Efficacy, acceptability and experiences of very low energy diets in adults with type 2 diabetes

PhD ThesisAims: Type 2 diabetes (T2DM) has traditionally been regarded as an irreversible and progressive chronic condition. Recent evidence suggests that T2DM can be reversed by dietary restriction of energy intake through very low energy diets (VLEDs), indicating its potential for the treatment of one of the most prevalent chronic conditions associated with overweight and obesity around the world. VLEDs represent the most rapid, non-surgical method of weight loss (WL), but evidence showing acceptability of VLEDs and their short- and long-term efficacy in people with T2DM is limited. This PhD project aims to: 1) determine efficacy of VLEDs for weight loss and diabetes remission; 2) explore peoples` experiences with adherence to VLEDs; and 3) evaluate acceptability of VLEDs. In order to determine long-term sustainability of weight loss through VLEDs, this project further aimed to 4) explore peoples` experience with weight maintenance following weight loss through VLEDs; 5) evaluate acceptability of different plans for weight loss maintenance (WLM); and 6) explore changes in peoples` experiences from the beginning of weight loss through to weight loss maintenance. Methods: A mixed-methods approach was used to achieve the above aims. Chapter 1 provides a review of literature relating to T2DM and its treatments. Chapter 2 gives an overview of the relevant theoretical perspectives and provides a theoretical background to this PhD project. To determine efficacy and acceptability of VLEDs from the existing literature, Chapter 3 presents a systematic review of controlled trials and qualitative studies of individuals with T2DM that compared the efficacy of VLEDs with standard care, minimal interventions and other WL interventions. Chapter 4 briefly describes the Counterbalance Study, which investigated the principle determinants of long term reversal of T2DM, consisting of a 2-month WL period with VLEDs, followed by a 6-month WLM phase. The Counterbalance Study was independent of this project, but provided a platform for all qualitative work I have conducted within this PhD. In Chapters 5 and 6, I employed qualitative methods to explore experiences with a VLED amongst people with T2DM, who were engaged on the Counterbalance Study, and to determine acceptability of the VLED as an intervention for weight loss and diabetes remission. For this study, I interviewed 15 of 30 participants in the Counterbalance Study at the start and the end of the VLED. I conducted thematic analyses to find out about peoples` motivation to take part in the Counterbalance study, their experiences, their perceived barriers and facilitators to adherence with the VLED, about behavioural strategies they used v to overcome the barriers, and about their views on acceptability of the VLED. In Chapters 7 and 8, I employed the same qualitative methods and interviewed 16 and 15 participants of the Counterbalance Study after the WL and the WLM phases respectively. The interviews aimed to explore peoples` experiences with the WLM phase including their motivation, experience, barriers and facilitators to adherence, behavioural strategies they employed, and support needs at this stage. In the last empirical chapter (Chapter 9), I analysed the narratives of 11 participants who were interviewed at all three stages (baseline, end of WL and end of WLM) to identify themes of change, and to find out how peoples` experience of WL relates to experience of WLM. Results: Chapter 1 described T2DM and its complications, comorbidities and the impact of T2DM on peoples` health and the economy. It provided an overview of the current invasive and non-invasive treatments of T2DM, introduced VLEDs and the existing evidence of their efficacy and acceptability. Chapter 2 provided an overview of the psychological literature relevant to WL, WLM and eating behaviours. It introduced the behaviour change theories relevant to this thesis, discussed their strengths and weaknesses, and discussed their utility in health psychology research. This chapter also provided a springboard for hypotheses that I further explored in the qualitative studies in Chapters 5-9. The systematic review in Chapter 3 identified 9 controlled trials that were included in meta-analyses and narrative syntheses. These analyses showed that VLEDs induced greater WL than minimal interventions, standard care or low energy diets, and equal WL compared to bariatric surgery, at 3 and 6 months. It also showed that a larger difference in energy prescription between the intervention and the comparator arms is associated with larger differences in WL and fasting blood glucose levels at 3 months. No qualitative studies were suitable for inclusion in the systematic review, however acceptability of VLEDs was suggested by attrition rates, which did not differ between the VLED and the comparator groups at any measurement point. The qualitative study of peoples` experiences with and acceptability of VLED in Chapters 5 and 6 found that the VLED was perceived as generally highly acceptable among motivated individuals involved in a clinical study. The following themes reflected the experience of people with a WL through VLEDs: 1) improving health-related quality of life and 2) enhancing appearance, which were the main motives for the participants to take part in the study; 3) exceeded expectations, and 4) positive feedback loop, which stimulated the continuous motivation to adhere with the diet, and 5) facilitation of adherence, vi including behaviour-regulation strategies that the people used to overcome barriers to adherence. In Chapter 7 and 8, I extended the qualitative enquiry to the WLM phase of the Counterbalance Study: The following themes reflected the participants` experience with and acceptability of the WLM phase: 1) shifting of goals, 2) from uncertainty to regaining control, transcending which was the notion of a 3) shifting identity. Uncertainty about transition to regular food and weight maintenance and a progress towards building healthier habits and growing control of behaviour was a common denominator of the themes. To facilitate successful WLM, people used behaviour-regulation strategies of monitoring and compensation by physical activity and calorie restriction. Acceptability of the WLM phase and WLM success were related with: 1) preference for a WLM plan; and 2) satisfaction with WL and WLM outcomes. The participants also evaluated which intervention features were useful and offered suggestions for improvement of the intervention. Lastly, in Chapter 9 I identified changes in the peoples` experiences with weight management over time. The results show that success during WL and WLM is facilitated by the experience of transition from behavioural inter-dependency (with other people) to behavioural independence, and by adaptation of their mindset from a regimented one during WL to more flexible one during WLM. The interviews also showed that behaviour change can be “contagious” and other people may benefit from one`s behaviour change. The longitudinal narratives also highlighted the shift in identity people experience during the process of behaviour change. Conclusions: The empirical studies in this PhD project found that VLEDs are effective and acceptable for WL and remission of T2DM among highly motivated individuals within a clinical setting. People who struggle adhering to a VLED or WLM following a VLED may use behaviour regulation strategies identified in this PhD to facilitate adherence. Social support was an important facilitator both, WL and WLM. The WL and WLM interventions can be improved by enabling the participants to meet each other to exchange experience, tips and to support each other. Monitoring and providing feedback on performance during the WL and WLM phases stimulates continuous effort and clinical support beyond WLM might facilitate long-term sustainability of the achieved outcomes. Future studies should explore efficacy and acceptability of VLEDs in a primary care setting, with more limited resources

The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial

Background: Despite improving evidence-based practice following clinical guidelines to optimise drug therapy, Type 2 diabetes (T2DM) still exerts a devastating toll from vascular complications and premature death. Biochemical remission of T2DM has been demonstrated with weight loss around 15kg following bariatric surgery and in several small studies of non-surgical energy-restriction treatments. The non-surgical Counterweight-Plus programme, running in Primary Care where obesity and T2DM are routinely managed, produces >15 kg weight loss in 33 % of all enrolled patients. The Diabetes UK-funded Counterpoint study suggested that this should be sufficient to reverse T2DM by removing ectopic fat in liver and pancreas, restoring first-phase insulin secretion. The Diabetes Remission Clinical Trial (DiRECT) was designed to determine whether a structured, intensive, weight management programme, delivered in a routine Primary Care setting, is a viable treatment for achieving durable normoglycaemia. Other aims are to understand the mechanistic basis of remission and to identify psychological predictors of response. Methods/Design: Cluster-randomised design with GP practice as the unit of randomisation: 280 participants from around 30 practices in Scotland and England will be allocated either to continue usual guideline-based care or to add the Counterweight-Plus weight management programme, which includes primary care nurse or dietitian delivery of 12-20weeks low calorie diet replacement, food reintroduction, and long-term weight loss maintenance. Main inclusion criteria: men and women aged 20-65years, all ethnicities, T2DM 0-6years duration, BMI 27-45 kg/m2. Tyneside participants will undergo Magnetic Resonance (MR) studies of pancreatic and hepatic fat, and metabolic studies to determine mechanisms underlying T2DM remission. Co-primary endpoints: weight reduction ≥ 15 kg and HbA1c <48 mmol/mol at one year. Further follow-up at 2 years. Discussion: This study will establish whether a structured weight management programme, delivered in Primary Care by practice nurses or dietitians, is a viable treatment to achieve T2DM remission. Results, available from 2018 onwards, will inform future service strategy

Participant experiences in the Diabetes REmission Clinical Trial (DiRECT).

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

Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial

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

Efficacy of behavioural interventions for transport behaviour change: systematic review, meta-analysis and intervention coding

BACKGROUND: Reducing reliance on motorised transport and increasing use of more physically active modes of travel may offer an opportunity to address physical inactivity. This review evaluates the evidence for the effects of behavioural interventions to reduce car use for journeys made by adults and codes intervention development and content. METHODS: The review follows the procedure stated in the registration protocol published in the PROSPERO database (registration number CRD42011001797). Controlled studies evaluating behavioural interventions to reduce car use compared with no interventions or alternative interventions on outcome measures of transport behaviours taken in adult participants are included in this review. Searches were conducted on all records in Applied Social Sciences Index and Abstracts (ASSIA), Ovid Embase, Ovid Medline, Ovid PsycInfo, Scopus, Sociological Abstracts, Transportation Research Information Service (TRIS), Transportation Research International Documentation (TRID), and Web of Science databases. Peer reviewed publications in English language meeting the inclusion criteria are eligible. Methodological quality is assessed using the Cochrane Risk of Bias Tool. Interventions are categorised in terms of behavioural frameworks, theories and techniques. RESULTS: 15 full text articles are included, representing 13 unique studies, with 4895 participants and 27 intervention arms. Risk of bias across the review is appraised as considerable due to the unclear methodological quality of individual studies. Heterogeneity of included studies is considerable. Meta-analyses reveal no significant effect on reduction of frequency of car use or on increasing the proportion of journeys by alternative, more active modes of transport. There is insufficient data relating to alternative outcomes such as distance and duration which may have important health implications. Interventions were top-down but could not be described as theory-based. Intervention efficacy was associated with the use of a combination of information provision and behavioural regulation techniques. There was a lack of consideration of opportunity for change and behaviour in context. CONCLUSIONS: There is no evidence for the efficacy of existing behavioural interventions to reduce car trips included in this review. The evidence for efficacy of behavioural interventions to decrease distance and duration of car journeys is limited and inconclusive. Overall the evidence is highly heterogeneous and is at considerable risk of bias. Future research should investigate alternative behavioural interventions in high quality, controlled studies informed by existing evidence, theory, and viewers of potential users. Future intervention studies should increase scientific rigour, include objective outcome measures, and incorporate thorough evaluations as standard. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12966-014-0133-9) contains supplementary material, which is available to authorized users

Qualitative evaluation of a weight loss intervention using total diet replacement (TDR) for diabetes reversal in the Diabetes REmission Clinical Trial (DiRECT)

Aims:To provide a qualitative evaluation of a 12-week TDR stage of the DiRECT intervention delivered in UK primary care,aiming to reverse Type 2 diabetes. Methods:Participants matched for gender and socioeconomic status across trial sites were interviewed at baseline (T1), six weeks into the TDR (T2) and two weeks after food reintroduction (FR)(T3). The interviews were semi-structured, audio-recorded, transcribed verbatim and analysed using the framework approach. Results: Out of 34 intervention participants interviewed at T1, 27 were available for a follow-up at T2 and 25 were available at T3. Eight participants withdrew from the study during the TDR. Narratives of 21 participants with complete data were analysed. Desiring normality in the form of normal blood glucose levels,body mass index or the ability to wear normal clothes and eat normal food were the main drivers to taking part in the study. The TDR phase was perceived as challenging but somewhat easier than anticipated. Willpower, use of behaviour–regulation strategies,social roles, behavioural independence and social and clinical support were vital determinants of adherence. Both the TDR and FR stages required resolving cognitive and emotional goal conflicts. Transition to regular food was perceived as destabilising and required increased effort, re-designing of one’s ‘Foodrobe’ and continuous support. Summary: Experience with the weight loss stage of the DiRECT intervention for diabetes remission was positive for most participants, but clinical and social support proved essential for a successful completion

Delivering the Diabetes Remission Clinical Trial (DiRECT) in primary care: experiences of healthcare professionals

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

Clinical and metabolic features of the randomised controlled Diabetes Remission Clinical Trial (DiRECT) cohort

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 201

Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial

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

Additional file 1: Table 1. of The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial

DiRECT schedule of assessments. (DOCX 26.4 kb