Early findings from the NHS Type 2 Diabetes Path to Remission Programme: a prospective evaluation of real-world implementation.

Background: Randomised controlled trials have shown that total diet replacement (TDR) can lead to remission of type 2 diabetes. In 2019, the English National Health Service (NHS) committed to establishing a TDR-based interventional programme delivered at scale within real-world environments; development followed of the NHS Type 2 Diabetes Path to Remission (T2DR) programme, a 12-month behavioural intervention to support weight loss involving an initial 3-month period of TDR. We assessed remission of type 2 diabetes for programme participants.

Understanding the cause of type 2 diabetes.

Type 2 diabetes has long been thought to have heterogenous causes, even though epidemiological studies uniformly show a tight relationship with overnutrition. The twin cycle hypothesis postulated that interaction of self-reinforcing cycles of fat accumulation inside the liver and pancreas, driven by modest but chronic positive calorie balance, could explain the development of type 2 diabetes. This hypothesis predicted that substantial weight loss would bring about a return to the non-diabetic state, permitting observation of the pathophysiology determining the transition.

Reliability and validity of the medial standing overhead arm reach (SOAR) test as a measure of functional hip adduction motion.

Objective: The Posterior Standing Overhead Arm Reach (SOAR) test has been previously reported as a reliable clinical measure of closed chain hip extension motion. The proposed Medial SOAR test expands on that testing approach to provide a similar measure of functional hip adduction motion. This was a preliminary intrarater and interrater reliability and validity study of the Medial SOAR test as a measure of functional hip adduction.

Low-calorie diets for people with isolated impaired fasting glucose.

Standard lifestyle interventions prove ineffective in preventing type 2 diabetes among individuals with isolated impaired fasting glucose, a highly prevalent prediabetes phenotype globally. Here, we propose low-calorie diets as a promising strategy for diabetes prevention in this high-risk population.

5-year follow-up of the randomised Diabetes Remission Clinical Trial (DiRECT) of continued support for weight loss maintenance in the UK: an extension study.

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.

Very low calorie diets and total diet replacement in type 2 diabetes: where are we now?

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.

Impact of weight loss on cancer-related proteins in serum: results from a cluster randomised controlled trial of individuals with type 2 diabetes.

Background: Type 2 diabetes is associated with higher risk of several cancer types. However, the biological intermediates driving this relationship are not fully understood. As novel interventions for treating and managing type 2 diabetes become increasingly available, whether they also disrupt the pathways leading to increased cancer risk is currently unknown.

Using trials of caloric restriction and bariatric surgery to explore the effects of body mass index on the circulating proteome.

Thousands of proteins circulate in the bloodstream; identifying those which associate with weight and intervention-induced weight loss may help explain mechanisms of diseases associated with adiposity. We aimed to identify consistent protein signatures of weight loss across independent studies capturing changes in body mass index (BMI). We analysed proteomic data from studies implementing caloric restriction (Diabetes Remission Clinical trial) and bariatric surgery (By-Band-Sleeve), using SomaLogic and Olink Explore1536 technologies, respectively.

Prediction of Cardiometabolic Health Through Changes in Plasma Proteins With Intentional Weight Loss in the DiRECT and DIADEM-I Randomized Clinical Trials of Type 2 Diabetes Remission.

Objective: To determine the extent to which changes in plasma proteins, previously predictive of cardiometabolic outcomes, predict changes in two diabetes remission trials.

Research Design And Methods: We applied SomaSignal predictive tests (each derived from ∼5,000 plasma protein measurements using aptamer-based proteomics assay) to baseline and 1-year samples of trial intervention (Diabetes Remission Clinical Trial [DiRECT], n = 118, and Diabetes Intervention Accentuating Diet and Enhancing Metabolism [DIADEM-I], n = 66) and control (DiRECT, n = 144, DIADEM-I, n = 76) group participants.

Results: Mean (SD) weight loss in DiRECT (U.

Aetiology of Type 2 diabetes in people with a 'normal' body mass index: testing the personal fat threshold hypothesis.

Weight loss in overweight or obese individuals with Type 2 diabetes (T2D) can normalize hepatic fat metabolism, decrease fatty acid oversupply to β cells and restore normoglycaemia. One in six people has BMI <27 kg/m2 at diagnosis, and their T2D is assumed to have different aetiology. The Personal Fat Threshold hypothesis postulated differing individual thresholds for lipid overspill and adverse effects on β-cell function.

What predicts drug-free type 2 diabetes remission? Insights from an 8-year general practice service evaluation of a lower carbohydrate diet with weight loss.

Background: Type 2 diabetes (T2D) is often regarded as a progressive, lifelong disease requiring an increasing number of drugs. Sustained remission of T2D is now well established, but is not yet routinely practised. Norwood surgery has used a low-carbohydrate programme aiming to achieve remission since 2013.

The Effects of Exam-Induced Stress on EEG Profiles and Memory Scores.

Common stressors amongst postsecondary students are exam-induced anxiety and stress. The purpose of this study was to measure stress alterations in the student population around examinations and determine how they affect electroencephalogram (EEG) profiles and memory scores. Twenty university students were measured multiple times in the study.

Physical activity, inactivity and sleep during the Diabetes Remission Clinical Trial (DiRECT).

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.

A proteomic surrogate for cardiovascular outcomes that is sensitive to multiple mechanisms of change in risk.

A reliable, individualized, and dynamic surrogate of cardiovascular risk, synoptic for key biologic mechanisms, could shorten the path for drug development, enhance drug cost-effectiveness and improve patient outcomes. We used highly multiplexed proteomics to address these objectives, measuring about 5000 proteins in each of 32,130 archived plasma samples from 22,849 participants in nine clinical studies. We used machine learning to derive a 27-protein model predicting 4-year likelihood of myocardial infarction, stroke, heart failure, or death.

Curating a longitudinal research resource using linked primary care EHR data-a UK Biobank case study.

Primary care EHR data are often of clinical importance to cohort studies however they require careful handling. Challenges include determining the periods during which EHR data were collected. Participants are typically censored when they deregister from a medical practice, however, cohort studies wish to follow participants longitudinally including those that change practice.

Intra-pancreatic fat deposition: bringing hidden fat to the fore.

Development of advanced modalities for detection of fat within the pancreas has transformed understanding of the role of intra-pancreatic fat deposition (IPFD) in health and disease. There is now strong evidence for the presence of minimal (but not negligible) IPFD in healthy human pancreas. Diffuse excess IPFD, or fatty pancreas disease (FPD), is more frequent than type 2 diabetes mellitus (T2DM) (the most common disease of the endocrine pancreas) and acute pancreatitis (the most common disease of the exocrine pancreas) combined.

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).

Lower carbohydrate diets for adults with type 2 diabetes.

In May 2021, the Scientific Advisory Committee on Nutrition (SACN) published a risk assessment on lower carbohydrate diets for adults with type 2 diabetes (T2D). The purpose of the report was to review the evidence on 'low'-carbohydrate diets compared with the current UK government advice on carbohydrate intake for adults with T2D. However, since there is no agreed and widely utilised definition of a 'low'-carbohydrate diet, comparisons in the report were between lower and higher carbohydrate diets.

Sex differences in intraorgan fat levels and hepatic lipid metabolism: implications for cardiovascular health and remission of type 2 diabetes after dietary weight loss.

Aims/hypothesis: Type 2 diabetes confers a greater relative increase in CVD risk in women compared with men. We examined sex differences in intraorgan fat and hepatic VLDL1-triacylglycerol (VLDL1-TG) export before and after major dietary weight loss.

Methods: A group with type 2 diabetes (n = 64, 30 male/34 female) and a group of healthy individuals (n = 25, 13 male/12 female) were studied.

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.