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Background: The persistence of symptoms for ≥12 weeks after a COVID-19 infection is known as Long COVID (LC), a condition with unclear pathophysiology and no proven treatments to date. Living with obesity is a risk factor for LC and has symptoms which may overlap with and aggravate LC. Methods: ReDIRECT is a remotely delivered trial assessing whether weight management can reduce LC symptoms. We recruited people with LC and BMI >27kg/m 2. The intervention was delivered remotely by dietitians, with online data collection (medical and dietary history, COVID-19 infection and vaccination, body composition, LC history/symptoms, blood pressure, quality of life, sociodemographic data). Participants self-selected the dominant LC symptoms they most wanted to improve from the intervention. Results: Participants (n=234) in England (64%) and Scotland (30%) were mainly women (85%) of white ethnicity (90%), with 13% living in the 20% most deprived areas, a mean age of 46 (SD10) years, and median BMI of 35kg/m 2 (IQR 32-40). Before starting the study, 30% reported more than one COVID-19 infection (82% confirmed with one or more positive tests). LC Diagnosis was mainly by GPs (71%), other healthcare professionals (9%), or self-diagnosed (21%). The median total number of symptoms was 6 (IQR 4-8). Self-selected dominant LC symptoms included fatigue (54%), breathlessness (16%), pain (12%), anxiety/depression (1%) and "other" (17%). At baseline, 82% were taking medication, 57% reported 1+ other medical conditions. Quality of life was poor; 20% were on long-term sick leave or reduced working hours. Most (92%) reported having gained weight since contracting COVID-19 (median weight change +11.5 kg, range -11.5 to +45.3 kg). Conclusions: Symptoms linked to LC and overweight are diverse and complex. Remote trial delivery enabled rapid recruitment across the UK yet certain groups (e.g. men and those from ethnic minority groups) were under-represented. Trial registration: ISRCTN registry ( ISRCTN12595520, 25/11/2021).
Long COVID (LC, symptoms lasting 12 weeks or more after a COVID-19 infection) is a poorly understood condition, with no proven treatments. Living with obesity increases the risk of developing LC; symptoms of obesity overlap and aggravate those of LC. The ReDIRECT study tests, in people living with both LC and overweight, whether weight management can reduce LC symptoms. The study involves total diet replacement (with porridge, soups and shakes) for 12 weeks and is delivered remotely, with dietitian support via internet and/or phone. Researchers collected all data via online forms (medical and diet history, COVID-19 infection and vaccination, weight, height, LC history and symptoms, blood pressure, quality of life, and other demographic data). Each participant selected the LC symptom they most wanted to see improve. Participants (n=234) lived across the UK, were mainly women (85%) of white ethnicity (90%), with 13% living in the 20% most deprived areas. Their average age was 46 years old with an average body mass index (BMI) of 35kg/m 2. Diagnosis of LC was mainly by GPs (71%), other healthcare professionals (9%), or self-diagnosed (21%). Participants reported on average 6 symptoms each, identifying fatigue (54%), breathlessness (16%), pain (12%), anxiety/depression (1%) and "other" (17%) as the symptom they would most like to see improve. At the start of the study, most (82%) were taking medication, half (57%) reported 1+ other medical conditions. Quality of life was poor, and 20% were on long-term sick leave or reduced working hours. Most (92%) reported gaining weight since contracting COVID-19, on average +11.5 kg. The baseline characteristics of ReDIRECT study participants show that symptoms linked to LC and overweight are diverse and complex. The study being "remote" means that recruitment was rapid and across the UK, yet certain groups (e.g. men and those from ethnic minority groups) were under-represented.
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Background: Obesity is linked to higher rates of complications; lower absolute recovery of mobility, pain, and function; and increased costs of care following total knee or hip arthroplasty (TKA, THA). The aim of this prospective cohort study was to evaluate the effectiveness of a 12-week partial meal replacement (PMR) weight loss program for people awaiting TKA or THA and living with obesity (body mass index (BMI) ≥ 30 kg/m2). Methods: The intervention was delivered remotely and included a 12-week PMR plan of 1200 calories/day, incorporating two meal replacement shakes/soups and a third suitable simple meal option. The intervention support was provided through online group education sessions, one-to-one teleconsultation with a dietitian, and access to a structured PMR App with functions for goal setting and providing educational content on diet, physical activity, and behaviour changes. Results: Of the 182 patients approached, 29 provided consent to participate, 26 participants commenced the program, and 22 participants completed the 12-week PMR plan. Completers exhibited statistically significant weight loss from baseline to 12 weeks, with a paired difference of 6.3 kg (95% CI: 4.8, 7.7; p < 0.001), with 15 out of 22 (68.2%) participants achieving at least 5% weight loss. Statistically significant reductions in HbA1c and low density lipoprotein (LDL) were observed at 12 weeks compared to baseline. Moreover, a significant increase in the proportion of participants in the action and maintenance phases of the readiness to change diet, physical activity, and weight were observed at 12 weeks. The majority of program completers (18 out of 22) expressed willingness to pay for the service if offered on a long-term basis following the arthroplasty. Conclusions: This study's findings demonstrated that significant weight loss is achievable for people living with obesity awaiting arthroplasty following a 12-week PMR weight loss program. The remote delivery of the intervention was feasible and well accepted by people awaiting TKA or THA.
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BACKGROUND: In DiRECT, a randomised controlled effectiveness trial, weight management intervention after 2 years resulted in mean weight loss of 7·6 kg, with 36% of participants in remission of type 2 diabetes. Of 36 in the intervention group who maintained over 10 kg weight loss at 2 years, 29 (81%) were in remission. Continued low-intensity dietary support was then offered up to 5 years from baseline to intervention participants, aiming to maintain weight loss and gain clinical benefits. This extension study was designed to provide observed outcomes at 5 years. METHODS: The DiRECT trial took place in primary care practices in the UK. Participants were individuals aged 20-65 years who had less than 6 years' duration of type 2 diabetes, a BMI greater than 27 kg/m2, and were not on insulin. The intervention consisted of withdrawal of antidiabetic and antihypertensive drugs, total diet replacement (825-853 kcal per day formula diet for 12-20 weeks), stepped food reintroduction (2-8 weeks), and then structured support for weight-loss maintenance. After sharing the 2-year results with all participants, UK National Health Service data were collected annually until year 5 from remaining intervention participants who received low-intensity dietary support, intervention withdrawals, and the original randomly allocated groups. The primary outcome was remission of type 2 diabetes; having established in the DiRECT trial that sustained weight loss was the dominant driver of remission, this was assumed for the Extension study. The trial is registered with the ISRCTN registry, number 03267836. FINDINGS: Between July 25, 2014, and Aug 5, 2016, 149 participants were randomly assigned to the intervention group and 149 were assigned to the control group in the original DiRECT study. After 2 years, all intervention participants still in the trial (101 [68%] of 149) were approached to receive low-intensity support for a further 3 years. 95 (94%) of 101 were able to continue and consented and were allocated to the DiRECT extension group. 54 participants were allocated to the non-extension group, where intervention was withdrawn. At 5 years, DiRECT extension participants (n=85) lost an average of 6·1 kg, with 11 (13%) of 85 in remission. Compared with the non-extension group, DiRECT extension participants had more visits with HbA1c <48 mmol/mol (<6·5%; 36% vs 17%, p=0·0004), without glucose-lowering medication (62% vs 30%, p<0·0001), and in remission (34% vs 12%, p<0·0001). Original control participants (n=149) had mean weight loss 4·6 kg (n=82), and 5 (5%) of 93 were in remission. Compared with control participants, original intervention participants had more visits with weight more than 5% below baseline (61% vs 29%, p<0·0001), HbA1c below 48 mmol/mol (29% vs 15%, p=0·0002), without antidiabetic medication (51% vs 16%, p<0·0001), and in remission (27% vs 4%, p<0·0001). Of those in remission at year 2, 26% remained in remission at 5 years. Serious adverse events in the original intervention group (4·8 events per 100 patient-years) were under half those in the control group (10·2 per 100 patient-years, p=0·0080). INTERPRETATION: The extended DiRECT intervention was associated with greater aggregated and absolute weight loss, and suggested improved health status over 5 years. FUNDING: Diabetes UK.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estudios de Seguimiento , Medicina Estatal , Hipoglucemiantes/uso terapéutico , Pérdida de Peso , Reino UnidoRESUMEN
Background: We aimed to assess whether a structured weight management programme incorporating a total diet replacement (TDR) (3-5 months â¼850 kcal/day formula diet) weight loss phase is acceptable to people of South Asian ethnicity and can achieve type 2 diabetes (T2D) remissions similarly to other populations. Methods: Adults of South Asian ethnicity, aged 18-65 years, with T2D for ≤4 years, and BMI 25-45 kg/m2 were recruited from primary care and social media, and randomised to commence TDR either immediately (iTDR), or delayed (dTDR) for 3-5 months as a usual care control arm during this period. Intervention effects were tested in randomised comparisons powered to detect significant weight loss, and in an expanded observational analysis to determine remission effect size, including both iTDR and dTDR groups. Acceptability in those recruited was explored by questionnaire and weight change. Trial registration: Current Controlled Trials, ISRCTN10720065. Date of Registration 27/09/2017. Findings: Twenty-five eligible individuals were recruited. Mean baseline (SD) age was 45.8 (11.1) years, weight 88.2 (13.7) kg, BMI 32.1 (3.8) kg/m2, HbA1c 60.4 (11.3) mmol/mol, liver fat by MRI 15.6 (9.4)%. In the RCT, mean(SD) weight change after TDR was -7.7 (7.2)% in the intervention group (n = 13), and -1.2 (1.4)% in the usual-care control group (n = 12) (p = 0.005), with T2D remission achieved by 5/13, compared to 0/12 respectively (p = 0.039). In the observational study, 23/25 started TDR and 19/23 participants completed the TDR phase. Median time spent in TDR was 105 days (IQR 77-134 days). T2D remission was achieved in 10/23 (43%), and weight changes were concordant with the RCT. Overall, 8/23 (35%) lost over 10% bodyweight. Absolute liver fat proportion near halved from 15.3% at the start of TDR to 8.6% (p < 0.001). Interpretation: In UK-based South Asians, TDR-led weight loss and T2D remission rates are comparable to those observed in white cohorts, and the intervention was acceptable in most of those recruited. There is potential to further improve outcomes, but one-third lost >10% body weight, and the mechanism underpinning T2D remission appears similar, driven by weight change with loss of excess ectopic body-fat. Funding: We gratefully acknowledge funding for the MRI scans from the, Miss MJM Smith Trust (registered charity: SC040586). No other external funds were provided for this trial. NS is supported by the British Heart Foundation Research Excellence Award (RE/18/6/34217).
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BACKGROUND: Obesity is often associated with uncontrolled, difficult-to-treat asthma and increased morbidity and mortality. Previous studies suggest that weight loss may improve asthma outcomes, but with heterogenous asthma populations studied and unclear consensus on the optimal method of weight management. The Counterweight-Plus Programme (CWP) for weight management is an evidence-based, dietitian-led total diet replacement (TDR) program. RESEARCH QUESTION: Can use of the CWP compared with usual care (UC) improve asthma control and quality of life in patients with difficult-to-treat asthma and obesity? STUDY DESIGN AND METHODS: We conducted a 1:1 (CWP to UC) randomized, controlled single-center trial in adults with difficult-to-treat asthma and BMI of ≥ 30 kg/m2. The CWP was a 12-week TDR phase (800 kcal/d low-energy formula) followed by stepwise food reintroduction and weight loss maintenance for up to 1 year. The primary outcome was the change in Asthma Control Questionnaire 6 (ACQ6) score over 16 weeks. The secondary outcome was change in Asthma Quality of Life Questionnaire (AQLQ) score. RESULTS: Thirty-five participants were randomized (36 screened) and 33 attended the 16-week follow-up (n = 17 in the CWP group, n = 16 in the UC group). Overall, mean ACQ6 score at baseline was 2.8 (95% CI, 2.4-3.1). Weight loss was greater in the CWP than UC group (mean difference, -12.1 kg; 95% CI, -16.9 to -7.4; P < .001). ACQ6 score improved more in the CWP than UC group (mean difference, -0.69; 95% CI, -1.37 to -0.01; P = .048). A larger proportion of participants achieved the minimal clinically important difference in ACQ6 score with CWP than with UC (53% vs 19%; P = .041; Number needed to treat, 3 [95% CI, 1.5-26.9]). AQLQ score improvement was greater in the CWP than UC group (mean difference, 0.76; 95% CI, 0.18-1.34; P = .013). INTERPRETATION: Using a structured weight management program results in clinically important improvements in asthma control and quality of life over 16 weeks compared with UC in adults with difficult-to-treat asthma and obesity. This generalizable program is easy to deliver for this challenging phenotype. Longer-term outcomes continue to be studied. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03858608; URL: www. CLINICALTRIALS: gov.
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Asma , Programas de Reducción de Peso , Humanos , Calidad de Vida , Programas de Reducción de Peso/métodos , Estudios de Factibilidad , Obesidad/complicaciones , Obesidad/terapia , Asma/complicaciones , Asma/terapia , Dieta , Pérdida de PesoRESUMEN
AIMS: As sustained weight loss is vital for achieving remission of type 2 diabetes, we explored whether randomisation to weight loss plus maintenance in the DiRECT trial was associated with physical activity, inactivity or sleep. METHODS: Participants were randomised to either a dietary weight management programme or best-practice care. The weight management group were encouraged to increase daily physical activity to their sustainable maximum. Objective measurement was achieved using a wrist-worn GENEActiv accelerometer for 7 days at baseline, 12 and 24 months in both groups. RESULTS: Despite average weight loss of 10 kg at 12 months in the intervention (n = 66) group, there were no differences in total physical activity or inactivity compared with the control (n = 104) at any time point. However, in our exploratory analysis, those who lost more than 10% of their baseline body weight performed on average 11 mins/day more light activity than the <10% group at 24 months (p = 0.033) and had significantly lower bouts of Inactivity30min (interaction, p = 0.005) across 12 and 24 months. At 24 months, the ≥10% group had higher daily acceleration (38.5 ± 12.1 vs. 33.2 ± 11.1 mg, p = 0.020), and higher accelerations in the most active 5-hour period (59.4 ± 21.8 vs. 50.6 ± 18.3 mg, p = 0.023). Wakefulness after sleep onset decreased in the intervention group compared with the control group and also in the ≥10% weight loss group at 12 and 24 months. CONCLUSIONS: Randomisation to a successful intensive weight loss intervention, including regular physical activity encouragement, was not associated with increased physical activity although sleep parameters improved. Physical activity was greater, and night-time waking reduced in those who maintained >10% weight loss at 12 and 24 months. TRIAL REGISTRATION ISRCTN03267836.
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Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/terapia , Peso Corporal , Pérdida de Peso , Ejercicio Físico , SueñoRESUMEN
Despite evidence that formula very low-energy diets (VLED) and low-energy diets (LED) are both effective and safe as treatments for obesity and type 2 diabetes, these diets remain underutilized in the United Kingdom. The aim of this study was to explore UK dietitians' attitudes and experiences of using formula VLED and LED. A cross-sectional survey was disseminated between September 2019 and April 2020 through websites, social media platforms and dietetic networks using snowball sampling. In total, 241 dietitians responded to the online survey with 152 participants included in the final analysis (female [94.1%], mean age 40.8 years [SD 9.5]; median 12 years [interquartile range 8, 22] within dietetic practice). One hundred and nine (71.7%) participants reported currently using VLED/LED in clinical practice and 43 (28.3%) did not. Those with lower motivation and confidence in implementing VLED/LED in clinical practice were less likely to use them. Cost and adherence were the two highest reported barriers to use. Dietitians perceived VLED/LED were effective, but concerns remained about long-term effectiveness, particularly for some patient groups. Dietitians also reported that further education, funding and service infrastructure, including access to clinic space and administrative support, were required to help embed VLED/LED into routine clinical practice. With clinical services now regularly offering VLED/LED programmes in the United Kingdom, dietitians are ideally placed to provide long-term support. However, understanding, reporting and addressing the potential barriers (funding/infrastructure and education) appear to be key requirements in increasing the delivery of VLED/LED programmes nationally.
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Diabetes Mellitus Tipo 2 , Nutricionistas , Adulto , Estudios Transversales , Dieta , Femenino , Conocimientos, Actitudes y Práctica en Salud , Humanos , Encuestas y CuestionariosRESUMEN
Objectves: The Remote Diet Intervention to Reduce Long COVID Symptoms Trial (ReDIRECT) evaluates whether the digitally delivered, evidence-based, cost-effective Counterweight-Plus weight management programme improves symptoms of Long COVID in people with overweight/obesity. Methods: Baseline randomised, non-blinded design with 240 participants allocated in a 1:1 ratio either to continue usual care or to add the remotely delivered Counterweight-Plus weight management programme, which includes a Counterweight dietitian supported delivery of 12 weeks total diet replacement, food reintroduction, and long-term weight loss maintenance. Randomisation is achieved by accessing a web-based randomisation system incorporated into the study web portal developed by a registered Clinical Trials Unit. We are using an innovative approach to outcome personalisation, with each participant selecting their most dominant Long COVID symptom as their primary outcome assessed at six months. Participants in the control arm enter the weight management programme after six months. We are recruiting participants from social media and existing networks (e.g., Long COVID Scotland groups), through newspaper advertisements and from primary care. Main inclusion criteria: people with Long COVID symptoms persisting > three months, aged 18 years or above, body mass index (BMI) above 27kg/m 2 (>25kg/m 2 for South Asians). The trial includes a process evaluation (involving qualitative interviews with participants and analysis of data on dose, fidelity and reach of the intervention) and economic evaluation (within-trial and long-term cost-utility analyses). Anticipated results: The recruitment for this study started in December 2021 and ended in July 2022. Project results are not yet available and will be shared via peer-reviewed publication once the six-months outcomes have been analysed. Trial registration: Current Controlled Trials ISRCTN12595520.
While most people infected with COVID-19 recover within a short amount of time, some people continue to have symptoms for 12 weeks or longer. This condition is known as Long COVID. Roughly two-thirds of people with Long COVID are overweight, a proportion similar to that found in the general population. Being overweight may worsen symptoms such as fatigue, breathlessness and pains. Weight management programmes in adults with overweight/obesity can reduce such symptoms, however we do not know how effective intentional weight loss is to reduce symptoms for people with Long COVID. The aim of this project is to test a well-established weight management programme, delivered and supported remotely, in people with Long COVID. The trial is conducted with 240 people with Long COVID, identified through their GP, patient groups, social media, or newspaper advertisements. A total of 120 individuals will receive the personalised, professionally supported weight management programme (treatment group), and 120 participants are allocated to usual care (control group). The one-year long weight management programme involves 12 weeks of total diet replacement (TDR) using soups and shakes, followed by food reintroduction and weight maintenance. Food based alternatives are available to those who are unable, or prefer not to, follow the TDR approach. The two groups will be compared for Long COVID symptoms, weight loss, quality of life and value for money after six months. After six months, the weight management programme will also be provided for the control group. Experiences while on the programme will be documented for 12 months for all participants. People with Long COVID have been involved extensively in developing this project. Their priorities are to reduce symptoms like fatigue, breathlessness and pain. They are keen to explore if effective weight management would help their symptoms and overall functioning, especially a programme that can be followed remotely from home. A group of patients and other stakeholders has been set up to provide advice throughout the project.
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OBJECTIVE: The Diabetes Remission Clinical Trial (DiRECT) used a formula total diet replacement programme followed by structured weight loss maintenance to induce and sustain weight loss and remission of type 2 diabetes (T2D) in 36% of participants after 2 years. Nurses and dietitians delivering DiRECT in 22 primary care practices in Tyneside and Scotland provided behavioural support to participants. Participant experiences with DiRECT highlighted the key role of support by healthcare professionals (HCPs). We evaluated HCPs' experiences with DiRECT. RESEARCH DESIGN AND METHODS: Healthcare professionals delivering DiRECT were interviewed at 12 months, while general practices (GPs) were sent an implementation questionnaire. The interviews were analysed thematically. The questionnaires were analysed using frequencies and a narrative synthesis. RESULTS: Healthcare professionals representing 11 of 22 intervention practices were interviewed and 10 of 22 GPs completed questionnaires. HCPs' initial concerns over perceived potential negative intervention effects, particularly withdrawing anti-diabetes and anti-hypertensive medications, were barriers to engagement. Trust of HCPs towards the research team and perceived credibility of the study facilitated engagement and adoption. Ongoing support by research dietitians was key to the management of participants. Involvement in DiRECT inspired more focus on behaviour modification in the treatment of other people living with T2D in routine practice. CONCLUSIONS: Diabetes Remission Clinical Trial was considered highly appropriate for the management of T2D in primary care when supported by trained dietitians. Addressing limitations, including varying training needs of HCPs may improve intervention scale-up and tailoring to clinical contexts.
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Diabetes Mellitus Tipo 2/terapia , Personal de Salud/psicología , Atención Primaria de Salud , Ensayos Clínicos Controlados Aleatorios como Asunto , Medicina General , Personal de Salud/educación , Humanos , Entrevistas como Asunto , Rol Profesional , Investigación Cualitativa , Encuestas y Cuestionarios , Reino UnidoRESUMEN
INTRODUCTION: The Diabetes REmission Clinical Trial (DiRECT) has shown that sustained remission of type 2 diabetes in primary care is achievable through weight loss using total diet replacement (TDR) with continued behavioural support. Understanding participants' experiences can help optimise the intervention, support implementation into healthcare, and understand the process of behaviour change. METHODS: Thirty-four DiRECT participants were recruited into this embedded qualitative evaluation study. In-person and telephone interviews were conducted before the TDR; at week 6-8 of the TDR; 2 weeks into food reintroduction (FR); and at 1 year, to learn about participant experiences with the programme. Transcribed narratives were analysed thematically, and we used interpretation to develop overarching themes. RESULTS: Initiation of the TDR and transition to FR were challenging and required increased behavioural support. In general, adhering to TDR proved easier than the participants had anticipated. Some participants chose the optional extension of TDR. Rapid weight loss and changes in diabetes markers provided ongoing motivation. Further weight loss, behavioural support and occasional use of TDR facilitated weight loss maintenance (WLM). A process of behaviour adaptation to change following regime disruption was identified in three stages: (1) expectations of the new, (2) overcoming difficulties with adherence, and (3) acceptance of continuous effort and establishment of routines. CONCLUSIONS: The DiRECT intervention was acceptable and regularity, continuity, and tailoring of behavioural support was instrumental in its implementation in primary care. The adaptation process accounts for some of the individual variability of experiences with the intervention and highlights the need for programme flexibility.
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Restricción Calórica/métodos , Diabetes Mellitus Tipo 2/dietoterapia , Motivación/fisiología , Investigación Cualitativa , Pérdida de Peso/fisiología , Programas de Reducción de Peso/métodos , Anciano , Diabetes Mellitus Tipo 2/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
AIMS/HYPOTHESIS: Our aim was to evaluate the safety and efficacy of a planned therapeutic withdrawal of all antihypertensive and diuretic medications, on commencing a formula low-energy diet replacement, targeting remission of type 2 diabetes. METHODS: Post hoc analysis of changes in BP, antihypertensive medication prescriptions and symptoms during the initial total diet replacement phase was performed in the intervention arm of the Diabetes Remission Clinical Trial (n = 143) and in the subset (n = 69) who discontinued antihypertensive medications at the start of total diet replacement. The Counterweight-Plus total diet replacement provided about 3470 kJ/day (830 kcal) with automatic reductions in all nutrients, including sodium, to achieve marked negative energy balance and rapid weight loss over 12-20 weeks, with regular BP monitoring and an antihypertensive reintroduction protocol based on current clinical guidelines. RESULTS: Of 143 intervention group participants who commenced total diet replacement, 78 (55%) were on treatment for hypertension at baseline. The overall mean BP fell significantly from the start of total diet replacement (week 1) and was significantly lower at week 20, after total diet replacement finished, and also at 12 and 24 months. Of the 78 participants previously on treatment for hypertension, 65 (83%) stopped all antihypertensive and diuretic medications as per protocol, and four (5%) stopped some drugs. These 69 participants experienced no immediate (within the first week) change in BP, but their mean BP fell significantly from 9 weeks. No excessive rises in BP were recorded in individuals, but antihypertensive medications were reintroduced during total diet replacement to manage raised BP for 19/69 (27.5%) participants, mostly within the first 3-7 weeks, despite some weight loss. Reintroduction of antihypertensive medications was necessary for 5/19 participants previously on one drug, and for 14/19 previously on two or more drugs. Of the 69 who stopped antihypertensives, 19 (28%) remained off medications at 24 months. Among the 53 participants who achieved sustained remissions of diabetes at 24 months (with a mean weight loss of 11.4 kg), 31 had been previously treated for hypertension. Twenty-seven stopped medication at baseline, and 15/27 required reintroduction of antihypertensive medications. Mild to moderate dizziness, suggesting some postural hypotension, was reported during total diet replacement by 51 participants, 15 of whom had recorded dizziness at baseline prior to starting total diet replacement, with nine of these on antihypertensive or diuretic medications. CONCLUSIONS/INTERPRETATION: Replacing antihypertensive medications with a 3470 kJ/day (830 kcal) diet to induce weight loss reduces BP substantially and may increase mild dizziness. It is safe to stop antihypertensives, but BP should be monitored regularly, particularly for those taking two or more antihypertensives, as over two-thirds will require reintroduction of some medications. Long-term support to maintain weight loss is vital. TRIAL REGISTRATION: ISRCTN registry, number 03267836.
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Diabetes Mellitus Tipo 2 , Hipertensión , Antihipertensivos/uso terapéutico , Presión Sanguínea , Humanos , Hipertensión/tratamiento farmacológico , Pérdida de Peso/fisiologíaRESUMEN
BACKGROUND: Weight loss maintenance (WLM) is critical for sustaining type 2 diabetes (T2D) remission, but poorly evidenced. We evaluated brief return to formula low-energy-diet (LED) as relapse treatments (RTs) during the WLM phase of the Diabetes Remission Clinical Trial (DiRECT). METHODS: This post-hoc evaluation included all participants commencing the WLM phase of DiRECT. The protocol offered RT when regain of >2 kg occurred. RESULTS: In total, 123/149 (83%) DiRECT intervention participants commenced the WLM phase after 26 (17%) had withdrawn prior to the WLM phase. Most participants [99/123 (80%)] regained >2 kg during the WLM phase, among whom 60/99 (61%) were recorded as using RT and 39/99 (39%) not using any RT. At baseline, RT users had a higher mean (SD) body mass index [35.8 (4.9) kg m-2 vs. 33.8 (3.9) kg m-2 , p = 0.0231] and had greater social deprivation (P = 0.0003) than non-users, although otherwise the groups were similar. Weight loss ≥ 2k g was achieved in 30/93 (32%) of RT attempts. At 2 years, those regaining >2 kg and using RT (n = 60) had mean (SD) weight losses of 7.4 (6.1) kg, with 25 (42%) remissions and 7 (12%) programme withdrawals. Those regaining >2 kg but not using RT (n = 39) had weight losses of 8.8 (6.0) kg, with 21 (54%) remissions and 4 (10%) programme withdrawals (all not significant). Twelve participants were never recorded as having regained >2 kg or using RTs and, at 2 years, their weight losses were 12.9 (9.2) kg, with 4 (33%) remissions and 8 (67%) programme withdrawals. CONCLUSIONS: Most people with T2D experience weight regain >2 kg during the 2 years after substantial weight loss with a LED. Only one-third of RTs corrected their 2-kg regain, resulting in similar weight losses, remissions and programme withdrawals at 2 years compared to those not using RTs; however, both groups had weight losses below those not recorded as regaining >2 kg during WLM.
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Mantenimiento del Peso Corporal , Restricción Calórica , Diabetes Mellitus Tipo 2/dietoterapia , Cooperación del Paciente , Prevención Secundaria/métodos , Programas de Reducción de Peso/métodos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Recurrencia , Aumento de Peso , Pérdida de PesoRESUMEN
AIM: To investigate whether appetite-related hormones were predictors of weight regain in the Diabetes Remission Clinical Trial (DiRECT). MATERIALS AND METHODS: DiRECT is a cluster-randomized clinical trial, designed to assess the effect of weight loss on type 2 diabetes remission. For this post hoc analysis, data were available for 253 (147 interventions, 106 controls) individuals with type 2 diabetes (age 53.6 ± 7.5 years, body mass index 34.7 ± 4.4 kg/m2 , 59% men). Intervention participants received a 24-month weight management programme, and controls remained on usual diabetes care. Fasting plasma concentrations of leptin, ghrelin, glucagon-like peptide-1 and peptide YY were measured at baseline, 12 months and 24 months in all participants, and at 5 months in a subset of participants in the intervention (n = 56) and control groups (n = 22). Potential predictors were examined using multivariable linear regression models. RESULTS: The intervention group lost 14.3 ± 6.0% body weight at 5 months but regained weight over time, with weight losses of 10.0 ± 7.5% at 12 months and 7.6 ± 6.3% at 24 months. Weight loss in controls was 1.1 ± 3.7% and 2.1 ± 5.0% at 12 and 24 months, respectively. Body weight increased by 2.3% (95% confidence interval [CI] 0.4, 4.1; P = 0.019) between 12 and 24 months for every 1-ng/mL increase in ghrelin between baseline and 12 months, and weight regain between 12 and 24 months was increased by 1.1% (95% CI 0.2, 2.0; P = 0.023) body weight for every 1-ng/mL increase in ghrelin at 12 months. CONCLUSION: The rise in ghrelin (but not any other measured hormone) during diet-induced weight loss was a predictor of weight regain during follow-up, and concentrations remained elevated over time, suggesting a small but significant compensatory drive to regain weight. Attenuating the effects of ghrelin may improve weight-loss maintenance.
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AIM: To investigate whether appetite-related hormones were predictors of weight regain in the Diabetes Remission Clinical Trial (DiRECT). MATERIALS AND METHODS: DiRECT is a cluster-randomised clinical trial designed to assess the effect of weight-loss on type 2 diabetes remission. For this post hoc analysis, data were available for 253 (147 interventions, 106 controls) individuals with type 2 diabetes (aged 53.6±7.5 years, BMI 34.7±4.4 kg/m2, 59% males). Intervention participants received a 24-month weight-management programme and controls remained on usual diabetes care. Fasting plasma concentrations of leptin, ghrelin, GLP-1, and PYY were measured at baseline, 12 and 24-months in all participants, and at 5-months in a subset of interventions (n=56) and controls (n=22). Potential predictors were examined using multivariable linear regression models. RESULTS: The intervention group lost 14.3±6.0% body-weight at 5-months but regained over time, with weight-losses of 10.0±7.5% at 12-months and 7.6±6.3% at 24-months. Weight-loss in controls was 1.1±3.7% and 2.1±5.0% at 12 and 24-months, respectively. Body-weight increased by 2.3% [95% CI: 0.4,4.1]; p=0.019) between 12 and 24-months for every 1 ng/ml increase in ghrelin between baseline and 12-months, and weight regain between 12 and 24-months was increased by 1.1% (95% CI: 0.2,2.0; p=0.023) body-weight for every 1 ng/ml increase in ghrelin at 12-months. CONCLUSION: The rise in ghrelin (but not any other measured hormone) during diet-induced weight-loss was a predictor of weight regain during follow-up, and concentrations remained elevated over time, suggesting a small but significant compensatory drive to regain weight. Attenuating the effects of ghrelin may improve WLM. This article is protected by copyright. All rights reserved.
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BACKGROUND/OBJECTIVES: Weight-loss maintenance is challenging, and few succeed in the long term. This study aimed to explain how appetite-related hormones, adaptive thermogenesis, perceived hunger and stress influence weight-loss maintenance. SUBJECTS/METHODS: Fifteen adult women (age, 46.3 ± 9.5 years; BMI, 39.4 ± 4.3 kg/m2) participated in a 24-month intervention, which included 3-5 months total diet replacement (825-853 kcal/d). Body weight and composition (Magnetic Resonance Imaging), resting metabolic rate (indirect calorimetry), and fasting plasma concentration of leptin, ghrelin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and growth differentiation factor 15 (GDF-15) were measured at baseline and after weight loss, around 6 months. Perceptions relating to weight-loss maintenance were explored using qualitative interviews. RESULTS: Mean (SD) changes in body weight (-13.8 ± 6.3 kg) and total adipose tissue (-11.5 ± 4.9 kg) were significant (P < 0.001). Weight loss was associated with a significant reduction in resting metabolic rate (-291 ± 226 kcal/day, P < 0.001) and adaptive thermogenesis (-150 ± 162 kcal/day, P = 0.003), reduction in leptin (P < 0.001) and GLP-1 (P = 0.015), an increase in ghrelin (P < 0.001), and no changes in PYY and GDF-15. Weight regain between 6 and 24 months (6.1 ± 6.3 kg, P < 0.05) was negatively correlated with GLP-1 at baseline (r = −0.7, P = 0.003) and after weight loss (r = -0.7, P = 0.005). Participants did not report increased hunger after weight loss, and stress-related/emotional eating was perceived as the main reason for regain. CONCLUSIONS: Weight regain is more likely with lower fasting GLP-1 at baseline and following weight loss, but psychological aspects of eating behaviour appear as important in attenuating weight-loss maintenance.
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Apetito , Pérdida de Peso , Adulto , Femenino , Ghrelina , Humanos , Hambre , Persona de Mediana Edad , Péptido YY , TermogénesisRESUMEN
BACKGROUND: The DiRECT trial assessed remission of type 2 diabetes during a primary care-led weight-management programme. At 1 year, 68 (46%) of 149 intervention participants were in remission and 36 (24%) had achieved at least 15 kg weight loss. The aim of this 2-year analysis is to assess the durability of the intervention effect. METHODS: DiRECT is an open-label, cluster-randomised, controlled trial done at primary care practices in the UK. Practices were randomly assigned (1:1) via a computer-generated list to provide an integrated structured weight-management programme (intervention) or best-practice care in accordance with guidelines (control), with stratification for study site (Tyneside or Scotland) and practice list size (>5700 or ≤5700 people). Allocation was concealed from the study statisticians; participants, carers, and study research assistants were aware of allocation. We recruited individuals aged 20-65 years, with less than 6 years' duration of type 2 diabetes, BMI 27-45 kg/m2, and not receiving insulin between July 25, 2014, and Aug 5, 2016. The intervention consisted of withdrawal of antidiabetes and antihypertensive drugs, total diet replacement (825-853 kcal per day formula diet for 12-20 weeks), stepped food reintroduction (2-8 weeks), and then structured support for weight-loss maintenance. The coprimary outcomes, analysed hierarchically in the intention-to-treat population at 24 months, were weight loss of at least 15 kg, and remission of diabetes, defined as HbA1c less than 6·5% (48 mmol/mol) after withdrawal of antidiabetes drugs at baseline (remission was determined independently at 12 and 24 months). The trial is registered with the ISRCTN registry, number 03267836, and follow-up is ongoing. FINDINGS: The intention-to-treat population consisted of 149 participants per group. At 24 months, 17 (11%) intervention participants and three (2%) control participants had weight loss of at least 15 kg (adjusted odds ratio [aOR] 7·49, 95% CI 2·05 to 27·32; p=0·0023) and 53 (36%) intervention participants and five (3%) control participants had remission of diabetes (aOR 25·82, 8·25 to 80·84; p<0·0001). The adjusted mean difference between the control and intervention groups in change in bodyweight was -5·4 kg (95% CI -6·9 to -4·0; p<0·0001) and in HbA1c was -4·8 mmol/mol (-8·3 to -1·4 [-0·44% (-0·76 to -0·13)]; p=0·0063), despite only 51 (40%) of 129 patients in the intervention group using anti-diabetes medication compared with 120 (84%) of 143 in the control group. In a post-hoc analysis of the whole study population, of those participants who maintained at least 10 kg weight loss (45 of 272 with data), 29 (64%) achieved remission; 36 (24%) of 149 participants in the intervention group maintained at least 10 kg weight loss. Serious adverse events were similar to those reported at 12 months, but were fewer in the intervention group than in the control group in the second year of the study (nine vs 22). INTERPRETATION: The DiRECT programme sustained remissions at 24 months for more than a third of people with type 2 diabetes. Sustained remission was linked to the extent of sustained weight loss. FUNDING: Diabetes UK.
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Continuidad de la Atención al Paciente , Diabetes Mellitus Tipo 2/terapia , Atención Primaria de Salud/organización & administración , Programas de Reducción de Peso/métodos , Adulto , Anciano , Análisis por Conglomerados , Continuidad de la Atención al Paciente/organización & administración , Continuidad de la Atención al Paciente/normas , Continuidad de la Atención al Paciente/estadística & datos numéricos , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Atención Primaria de Salud/estadística & datos numéricos , Inducción de Remisión , Factores de Tiempo , Reino Unido/epidemiología , Programas de Reducción de Peso/estadística & datos numéricos , Adulto JovenRESUMEN
AIMS/HYPOTHESIS: Substantial weight loss in type 2 diabetes can achieve a return to non-diabetic biochemical status, without the need for medication. The Diabetes Remission Clinical Trial (DiRECT), a cluster-randomised controlled trial, is testing a structured intervention designed to achieve and sustain this over 2 years in a primary care setting to determine practicability for routine clinical practice. This paper reports the characteristics of the baseline cohort. METHODS: People with type 2 diabetes for <6 years with a BMI of 27-45 kg/m2 were recruited in 49 UK primary care practices, randomised to either best-practice diabetes care alone or with an additional evidence-based weight management programme (Counterweight-Plus). The co-primary outcomes, at 12 months, are weight loss ≥15 kg and diabetes remission (HbA1c <48 mmol/mol [6.5%]) without glucose-lowering therapy for at least 2 months. Outcome assessors are blinded to group assignment. RESULTS: Of 1510 people invited, 423 (28%) accepted; of whom, 306 (72%) were eligible at screening and gave informed consent. Seven participants were later found to have been randomised in error and one withdrew consent, leaving 298 (176 men, 122 women) who will form the intention to treat (ITT) population for analysis. Mean (SD) age was 54.4 (7.6) years, duration of diabetes 3.0 (1.7) years, BMI 34.6 (4.4) kg/m2 for all participants (34.2 (4.2) kg/m2 in men and 35.3 (4.6) kg/m2 in women) and baseline HbA1c (on treatment) 59.3 (12.7) mmol/mol (7.6% [1.2%]). The recruitment rate in the intervention and control groups, and comparisons between the subgroups recruited in Scotland and England, showed few differences. CONCLUSIONS/INTERPRETATION: DiRECT has recruited a cohort of people with type 2 diabetes with characteristics similar to those seen in routine practice, indicating potential widespread applicability. Over 25% of the eligible population wished to participate in the study, including a high proportion of men, in line with the prevalence distribution of type 2 diabetes. TRIAL REGISTRATION: www.controlled-trials.com/ISRCTN03267836 ; date of registration 20 December 2013.
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Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/terapia , Adulto , Anciano , Glucemia/metabolismo , Estudios de Cohortes , Diabetes Mellitus Tipo 2/sangre , Inglaterra , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Calidad de Vida , Escocia , Pérdida de Peso , Adulto JovenRESUMEN
BACKGROUND: Type 2 diabetes is a chronic disorder that requires lifelong treatment. We aimed to assess whether intensive weight management within routine primary care would achieve remission of type 2 diabetes. METHODS: We did this open-label, cluster-randomised trial (DiRECT) at 49 primary care practices in Scotland and the Tyneside region of England. Practices were randomly assigned (1:1), via a computer-generated list, to provide either a weight management programme (intervention) or best-practice care by guidelines (control), with stratification for study site (Tyneside or Scotland) and practice list size (>5700 or ≤5700). Participants, carers, and research assistants who collected outcome data were aware of group allocation; however, allocation was concealed from the study statistician. We recruited individuals aged 20-65 years who had been diagnosed with type 2 diabetes within the past 6 years, had a body-mass index of 27-45 kg/m2, and were not receiving insulin. The intervention comprised withdrawal of antidiabetic and antihypertensive drugs, total diet replacement (825-853 kcal/day formula diet for 3-5 months), stepped food reintroduction (2-8 weeks), and structured support for long-term weight loss maintenance. Co-primary outcomes were weight loss of 15 kg or more, and remission of diabetes, defined as glycated haemoglobin (HbA1c) of less than 6·5% (<48 mmol/mol) after at least 2 months off all antidiabetic medications, from baseline to 12 months. These outcomes were analysed hierarchically. This trial is registered with the ISRCTN registry, number 03267836. FINDINGS: Between July 25, 2014, and Aug 5, 2017, we recruited 306 individuals from 49 intervention (n=23) and control (n=26) general practices; 149 participants per group comprised the intention-to-treat population. At 12 months, we recorded weight loss of 15 kg or more in 36 (24%) participants in the intervention group and no participants in the control group (p<0·0001). Diabetes remission was achieved in 68 (46%) participants in the intervention group and six (4%) participants in the control group (odds ratio 19·7, 95% CI 7·8-49·8; p<0·0001). Remission varied with weight loss in the whole study population, with achievement in none of 76 participants who gained weight, six (7%) of 89 participants who maintained 0-5 kg weight loss, 19 (34%) of 56 participants with 5-10 kg loss, 16 (57%) of 28 participants with 10-15 kg loss, and 31 (86%) of 36 participants who lost 15 kg or more. Mean bodyweight fell by 10·0 kg (SD 8·0) in the intervention group and 1·0 kg (3·7) in the control group (adjusted difference -8·8 kg, 95% CI -10·3 to -7·3; p<0·0001). Quality of life, as measured by the EuroQol 5 Dimensions visual analogue scale, improved by 7·2 points (SD 21·3) in the intervention group, and decreased by 2·9 points (15·5) in the control group (adjusted difference 6·4 points, 95% CI 2·5-10·3; p=0·0012). Nine serious adverse events were reported by seven (4%) of 157 participants in the intervention group and two were reported by two (1%) participants in the control group. Two serious adverse events (biliary colic and abdominal pain), occurring in the same participant, were deemed potentially related to the intervention. No serious adverse events led to withdrawal from the study. INTERPRETATION: Our findings show that, at 12 months, almost half of participants achieved remission to a non-diabetic state and off antidiabetic drugs. Remission of type 2 diabetes is a practical target for primary care. FUNDING: Diabetes UK.