Efficacy of probiotics and/or intermittent fasting to improve prediabetes

INTERVENTION: 1. Daily probiotic capsule (containing Lactobacillus rhamnosus HN001, at a dose of 6x10^9cfu) for 1 year plus usual healthy diet (according to standard dietary guidelines) for 1 year 2. Daily probiotic capsule (containing Lactobacillus rhamnosus HN001, at a dose of 6x10^9cfu) for 1 year plus intermittent fasting (2 out of 7 days) when 600kcal/day is consumed by women and 650kcal/day is consumed by men, for 1 year 3. Daily placebo capsule (containing corn‐derived maltodextrin with identical appearance and similar smell to the probiotic capsule) for 1 year plus intermittent fasting (2 out of 7 days) when 600kcal/day is consumed by women and 650kcal/day is consumed by men, for 1 year 4. Placebo capsule (containing corn‐derived maltodextrin with identical appearance and similar smell to the probiotic capsule) for 1 year plus usual healthy diet (according to standard dietary guidelines) for 1 year Strategies to monitor adherence with daily capsules will be empty capsule packet return and self‐reported adherence. Strategies to monitor adherence with diet will be food diary and reported adherence Guidance on intermittent fasting will include 4 x 1 hour duration group/individual sessions with a dietitian for tailored IF advice (at baseline, 2, 4 and 8 weeks), and resource list with written material, choice of apps, books and invited, closed social networking site for intermittent fasting study group members moderated by a dietitian. Participants will self‐select individual or group sessions. The intermittent fasting days will be selected by the participants as either consecutive or non‐consecutive days. No specific instruction for the 5 non‐fasting days will be given other than usual healthy diet pamphlet and recommendations regarding physical activity will be provided to both dietary groups. Guidance on usual health diet will include only a usual health diet pamphlet. No specific contact with a dietitian or additional resources will be provided. CONDITION: prediabetes type 2 diabetes PRIMARY OUTCOME: Change in HbA1c from baseline SECONDARY OUTCOME: Change in weight (measured by digital scales) Change in well being scores using SF12 Composite secondary outcome of alteration in insulin sensitivity and OGTT derived measures of beta cell function ; Insulin sensitivity is assessed using HOMA‐S ; OGTT derived measures of beta cell function uses insulinogenic index (insulin[30min]‐insulin[0min])/([glucose[30min]‐glucose[0min], and disposition index as product of 1/(fasting insulin x IGI) Composite secondary outcome of change in gut hormones and inflammatory markers (active GLP‐1, total GIP, active ghrelin, glucagon, pancreatic polypeptide, leptin, Il‐6, MCP‐1, TNF‐alpha, using Luminex magnetic bead technology of plasma samples) composite secondary outcome of any change in liver and pancreatic fat content on MRI/MRS metabolic syndrome components (blood pressure measured by sphygmomanometry, lipids measured by Roche Diagnosticc cobas analyser) from baseline INCLUSION CRITERIA: Prediabetes defined by HbA1c 41‐49 mmol/mol inclusive BMI of 30‐40 (or 27‐40 if Asian Indian ethnicity)