2.1. Study Objectives and Design
HC, anxiety, eating disorder, eating disorders, PCOS, FAI, Diabetes, depression, TG
SECONDARY, DIABETES
The primary study objective was to assess the effects of VLCD and conventional energy deficit diet on change in free androgen index (FAI), while the secondary study objective was to assess the effect of both diets on changes in weight, waist circumference, body composition, and other metabolic parameters.This open-label, randomised, comparative study in women with PCOS was performed in the Academic Diabetes, Endocrinology and Metabolism research centre at Hull Royal Infirmary. Participants were included if they were women wishing to lose weight, aged between 18 and 45 years, had a body mass index (BMI) between 30 and ≤45 kg/mParticipants attended an initial visit (Visit 1), during which they were screened against inclusion and exclusion criteria by medical history and clinical examination, routine blood tests (i.e., full blood count, liver function tests, urea and electrolytes, clotting screen), and anthropometric measurements. To screen out eating disorders and provide a baseline level for anxiety and depression, participants completed an eating disorder questionnaire, EDI-3 RF, and the Beck inventory questionnaires to assess levels of anxiety and depression. At screening, these were assessed by a psychologist, and a decision was made as to whether they should be excluded. Eligible participants were randomly assigned either a VLCD or a conventional approach of moderate energy deficit for 16 weeks (8 weeks intervention and 8 weeks of diet reintroduction and follow-up). The allocation was generated using an individual that was independent of the study team (unit manager), to ensure that the allocation was truly random and unbiased. Eligible participants were randomised on a 1:1 ratio using an online web-based randomisation service (During Visit 2 (baseline), conducted within 4 weeks of Visit 1, participants underwent anthropometric evaluation (weight, BMI, waist circumference (WC), and hip circumference (HC)) and an evaluation of body composition. They also had blood samples taken (fasting glucose, fasting insulin, HOMA-IR, total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), and high-sensitivity C-reactive protein (hs-CRP)), and their blood pressure measured. For the first eight weeks, the VLCD group was instructed to follow a prescription of 800 kcal a day (irrespective of their baseline body weight), in the form of soups and drinks made from pre-prepared sachets provided by the Cambridge Weight Plan™ company (Corby, UK). Each meal replacement drink provided 200 kcal, 21 g CHO, 15 g of protein, 3–4 g fats, and was nutritionally complete for micronutrients as they are specifically designed to be used as a sole source of nutrition and total meal replacement diets (The Cambridge Weight Plan Ltd., (Corby, UK)). Participants in this group were provided support and information regarding the consumption of the food replacement sachets, fibre supplement prescription, and fluid consumption. After these first eight weeks, participants in the VLCD arm were given a stepped return, an increase of 200 kcal/2 weeks whilst reducing meal replacement drinks until ~1600 kcal/d was reached. The energy deficit approach group acted as the control group in this trial. The kcal prescription was bespoke for each patient and calculated using the Henry equation based on gender, age, and weight to ascertain basal metabolic rate [The primary study results presented are from Visit 6, corresponding to the 8-week follow-up, during which all the measurements performed during Visit 2 (baseline) were repeated.