Do people with type 2 diabetes find continuous and intermittent low-energy diets for weight loss and diabetes remission acceptable?

BACKGROUND: The Manchester Intermittent versus Daily Diet App Study (MIDDAS) tested the feasibility and potential efficacy of two remotely delivered low-energy diet (LED) programmes (800 kcal/day) to support weight loss and remission of type 2 diabetes: continuous [CLED] (8 weeks of daily LED) and intermittent [ILED] (2 days of LED/week for 28 weeks). Understanding participant experiences can help us to understand the acceptability of LED programmes to people with type 2 diabetes, informing future programme development and implementation. METHODS: Twenty participants (10 CLED; 10 ILED) took part in interviews conducted at the end of the active weight loss phase (CLED week 12, ILED week 28). Interviews were transcribed and analysed thematically using the template analysis approach, with an a priori focus on acceptability. Four themes are presented: prospective acceptability, intervention coherence and perceived effectiveness, opportunity costs and self-efficacy. RESULTS: Both remotely supported CLED and ILED interventions appeared acceptable to participants. CLED participants found the rapid initial weight loss phase comparatively easy and highly motivating but expressed more concerns around weight maintenance. ILED participants found the more gradual weight loss initially frustrating but expressed greater confidence in their longer-term adherence. The importance of continued individualised support from healthcare professionals was emphasised, and evidence of weight loss and improvement in other medical markers through monitoring via the mobile phone app was useful. CONCLUSION: Different approaches to remotely delivered LEDs appear acceptable; therefore asking patients which approach may be more acceptable to them may be a useful way to offer individualised and tailored support.

Manchester Intermittent and Daily diet Type 1 Diabetes App Study (MIDDAS-Type 1): protocol for a randomised feasibility trial of an intermittent and continuous low-energy diet in patients with type 1 diabetes and overweight and obesity.

INTRODUCTION: Rising levels of overweight and obesity among people with type 1 diabetes (T1D) contribute to insulin resistance, dyslipidaemia, retinopathy, cardiometabolic complications and psychological morbidity. Continuous low-energy diets (CLED) providing approximately 800 kcal (3347 kJ)/day can produce significant weight loss in type 2 diabetes, and intermittent low-energy diets (ILED) may be an alternative. The Manchester Intermittent and Daily diet Type 1 Diabetes App Study (MIDDAS-Type 1) aims to assess the safety, acceptability and feasibility of remotely delivered ILED and CLED programmes for people with T1D and overweight and obesity. METHODS AND ANALYSIS: Twelve participants with T1D and body mass index ≥27.5 kg/m2 (≥25 kg/m2 in high-risk ethnic minorities) recruited from an National Health Service (NHS) trust and research register in England will be randomised to a remotely delivered CLED (n=6) or ILED (n=6) for 12 weeks. The CLED includes a daily Optifast 850 kcal (3556 kJ) 75 g carbohydrate formula diet. The ILED includes 2 days/week of Optifast and 5 days of a portion-controlled Mediterranean diet (170-250 g carbohydrate/day). Both groups will receive matched high-frequency remote support from a dietitian, nurse and psychologist via telephone and/or the Oviva app. The primary outcome will assess safety (occurrence of severe hypoglycaemia, ketonaemia, ketoacidosis and time above and below target blood glucose). Secondary outcomes include study uptake, retention, dietary adherence, acceptability, intervention delivery fidelity and potential efficacy in relation to change in weight, insulin requirements, glycated haemoglobin, lipids, insulin resistance (estimated glucose disposal rate) and quality of life. Participants will be invited for optional repeat measurements at 52 weeks. ETHICS AND DISSEMINATION: The trial protocol (V4.0/08.06.2022) was granted ethical approval by Cambridge East Research Ethics Committee (Ref: 21/EE/0014). The study will inform progression to a full-scale randomised controlled trial to test the efficacy of these programmes for patients with T1D and overweight and obesity. TRIAL REGISTRATION NUMBER: NCT04674384; Pre-results.

Randomised controlled trial of intermittent vs continuous energy restriction during chemotherapy for early breast cancer.

BACKGROUND: Excess adiposity at diagnosis and weight gain during chemotherapy is associated with tumour recurrence and chemotherapy toxicity. We assessed the efficacy of intermittent energy restriction (IER) vs continuous energy restriction (CER) for weight control and toxicity reduction during chemotherapy. METHODS: One hundred and seventy-two women were randomised to follow IER or CER throughout adjuvant/neoadjuvant chemotherapy. Primary endpoints were weight and body fat change. Secondary endpoints included chemotherapy toxicity, cardiovascular risk markers, and correlative markers of metabolism, inflammation and oxidative stress. RESULTS: Primary analyses showed non-significant reductions in weight (-1.1 (-2.4 to +0.2) kg, p = 0.11) and body fat (-1.0 (-2.1 to +0.1) kg, p = 0.086) in IER compared with CER. Predefined secondary analyses adjusted for body water showed significantly greater reductions in weight (-1.4 (-2.5 to -0.2) kg, p = 0.024) and body fat (-1.1 (-2.1 to -0.2) kg, p = 0.046) in IER compared with CER. Incidence of grade 3/4 toxicities were comparable overall (IER 31.0 vs CER 36.5%, p = 0.45) with a trend to fewer grade 3/4 toxicities with IER (18%) vs CER (31%) during cycles 4-6 of primarily taxane therapy (p = 0.063). CONCLUSIONS: IER is feasible during chemotherapy. The potential efficacy for weight control and reducing toxicity needs to be tested in future larger trials. CLINICAL TRIAL REGISTRATION: ISRCTN04156504.

Manchester Intermittent versus Daily Diet App Study (MIDDAS): A pilot randomized controlled trial in patients with type 2 diabetes.

AIMS: To test the feasibility and potential efficacy of remotely supported intermittent low-energy diets (ILEDs) and continuous low-energy diets (CLEDs) in people with type 2 diabetes (T2D) and the feasibility of a randomized controlled trial comparing the two approaches. MATERIALS AND METHODS: Seventy-nine adults with overweight/obesity and T2D (≤8 years duration) were randomized 1:1 to CLED (8 weeks/56 days of daily Optifast 820 kcal (3430 kJ) diet) or isoenergetic ILED (2 days of Optifast and 5 days of a Mediterranean diet/week for 28 weeks). Weight maintenance/continued weight loss was undertaken for the remainder of the 52 weeks. Both groups received frequent telephone or the Oviva app support. Feasibility outcomes included study uptake, retention, app usage, dietary adherence, weight loss and change in glycated haemoglobin (HbA1c) at 52 weeks. RESULTS: We enrolled 39 ILED and 40 CLED participants and 27 (69%) ILED and 30 CLED (75%) attended the 52-week follow-up. Eighty-nine per cent (70 of 79) started using the app and 86% (44 of 51) still used the app at 52 weeks. Intention-to-treat analysis at 52 weeks showed percentage weight loss was mean (95% confidence interval) -5.4% (-7.6, -3.1%) for ILED and -6.0% (-7.9, -4.0%) for CLED. HbA1c <48 mmol/mol was achieved in 42% of both groups. Mean (95% confidence interval) changes in the T2D medication effect score were 0.0008 (-0.3, 0.3) for ILED and -0.5 (-0.8, -0.3) for CLED. CONCLUSION: The study shows the feasibility and potential efficacy of remotely delivered ILED and CLED programmes for weight loss and HbA1c reduction, and the feasibility of a randomized controlled trial comparing the two approaches.

Testing a breast cancer prevention and a multiple disease prevention weight loss programme amongst women within the UK NHS breast screening programme-a randomised feasibility study.

BACKGROUND: Excess weight and unhealthy behaviours (e.g. sedentariness, high alcohol) are common amongst women including those attending breast screening. These factors increase the risk of breast cancer and other diseases. We tested the feasibility and acceptability of a weight loss/behaviour change programme framed to reduce breast cancer risk (breast cancer prevention programme, BCPP) compared to one framed to reduce risk of breast cancer, cardiovascular disease (CVD) and diabetes (T2D) (multiple disease prevention programme, MDPP). METHODS: Women aged 47-73 years with overweight or obesity (n = 1356) in the NHS Breast Screening Programme (NHSBSP) were randomised (1:2) to be invited to join a BCPP or a MDPP. The BCPP included personalised information on breast cancer risk and a web and phone weight loss/behaviour change intervention. The MDPP also included an NHS Health Check (lipids, blood pressure, HbA1c and personalised feedback for risk of CVD [QRISK2] and T2D [QDiabetes and HbA1c]). Primary outcomes were uptake and retention and other feasibility outcomes which include intervention fidelity and prevalence of high CVD and T2D risk. Secondary outcomes included change in weight. RESULTS: The BCPP and MDPP had comparable rates of uptake: 45/508 (9%) vs. 81/848 (10%) and 12-month retention; 33/45 (73%) vs. 53/81 (65%). Both programmes had a high fidelity of delivery with receipt of mean (95% CI) 90 (88-98% of scheduled calls, 91 (86-95%) of scheduled e-mails and 89 (76-102) website entries per woman over the 12-month period. The MDPP identified 15% of women with a previously unknown 10-year CVD QRISK2 of ≥ 10% and 56% with 10-year Qdiabetes risk of ≥ 10%. Both groups experienced good comparable weight loss: BCPP 26/45 (58%) and MDPP 46/81 (57%) with greater than 5% weight loss at 12 months using baseline observation carried forward imputation. CONCLUSIONS: Both programmes appeared feasible. The MDPP identified previously unknown CVD and T2D risk factors but does not appear to increase engagement with behaviour change beyond a standard BCPP amongst women attending breast screening. A future definitive effectiveness trial of BCPP is supported by acceptable uptake and retention, and good weight loss. TRIAL REGISTRATION: ISRCTN91372184 , registered 28 September 2014.

Intermittent Versus Continuous Low-Energy Diet in Patients With Type 2 Diabetes: Protocol for a Pilot Randomized Controlled Trial.

BACKGROUND: Intensive face-to-face weight loss programs using continuous low-energy diets (CLEDs) providing approximately 800 kcal per day (3347 kJ per day) can produce significant weight loss and remission from type 2 diabetes (T2D). Intermittent low-energy diets (ILEDs) and remotely delivered programs could be viable alternatives that may support patient choice and adherence. OBJECTIVE: This paper describes the protocol of a pilot randomized controlled trial to test the feasibility and potential efficacy of remotely supported isocaloric ILED and CLED programs among patients with overweight and obesity and T2D. METHODS: A total of 79 participants were recruited from primary care, two National Health Service hospital trusts, and a voluntary T2D research register in the United Kingdom. The participants were randomized to a remotely delivered ILED (n=39) or CLED (n=40). The active weight loss phase of CLED involved 8 weeks of Optifast 820 kcal/3430 kJ formula diet, followed by 4 weeks of food reintroduction. The active weight loss phase of ILED (n=39) comprised 2 days of Optifast 820 kcal/3430 kJ diet and 5 days of a portion-controlled Mediterranean diet for 28 weeks. Both groups were asked to complete 56 Optifast 820 kcal/3430 kJ days during their active weight loss phase with an equivalent energy deficit. The diets were isocaloric for the remainder of the 12 months. CLED participants were asked to follow a portion-controlled Mediterranean diet 7 days per week. ILED followed 1-2 days per week of a food-based 820 kcal/3430 kJ diet and a portion-controlled Mediterranean diet for 5-6 days per week. Participants received high-frequency (weekly, fortnightly, or monthly depending on the stage of the trial) multidisciplinary remote support from a dietitian, nurse, exercise specialist, and psychologist via telephone or the Oviva smartphone app. The primary outcomes of the study were uptake, weight loss, and changes in glycated hemoglobin at 12 months. An outcome assessment of trial retention was retrospectively added. Secondary outcomes included an assessment of adherence and adverse events. A qualitative evaluation was undertaken via interviews with participants and health care professionals who delivered the intervention. RESULTS: A total of 79 overweight or obese participants aged 18-75 years and diagnosed with T2D in the last 8 years were recruited to the Manchester Intermittent and Daily Diet Diabetes App Study (MIDDAS). Recruitment began in February 2018, and data collection was completed in February 2020. Data analysis began in June 2020, and the first results are expected to be submitted for publication in 2021. CONCLUSIONS: The outcomes of the MIDDAS study will inform the feasibility of remotely delivered ILED and CLED programs in clinical practice and the requirement for a larger-scale randomized controlled trial. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number (ISRCTN) 15394285; http://www.isrctn.com/ISRCTN15394285. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21116.

Breast cancer risk status influences uptake, retention and efficacy of a weight loss programme amongst breast cancer screening attendees: two randomised controlled feasibility trials.

BACKGROUND: Excess body weight and sub-optimal lifestyle are modifiable causes of breast cancer and other diseases. There is little evidence that behaviour change is possible within screening programmes and whether this is influenced by prior knowledge of disease risk. We determined whether breast cancer risk influences uptake, retention and efficacy of a weight control programme in the UK National Health Service Breast Screening Programme, and whether additional cardiovascular disease and type 2 diabetes risk information improves uptake and retention further. METHOD: Overweight/obese women in the UK National Health Service Breast Screening Programme identified at high, moderately increased, average and low-risk of breast cancer were randomised to receive individualised breast cancer risk information (breast cancer prevention programme), or individualised breast cancer, cardiovascular disease (QRISK2) and type 2 diabetes (QDiabetes, HbA1c) information (multiple disease prevention programme). Personalised breast cancer risk feedback was given before randomisation in Study-1, and after randomisation in Study-2. RESULTS: Recruitment was 9% (126/1356) in Study-1 and 7% (52/738) in Study-2. With respect to breast cancer risk, odds ratio of uptake for high/moderately increased vs low risk women was 1.99 (95% CI 1.24-3.17, P = 0.004) in Study-1 and 3.58 (95% CI 1.59-8.07, P = 0.002) in Study-2. Odds ratio of retention for high/moderately increased -risk vs. low risk women was 2.98 (95% CI 1.05-8.47, P = 0.041) in Study-1 and 3.88 (95% CI 1.07-14.04, P = 0.039) in Study-2. Weight loss of ≥5% at 12 months was achieved by 63% high/moderate vs. 43% low-risk women in Study-1 (P = 0.083) and 39% vs. 8% in Study-2 (P = 0.008). Uptake, retention and weight loss were equivalent in both the breast cancer prevention programme and the multiple disease prevention programme in both studies. CONCLUSIONS: Women who are informed that they are at increased breast cancer risk were significantly more likely to join and remain in the programmes and consequently lose more weight across both studies. High risk women are more likely engage in a lifetyle prevention programme and also have the greatest potential benefit fom risk reduction strategies. TRIAL REGISTRATION: ISRCTN91372184 Registered 28 September 2014.

Predictors of weight gain in a cohort of premenopausal early breast cancer patients receiving chemotherapy.

AIM: In breast cancer patients, post chemotherapy weight gain is linked with increased risk of cancer recurrence. We prospectively studied a cohort of premenopausal women receiving contemporary chemotherapy following a diagnosis of breast cancer to examine factors predicting weight increase. METHODS: Between May 2005 and January 2008, 523 patients from the Prospective Outcomes in Sporadic versus Hereditary (POSH) breast cancer study entered this sub-study comparing weight prior to chemotherapy and weight and waist/hip measurements 12-months following chemotherapy. RESULTS: Data from 380 patients were available. Mean (standard deviation [SD]) pre-treatment body mass index (BMI) was 26.3 (5.6) kg/m2; 30% women gained > 5% body weight during the study period. Lower BMI at diagnosis predicted greater subsequent post treatment weight gain (4.3% relative weight gain for those in the 1st quartile of BMI compared to 0.8% for those in the 4th quartile; r = -0.22; p < 0.001). No link to chemotherapy regimens, cigarette smoking, previous parity or chemotherapy induced amenorrhoea was noted. A total of 44% of women had central obesity (post-treatment waist measurement of ≥88 cm). CONCLUSIONS: Almost a third of premenopausal patients receiving adjuvant chemotherapy for breast cancer will gain clinically significant weight and over 40% will have central obesity 12-months following diagnosis. A greater weight gain is predicted by lower pretreatment BMI.