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Introduction: Subjects with obesity have metabolic risk factors for nerve fibre damage. Because bariatric surgery improves these risk factors we have assessed whether this can ameliorate nerve fibre damage., Methods: Twenty-six obese subjects without diabetes (age: 46.23 ± 8.6, BMI: 48.7 ± 1.5, HbA1c: 38.0 ± 4.5) and 20 controls (age: 48.3 ± 6.2, BMI: 26.8 ± 4.2, HbA1c: 39.1 ± 2.6) underwent detailed assessment of neuropathy at baseline and 12 months after bariatric surgery., Results: Obese subjects had normal peroneal (45.9 ± 5.5 vs. 48.1 ± 4.5, P = 0.1) and sural (46.9 ± 7.6 vs. 47.9 ± 10.6, P = 0.1) nerve conduction velocity, but a significantly higher neuropathy symptom profile (NSP) (4.3 ± 5.7 vs. 0.3 ± 0.6, P = 0.001), vibration perception threshold (VPT) (V) (10.2 ± 6.8 vs. 4.8 ± 2.7, P < 0.0001), warm threshold (C°) (40.4 ± 3.5 vs. 37.2 ± 1.8, P = 0.003) and lower peroneal (3.8 ± 2.2 vs. 4.9 ± 2.2, P = 0.02) and sural (8.9 ± 5.8 vs. 15.2 ± 8.5, P < 0.0001) nerve amplitude, deep breathing-heart rate variability (DB-HRV) (beats/min) (21.7 ± 4.1 vs. 30.1 ± 14, P = 0.001), corneal nerve fibre density (CNFD) (n/mm 2 ) (25.6 ± 5.3 vs. 32.0 ± 3.1, P < 0.0001), corneal nerve branch density (CNBD) (n/mm 2 ) (56.9 ± 27.5 vs. 111.4 ± 30.7, P < 0.0001) and corneal nerve fibre length (CNFL) (mm/mm 2 ) (17.9 ± 4.1 vs. 29.8 ± 4.9, P < 0.0001) compared to controls at baseline. In control subjects there was no change in neuropathy measures over 12 months. However, 12 months after bariatric surgery there was a significant reduction in BMI (33.7 ± 1.7 vs. 48.7 ± 1.5, P = 0.001), HbA1c (34.3 ± 0.6 vs. 38.0 ± 4.5, P = 0.0002), triglycerides (mmol/l) (1.3 ± 0.6 vs. 1.6 ± 0.8, P = 0.005) and low-density lipoprotein cholesterol (mmol/l) (2.7 ± 0.7 vs. 3.1 ± 0.9, P = 0.02) and an increase in high-density lipoprotein cholesterol (mmol/l) (1.2 ± 0.3 vs. 1.04 ± 0.2, P = 0.002). There was a significant improvement in NSP (1.6 ± 2.7 vs. 4.3 ± 5.7, P = 0.004), neuropathy disability score (0.3 ± 0.9 vs. 1.3 ± 2.0, P = 0.03), CNFD (28.2 ± 4.4 vs. 25.6 ± 5.3, P = 0.03), CNBD (64.7 ± 26.1 vs. 56.9 ± 27.5, P = 0.04) and CNFL (20.4 ± 1.2 vs. 17.9 ± 4.1, P = 0.02), but no change in cold and warm threshold, VPT, DB-HRV or nerve conduction velocity and amplitude. Increase in CNFD correlated with a decrease in triglycerides (r = -0.45, P = 0.04)., Conclusion: Obese subjects have evidence of neuropathy, and bariatric surgery leads to an improvement in weight, HbA1c, lipids, neuropathic symptoms and deficits and small nerve fibre regeneration without a change in quantitative sensory testing, autonomic function or neurophysiology.

Obesity is an emerging independent risk factor for susceptibility to and severity of coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Previous viral pandemics have shown that obesity, particularly severe obesity (BMI > 40 kg/m 2 ), is associated with increased risk of hospitalization, critical care admission and fatalities. In this narrative review, we examine emerging evidence of the influence of obesity on COVID-19, the challenges to clinical management from pulmonary, endocrine and immune dysfunctions in individuals with obesity and identify potential areas for further research. We recommend that people with severe obesity be deemed a vulnerable group for COVID-19; clinical trials of pharmacotherapeutics, immunotherapies and vaccination should prioritize inclusion of people with obesity., (© 2020 The Authors. Clinical Obesity published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

We conducted a narrative review of the medical and surgical management of people with obesity and diabetes. Results of this review showed that a 5-10% loss in body weight can be achieved with a change in lifestyle, diet and behaviour and with approved pharmacological therapies in people with obesity and diabetes. New targeted therapies are now available for patients with previously untreatable genetic causes of obesity. Compared to medical treatment, metabolic and bariatric surgery is associated with significantly higher rates of remission from type 2 diabetes and lower rates of incident macrovascular and microvascular complications and mortality. The National Institute for Health and Care Excellence and the American Diabetes Association endorse metabolic and bariatric surgery in obese adults with type 2 diabetes and there may also be a role for this in obese individuals with type 1 diabetes. The paediatric committee of the American Society for Metabolic and Bariatric Surgery have recommended metabolic and bariatric surgery in obese adolescents with type 2 diabetes. Earlier and more aggressive treatment with metabolic and bariatric surgery in obese or overweight people with diabetes can improve morbidity and mortality., (© 2019 Diabetes UK.)

Context: Multiple factors contribute to sexual dysfunction in men with obesity. Sex hormone levels are commonly abnormal in men with obesity and this abnormality is often the focus of management in clinical practice. The role of small fibre neuropathy in obesity-related sexual dysfunction is not well established., Objective: We aimed to investigate the relationship between sexual function, sex hormone levels and small nerve fibre morphology in men with severe obesity., Materials and Methods: A prospective study of 29 men with severe obesity was undertaken. Sexual function was assessed using the European Male Ageing Study Sexual Function Questionnaire. Small nerve fibre morphology was quantified using corneal confocal microscopy. Sex hormone levels were measured by mass spectrophotometry., Results: Erectile dysfunction was present in 72% of the cohort with a higher prevalence of diabetes among the symptomatic group (88% vs 38%, p = 0.006). Corneal nerve fibre length (CNFL) and corneal nerve fibre density (CNFD) were both significantly lower in participants with erectile dysfunction compared to those without (p = 0.039 and p = 0.048 respectively). The erectile function score correlated with CNFL (r = -0.418, p = 0.034) and CNFD (r = -0.411, p = 0.037). Total testosterone and calculated free testosterone levels did not differ significantly between men with or without erectile dysfunction (median 8.8 nmol/L vs 9.0 nmol/L, p = 0.914; and median 176 pmol/L vs 179 pmol/L, p = 0.351 respectively), infrequent sexual thoughts (median 8.1 nmol/L vs 9.2 nmol/L, p = 0.650; and median 184 pmol/L, vs 176 pmol/L, p = 0.619 respectively) and decreased morning erections (median 9.0 nmol/L vs 8.8 nmol/L, p = 0.655; and median 170 pmol/L vs 193 pmol/L, p = 0.278 respectively)., Conclusion: Sexual dysfunction is highly prevalent in men with severe obesity. We found an association between small fibre neuropathy with erectile dysfunction with presence of diabetes a likely a significant contributing factor. We found no associations between testosterone levels with sexual symptoms (including frequency of sexual thoughts). The influence of small nerve fibre neuropathy on response to therapeutic interventions and whether interventions that improve small fibre neuropathy can improve erectile function in this population merits further study., Competing Interests: This study was partially funded by a research donation from AMGEN. This does not alter our adherence to PLOS ONE policies on sharing data and materials. There are no patents, products in development or marketed products associated with this research to declare.

Background: Reaven originally described the clustering of insulin resistance/hyperinsulinaemia, obesity (particularly visceral), altered cytokine levels, glucose intolerance, hypertriglyceridaemia and low high-density lipoprotein cholesterol. Subsequently, a potentially highly atherogenic small, dense low-density lipoprotein was also reported. We have studied the effect of bariatric surgery on this and other risk factors for atherosclerosis., Methods: Forty patients (20 with type 2 diabetes mellitus) undergoing bariatric surgery were studied before and 1 year after bariatric surgery., Results: Twelve months after bariatric surgery, median body mass index had decreased from 49.5 to 36.5 kg/m 2 , fasting insulin from 21.3 to 7.8 mU/L and insulin resistance (homeostatic model assessment of insulin resistance) from 5.9 to 1.8 (all p < 0.001). Thirteen out of 20 patients had remission from type 2 diabetes mellitus. Highly sensitive C-reactive protein, interleukin-6, fasting triglycerides ( p < 0.001) and small, dense low-density lipoprotein ( p < 0.001) decreased, while high-density lipoprotein cholesterol increased ( p < 0.001) significantly, irrespective of having type 2 diabetes mellitus and/or being treated with statin therapy before surgery., Conclusion: The association between marked weight loss and change in insulin resistance and hyperinsulinaemia with the change in small, dense low-density lipoprotein and interleukin-6 warrants further investigation. Bariatric surgery provides a model for investigating the mechanisms linking insulin resistance/hyperinsulinaemia to atherosclerosis.

Obesity is a major risk factor for metabolic disease, with white adipose tissue (WAT) inflammation emerging as a key underlying pathology. We detail that mice lacking Reverbα exhibit enhanced fat storage without the predicted increased WAT inflammation or loss of insulin sensitivity. In contrast to most animal models of obesity and obese human patients, Reverbα(-/-) mice exhibit elevated serum adiponectin levels and increased adiponectin secretion from WAT explants in vitro, highlighting a potential anti-inflammatory role of this adipokine in hypertrophic WAT. Indeed, adiponectin was found to suppress primary macrophage responses to lipopolysaccharide and proinflammatory fatty acids, and this suppression depended on glycogen synthase kinase 3β activation and induction of A20. Attenuated inflammatory responses in Reverbα(-/-) WAT depots were associated with tonic elevation of A20 protein and ex vivo shown to depend on A20. We also demonstrate that adipose A20 expression in obese human subjects exhibits a negative correlation with measures of insulin sensitivity. Furthermore, bariatric surgery-induced weight loss was accompanied by enhanced WAT A20 expression, which is positively correlated with increased serum adiponectin and improved metabolic and inflammatory markers, including C-reactive protein. The findings identify A20 as a mediator of adiponectin anti-inflammatory action in WAT and a potential target for mitigating obesity-related pathology., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Background: Gastric bypass surgery induces early remission or significant improvement in type 2 diabetes (T2D)., Aim: To assess effectiveness of stopping glucose-lowering treatment at the time of surgery., Design: Observational cohort analysis., Methods: We identified 101 patients (62 women) with T2D who had undergone gastric bypass surgery at a mean (SD, standard deviation) age of 51.4 (9.0) years. We recorded weight, body mass index (BMI), glycosylated haemoglobin (HbA1c), blood pressure (BP), total and high-density lipoprotein (HDL) cholesterol preoperatively and at a median 4, 12 and 24 months postoperatively, and changes to glucose-lowering therapy., Results: Mean (SD) baseline BMI was 50.3 (6.3) kg/m(2), HbA1c 65.3 (18.5) mmol/mol, systolic BP 146.0 (18.0) mmHg, diastolic BP 87.0 (10.8) mmHg and total cholesterol-to-HDL cholesterol ratio 4.0 (1.2). Mean (95% confidence interval) reduction in BMI was 16.4 (14.1-18.7) kg/m(2), HbA1c 23.6 (17.6-29.6) mmol/mol, systolic BP 12.9 (5.9-19.8) mmHg, diastolic BP 6.1 (1.8-10.5) mmHg and total cholesterol-to-HDL cholesterol ratio 1.1 (0.6-1.5) at 24 months (P < 0.001 for all measures). Although 91% of patients were receiving glucose-lowering therapies preoperatively, complete (HbA1c < 42 mmol/mol) and partial (HbA1c 42-48 mmol/mol) remissions of T2D were seen in 62.1% and 5.2% at 2 years postoperatively., Conclusions: Cessation of glucose-lowering therapies in people with T2D at the time of gastric bypass surgery was clinically effective. The majority of patients remained in complete or partial remission of diabetes up to 2 years postoperatively., (© The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

In recent decades we have seen a surge in the incidence of diabetes in industrialized nations; a threat which has now extended to the developing world. Type 2 diabetes is associated with significant microvascular and macrovascular disease, with considerable impact on morbidity and mortality. Recent evidence has cast uncertainty on the benefits of very tight glycaemic goals in these individuals. The natural history of disease follows an insidious course from disordered glucose metabolism in a pre-diabetic state, often with metabolic syndrome and obesity, before proceeding to diabetes mellitus. In the research setting, lifestyle, pharmacological and surgical intervention targeted against obesity and glycaemia has shown that metabolic disturbances can be halted and indeed regressed if introduced at an early stage of disease. In addition to traditional anti-diabetic medications such as the glinides, sulphonylureas and the glitazones, novel therapies manipulating the endocannabinoid system, neurotransmitters, intestinal absorption and gut hormones have shown dual benefit in weight loss and glycaemic control normalisation. Whilst these treatments will not and should not replace lifestyle change, they will act as invaluable adjuncts for weight loss and aid in normalising the metabolic profile of individuals at risk of diabetes. Utilizing novel therapies to prevent diabetes should be the focus of future research, with the aim of preventing the challenging microvascular and macrovascular complications, and ultimately cardiovascular death.