Alterations in bile acid kinetics after bariatric surgery in patients with obesity with or without type 2 diabetes.

BACKGROUND: Bariatric surgery is an effective treatment option for obesity and provides long-term weight loss and positive effects on metabolism, but the underlying mechanisms are poorly understood. Alterations in bile acid metabolism have been suggested as a potential contributing factor, but comprehensive studies in humans are lacking. METHODS: In this study, we analysed the postprandial responses of bile acids, C4 and FGF19 in plasma, and excretion of bile acids in faeces, before and after bariatric surgery in patients (n = 38; 74% females) with obesity with or without type 2 diabetes from the BARIA cohort. FINDINGS: We observed that total fasting plasma bile acid levels increased, and faecal excretion of bile acids decreased after surgery suggesting increased reabsorption of bile acids. Consistent with increased bile acid levels after surgery we observed increased postprandial levels of FGF19 and suppression of the bile acid synthesis marker C4, suggesting increased FXR activation in the gut. We also noted that a subset of bile acids had altered postprandial responses before and after surgery. Finally, fasting plasma levels of 6α-hydroxylated bile acids, which are TGR5 agonists and associated with improved glucose metabolism, were increased after surgery and one of them, HDCA, covaried with diabetes remission in an independent cohort. INTERPRETATION: Our findings provide new insights regarding bile acid kinetics and suggest that bariatric surgery in humans alters bile acid profiles leading to activation of FXR and TGR5, which may contribute to weight loss, improvements in glucose metabolism, and diabetes remission. FUNDING: Novo Nordisk Fonden, Leducq Foundation, Swedish Heart-Lung Foundation, Knut and Alice Wallenberg Foundation, the ALF-agreement, ZonMw.

Diabetes remission and nonalcoholic fatty pancreas disease.

This editorial focuses on the relationship between nonalcoholic fatty pancreas disease (NAFPD) and the development and remission of type 2 diabetes (T2D). NAFPD is characterized by intrapancreatic fatty deposition associated with obesity and not associated with alcohol abuse, viral infections, and other factors. Ectopic fat deposition in the pancreas is associated with the development of T2D, and the underlying mechanism is lipotoxic ß-cell dysfunction. However, the results on the relationship between intrapancreatic fat deposition (IPFD) and ß-cell function are conflicting. Regardless of the therapeutic approach, weight loss improves IPFD, glycemia, and ß-cell function. Pancreatic imaging is valuable for clinically monitoring and evaluating the management of T2D.

Reassessing type 2 diabetes in adolescents and its management strategies based on insulin resistance.

With changes in lifestyle behaviors, including dietary structure and habits, the prevalence of Youth-onset Type 2 Diabetes Mellitus (YODM) has increased 2 to 3 times compared to 30 years ago. YODM patients experience complications earlier, progress faster, and exhibit more severe symptoms. However, limited and inconclusive direct evidence, coupled with poor patient compliance, poses challenges in the clinical management of YODM. Apart from the continuous decline in pancreatic ß-cell function and quantity, tissue-specific insulin resistance (IR) is also a typical characteristic of YODM. The main mechanisms of IR in YODM involve different aspects such as obesity, dietary imbalance, abnormal substance metabolism, chronic inflammation, oxidative stress, and hormonal fluctuations during adolescence. For the comprehensive management of YODM, besides achieving good control of blood glucose levels, it may be necessary to apply the most appropriate methods considering the uniqueness of the patient population and the specifics of the disease. Early identification and detection of the disease are crucial. Precise screening of patients with well-functioning pancreatic insulin ß-cells, primarily characterized by IR and obesity, represents the population most likely to achieve diabetes remission or reversal through lifestyle modifications, medications, or even surgical interventions. Additionally, considering potential emotional disorders or the impact of adolescent hormones in these patients, health education for patients and caregivers is essential to make them aware of the long-term benefits of well-controlled blood glucose. In conclusion, adopting comprehensive management measures to achieve diabetes remission or reversal is the ideal goal. Controlling high blood glucose, obesity, and other risk factors related to diabetes complications is the next priority to delay the occurrence and progression of complications. A comprehensive perspective on IR provides insights and references for identifying YODM and its management strategies.

Response to lowering plasma glucose is characterised by decreased oxyntomodulin: Results from a randomised controlled trial.

BACKGROUND: With the prevalence of diabetes reaching an epidemic level, there is a growing interest in the investigation of its remission. Proglucagon-derived peptides (PGDP) have been shown to have a glucose-regulating effect. However, whether they play a role in diabetes remission remains poorly understood. AIM: To investigate changes in plasma levels of PGDP in glycaemic responders versus non-responders. METHODS: The study was a randomised placebo-controlled trial comprising 18 adults with prediabetes (registered at www. CLINICALTRIALS: gov as NCT03889210). Following an overnight fast, participants consumed ketone ß-hydroxybutyrate (KEßHB)-supplemented beverage and placebo beverage in crossover manner. Serial blood samples were collected from baseline to 150 min at 30-min intervals. The endpoints were changes in glucagon-like peptide-1 (GLP-1), glicentin, oxyntomodulin, glucagon, and major proglucagon fragment (MPGF). Participants were stratified into the 'responders' and 'non-responders' subgroups based on their glycaemic changes following the ingestion of KEßHB. The area under the curve (AUC) was calculated to estimate the accumulated changes in the studied PGDP and compared using paired-t test between the KEßHB and placebo beverages. RESULTS: Responders had a significantly greater reduction in plasma glucose compared with non-responders following acute ketosis (p < 0.001). The AUC0-150 for oxyntomodulin was significantly lower following the KEßHB beverage compared with the placebo (p = 0.045) in responders, but not in non-responders (p = 0.512). No significant differences in AUCs0-150 were found for GLP-1, glicentin, glucagon, and MPGF in either responders or non-responders. CONCLUSION: Oxyntomodulin is involved in lowering plasma glucose and may play an important role in diabetes remission.

Transferability of the NHS low-calorie diet programme: A qualitative exploration of factors influencing the programme's transfer ahead of wide-scale adoption.

INTRODUCTION: Although behavioural interventions have been found to help control type 2 diabetes (T2D), it is important to understand how the delivery context can influence implementation and outcomes. The NHS committed to testing a low-calorie diet (LCD) programme designed to support people living with excess weight and T2D to lose weight and improve diabetes outcomes. Understanding what influenced implementation during the programme pilot is important in optimising rollout. This study explored the transferability of the NHS LCD Programme prior to wider adoption. METHODS: Twenty-five interviews were undertaken with stakeholders involved in implementing the LCD programme in pilot sites (health service leads, referring health professionals and programme deliverers). Interviews with programme participants (people living with T2D) were undertaken within a larger programme of work, exploring what worked, for whom and why, which is reported separately. The conceptual Population-Intervention-Environment-Transfer Model of Transferability (PIET-T) guided study design and data collection. Constructs of the model were also used as a deductive coding frame during data analysis. Key themes were identified which informed recommendations to optimise programme transfer. RESULTS: Population: Referral strategies in some areas lacked consideration of population characteristics. Many believed that offering a choice of delivery model would promote acceptability and accessibility of the eligible population. INTERVENTION: Overall, stakeholders had confidence in the LCD programme due to the robust evidence base along with anecdotal evidence, but some felt the complex referral process hindered engagement from GP practices. ENVIRONMENT: Stakeholders described barriers to accessing the programme, including language and learning difficulties. Transferability: Multidisciplinary working and effective communication supported successful implementation. CONCLUSION: Referral strategies to reach underrepresented groups should be considered during programme transfer, along with timely data from service providers on access and programme benefits. A choice of delivery models may optimise uptake. Knowledge sharing between sites on good working practices is encouraged, including increasing engagement with key stakeholders.

Gluco-regulation & type 2 diabetes: entrenched misconceptions updated to new governing principles for gold standard management.

Our understanding of type 2 diabetes (T2D) has evolved dramatically. Advances have upended entrenched dogmas pertaining to the onset and progression of T2D, beliefs that have prevailed from the early era of diabetes research-and continue to populate our medical textbooks and continuing medical education materials. This review article highlights key insights that lend new governing principles for gold standard management of T2D. From the historical context upon which old beliefs arose to new findings, this article outlines evidence and perspectives on beta cell function, the underlying defects in glucoregulation, the remediable nature of T2D, and, the rationale supporting the shift to complication-centric prescribing. Practical approaches translate this rectified understanding of T2D into strategies that fill gaps in current management practices of prediabetes through late type 2 diabetes.

Association between previous consumption of sugar-sweetened beverages and diabetes remission in patients with newly diagnosed type 2 diabetic ketoacidosis.

This study examined the potential correlation between the immoderate intake of sugar-sweetened beverages (SSBs) and the subsequent rate of diabetes remission (DR). 206 individuals who met the eligibility criteria between January 2019 and June 2022 were recruited. Inquiries were conducted to gather information on the participants' beverage consumption before the onset. Subsequently, the participants were separated into the diabetes remission group (DR group) and nondiabetes remission group (NDR group) depending on whether they met the diagnostic criteria for diabetes remission. Baseline clinical elements within the two groups were juxtaposed, and factors influencing diabetes remission were identified through logistic regression analyses. The cutoff values of each critical factor were determined based on the receiver operating characteristic curve. One hundred and nine patients reported a history of SSB consumption, while the remaining 58 reported no such history. After 1 year, 40 patients achieved remission from diabetes. Compared with the NDR group, a higher SSBs ratio, body mass index (BMI), and blood creatinine (BCr) was observed in the DR group after adjusting for confounders, SSBs (odds ratio [OR] = 3.503; 95% confidence interval [CI] = 1.334-9.202; p = 0.011) and BCr (OR = 1.038; 95% CI = 1.003-1.079; p = 0.042) emerged as independent predictors of DR. The composite index of SSBs and BCr efficaciously predicted DR (area under the ROC curve [AUC] = 0.810, p < 0.001). SSBs and BCr were independent risk factors for DR. The amalgamation of these markers could more accurately predict DR.

A systematic review and meta-analysis of environmental contaminant exposure impacts on weight loss and glucose regulation during calorie-restricted diets in preclinical studies: Persistent organic pollutants may impede glycemic control.

Epidemiological evidence links chemical exposure with type 2 diabetes (T2DM) risk and prevalence. Chemical exposure may therefore also limit success of weight loss or restoration of glycemic control during calorie restricted diets. Few human studies examine this hypothesis. This systematic review and clustered meta-analysis examines preclinical evidence that exposure to anthropogenic environmental contaminants impedes weight loss and resumption of glycemic control during calorie restriction. Of five eligible papers from 212 unique citations, four used C57BL/6 mice and one used Sprague Dawley rats. In four the animals received high fat diets to induce obesity and impaired glycemic control. All examined persistent organic pollutants (POPs). Polychlorinated biphenyl (PCB) 77 exposure did not affect final mass (standardised mean difference (SMD) = -0.35 [-1.09, 0.39]; n = 5 (experiments); n = 3 (papers)), or response to insulin in insulin tolerance tests (SMD = -1.54 [-3.25, 0.16] n = 3 (experiments); n = 2 (papers)), but impaired glucose control in glucose tolerance tests (SMD = -1.30 [-1.96, -0.63]; n = 6 (experiments); n = 3 (papers)). The impaired glycemic control following perfluoro-octane sulphonic acid (PFOS) exposure and enhanced mass loss following dichlorodiphenyltrichloroethane (DDT) exposure have not been replicated. Animal studies thus suggest some chemical groups, especially PCB and PFOS, could impair glucose control management during calorie restriction, similar to conclusions from limited existing clinical studies. We discuss the research that is urgently required to inform weight management services that are now the mainstay prevention initiative for T2DM.

Do people with type 2 diabetes find continuous and intermittent low-energy diets for weight loss and diabetes remission acceptable?

BACKGROUND: The Manchester Intermittent versus Daily Diet App Study (MIDDAS) tested the feasibility and potential efficacy of two remotely delivered low-energy diet (LED) programmes (800 kcal/day) to support weight loss and remission of type 2 diabetes: continuous [CLED] (8 weeks of daily LED) and intermittent [ILED] (2 days of LED/week for 28 weeks). Understanding participant experiences can help us to understand the acceptability of LED programmes to people with type 2 diabetes, informing future programme development and implementation. METHODS: Twenty participants (10 CLED; 10 ILED) took part in interviews conducted at the end of the active weight loss phase (CLED week 12, ILED week 28). Interviews were transcribed and analysed thematically using the template analysis approach, with an a priori focus on acceptability. Four themes are presented: prospective acceptability, intervention coherence and perceived effectiveness, opportunity costs and self-efficacy. RESULTS: Both remotely supported CLED and ILED interventions appeared acceptable to participants. CLED participants found the rapid initial weight loss phase comparatively easy and highly motivating but expressed more concerns around weight maintenance. ILED participants found the more gradual weight loss initially frustrating but expressed greater confidence in their longer-term adherence. The importance of continued individualised support from healthcare professionals was emphasised, and evidence of weight loss and improvement in other medical markers through monitoring via the mobile phone app was useful. CONCLUSION: Different approaches to remotely delivered LEDs appear acceptable; therefore asking patients which approach may be more acceptable to them may be a useful way to offer individualised and tailored support.

Knowledge interface co-design of a diabetes and metabolic syndrome initiative with and for Aboriginal people living on Ngarrindjeri country.

Objectives: This research program involves two phases to identify enablers and barriers to diabetes care for Aboriginal people on Ngarrindjeri country; and co-design a strength-based metabolic syndrome and Type 2 Diabetes (T2D) remission program with the Ngarrindjeri community. Study design: A study protocol on qualitative research. Methods: The study will recruit Aboriginal people living on Ngarrindjeri country above 18 years of age with a diagnosis of metabolic syndrome or T2D. Recruitment for phases one and two will occur through the Aboriginal Health Team at the Riverland Mallee Coorong Local Health Network. The lived experiences of T2D will be explored with 10-15 Aboriginal participants, through an Aboriginal conversational technique called 'yarning' (60-90 min) in phase 1. Elders and senior community representatives (n = 20-30) will participate in four co-design workshops (2-4 h) in phase 2. Qualitative data will be transcribed and thematically analysed (NVivo version 12). The analysis will focus on protective factors for the Cultural Determinants of Health. Ethics approval was obtained from Aboriginal Health Research Ethics Committee in South Australia (04-22-1009), and Flinders University Human Research Ethics Committee (5847). Results: This work will be used to pilot the co-designed diabetes remission trial. Outcomes will be published in peer-reviewed journals, presented at conferences, focusing on following best practice guidelines from the Australian Institute of Aboriginal and Torres Strait Islander Studies and National Health and Medical Research Council. Research translation will occur through digital posters, manuals, and infographics. Conclusions: The findings will be summarised to all Aboriginal organisations involved in this study, along with peak bodies, stakeholders, Aboriginal Services, and interested participants.

Applicability of individualized metabolic surgery score for prediction of diabetes remission after endoscopic sleeve gastroplasty.

Background: Endoscopic sleeve gastroplasty (ESG) is a safe and effective obesity treatment. The individualized metabolic score (IMS) is a validated score that uses preoperative variables predicting T2D remission (DR) in bariatric surgery. Objectives: We evaluated the applicability of using the IMS score to predict DR in patients after ESG. Design/Methods: We performed a retrospective review of patients with obesity and T2D who underwent ESG. We calculated DR, IMS score, and severity, and divided patients based on IMS category. Results: The cohort comprised 20 patients: 25% (5) mild, 55% (11) moderate, and 20% (4) severe IMS stages. DR was achieved in 60%, 45.5%, and 0% of patients with mild, moderate, and severe IMS scores (p = 0.08), respectively. IMS score was significantly associated with DR (p = 0.03), with the area under the curve of the receiver operating characteristic for predicting DR 0.85. Conclusion: These pilot data demonstrate that the IMS score appears to be useful in predicting DR after ESG.

Use of individualized metabolic surgery score in endoscopic sleeve gastroplasty Why was the study done? Endoscopic sleeve gastroplasty (ESG) is effective and safe as a treatment for obesity and has also shown improvement in diabetes in previous studies. However, there is no data showing the rates of diabetes remission after this procedure and no measures to predict this outcome. This study uses the individualized metabolic score (IMS) to predict diabetes remission after ESG. What did the researchers do? They analyzed a sample of patients who had undergone ESG, and evaluated the change in their diabetes parameters at 1 year compared to baseline, and then correlated this with their calculated baseline IMS score. What did the researchers find? Patients with a higher IMS score, representing more severe disease, were less likely to have an improvement in their diabetes after ESG. What do the findings mean? ESG can be an effective treatment option for patients with obesity and early-stage diabetes.

Practice effects of personalized interventions with interdisciplinary teamwork in type 2 diabetes remission: a retrospective study.

Objectives: A retrospective analysis of the clinical outcomes of personalized interventions for type 2 diabetes mellitus (T2DM) in an interdisciplinary team. Methods: Under the guidance of an interdisciplinary team, 40 patients with T2DM underwent a systematic examination at the beginning of the intervention, 3 months after the intervention, and 3 months of follow-up at the end of the intervention (i.e., at 6 months). Key indicators such as fasting plasma glucose (FPG), 2-hour postprandial glucose (2hPG), fasting insulin level (FINS), glycated hemoglobin (HbA1c), blood lipids, and body mass index (BMI) were measured. Results: After the 3-month intervention, participants' BMI, FPG, 2hPG, FINS, and HbA1c improved significantly, with statistically significant differences (P<0.05).These metrics remained essentially stable at the 3-month follow-up. Of all the participants, 92.5% (37 cases in total) successfully discontinued their medication after 3 months of intervention, of which 80% (32 cases) remained stable during the 3-month follow-up after discontinuation, fulfilling the criteria for remission of T2DM; 2 cases successfully reduced the dose of their medication, and only 1 case was maintained on the original treatment. Conclusions: Through an interdisciplinary team intervention strategy, we significantly optimized the glucose metabolism, lipid metabolism, and BMI status of patients with T2DM, making diabetes remission an achievable goal, which provides valuable experience for further optimization of diabetes prevention and control protocols.

Is the NHS low-calorie diet programme delivered as planned? An observational study examining adherence of intervention delivery to service specification.

Obesity and Type 2 Diabetes Mellitus (T2DM) are chronic conditions with significant personal, societal, and economic impacts. Expanding on existing trial evidence, the NHS piloted a 52-week low-calorie diet programme for T2DM, delivered by private providers using total diet replacement products and behaviour change support. This study aimed to determine the extent to which providers and coaches adhered to the service specification outlined by NHS England. An observational qualitative study was conducted to examine the delivery of both one-to-one and group-based delivery of programme sessions. Observations of 122 sessions across eight programme delivery samples and two service providers were completed. Adherence to the service specification was stronger for those outcomes that were easily measurable, such as weight and blood glucose, while less tangible elements of the specification, such as empowering service users, and person-centred delivery were less consistently observed. One-to-one sessions were more successful in their person-centred delivery, and the skills of the coaches delivering the sessions had a strong impact on adherence to the specification. Overall, the results show that there was variability by provider and delivery mode in the extent to which sessions of the NHS Low-Calorie Diet Programme reflected the intended service specification. In subsequent programmes it is recommended that one-to-one sessions are used, with accompanying peer support, and that providers improve standardised training and quality assurance to ensure specification adherence.

Ketogenic diet combined with intermittent fasting: an option for type 2 diabetes remission?

With increasing attention to diabetes remission, various special dietary patterns have been found to be effective in achieving diabetes remission. The effect of a single dietary pattern on lowering blood glucose is clear, but studies on the synergistic effects of different dietary patterns are limited. This article describes the types of intermittent fasting and ketogenic diets, potential mechanisms, contraindications of combination diets, recommendations for combination diets, and their health outcomes. This paper aims to illustrate the evidence for intermittent fasting combined with a ketogenic diet on outcomes of diabetes remission and effect on blood glucose control. Knowledge of these findings can help doctors and patients determine dietary patterns for achieving diabetes remission and understanding their application.

A qualitative study of the perceptions and experiences of participants and healthcare professionals in the DiRECT-Australia type 2 diabetes remission service.

BACKGROUND: The UK Diabetes Remission Clinical Trial (DiRECT) study was replicated in an Australian primary care setting. This qualitative study aimed to explore and understand the perceptions and experiences of both participants and healthcare professionals (HCPs) involved in the DiRECT-Australia Type 2 Diabetes Remission Service. METHODS: All participants and HCPs delivering the service were invited to participate in semi-structured interviews via online videoconferencing. The interview guides explored perceptions and experiences in DiRECT-Australia, covering aspects such as barriers and facilitators to recruitment and participation, motivations and challenges across service phases, adequacy of support provided and the overall acceptability of the service. All interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. RESULTS: Eight DiRECT-Australia participants and six HCPs (three general practitioners, two practice nurses and one dietitian) participated. Four overarching themes were identified: (1) Enablers and barriers to recruitment and continuous participation in DiRECT-Australia; (2) Motivators and overcoming barriers across the total diet replacement, food reintroduction and weight maintenance phases; (3) Importance of participant-HCP interactions and continuous support; (4) Acceptance and long-term need for DiRECT-Australia. Adherence to total diet replacement was less challenging than anticipated by participants. Transitioning to the food reintroduction phase was difficult but overcome through HCP support. DiRECT-Australia was well accepted by both participants and HCPs, and participants expressed willingness to continue with the service, if provided on a long-term basis. CONCLUSIONS: Both participants and HCPs were highly interested in the new diabetes remission service set up in an Australian primary care setting. The acceptability of DiRECT-Australia was underscored by participants emphasising the effectiveness of the service in achieving significant weight loss and diabetes remission. There is a need for long-term and wider implementation of the service to ensure that anyone with recent onset type 2 diabetes is offered the best possible chance to achieve remission.

Mid-Term Diabetes Remission Outcome in Patients with BMI ≤ 30 kg/m2 Following Sleeve Gastrectomy.

BACKGROUND: Bariatric and metabolic surgery is recommended for Asian patients with type 2 diabetes mellitus (T2DM) and BMI ≥ 27.5 kg/m2. However, mid to long-term ·evidence is still lacking. METHODS: Patients' data that underwent laparoscopic sleeve gastrectomy (SG) as the primary surgery at the Affiliated Hospital of Xuzhou Medical University were analyzed. Patients with T2DM diagnosed with either fasting blood glucose (FBG) ≥ 7.0 mmol/L or glycosylated hemoglobin (HbA1c) level ≥ 7.0% and 27.5 ≤ BMI ≤ 30 kg/m2 were included. RESULTS: 24 patients (7 male and 17 female) were included in this study. With a mean follow-up duration of 4.5 ± 1.1 years, the mean percentage of total weight loss (%TWL) was 14.4 ± 6.7%. Postoperatively, nine patients (37%) still required oral anti-diabetic medications, while no patients used insulin. FBG and HbA1c levels declined to 6.3 ± 1.5 mmol/L and 6.0 ± 1.0%, respectively. Fifteen patients (63%) were with HbA1c levels < 7% and without medication requirements, five patients (21%) were with HbA1c levels < 7% with the help of oral anti-diabetic medication, and four patients (16%) were with HbA1c levels > 7% with the help of oral anti-diabetic medication. CONCLUSIONS: Our study provides further evidence that SG could result in both T2DM improvement and remission in patients with BMI ≤ 30 kg/m2. Longer follow-up duration and larger sample will be needed in the future.

A novel model for predicting diabetes remission after bariatric surgery based on the measurement of C-peptide and creatinine in serum: A pilot study.

BACKGROUND AND AIMS: Bariatric surgery is effective for treating type 2 diabetes (T2D) in patients with obesity, although a significant proportion of these patients do not achieve diabetes remission after the surgery even after significant weight loss and metabolic improvement. C-peptide is a valuable marker of beta cell function and insulin secretion, but renal function must be considered when interpreting measurements in patients with T2D. The study aims to investigate the association of serum levels of C-peptide adjusted for creatinine with diabetes remission and glycemic target achievement after bariatric surgery in patients with obesity and T2D. METHODS AND RESULTS: Prospective data from a cohort of 84 patients with obesity and T2D submitted to Roux-en-Y gastric bypass (RYGB) were collected at baseline and at least a 6-month follow up. A multivariate binomial regression model showed that Ln(C-peptide/creatinine) and age were significantly associated with 6-month T2D remission. The area under the curve for the receiver operating characteristic analysis (AUROC) to predict remission was 0.87, and more accurate than the AUROC based on C-peptide levels alone (0.75). The same model was also able to predict achieving an HbA1c target of 7 % (53 mmol/mol) (AUROC 0.96). CONCLUSION: In conclusion, Ln(C-peptide/creatinine) ratio could be a useful tool in predicting T2D remission and target achievement after RYGB surgery, providing a more accurate reflection of beta cell function in bariatric patients.

Effectiveness of lifestyle interventions/culturally bespoke programmes in South Asian ethnic groups targeting weight loss for prevention and/or remission of type 2 diabetes: a systematic review and meta-analysis of intervention trials.

BACKGROUND: People from South Asian heritage are at high risk of type 2 diabetes, but there are limited specific strategies to prevent and manage this condition. The aim was to assess the effectiveness of culturally bespoke lifestyle programmes in South Asians that target weight loss for the prevention or remission of type 2 diabetes mellitus (T2DM). METHODS: We performed a systematic review and meta-analysis of intervention trials. PubMed, Scopus, MEDLINE (EBSCOhost), CINAHL, PsycINFO and CENTRAL were searched. Human intervention trials (randomised controlled trials and quasi-experimental) investigating the effect of lifestyle interventions on the prevention and remission of T2DM in South Asians were included. Studies including participants at risk of T2DM (prevention trials) and having the disease (remission trials) with duration ≥12 weeks were eligible. For prevention trials, the primary outcome was change in weight (kg) from baseline; for remission trials, it was decrease in HbA1c to non-diabetic levels (HbA1c ≤ 6.5%) without diabetes medications. Prevention trials were separated into (i) lifestyle modification advice and (ii) lifestyle modification advice including a supervised physical activity programme. RESULTS: Twenty-four trials were eligible (21 prevention trials and 3 remission trials). In T2DM prevention trials involving only lifestyle modification advice, the mean postintervention difference in weight between intervention and control groups was -0.65 kg (95% confidence interval [CI]: -1.04, -0.26; p = 0.01). Lifestyle modification advice including a physical activity programme was associated with greater decreases in weight: -1.13 kg (95% CI: -2.04, -0.21; p = 0.02). Fasting blood glucose levels were slightly lower in intervention groups for both intervention subtypes, although there was no significant change in HbA1c levels or 2-h plasma glucose levels. Diabetes remission trials showed potential acceptability but were limited in number and involved a small sample size, and some did not include a control group. CONCLUSIONS: In South Asians, lifestyle interventions for prevention of T2DM offer only modest impacts on weight and glucose control and will unlikely reduce diabetes incidence. Alternative lifestyle interventions co-designed with members of the communities and aimed at both prevention and remission of T2DM must be urgently considered. Systematic review registration number: PROSPERO CRD42022385174 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=385174.

Honeymoon phase in type 1 diabetes mellitus: A window of opportunity for diabetes reversal?

The knowledge of the pathogenesis of type 1 diabetes mellitus (T1DM) continues to rapidly evolve. The natural course of the disease can be described in four clinical stages based on the autoimmune markers and glycemic status. Not all individuals of T1DM progress in that specific sequence. We hereby present a case of T1DM with a classical third phase (honeymoon phase) and discuss the intricacies of this interesting phase along with a possible future promise of "cure" with the use of immunotherapies. We now know that the course of T1DM may not be in only one direction towards further progression; rather the disease may have a waxing and waning course with even reversal of type 1 diabetes concept being discussed. The third phase popularly called the "honeymoon phase", is of special interest as this phase is complex in its pathogenesis. The honeymoon phase of T1DM seems to provide the best window of opportunity for using targeted therapies using various immunomodulatory agents leading to the possibility of achieving the elusive "diabetes reversal" in T1DM. Identifying this phase is therefore the key, with a lot of varying criteria having been proposed.