The many faces of diabetes. Is there a need for re-classification? A narrative review

The alarming rise in the worldwide prevalence of obesity and associated type 2 diabetes mellitus (T2DM) have reached epidemic portions. Diabetes in its many forms and T2DM have different physiological backgrounds and are difficult to classify. Bariatric surgery (BS) is considered the most effective treatment for obesity in terms of weight loss and comorbidity resolution, improves diabetes, and has been proven superior to medical management for the treatment of diabetes. The term metabolic surgery (MS) describes bariatric surgical procedures used primarily to treat T2DM and related metabolic conditions. MS is the most effective means of obtaining substantial and durable weight loss in individuals with obesity. Originally, BS was used as an alternative weight-loss therapy for patients with severe obesity, but clinical data revealed its metabolic benefits in patients with T2DM. MS is more effective than lifestyle or medical management in achieving glycaemic control, sustained weight loss, and reducing diabetes comorbidities. New guidelines for T2DM expand the use of MS to patients with a lower body mass index.Evidence has shown that endocrine changes resulting from BS translate into metabolic benefits that improve the comorbid conditions associated with obesity, such as hypertension, dyslipidemia, and T2DM. Other changes include bacterial flora rearrangement, bile acids secretion, and adipose tissue effect.This review aims to examine the physiological mechanisms in diabetes, risks for complications, the effects of bariatric and metabolic surgery and will shed light on whether diabetes should be reclassified.

The Impact of Bariatric Surgery on the Muscle Mass in Patients with Obesity: 2-Year Follow-up

Purpose Bariatric surgery (BS) induces a significant and sustained weight loss in patients with severe obesity (SO). Nevertheless, apart from significantly reducing body fat, fat-free mass (FFM) might also be lost. At present, there is little and controversial data in the literature regarding the impact of BS on FFM. In recent years, bioimpedance (BIA) has emerged as a reliable test to assess body composition easily to use in the daily clinical practice. On the bases, the aim of the present study is to evaluate the impact of BS on the FFM, evaluated by means of BIA. Material and Methods This is a prospective, observational study, including consecutive patients with SO that underwent BS between February 2018 and February 2019 at our center. At baseline, 1, 6, 12, and 24 months after the BS, all the patients underwent complete medical history, physical and anthropometric evaluation, and body composition assessment by means of BIA (using Bodystat QuadScan4000®). Results Eighty-five patients with SO were recruited, 72.9% females, aged 45.54 ± 9.98 years, pre-BS BMI 43.87 ± 6.52 kg/m2. FFM significantly decreased continuously after BS at all timepoints. The loss of FFM 24 months post-BS accounted for approximately 21.71 ± 13.9% of the total weight loss, and was independent of BS technique or protein metabolism. Pre-BS HOMA-IR and FFM were independent predictors of FFM at 24 months. Conclusions Significant and early loss of FFM in patients with SO that undergo BS was seen, not related to protein metabolism parameters or the BS technique used, suggesting an independent mechanism. Graphical abstract

Impact of Bariatric Surgery on Adipose Tissue Biology

Bariatric surgery (BS) procedures are actually the most effective intervention to help subjects with severe obesity achieve significant and sustained weight loss. White adipose tissue (WAT) is increasingly recognized as the largest endocrine organ. Unhealthy WAT expansion through adipocyte hypertrophy has pleiotropic effects on adipocyte function and promotes obesity-associated metabolic complications. WAT dysfunction in obesity encompasses an altered adipokine secretome, unresolved inflammation, dysregulated autophagy, inappropriate extracellular matrix remodeling and insufficient angiogenic potential. In the last 10 years, accumulating evidence suggests that BS can improve the WAT function beyond reducing the fat depot sizes. The causal relationships between improved WAT function and the health benefits of BS merits further investigation. This review summarizes the current knowledge on the short-, medium- and long-term outcomes of BS on the WAT composition and function.

Nutritional Management in Bariatric Surgery Patients

The obesity epidemic, mainly due to lifestyle changes in recent decades, leads to serious comorbidities that reduce life expectancy. This situation is affecting the health policies of many nations around the world. Traditional measures such as diet, physical activity, and drugs are often not enough to achieve weight loss goals and to maintain the results over time. Bariatric surgery (BS) includes various techniques, which favor rapid and sustained weight loss. BS is a useful and, in most cases, the best treatment in severe and complicated obesity. In addition, it has a greater benefit/risk ratio than non-surgical traditional therapies. BS can allow the obese patient to lose weight quickly compared with traditional lifestyle changes, and with a greater probability of maintaining the results. Moreover, BS promotes improvements in metabolic parameters, even diabetes remission, and in the quality of life. These changes can lead to an increase of life expectancy by over 6 years on average. The nutrition of people before and after BS must be the subject of indications from a trained staff, and patients must be followed in the subsequent years to reduce the risk of malnutrition and the associated problems. In particular, it is still debated whether it is necessary to lose weight prior to surgery, a procedure that can facilitate the surgeon’s work reducing the surgical risk, but at the same time, lengthens preparation times increasing the risks associated with concomitant pathologies. Furthermore, preventing nutritional deficiencies prior to the intervention can improve the results and reduce short- and long-term mortality.

Effects of sustained weight loss on outcomes associated with obesity comorbidities and healthcare resource utilization

Objective Determine the impact of long-term non-surgical weight loss maintenance on clinical relevance for osteoarthritis, cancer, opioid use, and depression/anxiety and healthcare resource utilization. Methods A cohort of adults receiving primary care within Geisinger Health System between 2001–2017 was retrospectively studied. Patients with ≥3 weight measurements in the two-year index period and obesity at baseline (BMI ≥30 kg/m2) were categorized: Obesity Maintainers (reference group) maintained weight within +/-3%; Weight Loss Rebounders lost ≥5% body weight in year one, regaining ≥20% of weight loss in year two; Weight Loss Maintainers lost ≥5% body weight in year one, maintaining ≥80% of weight loss. Association with development of osteoarthritis, cancer, opioid use, and depression/anxiety, was assessed; healthcare resource utilization was quantified. Magnitude of weight loss among maintainers was evaluated for impact on health outcomes. Results In total, 63,567 patients were analyzed including 67% Obesity Maintainers, 19% Weight Loss Rebounders, and 14% Weight Loss Maintainers; median follow-up was 9.7 years. Time until osteoarthritis onset was delayed for Weight Loss Maintainers compared to Obesity Maintainers (Logrank test p <0.0001). Female Weight Loss Maintainers had a 19% and 24% lower risk of developing any cancer (p = 0.0022) or obesity-related cancer (p = 0.0021), respectively. No significant trends were observed for opioid use. Weight loss Rebounders and Maintainers had increased risk (14% and 25%) of future treatment for anxiety/depression (both <0.0001). Weight loss maintenance of >15% weight loss was associated with the greatest decrease in incident osteoarthritis. Healthcare resource utilization was significantly higher for Weight Loss Rebounders and Maintainers compared to Obesity Maintainers. Increased weight loss among Weight Loss Maintainers trended with lower overall healthcare resource utilization, except for hospitalizations. Conclusions In people with obesity, sustained weight loss was associated with greater clinical benefits than regained short-term weight loss and obesity maintenance. Higher weight loss magnitudes were associated with delayed onset of osteoarthritis and led to decreased healthcare utilization.

Evaluation of the Effects of Bariatric Surgery in Terms of Weight Loss and Diabetes Remission in the Indian Population

<b><i>Objectives:</i></b> The growing prevalence of obesity rates worldwide is associated with an upsurge in its comorbidities, particularly type 2 diabetes mellitus (T2DM). Bariatric surgery is a proven treatment modality for producing sustained weight loss and resolution of associated T2DM providing marked improvement in quality of life with rapid recovery. This study aims to investigate the effects of laparoscopic sleeve gastrectomy (LSG), Roux-en-Y gastric bypass (RYGB), and mini-gastric bypass (MGB) on obese patients suffering from T2DM in the Indian population and their long-term association with regard to diabetes remission, resolution of comorbidities, and percentage EWL. <b><i>Methods:</i></b> Retrospective data of obese patients with T2DM (preoperative BMI 45.37 ± 8.1) who underwent bariatric surgery (RYGB, LSG, and MGB) were analyzed in this study over a period of 9 years. The mean follow-up period was 2.2 years. Following surgery, the clinical outcome on BMI, resolution of percentage weight loss, and T2DM were studied. The predictive factors of diabetic remission after surgery were determined. Student’s <i>t</i> test and ANOVA and McNemar’s test were applied. <b><i>Results:</i></b> Out of a total of 274 patients, complete remission of T2DM was achieved in 52.9% (<i>n</i> = 145) with mean fasting blood glucose and glycated hemoglobin values being 6.1 ± 0.769 (<i>p</i> = 0.00) at 1 year after surgery. The independent predictive factors of remission were age, gender, BMI, preoperative comorbidities, and % EWL. Gender had no correlation with the chance of achieving disease remission. <b><i>Conclusion:</i></b> Based on our results, bariatric surgery proves to be a successful treatment option resulting in sustained weight loss in obese patients suffering from T2DM. It is found to be beneficial for the long-term resolution of T2DM and improving comorbidities such as hypertension and dyslipidemia. The outcome of the different surgical methods is found to be similar for all patients irrespective of the independent predictors of complete remission.

1129 UK Based Experience of The Elipsetm Intragastric Balloon; Short Term Safety and Effectiveness

Aim Intra Gastric Balloons (IGB) have been used over the last three decades as a minimally invasive, non-surgical weight-loss option. The ElipseTM gastric balloon (EIGB) is a ‘procedure-less’ gastric balloon which can be placed in an average of 20 minutes without the need of endoscopy or sedation. The aim of our study is to investigate the first cohort of patients in uk who underwent IGB capsule and short term follow up. Method Single centre retrospective study of the first consecutive 202 patients that had the Eclipse IGB inserted between May 2018 and November 2020. Patients swallow the ElipseTM capsule and pre-inflation x-ray is taken to confirm correct positioning after which the gastric balloon is inflated with 550mls of sterile water and a post-inflation x-ray is taken. The balloon is designed to be in-situ for 4 months and then automatically deflates. Results Out of 202 patients 24 were lost to follow-up, 146 patients followed up to an average of 15 weeks, while 26 patients followed up to 4 weeks. Average weight loss at 4 weeks was 6% Total Weight Loss (%TWL) while at last follow up 9.63% TWL. Majority of patients experienced post procedural reflux, abdominal pain, bloating and vomiting. 6 patients had early removal of the balloon due to severe symptoms (4), pancreatitis (1) and hyperinflation (1). 1 had early expulsion at 2 months. Conclusions Eclipse IGB is safe and effective in selective patients, however long-term follow is needed to compare it with the other balloons in terms of significant and sustained weight loss.

Bariatric Surgery Outcomes in Patients with Latent Autoimmune Diabetes of the Adult

Bariatric surgery is a very effective treatment for obesity-associated type 2 diabetes. However, the benefits of bariatric surgery in patients with obesity and autoimmune diabetes, such as type 1 diabetes and latent autoimmune diabetes in adults (LADA), are controversial. We report 3 female patients with obesity and LADA who underwent laparoscopic Roux-en-Y gastric bypass &#x3e;10 years ago. The patients were diagnosed with LADA both 1 and 9 years before (<i>n</i> = 2) or 11 years after the surgery (<i>n</i> = 1). Patients preoperative body mass index ranged from 36 to 47 kg/m² and improved to 23–37 kg/m² in the last follow-up visit, 10–15 years after surgery. Daily insulin dose also decreased from an average of 0.68 to 0.45 IU/kg in those patients treated with insulin before bariatric surgery. Only one patient developed diabetes-related target organ damage. This study shows that patients with LADA depict remarkable reduction of body weight and insulin requirements over long-term after bariatric surgery. So, LADA should not be considered a contraindication for bariatric surgery yet should only be recommended for patients with concomitant obesity with the primary aim of achieving sustained weight loss.

Differing susceptibility of C57BL/6J and DBA/2J mice—parents of the murine BXD family, to severe acute respiratory syndrome coronavirus infection

The ongoing coronavirus disease-2019 (COVID-19) pandemic, caused by a novel coronavirus termed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that is closely related to SARS-CoV, poses a grave threat to global health and has devastated societies worldwide. One puzzling aspect of COVID-19 is the impressive variation in disease manifestations among infected individuals, from a majority who are asymptomatic or exhibit mild symptoms to a smaller, largely age-dependent fraction who develop life-threatening conditions. Some of these differences are likely the consequence of host genetic factors. Systems genetics using diverse and replicable cohorts of isogenic mice represents a powerful way to dissect those host genetic differences that modulate microbial infections. Here we report that the two founders of the large BXD family of mice—C57BL/6J and DBA/2J, differ substantially in their susceptibility to a mouse-adapted SARS-CoV, MA15. Following intranasal viral challenge, DBA/2J develops a more severe disease than C57BL/6J as evidenced by more pronounced and sustained weight loss. Disease was accompanied by high levels of pulmonary viral replication in both strains early after infection but substantially delayed viral clearance in DBA/2J. Our data reveal that the parents of the BXD family are segregated by clear phenotypic differences during MA15 infection and support the feasibility of using this family to systemically dissect the complex virus-host interactions that modulate disease progression and outcome of infection with SARS-CoV, and provisionally also with SARS-CoV-2.