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Abstract
Management of type 2 diabetes has now been simplified by the understanding that the condition is caused by excess fat in the liver together with suppression of beta cell function by the associated excess liver export of fat. These factors can be reversed by substantial weight loss leading to remission in the early years after diagnosis, or at least major decrease in cardiovascular risks and improvement in glucose control for all. Weight loss by any means is successful, but it is most easily achieved by rapid action using a low or very low calorie diet of around 800 kcal/day followed by sustained modest restraint of dietary habits. Oral hypoglycaemic agents and one antihypertensive drug can be withdrawn on day 1 of the weight loss diet, raising the importance of appropriate deprescribing.
- Diabetes mellitus
- Diet food and nutrition
- Metabolic Diseases
- Blood pressure
- Endocrine System Diseases
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Key learning points
Type 2 diabetes has been regarded as a lifelong, progressive disease.
Substantial weight loss can bring about remission by decreasing liver fat and supply of excess fat to beta cells.
A diet of around 800 kcal/day is well accepted and has been successfully used in primary care to bring about the required weight loss of 10–15 kg.
Such a diet is not associated with tiredness in most people nor any serious adverse effects.
In the early years after diagnosis, complete remission of diabetes is possible but even if this is not achieved 10-year cardiovascular risk and drug therapy can be decreased.
Knowledge of the impact of a low calorie diet introduces a paradigm shift in the management of type 2 diabetes and hope of regaining health to people with the condition.
Introduction: new understanding of type 2 diabetes
Type 2 diabetes is now known to be a condition of excess fat supply within the liver and pancreas, causing hepatic insulin resistance and beta cell dysfunction, respectively. The twin cycle hypothesis (chronic calorie excess causes accumulation of liver fat with eventual spill over into the pancreas leading to metabolic inhibition of insulin secretion after meals and onset of hyperglycaemia) originally laid out the theoretical basis for remission of type 2 diabetes, and a dietary research tool had to be developed to test this.1 Using this, the Counterpoint (COUNTERacting the Pancreatic inhibitiOn of INsulin secretion by Triglyceride) study achieved substantial weight loss in 8 weeks and triggered worldwide interest in dietary weight loss for remission of type 2 diabetes.2 Removal of the excess fat permits return of normal hepatic and beta cell function and hence restoration of non-diabetic levels of blood glucose. Individuals vary markedly in how much fat exposure can be tolerated without dysfunction.3 Substantial weight loss is the only way yet identified of removing the excess intraorgan fat, but the time course of losing weight is not important. Remission is most likely in the first few years after diagnosis of type 2 diabetes, but remains possible for much longer.4 5 This understanding is vital not only to advise people with diabetes about escaping diabetes by dietary weight loss, but also underpins a logical approach to use of oral agents. Deprescribing of hypoglycaemia agents on commencing a very low calorie diet is consequently a current topic of interest.
Description and definitions
A very low calorie diet is defined as less than 800 kcal/day, but this should be taken as a general guide only because of the very wide range of body weight and hence basal calorie requirements.6 A liquid replacement diet readily combines the low energy intake with adequate protein and other essential nutrients. It is usefully combined with non-starchy vegetables (salads and leafy vegetables) to minimise constipation.
A low carbohydrate diet is defined as less than 130 g/day or 10%–26% of total energy intake.7 For comparison, average intake of carbohydrate in the UK is 46% of total energy intake or approximately 280 g.8 A low carbohydrate Mediterranean diet is defined as a diet high in monounsaturated fat (eg, olive oil), low in red meat and with less than 150 g of carbohydrate per day.9 Intermittent fasting is restriction of eating to set times daily (eg, 12:00 to 19:00) or consumption of less than 400 kcal on 2 days per week.10
An international consensus defining remission of type 2 diabetes has recently been published: achievement of a non-diabetic HbA1c (<48 mmol/mol or <6.5%) on two occasions over six months off all hypoglycaemic medication.11
What interventions have been tested?
The two greatest barriers to effective dietary weight loss are hunger, and the cumulative day-to-day burden of decisions on what and how much to eat. To minimise these, the low calorie liquid diet with non-starchy vegetables was developed (600–800 kcal/day).2 The method has subsequently proved to be robust in clinical practice.12 Although it is not necessary to lose weight rapidly to achieve remission, it is easier to achieve for most people.13 No major adverse effects of rapid weight loss have been identified either in studies or in several thousand people who have taken part in the current NHS England Path To Remission Programme. The addition of non-starchy vegetables ensures constipation is rare. During the early days of dieting, headache and fatigue have been reported but are unusual. Other weight loss diets can be effective, and individual preferences are important in this respect. They include intermittent fasting and low carbohydrate diets focused on weight loss but randomised controlled trial evidence for these is scarce.10 14
Especially in people who are no longer young and are overweight, the onset of an exercise programme is associated with gain in weight due to compensatory overeating.15 People who are overweight and no longer young are particularly susceptible to this. Contrary to popular belief, regular exercise in this group under real-life conditions has minimal effect on metabolic control.16 To achieve substantial weight loss, dietary restriction alone is highly effective, and commencing new exercise is discouraged.2 12 However, in the phase of avoidance of weight regain, increased daily physical activity appears to be a major ingredient of success even though sustaining this is challenging.17 18
What weight losses have been achieved?
The Counterpoint study was designed as a definitive test of the twin cycle hypothesis and as the predicted effect size was large the prior power calculation indicated that a definitive result could be obtained with only 11 people with type 2 diabetes.2 A low calorie liquid diet (510 kcal/day) supplemented with three portions of non-starchy vegetables (total energy intake 600 kcal/day) was used for 8 weeks. The average weight loss during the 8 weeks of dietary intervention was 15.3 kg (15% of initial bodyweight).2 A modification of this approach in the Diabetes Remission Controlled Trial (DiRECT) conducted in primary care randomised 306 people with type 2 diabetes to a structured weight management programme including a diet of 850 kcal/day or best-practice care.12 Participants who received the structured weight management programme showed identical weight loss at 4 months, 10 kg at 12 months, 8.8 kg at 24 months and 6.1 kg at 5 years in an intention-to-treat analysis.12 19 20 Using similar methodology delivered by health advisers, a study in 278 people with obesity rather than type 2 diabetes randomised to total diet replacement (810 kcal/day) or usual care reported 6.3 kg weight loss in the diet group at 3 years.21 Low carbohydrate diets are generally ineffective in achieving major weight loss, but with intensive application and close supervision have been reported to achieve 13.8 kg weight loss and 25% achieved remission of diabetes at 12 months in an observational series.22 23 When weight loss is emphasised as the primary goal of low carbohydrate dieting in a supportive environment, a single-practice primary care audit has demonstrated 10 kg weight loss at 33 months.14 Intermittent fasting can achieve weight loss of 5–9 kg over 6 months, and this range emphasises the critical importance of the overall management and support for individuals for any weight loss programme.10
Remission of type 2 diabetes and other benefits
Following appropriate weight loss, duration of disease is the primary factor determining rate of remission.24 In view of this, a duration of 6 years was used in the DiRECT study and is now accepted for the NHS England Type 2 Diabetes Pathway to Remission programme now to be rolled out nationally.12 However, the 10-year risk of cardiovascular disease (QRISK3) calculated from the published data decreases with weight loss in those achieving remission (17.7% to 8.1%) and those who do not (19.9% to 13.7%) 24 This is largely because hepatic lipid abnormalities are corrected irrespective of beta cell recovery.25 At 2 years in the DiRECT study, there were significantly fewer adverse outcomes, driven by decrease in cardiovascular disease and weight related cancers.12 Other methods achieving weight loss of similar extent would be expected to achieve similar outcomes.
How do these compare with other strategies?
Conventional management of type 2 diabetes using oral agents and insulin does not correct the underlying cause of the beta cell dysfunction, which steadily progresses such that 50% of people with type 2 diabetes require insulin therapy 10 years after diagnosis.26 Using a rapid weight loss programme, the DiRECT study established that 36% of people managed by primary care nurses or dietitians were in remission of type 2 diabetes by 2 years.12 The Diabetes Intervention Accentuating Diet and Enhancing Metabolism (DIADEM1) study in Qatar compared the effects of intensive lifestyle intervention including a low energy diet of 820 kcal/day with usual care on weight loss and glycaemic outcomes in 158 people aged 18–50 years with type 2 diabetes.27 The study showed that younger people with type 2 diabetes responded well to a rapid weight loss diet and is one of the many studies reporting remission of type 2 diabetes in non-European populations.27 The clear-cut remission of type 2 diabetes using very low calorie diets is not matched by other dietary approaches except in a high-input research environment. Gradual weight loss using modest calorie restriction does not achieve sufficient weight loss for most people. Results are modestly better for time restricted eating and a weight loss-focused low carbohydrate diet. Intensive interventions such as those used in the Look AHEAD (Action for Health in Diabetes) study are very expensive but can produce around 9 kg weight loss at 4 years.28 The degree of weight loss rather than that of exercise is proportional to both remission of type 2 diabetes and risk of cardiovascular events.28 29
Potent appetite suppressants such as tirzepatide and semaglutide have been reported to achieve weight loss of around 12 kg and knowledge of the physiological consequences of weight loss would predict that the effect on remission of type 2 diabetes will be in line with that achieved by very low calorie diets.19 Evidence of this effect is awaited.
Are these strategies currently in use in the NHS?
The NHS England Type 2 Diabetes Pathway to Remission Programme was successful as a pilot programme and is being rolled out across England to people aged 18–65 years with type 2 diabetes diagnosed within the last 6 years and who have a body mass index >27 kg/m2 (or >25 kg/m2 for people from some ethnic groups).30 31 Similar programmes are funded by regional Health Boards in Scotland. Healthcare professionals were initially reluctant to advise rapid weight loss following publication of the Counterpoint study in 2011. Analysis of communication received following publication of the study found that out of 77 responses, 25 people felt that they had received a negative response from a healthcare professional following a request for a very low calorie diet and only 27 received support.4 However, the concept of achieving remission as a potential goal of management is now well established.11
How can we support patients?
Information on how to achieve remission was made freely available online in 2011 in response to a very large numbers of requests following publication of the Counterpoint study.2 The most complete description is available as a book.32 Basic information is freely available online (https://go.ncl.ac.uk/diabetes-reversal). Advice and case reports can be found on the Diabetes UK website (https://www.diabetes.org.uk/guide-to-diabetes/managing-your-diabetes/treating-your-diabetes/type2-diabetes-remission). In 2023, the NHS England Path to Remission Programme was extended and discussion of possible referral is encouraged with all eligible people in the first 6 years after diagnosis.30 In the UK, the Fast 800 is a commercial weight loss programme for which subscriptions can be purchased. At present, there is no established online community for those who have achieved or want to achieve remission.
Deprescribing opportunities
The rapidity of fall in blood glucose after stopping oral agents and commencing a very low calorie diet is such that all agents can be stopped on day 1 of the diet.2 24 Over 5 years, the incidence of serious medical events in the weight loss group was less than half that in the group treated in line with guidelines issued by the National Institute for Health and Care Excellence or the Scottish Intercollegiate Guidelines Network.20 Blood pressure also decreases and antihypertensive medication should be decreased. During recruitment of primary care doctors for DiRECT, stopping oral hypoglycaemic agents was not seen as contentious, but it was necessary to show a graph of blood pressure results from the Counterbalance (COUNTERacting BetA cell failure by Long term Action to Normalise Calorie intakE) study to persuade doctors to withdraw antihypertensive agents.24 It has been since been demonstrated that stopping one antihypertensive agent is optimal.33
Challenges
Independent assessments of the Counterbalance and DiRECT studies have shown the high acceptability of low calorie, rapid weight loss programmes, but the challenge is considerable of avoiding weight regain given the persistence of the food environment which facilitated the initial weight gain.13 Close personal support in primary care has been shown to achieve weight stability over a median period of 3 years.14 In a US registry study, 87% of those who lost 30 pounds or more sustained this over 10 years.17 Long-term maintenance of weight loss achieves continuing remission of type 2 diabetes, although the majority do regain some weight. However, some benefit is maintained for the weight regainers, with lower rates of cardiovascular episodes than those who do not lose weight (although not as low as those who maintain weight loss).29 Nonetheless, a significant minority do avoid weight regain after substantial weight loss (6.1 kg at 4 years in DiRECT) and these people derive major benefit.20 Additionally, moving forwards the onset of type 2 diabetes by several years will confer benefit as complications are most severe in younger people and largely absent in later life.
Conclusion
National and international guidelines do not yet reflect the recent knowledge about achieving and maintaining at least 10 kg weight loss for people diagnosed with type 2 diabetes. Focus on ‘remission’ as a primary goal has obscured the effects of weight loss on decrease in medication and improvement of control short of remission—irrespective of duration of diabetes and prior insulin therapy. However, clarity about the simple pathophysiology of type 2 diabetes provides a sound basis for practitioners to explain therapy to patients and to advise on evidence-based approaches to avoid or decrease drug prescribing.
Information for patients
Type 2 diabetes is caused by having more fat inside your internal organs than you can tolerate. It only happens to people genetically predisposed.
The fat inside the organs can be decreased to normal by weight loss of 10–15 kg irrespective of your initial body mass index.
Weight loss is most effectively achieved by planning for an 8–12 week period of following a diet of 800 calories/day.
Although this sounds drastic, it is found to be much easier than anticipated and brings about rapid improvement in well-being.
After the weight loss period, a careful stepwise return to normal eating is necessary, followed by long-term modest dietary restraint.
Regular weighing and support from others are important to avoid weight regain.
Not everyone achieves remission from diabetes (which is defined as a non-diabetic HbA1c for at least 6 months, off all diabetes drugs) but day-to-day well-being is improved, and risk of heart disease is decreased.
Ideally, a person should discuss with their healthcare professional before weight loss and this is essential for anyone taking medication for diabetes or hypertension.
References
Footnotes
Competing interests None declared. Refer to the online supplementary files to view the ICMJE form(s).
Provenance and peer review Commissioned; externally peer reviewed.