Month: November 2021

Professor Anthony Leeds, senior fellow at the Parker Institute, Copenhagen, and chair of TDMR Europe reviewed the characteristics and mechanism of action of total diet replacement in TDMR Europe’s webinar “Total Diet Replacement: exploring sustainable weight loss and health benefits, including diabetes remission and prevention” held on 27th October 2021. He noted that Total Diet Replacement (TDR) offers a potential additional intervention, especially to bridge the gap between weight losses of 3 to 5kg with conventional reducing diets and losses in excess of 20kg with bariatric surgery. TDR delivers fast rates of weight loss (average 1.3 to 1.5kg/week) which is highly motivating for users and can be delivered in specialist units and primary care and community settings. Safety profiles are fully published and cost-effectiveness especially in older and heavier people has been demonstrated partly through reduced costs of medications.

Prof Leeds added ‘The recent publication by Chaitong Churuangsuk and colleagues in Glasgow of a review of meta-analyses of randomised controlled trials of TDR for diabetes remission concluded that an initial weight reduction with a total diet replacement was the most effective way to achieve type 2 diabetes remission. The challenge of achieving weight maintenance afterwards is addressed by some longer-term maintenance trials such as the DiRECT diabetes remission trial and the LIGHT trial on elderly people with obesity and osteoarthritis in Copenhagen. There are published reports including one by GeorgeThom and colleagues, identifying the characteristics of ‘maintainers’ (recognising maintenance as a lifestyle not a diet, flexible control and diet vigilance) and ‘regainers’ (life stresses, negative mood states, motivational conflicts and self-regulation inconsistency) indicating a clear need to develop proven methods to address the challenges experienced by those who regain weight more easily than others after a good initial weight loss.’

 On 27th October, TDMR Europe’s online seminar brought together industry stakeholders, academics and others and showed the potential role of TDR in bringing down the incidence of obesity and severity of weight related comorbidities, such as type 2 diabetes, cardiovascular disease risk factors, osteoarthritis, and obstructive sleep apnoea. The recording of the webinar will be available soon on the TDMR Europe website.

More information on TDR is available here.

Professor Anthony Leeds is senior visiting fellow at the Parker Institute, Frederiksberg Hospital, Copenhagen; adjunct professor at the International Medical University, Kuala Lumpur, Malaysia and visiting fellow at the University of Glasgow.  He chairs TDMR Europe.

 

Abstract

Total diet replacement – amount, safety and sustainability of weight loss

Parker Institute, Frederiksberg Hospital, Copenhagen, Denmark;

School of Medicine, Dentistry and Nursing, University of Glasgow, Scotland;

School of Health Sciences, International Medical University, Malaysia.

Formula 800kcal/d low calorie diets (LCD) are composed of nutritionally complete soups, shakes bars and other products, formulated to provide all needed vitamins, minerals, essential fats and protein. They are always offered with a behavioural component and physical activity guidance. When used exclusively LCD are defined as Total diet replacements (TDR) and facilitate 1–2kg weight loss weekly with metabolic improvement in glucose, insulin, blood lipids and blood pressure in people with pre-diabetes, early diabetes, advanced diabetes, osteoarthritis, psoriasis, obstructive sleep apnoea, and heart disease.

In 2016 the American Association of Clinical Endocrinologists and American College of Endocrinology Guidelines recommended target weight losses for a range of obesity co-morbidities for example 5-15% or more to achieve remission or medication dose reduction or improved control in type 2 diabetes.

Very low-calorie diets (<800kcal/d) can give rapid weight-loss especially in men, for example Johansson showed an average 18kg weight loss in 9 weeks in men with moderate and severe obstructive sleep apnoea. Christensen showed that 800kcal/d TDRs typically gave an average eight-week weight loss of 10-12 kg in elderly people with knee osteoarthritis and subsequently showed that one meal replacement or intermittent use of 800kcal/d TDR maintained most of the weight lost over 3 years in those who stayed in the programme. Continued behavioural support, physical activity and ‘rescue packages’ can play an important part in weight maintenance.

Low-calorie and very low-calorie diets are sometimes associated with fatigue initially, constipation, dizziness, and a very small increased risk of gout and very rarely gallstone events. Adjustment of anti-diabetes and antihypertension drugs has been successfully demonstrated in DiRECT and in another GP led study (DROPLET) published with medication adjustment guidelines.

References

Brown A, Leeds AR Very low-energy and low-energy formula diets: Effects on weight loss, obesity co-morbidities and type 2 diabetes remission – an update on the evidence for their use in clinical practice   Nutrition Bulletin 2019 44 (1) 7-24 First published: 20 February 2019| https://onlinelibrary.wiley.com/doi/epdf/10.1111/nbu.12372

Garvey WTE et al. American Association of Clinical Endocrinologists and American College of Endocrinology Comprehensive Clinical Practice Guidelines. Endocrine Practice 2016 22 (S3) 2016 1  DOI:10.4158/EP161365.GL

Christensen P, Bliddal, Riecke BF, et al Comparison of a low-energy diet and a very low-energy diet in sedentary obese individuals: a pragmatic randomized controlled trial Clinical Nutrition 2011 1  31- 40 https://onlinelibrary.wiley.com/doi/epdf/10.1111/j.1758-8111.2011.00006.x

 

Dr Nerys Astbury, Senior Research Fellow at the Nuffield Department of Primary Care Sciences, University of Oxford reviewed the results of the DROPLET trial and three-year follow up in TDMR Europe’s webinar “Total Diet Replacement: exploring sustainable weight loss and health benefits, including diabetes remission and prevention” held on 27^th October 2021.  Dr Astbury showed that delivery of Total Diet Replacement (TDR) and subsequent weight maintenance was feasible and cost-effective in a primary care setting, and that some weight loss was maintained in some participants for up to three years.

Professor Anthony Leeds, chairman of TDMR Europe said: ‘The DROPLET study showed clearly that a total diet replacement weight loss and maintenance programme could be delivered within a primary care setting in collaboration with a commercial TDR provider working in a community setting. Medical management was maintained by the GPs. The cost-effectiveness analysis showed that delivered in this setting the programme was most cost-effective among heavier people and among middle-aged and older people.’

On 27^th October, TDMR Europe’s online seminar brought together industry stakeholders, academics and others and showed the potential role of TDR in bringing down the incidence of obesity and severity of weight related comorbidities, such as type 2 diabetes, cardiovascular disease risk factors, osteoarthritis, and obstructive sleep apnoea. The recording of the webinar will be available soon on the TDMR Europe website.

More information on TDR is available here.

Dr Nerys Astbury is Senior Research Fellow in Diet & Obesity at the Nuffield Department of Primary Care Health Sciences, University of Oxford and one of the DROPLET trial investigators.  The DROPLET trial was designed to explore if the provision of a low-energy total diet replacement programme offered by GP’s was a clinically feasible and cost-effective method to help people with obesity manage their weight in the community.

The DROPLET clinical trial was funded by an investigator-initiated research grant from Cambridge Weight Plan UK Ltd to the University of Oxford. The three-year follow up was funded by National Institute of Health Research Applied Research Collaboration at Oxford Health NHS Foundation Trust.  Some research team members were also supported by the Oxford NIHR Biomedical Research Centre.

 

Total Diet Replacement in a primary care/community setting – sustainability and health economics

Nerys Astbury, DROPLET research team, University of Oxford, England

Abstract

DROPLET was a randomised controlled trial testing the clinical effectiveness of primary care referral to total diet replacement (TDR) weight loss programme for the treatment of obesity. 272 participants from ten primary care practices were individually randomised to usual care (UC) weight management (n = 138) or a TDR weight loss programme (n = 134), delivered by lay counsellors in the community over 6 months. At one year weight loss in the TDR group was -10.7 kg and UC was -3.1 kg, a difference of 7.2kg (95%CI: -9.4 to -4.9) (1).

Participants were re-contacted and weighed approximately 3 years after randomisation. We used a linear mixed-effect model, adjusting for baseline weight, to assess the change in weight from baseline.

Of the 272 participants who took part in the DROPLET study, weight was recorded in 66% people (83 UC, 96 TDR). Mean (SD) age was 51 years (11.7) and 99 (55%) were female. Mean (SD) weight change from baseline was -2.7 kg (7.7) in UC and -6.3kg (9.1) in TDR group, an adjusted difference of -3.3kg (95% CI: -5.2 to -1.5; P=0.0005).

Primary care referral to a TDR programme in the community for the treatment of obesity leads to greater weight loss than usual care which is sustained for at least 3 years. Even without additional support after the initial weight loss intervention, two thirds of the weight loss achieved at one year was still apparent two years later.

References:

Astbury NM, Aveyard P, Nickless A, et al Doctor Referral of Overweight People to Low Energy total diet replacement Treatment (DROPLET): pragmatic randomised controlled trial.  BMJ 2018; 362:k3760 http://dx.doi.org/10.1136/bmj.k3760

Kent S, Aveyard P, Astbury N, et al Is Doctor referral to a low-energy total diet replacement program cost-effective for the routine treatment of obesity?
Obesity 2019 27, 391-398  https://doi.org/10.1002/oby.22407

Astbury NM, Edwards RM, Ghebretinsea F, et al Extended follow-up of a short total diet replacement programme: results of the Doctor Referral of Overweight People to Low Energy total diet replacement Treatment (DROPLET) randomised controlled trial at 3 years. Int J Obes (Lond) 2021 45(11): 2432-2438. doi: 10.1038/s41366-021-00915-1

Mike Lean, Professor of Human Nutrition at the University of Glasgow reviewed the DiRECT trial of Total Diet Replacement (TDR) weight loss with behavioural and lifestyle guidance followed by weight maintenance to achieve diabetes remission in people with type 2 diabetes in TDMR Europe’s recent webinar. Prof Lean showed that the combination of significant weight loss using TDR followed by weight maintenance can achieve 10-15kg weight loss and diabetes remission in a proportion of participants.  Two-year follow up results were presented and information about the roll-out of remission programmes was given.

Professor Anthony Leeds, chair of TDMR Europe said ‘The team in Glasgow lead by Professor Lean in association with Professor Roy Taylor and colleagues at the University of Newcastle have marked the centenary of the discovery of insulin with landmark papers that may revolutionise the management of diabetes as much as did the first effective use of an insulin extract around one hundred years ago. Revolutions don’t happen quickly.  A huge number of first-rate clinical trials and investigations of mechanism has been undertaken over a number of years, along with health economic analyses of the cost benefits of this intervention. Translation into practice is underway in several countries.  Diabetes and its complications cause much human suffering and cost an appreciable proportion of national drug budgets, and are becoming increasingly prevalent, very rapidly. This may be slowed and the trend reversed over the coming five years or so by introducing effective weight loss and weight maintenance programmes.’

On 27th October, TDMR Europe’s online seminar brought together industry stakeholders, academics and others and showed the potential role of TDR in bringing down the incidence of obesity and severity of weight related comorbidities, such as type 2 diabetes, cardiovascular disease risk factors, osteoarthritis, and obstructive sleep apnoea. The recording of the webinar will be available soon on the TDMR Europe website.

More information on TDR is available here.

Professor Mike Lean is a principal investigator of the DiRECT study, chair of the department of human nutrition at the University of Glasgow, visiting professor at Otago University and visiting professor at the University of Sydney. He is a keen fiddle-player and climbs mountains.

FUNDING – The DiRECT trial was funded as a Strategic Research Initiative by Diabetes

1. The Cambridge Weight Plan donated all formula diet products.

 

Diabetes remission – update on global roll-out of remission programmes

Abstract

Many people can achieve “remission” from early type 2 diabetes (T2D) through weight loss from dietary changes. Remission (reducing blood sugar and HbA1c to non-diabetic levels without medication) improves wellbeing, reduces heart disease risks and reduces healthcare costs.

DiRECT, and DIADEM-1, both RCT trials, achieved mean weight losses >10kg at 12 months using established formula diets (low-calorie but nutrient-complete soups and shakes), and remissions for 46% or 61% of participants on an Intention to Treat (ITT) basis. Weight loss >10 kg led to remissions for 70-80%, which were well maintained at 2 years by keeping that weight off. Blood pressures fell, so about 30% were able to remain off medication. NAFLD, which often accompanies T2D, improved similarly.  A subset underwent mechanistic studies and MRI, which demonstrated high ectopic fat contents in liver and pancreas at baseline, which fell to normal (restoring normal pancreas morphology) with weight loss and remission.  Insulin production capacity was 50% at baseline, but rose to normal in those sustaining remissions.  Serious adverse events were fewer in the intervention group, and total medical care costs fell, so in a formal health economic analysis, the intervention helped people live longer, feel better and cost less.

Although proponents of low-carb and ketogenic diets are claiming that remission of T2D can be achieved, there is no RCT evidence, and the observational studies show remission rates on 12-20% on an ITT basis.

The DiRECT intervention (Counterweight-Plus) was delivered entirely in the community, and highly cost-effective (predicted cost-saving over >5 years).  However, weight loss maintenance is not easy and many need support to manage stress and cravings, emotional eating and handling relationships with others. Face-to-face support from healthcare professionals proved effective, but has high demands on staff and patients. The same diet intervention is now delivered remotely (via app or online, with video or telephone support) with similar weight loss results, but reduced demands on patients and staff time, and being cheaper can potentially reach more people.

Driven partly by the wishes of people currently living with T2D and partly by the cost-effectiveness analysis of DiRECT, interventions based on the ‘DiRECT Principles’ are now being provided within routine medical care.  In Scotland the evidence-based highly cost-effective Counterweight-Plus programme is provided in every NHS Scotland Health Board.  NHS England is instead offering a number of other interventions to an evaluated 5000 patients.  These programmes aimed at remission of T2D are also available, and popular, remotely-delivered to the public.

References:

1. Lean MEJ et al. Primary care-led weight management for remission of type 2 diabetes (DiRECT): an open-label, cluster-randomised trial. The Lancet 391, 541-551 (2018)
2. Lean MEJ et al. 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. The Lancet Diabetes & Endocrinology, 7, 344-355 (2019)
3. Thom G et al. Predictors of type 2 diabetes remission in the Diabetes Remission Clinical Trial (DiRECT). Diabetic Medicine, 38, 8, e14395 (2020)
4. Al-Mrabeh A et al. 2-year remission of type 2 diabetes and pancreas morphology: A post-hoc analysis of the DiRECT open-label, cluster-randomised trial. The Lancet Diabetes & Endocrinology 8 (12), 939-948 (2020)
5. Xin Y et al. Type 2 diabetes remission: 2 year within-trial and lifetime-horizon cost-effectiveness of the Diabetes Remission Clinical Trial (DiRECT)/Counterweight-Plus weight management. Diabetologia 63 (10), 2112-2122 (2020)
6. The DiRECT principles: giving Type 2 diabetes remission programmes the best chance of success. Hopkins MD, Taylor R, Lean MEJ,  Diabetic Medicine 36 (12), 1703-1704 (2019)
7. Churuangsuk C et al. Diets for weight management in adults with type 2 diabetes: an umbrella review of published meta-analyses and systematic review of trials of diets for diabetes remission. Diabetologia, 2021

Jennie Brand Miller, Professor of Human Nutrition at the University of Sydney, reviewed the benefits of Total Diet Replacement for weight loss and low GI/high protein diet for weight maintenance and  diabetes prevention in TDMR Europe’s webinar “Total Diet Replacement: exploring sustainable weight loss and health benefits, including diabetes remission and prevention”  held on 27^th October 2021. Presenting the results of the PREVIEW research, Prof Brand Miller showed that the combination of significant weight loss using total diet replacements and a low-glycaemic load diet facilitated diabetes prevention.

Professor Anthony Leeds, chairman of TDMR Europe said “The PREVIEW study has provided strong evidence for the use of an initial weight loss with total diet replacement as the first stage of a diabetes prevention programme. Ninety percent of participants were able to complete the eight-week diet intervention period, losing an average weight of 10.7kg, with 83.5% achieving >8% weight loss.  All diabetes prevention programmes have shown that the more weight loss achieved and maintained the smaller the proportion of participants who develop diabetes. PREVIEW has confirmed the importance of this but has shown the added benefit of using a low glycaemic index/low glycaemic load diet to help reduce weight regain and keep HbA1c as low as possible. This is hugely important evidence that ought to be considered when diabetes prevention programmes are designed.”

On 27^th October, TDMR Europe’s online seminar brought together industry stakeholders, academics and others and showed the potential role of TDR in bringing down the incidence of obesity and severity of weight related comorbidities, such as type 2 diabetes, cardiovascular disease risk factors, osteoarthritis, and obstructive sleep apnoea. The recording of the webinar will be available soon on the TDMR Europe website.

More information on TDR is available here.

Prof Brand Miller is a Principal Investigator of the PREVIEW trial, a landmark three-year multicentre study conducted in eight countries that examined  the impact of TDR followed by a three year weight maintenance programme on type 2 diabetes risk.

The PREVIEW trial was funded through the EU framework programme 7 (FP7/2007–2013) grant agree-ment # 312057, National Health and Medical Research Council – EU Collaborative Grant, AUS 8, ID 1067711 and The Glycemic Index Foundation Australia. The Cambridge Weight Plan donated all products for the 8-week LED period.

 

Diabetes prevention with TDR and low GI/GL diet

Jennie Brand Miller, PREVIEW research team, University of Sydney, Australia

Abstract

The PREVIEW randomised controlled trial was a landmark 3-year multicentre, type 2 diabetes prevention study carried out in 8 countries comparing 2 diets and 2 levels of exercise intensity [1]. In total 2326 adults aged 25-70 years, body mass intake BMI ≥25 and prediabetes were enrolled.  In the first phase, participants needed to lose ≥8% of body weight in 8 weeks using total meal replacements [2] to be eligible for the second phase (34 months) of weight loss maintenance. Eligible adults (79%) received a behavioural intervention including instructions to follow either a conventional healthy diet or the high protein-low glycemic index diet (25%E from protein, 45%E from carbohydrates, GI ≤ 50).  Results: Average weight loss was 11% (11 kg) at 8 weeks. At 12-months, 74% of participants remained and 52% at 3 years.  Among the completers, the incidence of diabetes was much lower than anticipated – only 3 in 100 participants whereas 13.5% was predicted (a relative risk reduction of 77%).  The incidence was the same in centres where the attrition rate was low versus those with high rate. There were no significant differences between the two diets or two exercise groups. In post-hoc analyses, the lowest vs highest tertile of dietary glycemic index and glycemic load re-gained less weight, fat mass and showed smaller increases in HbA1c, independently of weight loss [3]. The findings suggest that the combination of significant weight loss using meal replacements and a low glycemic load diet facilitates diabetes prevention.

References:

1. Raben, A.; Vestentoft, P.S.; Brand-Miller, J.; Jalo, E.; Drummen, M.; Simpson, L.; Martinez, J.A.; Handjieva-Darlenska, T.; Stratton, G.; Huttunen-Lenz, M., et al. The preview intervention study: Results from a 3-year randomized 2 x 2 factorial multinational trial investigating the role of protein, glycaemic index and physical activity for prevention of type 2 diabetes. Diabetes, Obesity and Metabolism 2021, 23, 324-337.
2. Christensen P, Larsen TL, Westerterp-Plantenga M et al 2018 Men and women respond differently to rapid weight loss: Metabolic outcomes of a multi-centre intervention study after a low-energy diet in 2500 overweight, individuals with pre-diabetes (PREVIEW) Diabetes Obes Metab. 2018;20: 2840–2851 https://dom-pubs.onlinelibrary.wiley.com/doi/epdf/10.1111/dom.13466
3. Zhu, R.; Larsen, T.M.; Fogelholm, M.; Poppitt, S.D.; Vestentoft, P.S.; Silvestre, M.P.; Jalo, E.; Navas-Carretero, S.; Huttunen-Lenz, M.; Taylor, M.A., et al. Dose-dependent associations of dietary glycemic index, glycemic load, and fiber with 3-year weight loss maintenance and glycemic status in a high-risk population: A secondary analysis of the diabetes prevention study preview. Diabetes Care 2021, 44, 1672.