcutaneous fat biopsy using fine needle aspiration and immunoblotting method. |
| Change in resting metabolic rate (RMR) expressed in kcal/day | From day 8 (start of the maintenance diet) to end of the intervention (day 53) | Measured using ventilated hood indirect calorimetry |
| Change in bone mineral content in grams (g) | From day 8 (start of the maintenance diet) to end of the intervention (day 53) | Measured using Dual Energy X-Ray Absorptiometry (DXA) scan |
| Change in total body water (TBW) in litres (l) | From day 11 (start of the calorie-restricted diet) to end of the intervention (day 53) | Measured using deuterium dilution, with urine sample collection |
| Change in body fat-mass percentage (%) | From day 8 (start of the maintenance diet) to end of the intervention (day 53) | Derived from Lohman's 4-compartment model (body mass; body density; total body water; and bone mineral content) |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in fasting concentration of Glucose Ketone Index (GKI) | From day 8 (start of the maintenance diet) to end of the intervention (day 53) | Calculated from glucose and ketone values |
| Change in levels of physical activity (PA) expressed as energy expenditure (kcal/day) | Every day of the study (days 1-53) | Actigraph wearable device for recording physical activity via accelerometery method |
| Change in physical activity intensity expressed as minutes spent on Moderate to vigorous (MVPA) per day | Every day of the study (days 1-53) | Measured accelerometry (with Actigraph wearable device) and calculated using energy expenditure and time spent in MVPA |
| Change in food intake | Starting from ad libitum intake (days 1-7) and every day of the study diets (day 8-52) | Measured using weighted intake record |
| Change in glycaemic control in response to caloric restriction diet | Every day of the study (days 1-53) | Measured with continuous glucose monitoring (CGM) Freestyle Libre |
| Change in fasting concentration of ketones | From day 8 (start of the maintenance diet) to end of the intervention (day 53) | Measured from capillary blood from a finger |
| Change in fasting concentration of glucose | From day 8 (start of the maintenance diet) to end of the intervention (day 53) | Measured from capillary blood from a finger |
Countries
United Kingdom
Contacts
Primary ContactAlexandra M. Johnstone, Professor
Backup ContactMarta Lonnie, Dr
Outcome results
None listed