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The global escalation of obesity has made it a worldwide health concern, notably as a leading risk factor for cardiovascular disease (CVD). Extensive evidence corroborates its association with a range of cardiac complications, including coronary artery disease, heart failure, and heightened vulnerability to sudden cardiac events. Additionally, obesity contributes to the emergence of other cardiovascular risk factors including dyslipidaemia, type 2 diabetes, hypertension, and sleep disorders, further amplifying the predisposition to CVD. To adequately address CVD in patients with obesity, it is crucial to first understand the pathophysiology underlying this link. We herein explore these intricate mechanisms, including adipose tissue dysfunction, chronic inflammation, immune system dysregulation, and alterations in the gut microbiome.Recent guidelines from the European Society of Cardiology underscore the pivotal role of diagnosing and treating obesity to prevent CVD. However, the intricate relationship between obesity and CVD poses significant challenges in clinical practice: the presence of obesity can impede accurate CVD diagnosis while optimizing the effectiveness of pharmacological treatments or cardiac procedures requires meticulous adjustment, and it is crucial that cardiologists acknowledge the implications of excessive weight while striving to enhance outcomes for the vulnerable population affected by obesity. We, therefore, sought to overcome controversial aspects in the clinical management of heart disease in patients with overweight/obesity and present evidence on cardiometabolic outcomes associated with currently available weight management interventions, with the objective of equipping clinicians with an evidence-based approach to recognize and address CVD risks associated with obesity., Competing Interests: Conflict of interest: All the authors have no conflict of interest to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Introduction: Patient engagement is essential to achieve long-term goals in obesity management. It is crucial to identify patients' perspectives, misperceptions and unmet educational needs on obesity etiology and treatments, to establish a correct therapeutic alliance between healthcare providers and patients., Methods: Objective: This study, promoted by the regional section of the Italian Obesity Society (SIO Lazio), explores attitudes towards obesity, self-awareness, misperceptions of weight loss strategies, experiences of weight stigma and educational needs of patients living with overweight or obesity. Design and subject: We conducted an anonymous survey among patients who accessed an Obesity Management Centers across the Lazio region of Italy for the first time, from October 2023 to April 2024. Approach: The survey consisted of 27 closed-ended questions grouped into 4 sections: (1) sociodemographic factors and self-reported anthropometric measures; (2) self-awareness and attitudes towards obesity and weight loss strategies; (3) experiences of obesity-related stigma; (4) knowledge and perceptions of obesity treatment options., Results: A total of 300 patients (67.9% women, aged 49.1 ± 14.4 years) returned completed surveys. Despite the self-reported BMI 35.3 ± 7.0 kg/m 2 with three out of four (75.3%) of participants having a BMI ≥ 30 kg/m 2 , only 49% correctly identified themselves as affected by obesity. Almost one-third of the patients believed that obesity does not imply a genetic predisposition (31.9%) and that it is always secondary to psychological or behavioral disorders (29.7%). Interestingly, 66.7% of the patients declared themselves as completely responsible for their own condition and 39.4% considered obesity always treatable by means of lifestyle interventions. Stigma and weight discrimination in healthcare settings were reported by a substantial portion of patients (31.9%). A perception of inadequate support from the National Healthcare System emerged in most of the interviews (61.9%). Most patients (72.1%) felt they were not sufficiently informed about anti-obesity medications and a relevant part of their knowledge was derived from healthcare providers (57.7%) and social networks (19.1%). Weight loss medications were considered useful (63.2%) or necessary (18.4%) by the majority of patients, but only 60.1% would accept without any hesitation a pharmacologic treatment. The main reasons for refusal of pharmacological treatments were the belief that lifestyle intervention is a sufficient treatment (46.9%), the fear of adverse effects (28.1%) and feeling defeated (12.5%). Similarly, for most of participants bariatric surgery is useful (73.3%) or necessary (13.6%)., Conclusion: Despite advancements in obesity research, this study underscores the need to improve patient education and public awareness to optimize the management and treatment of obesity. Addressing misconceptions, stigma, and gaps in knowledge are critical steps towards improving patient outcomes and fostering a supportive healthcare environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The handling editor MW declared a shared affiliation with the authors SM & DC at the time of review. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Colangeli, Russo, Capristo, Mariani, Tuccinardi, Manco, Scipione, Parrotta, Capoccia and Guglielmi.)

Post-bariatric hypoglycaemia (PBH) is a metabolic complication of bariatric surgery (BS), consisting of low post-prandial glucose levels in patients having undergone bariatric procedures. While BS is currently the most effective and relatively safe treatment for obesity and its complications, the development of PBH can significantly impact patients' quality of life and mental health. The diagnosis of PBH is still challenging, considering the lack of definitive and reliable diagnostic tools, and the fact that this condition is frequently asymptomatic. However, PBH's prevalence is alarming, involving up to 88% of the post-bariatric population, depending on the diagnostic tool, and this may be underestimated. Given the prevalence of obesity soaring, and an increasing number of bariatric procedures being performed, it is crucial that physicians are skilled to diagnose PBH and promptly treat patients suffering from it. While the milestone of managing this condition is nutritional therapy, growing evidence suggests that old and new pharmacological approaches may be adopted as adjunct therapies for managing this complex condition., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Fibroblast growth factor 21 (FGF-21), previously recognized as a marker of liver damage and a potential drug target in non-alcoholic fatty liver disease (NAFLD), has unclear implications in hepatitis C virus (HCV) infections. This study aimed to investigate the relationship between FGF-21 levels and liver health in patients with HCV undergoing direct-acting antiviral (DAA) treatment. Forty-five patients were assessed for liver stiffness, blood chemistry, and other relevant metrics before and after achieving sustained viral response (SVR), defined as the absence of detectable HCV-RNA after 24 weeks of treatment. Post-treatment, all patients showed a decrease in liver stiffness and improved liver enzyme levels (AST and ALT), alongside an increase in FGF-21 levels. Interestingly, the increase in FGF-21 correlated negatively with liver stiffness but showed no correlation with hepatic steatosis. The observed elevation in FGF-21 levels at SVR following DAA therapy for chronic HCV infection can be attributed to the restoration of hepatic function, including its synthetic capabilities. Specifically, the mitigation of liver fibrosis post-HCV eradication is expected to lead to improvements in liver function, such as enhanced albumin and FGF-21 production. This improvement in synthetic function likely drives the increase in FGF-21 levels, rather than changes in liver fat content. We suggest a potential role of FGF-21 as a marker of fibrosis and hepatic cytotoxicity and as a drug target beyond NAFLD, to be confirmed by additional studies.

Purpose: Women with type 1 diabetes mellitus (T1D), especially those with suboptimal glucose control, have 3-4 greater chances of having babies with birth defects compared to healthy women. We aimed to evaluate glucose control and insulin regimen modifications during the pregnancy of women with T1D, comparing the offspring's weight and the mother's weight change and diet with those of non-diabetic, normal-weight pregnant women., Methods: Women with T1D and age-matched healthy women controls (CTR) were consecutively enrolled among pregnant women with normal weight visiting our center. All patients underwent physical examination and diabetes and nutritional counseling, and completed lifestyle and food intake questionnaires., Results: A total of 44 women with T1D and 34 healthy controls were enrolled. Women with T1D increased their insulin regimen during pregnancy, going from baseline 0.9 ± 0.3 IU/kg to 1.1 ± 0.4 IU/kg (p = 0.009), with a concomitant significant reduction in HbA1c (p = 0.009). Over 50% of T1D women were on a diet compared to < 20% of healthy women (p < 0.001). Women with T1D reported higher consumption of complex carbohydrates, milk, dairy foods, eggs, fruits, and vegetables, while 20% of healthy women never or rarely consumed them. Despite a better diet, women with T1D gained more weight (p = 0.044) and gave birth to babies with higher mean birth weight (p = 0.043), likely due to the daily increase in insulin regimen., Conclusion: A balance between achieving metabolic control and avoiding weight gain is crucial in the management of pregnant women with T1D, who should be encouraged to further improve lifestyle and eating habits with the aim of limiting upward insulin titration adjustments to a minimum., (© 2023. The Author(s).)

Background & Aims: Noninvasive assessment of histological features of nonalcoholic fatty liver disease (NAFLD) has been an intensive research area over the last decade. Herein, we aimed to develop a simple noninvasive score using routine laboratory tests to identify, among individuals at high risk for NAFLD, those with fibrotic nonalcoholic steatohepatitis (NASH) defined as NASH, NAFLD activity score ≥4, and fibrosis stage ≥2., Methods: The derivation cohort included 264 morbidly obese individuals undergoing intraoperative liver biopsy in Rome, Italy. The best predictive model was developed and internally validated using a bootstrapping stepwise logistic regression analysis (2000 bootstrap samples). Performance was estimated by the area under the receiver operating characteristic curve (AUROC). External validation was assessed in 3 independent European cohorts (Finland, n = 370; Italy, n = 947; England, n = 5368) of individuals at high risk for NAFLD., Results: The final predictive model, designated as Fibrotic NASH Index (FNI), combined aspartate aminotransferase, high-density lipoprotein cholesterol, and hemoglobin A1c. The performance of FNI for fibrotic NASH was satisfactory in both derivation and external validation cohorts (AUROC = 0.78 and AUROC = 0.80-0.95, respectively). In the derivation cohort, rule-out and rule-in cutoffs were 0.10 for sensitivity ≥0.89 (negative predictive value, 0.93) and 0.33 for specificity ≥0.90 (positive predictive value, 0.57), respectively. In the external validation cohorts, sensitivity ranged from 0.87 to 1 (negative predictive value, 0.99-1) and specificity from 0.73 to 0.94 (positive predictive value, 0.12-0.49) for rule-out and rule-in cutoff, respectively., Conclusion: FNI is an accurate, simple, and affordable noninvasive score which can be used to screen for fibrotic NASH in individuals with dysmetabolism in primary health care., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Erectile dysfunction is recognized as one of the complications of diabetes mellitus. To date, a wide gap of knowledge is present on the efficacy of pharmacological treatments of diabetes mellitus on erectile function, acting not only through metabolic control. Similarly, the effects of different diet regimens on erectile dysfunction are still debated., Objectives: We aimed to explore the effects of diet and antihyperglycemic drugs, considering both old and novel therapeutic approaches, on erectile function., Materials/methods: We performed a systematic review, following the PRISMA guidelines. The research was conducted on studies reporting erectile dysfunction assessment in subjects with diabetes and the relationship with diet and antihyperglycemic drugs., Results: The Mediterranean diet was effective in most studies for the protection of erectile function. Furthermore, antihyperglycemic drugs seem to show an overall protective role on erectile function., Discussion/conclusion: Although encouraging results are present for all classes of antihyperglycemic drugs, several studies are needed in humans, mainly on acarbose, pioglitazone, dipeptidyl-peptidase-4 inhibitors, and sodium-glucose cotransporter-2 inhibitors., (© 2022 American Society of Andrology and European Academy of Andrology.)

Introduction: The Very Low-Calorie Ketogenic Diet (VLCKD) has emerged as a safe and effective intervention for the management of metabolic disease. Studies examining weight loss predictors are scarce and none has investigated such factors upon VLCKD treatment. Among the molecules involved in energy homeostasis and, more specifically, in metabolic changes induced by ketogenic diets, Fibroblast Growth Factor 21 (FGF21) is a hepatokine with physiology that is still unclear., Methods: We evaluated the impact of a VLCKD on weight loss and metabolic parameters and assessed weight loss predictors, including FGF21. VLCKD is a severely restricted diet (<800 Kcal/die), characterized by a very low carbohydrate intake (<50 g/day), 1.2-1.5 g protein/kg of ideal body weight and 15-30 g of fat/day. We treated 34 patients with obesity with a VLCKD for 45 days. Anthropometric parameters, body composition, and blood and urine chemistry were measured before and after treatment., Results: We found a significant improvement in body weight and composition and most metabolic parameters. Circulating FGF21 decreased significantly after the VLCKD [194.0 (137.6-284.6) to 167.8 (90.9-281.5) p < 0.001] and greater weight loss was predicted by lower baseline FGF21 (Beta = -0.410; p = 0.012), male sex (Beta = 0.472; p = 0.011), and central obesity (Beta = 0.481; p = 0.005)., Discussion: VLCKD is a safe and effective treatment for obesity and obesity related metabolic derangements. Men with central obesity and lower circulating FGF21 may benefit more than others in terms of weight loss obtained following this diet. Further studies investigating whether this is specific to this diet or to any caloric restriction are warranted., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ernesti, Baratta, Watanabe, Risi, Camajani, Persichetti, Tuccinardi, Mariani, Lubrano, Genco, Spera, Gnessi and Basciani.)

With the prevalence of obesity alarmingly increasing, it is of primary interest to identify those factors predicting the success of anti-obesity therapeutic strategies currently adopted in clinical practice, and in particular, those of bariatric procedures showing the greatest success in terms of weight loss and maintenance in both the short and long term. Given sex-related differences in psychosocial status, hormonal homeostasis, and body fat distribution, it is likely that the response to different weight management strategies differs by sex. The objective was to elucidate the effect of sex on different bariatric procedures' efficacy and safety outcomes. Searches of PubMed, Cochrane, and Embase databases were performed, followed by hand-searching of reference lists from all relevant articles. We included all the studies evaluating the effect of bariatric procedures on body mass index loss (BMIL), and/or percentage excess weight loss (%EWL), and/or percentage excess body mass index loss, and/or percentage of responders, and/or short-/long-term complications and co-morbidity resolution, broken down by sex. Twenty-seven studies with a total of 114,919 patients were included. Men were more likely to achieve greater BMIL, consistent with higher male baseline BMI, and women were 2.87 times more likely to be classified as weight responders (95% confidence interval [CI]: 1.90-4.34), as well as to perform better in terms of %EWL (95% CI: .13-.54). Upon subgroup analysis based on bariatric procedure, women were more likely to be successful in terms of %EWL upon bioenteric intragastric balloon (BIB) placement (.72, 95% CI: .42-1.02). There was no sex difference regarding investigated co-morbidity resolution (hypertension, diabetes, and obstructive sleep apnea syndrome) or occurrence of short-term complications, whereas women were more likely to develop long-term complications, with an odds ratio of 1.97 (95% CI: 1.57-2.49). Sex does not have a clear effect on efficacy outcomes of bariatric procedures. Differentiating by procedure, BIB may be more effective in women, although results are discordant based on the weight loss outcome considered. If the short-term postoperative complication rate is similar across both sexes, long-term complications occur more frequently in women. To clarify the real effect of sex on bariatric procedure-derived health benefits, it is crucial to report sex-stratified results in future studies, as well as evaluate body composition changes that go beyond simple body weight reduction., (Copyright © 2022 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Heart failure (HF) represents a major global health and economic burden with still unacceptably high morbidity and mortality rates. In recent decades, novel therapeutic opportunities with a significant impact on HF outcomes have been introduced in addition to angiotensin-converting enzyme (ACE) inhibitors, β-blockers, and mineralocorticoid receptor antagonists. These include drugs such as ivabradine, sacubitril-valsartan, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors. The availability of an extremely large pharmacological armamentarium to face this chronic global disease highlights the importance of assessing cost effectiveness to promote sustainable healthcare. In light of the recent approval of SGLT-2 inhibitors for the treatment of HF with reduced ejection fraction, including in individuals without type 2 diabetes mellitus, the aim of this review was to provide an updated comparative evaluation of the efficacy and cost effectiveness of different pharmacological treatments for the prevention (stage A) and treatment of asymptomatic (stage B) and symptomatic (stages C-D) left ventricular dysfunction., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Background: Obesity is among the main determinants of nonalcoholic fatty liver disease progression towards severe liver disease (SLD). However, risk factors for SLD in individuals with obesity have not been examined., Objectives: To identify the independent risk factors for SLD among participants with obesity from the UK Biobank., Methods: A total of 80,224 UK Biobank participants with obesity (body mass index[BMI] > 30 kg/m 2 ) and 242,822 without obesity, of European descent without clinical history of liver disease and liver cancer were prospectively followed for the onset of SLD, defined as a composite diagnosis of cirrhosis, decompensated liver disease, hepatocellular carcinoma and/or liver transplantation. Risk factors for incident SLD were assessed by Cox proportional hazards models. Different clinical phenotypes were derived by latent class analysis (LCA)., Results: Obesity conferred a 2.6-fold increased risk for SLD that was abolished after the inclusion of waist circumference (WC) in the model. Among individuals with obesity, age (adjusted hazard ratio [aHR] 1.05, 95%CI 1.03-1.07, p = 3.9 * 10 -7 ), type 2 diabetes (aHR 2.18, 95%CI 1.55-3.05, p = 6.2 * 10 -6 ), PNPLA3 rs738409 (aHR 1.59, 95%CI 1.33-1.9, p = 3.1 * 10 -7 ) and WC (aHR 1.04, 95%CI 1.02-1.06, p = 8.5 * 10 -6 ) were independent predictors of SLD. BMI category-specific WC thresholds allowed a better risk stratification compared to traditional ones. By LCA, the clinical phenotype at highest risk for SLD was that with BMI < 35 kg/m 2 and WC above BMI-category specific thresholds., Conclusions: Age, WC, type 2 diabetes, and the PNPLA3 variant are the main risk factors for SLD in individuals with obesity. WC is the principal mediator of SLD risk conveyed by increased BMI. BMI category-specific WC-thresholds may refine the SLD risk more accurately than traditional thresholds., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Aims: To investigate if extra virgin olive oil (EVOO) or palm oil enriched chocolate spreads consumption leads to different results in terms of plasma ceramides concentration, glucose and lipid metabolism, inflammatory markers and appetite regulation in young healthy subjects., Methods: In a 2-week, double-blind, cross-over, randomised controlled trial, 20 healthy, normal-weight subjects with a mean age of 24.2 years (SD: 1.2), consumed chocolate spread snacks (73% of energy [%E] from fat, 20% from carbohydrates and 7% from proteins), providing 570 Kcal/day added to an isocaloric diet. The chocolate spreads were identical, except for the type of fat: EVOO oil, rich in monounsaturated fatty acids (MUFAs), or palm oil, rich in Saturated Fatty Acids (SFAs)., Results: EVOO-enriched chocolate spread consumption led to better circulating sphingolipids and glucose profile, with reduced plasma ceramide C16:0, ceramide C16:0/ceramide C22:0-ceramide C24:0 ratio and sphingomyelin C18:0 (P = 0.030, P= 0.032 and P = 0.042, respectively) compared to the palm oil-enriched chocolate spread diet. HOMA-IR and plasma insulin were lower, while the Quicki and the McAuley Index were higher after the EVOO diet compared to the palm oil diet (P = 0.046, P = 0.045, P = 0.018 and P = 0.039 respectively). Subjects maintained a stable weight throughout the study. No major significant changes in total cholesterol, triglycerides, HDL, inflammatory markers, and appetite-regulating hormones/visual analogue scale were observed between the groups., Conclusions: Partially replacing SFAs with MUFAs in a chocolate-based snack as part of a short-term isocaloric diet in healthy individuals may limit SFAs detrimental effects on insulin sensitivity and decrease circulating harmful sphingolipids in young adults., (© 2021 VENCHI SpA. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background & Aims: The ultrasound-based controlled attenuation parameter (CAP) is a non-invasive tool widely validated for assessing liver steatosis across different etiologies. However, few studies, with liver biopsy available, have investigated its performance in individuals with morbid obesity. Herein, we aimed to evaluate the diagnostic accuracy of CAP in participants with morbid obesity from the MAFALDA study before bariatric surgery., Methods: A total of 120 individuals with valid examinations within three months from bariatric surgery were included. Clinical, laboratory, FibroScan ® (XL probe), and liver biopsy data were collected using standardized procedures. The overall accuracy of CAP for detecting liver steatosis was estimated by the area under the receiver-operating characteristics curve (AUROC). Optimal cut-offs were chosen at points with the highest Youden index., Results: The AUROCs of CAP for detecting S ≥ S1, S ≥ S2, and S = S3 were 0.91 (95% CI 0.86-0.97), 0.83 (95% CI 0.76-0.90), and 0.86 (95% CI 0.79-0.94), respectively. The best CAP cut-offs for S ≥ S1, S ≥ S2, and S = S3 were 300 dB/m (95% CI 275-316), 328 dB/m (95% CI 296-345), and 344 dB/m (95% CI 343-352), respectively. CAP values were independently influenced by steatosis grade (estimate 20.60, 95% CI 12.70-28.40, P = 1.05 × 10 -6 ). The AUROC of FibroScan-AST (FAST) score for detecting progressive non-alcoholic steatohepatitis was 0.76 (95% CI 0.66-0.86)., Conclusions: In individuals with morbid obesity, CAP measured by XL probe is an accurate non-invasive tool for grading liver steatosis. Measurement of liver fat content by CAP may help identify those eligible for bariatric procedures and estimate the effect of bariatric surgery on hepatic steatosis., Lay Summary: The ultrasound-based controlled attenuation parameter (CAP) by using the XL probe has an excellent performance for grading liver steatosis among individuals with morbid obesity. CAP may represent an accurate tool for the non-invasive assessment of liver steatosis among individuals with morbid obesity before and after bariatric surgery., (© 2021 The Authors. Liver International published by John Wiley & Sons Ltd.)

Obesity is associated with a poor COVID-19 prognosis, and it seems associated with reduced humoral response to vaccination. Public health campaigns have advocated for weight loss in subjects with obesity, hoping to eliminate this risk. However, no evidence proves that weight loss leads to a better prognosis or a stronger immune response to vaccination. We aimed to investigate the impact of rapid weight loss on the adaptive immune response in subjects with morbid obesity. Twenty-one patients followed a hypocaloric, very-low-carbohydrate diet one week before to one week after the two mRNA vaccine doses. The diet's safety and efficacy were assessed, and the adaptive humoral (anti-SARS CoV-2 S antibodies, Abs) and cell-mediated responses (IFNγ secretion on stimulation with two different SARS CoV-2 peptide mixes, IFNγ-1 and IFNγ-2) were evaluated. The patients lost ~10% of their body weight with metabolic improvement. A high baseline BMI correlated with a poor immune response (R -0.558, p = 0.013 for IFNγ-1; R -0.581, p = 0.009 for IFNγ-2; R -0.512, p = 0.018 for Abs). Furthermore, there was a correlation between weight loss and higher IFNγ-2 (R 0.471, p = 0.042), and between blood glucose reduction and higher IFNγ-1 (R 0.534, p = 0.019), maintained after weight loss and waist circumference reduction adjustment. Urate reduction correlated with higher Abs (R 0.552, p = 0.033). In conclusion, obesity is associated with a reduced adaptive response to a COVID-19 mRNA vaccine, and weight loss and metabolic improvement may reverse the effect.

Aims: To explore variables associated with the serological response following COVID-19 mRNA vaccine., Methods: Eighty-six healthcare workers adhering to the vaccination campaign against COVID-19 were enrolled in January-February 2021. All subjects underwent two COVID-19 mRNA vaccine inoculations (Pfizer/BioNTech) separated by 3 weeks. Blood samples were collected before the 1st and 1-4 weeks after the second inoculation. Clinical history, demographics, and vaccine side effects were recorded. Baseline anthropometric parameters were measured, and body composition was performed through dual-energy-X-ray absorptiometry., Results: Higher waist circumference was associated with lower antibody (Ab) titres (R = -0.324, p = 0.004); smokers had lower levels compared to non-smokers [1099 (1350) vs. 1921 (1375), p = 0.007], as well as hypertensive versus normotensive [650 ± 1192 vs. 1911 (1364), p = 0.001] and dyslipideamic compared to those with normal serum lipids [534 (972) vs 1872 (1406), p = 0.005]. Multivariate analysis showed that higher waist circumference, smoking, hypertension, and longer time elapsed since second vaccine inoculation were associated with lower Ab titres, independent of BMI, age. and gender., Conclusions: Central obesity, hypertension, and smoking are associated with lower Ab titres following COVID-19 vaccination. Although it is currently impossible to determine whether lower SARS-CoV-2 Abs lead to higher likelihood of developing COVID-19, it is well-established that neutralizing antibodies correlate with protection against several viruses including SARS-CoV-2. Our findings, therefore, call for a vigilant approach, as subjects with central obesity, hypertension, and smoking could benefit from earlier vaccine boosters or different vaccine schedules., (© 2021 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Cancer cells (CCs) predominantly use aerobic glycolysis (Warburg effect) for their metabolism. This important characteristic of CCs represents a potential metabolic pathway to be targeted in the context of tumor treatment. Being this mechanism related to nutrient oxidation, dietary manipulation has been hypothesized as an important strategy during tumor treatment. Ketogenic diet (KD) is a dietary pattern characterized by high fat intake, moderate-to-low protein consumption, and very-low-carbohydrate intake (<50 g), which in cancer setting may target CCs metabolism, potentially influencing both tumor treatment and prognosis. Several mechanisms, far beyond the originally proposed inhibition of glucose/insulin signaling, can underpin the effectiveness of KD in cancer management, ranging from oxidative stress, mitochondrial metabolism, and inflammation. The role of a qualified Nutritionist is essential to reduce and manage the short and long-term complications of this dietary therapy, which must be personalized to the individual patient for the planning of tailored KD protocol in cancer patients. In the present review, we summarize the proposed antitumor mechanisms of KD, the application of KD in cancer patients with obesity and cachexia, and the preclinical and clinical evidence on KD therapy in cancer.

The Fuegians, ancient inhabitants of Tierra del Fuego, are an exemplary case of a cold-adapted population, since they were capable of living in extreme climatic conditions without any adequate clothing. However, the mechanisms of their extraordinary resistance to cold remain enigmatic. Brown adipose tissue (BAT) plays a crucial role in this kind of adaptation, besides having a protective role on the detrimental effect of low temperatures on bone structure. Skeletal remains of 12 adult Fuegians, collected in the second half of XIX century, were analyzed for bone mineral density and structure. We show that, despite the unfavorable climate, bone mineral density of Fuegians was close to that seen in modern humans living in temperate zones. Furthermore, we report significant differences between Fuegians and other cold-adapted populations in the frequency of the Homeobox protein Hox-C4 (HOXC4) rs190771160 variant, a gene involved in BAT differentiation, whose identified variant is predicted to upregulate HOXC4 expression. Greater BAT accumulation might therefore explain the Fuegians extreme cold-resistance and the protection against major cold-related damage. These results increase our understanding of how ecological challenges have been important drivers of human-environment interactions during Humankind history., (© 2021. The Author(s).)

Purpose: Malnutrition, whether characterized by not enough or too much nutrient intake, is detrimental to the liver. We herein provide a narrative literature revision relative to hepatic disease occurrence in over or undernourished subjects, to shed light on the paradox where both sides of malnutrition lead to similar liver dysfunction and fat accumulation., Methods: Medline, EMBASE, and Cochrane Library were searched for publications up to July 2020. Articles discussing the association between both chronic and acute liver pathology and malnutrition were evaluated together with studies reporting the dietary intake in subjects affected by malnutrition., Results: The association between overnutrition and non-alcoholic fatty liver disease (NAFLD) is well recognized, as the beneficial effects of calorie restriction and very low carbohydrate diets. Conversely, the link between undernutrition and liver injury is more complex and less understood. In developing countries, early exposure to nutrient deficiency leads to marasmus and kwashiorkor, accompanied by fatty liver, whereas in developed countries anorexia nervosa is a more common form of undernutrition, associated with liver injury. Weight gain in undernutrition is associated with liver function improvement, whereas no study on the impact of macronutrient distribution is available. We hypothesized a role for very low carbohydrate diets in the management of undernutrition derived liver pathology, in addition to the established one in overnutrition-related NAFLD., Conclusions: Further studies are warranted to update the knowledge regarding undernutrition-related liver disease, and a specific interest should be paid to macronutrient distribution both in the context of refeeding and relative to its role in the development of hepatic complications of anorexia nervosa., Level of Evidence: Narrative review, Level V., (© 2020. Springer Nature Switzerland AG.)

Aim: To compare a Mediterranean diet (MED) with a high-fibre vegetarian diet (HFV) in terms of hunger-satiety perception through post-prandial assessment of appetite-related hormones glucagon-like peptide 1 (GLP-1) and oxyntomodulin, as well as self-rated visual analogue scale (VAS) quantification, in overweight/obese subjects with type 2 diabetes (T2D)., Materials and Methods: Twelve T2D subjects (Male to female ratio = 7:5), mean age 63 ± 8.5 years, were enrolled in a randomized, controlled, crossover study. Participants consumed an MED meal as well as an isocaloric meal rich in complex carbohydrate as well as an isocaloric MED meal in two different visits with a 1-week washout period between the two visits. Appetite ratings, glucose/insulin, and gastrointestinal hormone concentrations were measured at fasting and every 30' until 210' following meal consumption., Results: GLP-1 and oxyntomodulin levels were significantly higher following MED meal compared with HFV meals (210' area under the curve, p < 0.022 and p < 0.023, respectively). Both MED and HFV meal resulted in a biphasic pattern of GLP-1 and oxyntomodulin, although MED meal was related to a delayed, significantly higher second GLP-1 peak at 150' compared with that of HFV meal (p < 0.05). MED meal was related to lower glucose profile compared with HFV meal (p < 0.039), whereas we did not observe significant changes in terms of self-reported VAS scores and insulin trend., Conclusions: In T2D overweight/obese subjects, an MED meal is more effective than a HFV meal in terms of post-prandial plasma glucose homoeostasis and GLP-1 and oxyntomodulin release. These changes were not confirmed by VAS appetite self-assessment over a 210' period., (© 2020 John Wiley & Sons Ltd.)

Purpose: The COVID-19 pandemic has radically impacted the world lifestyle. Epidemics are well-known to cause mental distress, and patients with a current or past history of obesity are at increased risk for the common presence of psychological comorbidities. This study investigates the psychological impact of the current pandemic in patients participating in a bariatric surgery program., Methods: Patients were consecutively enrolled during the Italian lockdown among those waiting for bariatric surgery or attending a post-bariatric follow-up, and were asked to complete through an online platform the Depression Anxiety Stress Scales-21 and a self-assessment questionnaire of 22 items evaluating the resilience, change in eating behavior and emotional responses referring to the ongoing pandemic., Results: 59% of the 434 enrolled subjects reported of being worried about the pandemic, and 63% specifically reported of being worried about their or their relatives' health. 37% and 56% felt lonelier and more bored, respectively. 66% was hungrier with increased frequency of snacking (55%) and 39% reported more impulse to eat. Noteworthy, 49% felt unable to follow a recommended diet. No difference in terms of psychological profile was recorded among pre and post-bariatric subjects. Logistic regression analysis on post-bariatric patients showed a relationship between snacking, hunger, eating impulsivity, and anxiety, stress, and/or depression symptoms., Conclusion: The pandemic led to increased psychological distress in patients with a current or past history of obesity, reducing quality of life and affecting dietary compliance. Targeted psychological support is warranted in times of increased stress for fragile subjects such as pre- and post-bariatric patients., Level of Evidence: Level V: cross-sectional descriptive study., (© 2020. Springer Nature Switzerland AG.)

Purpose: The Laparoscopic Roux-en-Y Gastric Bypass (LRYGB) is an effective weight loss procedure. The gastro-jejunal (GJ) anastomosis required can be performed on the anterior or posterior gastric pouch wall. No studies have compared these variants in terms of efficacy and onset of dumping syndrome (DS) and weight regain (WR). We aimed at assessing the prevalence of DS in relation to the site of anastomosis together with identifying prognostic factors of DS and WR., Methods: Patients who had undergone LRYGB with anterior (AGJ) or posterior (PGJ) anastomosis in 2010-2019 were retrospectively analyzed. We collected demographic data, medical history and the prevalence of DS evaluated through the Sigstad Score, together with WR data., Results: 213 patients were enrolled, of which 51.6% had an AGJ and 48.4% had a PGJ. The mean follow-up time was 81 ± 18 and 27 ± 13 months in the AGJ and PGJ group, respectively (p < 0.0001). Excess weight loss was 77.59% and 94.13% in patients with AGJ and PGJ, respectively (p < 0.001). WR rate was 16% and 4% in the AGJ and PGJ population, respectively (p < 0.001). DS prevalence was 38% and 76% in the AGJ and the PGJ population, respectively (p < 0.0001). The site of anastomosis was identified as an independent predictor of DS (OR5.15; 95% CI 2.82-9.41; p < 0.0001) and WR (OR5.31; 95% CI 2.32-12.15; p < 0.0001). Obesity-related complications significantly improved after surgery independent of the anastomosis site., Conclusion: LRYGB is effective in determining long-term weight loss and improvement of complications. AGJ is associated with lower prevalence of DS but more frequent WR. The anastomosis site is a factor to be considered when performing LRYGB., Level of Evidence: Level V, cross-sectional descriptive study., (© 2020. Springer Nature Switzerland AG.)

In type 2 diabetes, anti-thrombotic management is challenging, and current anti-platelet agents have demonstrated reduced efficacy. Old and new anti-diabetic drugs exhibited-besides lowering blood glucose levels-direct and indirect effects on platelet function and on thrombotic milieu, eventually conditioning cardiovascular outcomes. The present review summarizes existing evidence on the effects of glucose-lowering agents on platelet properties, addressing pre-clinical and clinical research, as well as drug-drug interactions with anti-platelet agents. We aimed at expanding clinicians' understanding by highlighting new opportunities for an optimal management of patients with diabetes and cardiovascular disease. We suggest how an improvement of the thrombotic risk in this large population of patients may be achieved by a careful and tailored combination of anti-diabetic and anti-platelet therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Nusca, Tuccinardi, Pieralice, Giannone, Carpenito, Monte, Watanabe, Cavallari, Maddaloni, Ussia, Manfrini and Grigioni.)

Background&aims: To assess whether the concentrations of circulating Branched-Chain Amino Acids (BCAAs) change after walnut consumption and, whether these changes are associated with alterations in markers of insulin resistance and food preferences., Methods: In a crossover, randomized, double-blind, placebo-controlled study, ten subjects participated in two 5-day inpatient study admissions, during which they had a smoothie containing 48 g walnuts or a macronutrient-matched placebo smoothie without nuts every morning. Between the two phases there was a 1-month washout period., Results: Fasting valine and isoleucine levels were reduced (p = .047 and p < .001) and beta-hydroxybutyrate levels were increased after 5-days of walnut consumption compared to placebo (p = .023). Fasting valine and isoleucine correlated with HOMA-IR while on walnut (r = 0.709, p = .032 and r = 0.679, p = .044). The postprandial area under the curve (AUC) of leucine in response to the smoothie consumption on day 5 was higher after walnut vs placebo (p = .023) and correlated negatively with the percentage of Kcal from carbohydrate and protein consumed during an ad libitum buffet meal consumed the same day for lunch (r = -0.661, p = .037; r = -0.628, p = .05, respectively)., Conclusion: The fasting and postabsorptive profiles of BCAAs are differentially affected by walnut consumption. The reduction in fasting valine and isoleucine may contribute to the longer-term benefits of walnuts on insulin resistance, cardiovascular risk and mortality, whereas the increase in postabsorptive profiles with walnuts may influence food preference. TRIAL REGISTRATION CLINICALTRIALS.GOV: Number: NCT02673281, Website: https://clinicaltrials.gov/ct2/show/NCT02673281., Competing Interests: Conflict of interests All other authors have no conflicts of interest to disclose., (Copyright © 2021 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Introduction: The prevalence of obesity is soaring all over the world, and Italy is reaching the same pace. Similar to other countries, the Italian healthcare system counts on a three-tier model for obesity care, and each region has freedom in the implementation of guidelines. No national record is currently available to monitor the actual situation throughout the country., Purpose: To provide a report of the current status on the availability of specialized public obesity care services in Italy., Methods: Regional prevalence of obesity was extrapolated from publicly available data. Data on facilities for the management of obesity were retrieved from records provided by national scientific societies. Whenever possible, data was verified through online research and direct contact., Results: We report a north-south and east-west gradient regarding the presence of obesity focused facilities, with an inverse correlation with the regional prevalence of obesity (R = 0.25, p = 0.03). Medical-oriented centers appear homogeneous in the multidisciplinary approach, the presence of a bariatric surgery division, the availability of support materials and groups, with no major difference on follow-up frequency. Surgery-oriented centers have a more capillary territorial distribution than the medically oriented, but not enough data was retrieved to provide a thorough description of their characteristics., Conclusion: Obtaining a clear picture of the situation and providing consistent care across the country is a challenging task due to the decentralized organization of regions. We provide a first sketch, reporting that the model is applied unevenly, and we suggest feasible actions to improve the situation in our country and elsewhere., Level of Evidence: Level V, narrative review.

Hypoglycaemia is common in patients with type 1 diabetes and type 2 diabetes and constitutes a major limiting factor in achieving glycaemic control among people with diabetes. While hypoglycaemia is defined as a blood glucose level under 70 mg/dL (3.9 mmol/L), symptoms may occur at higher blood glucose levels in individuals with poor glycaemic control. Severe hypoglycaemia is defined as an episode requiring the assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions to assure neurologic recovery. Hypoglycaemia is the most important safety outcome in clinical studies of glucose lowering agents. The American Diabetes Association Standards of Medical Care recommends that a management protocol for hypoglycaemia should be designed and implemented by every hospital, along with a clear prevention and treatment plan. A tailored approach, using clinical and pathophysiologic disease stratification, can help individualize glycaemic goals and promote new therapies to improve quality of life of patients. Data from recent large clinical trials reported low risk of hypoglycaemic events with the use of newer anti-diabetic drugs. Increased hypoglycaemia risk is observed with the use of insulin and/or sulphonylureas. Vulnerable patients with T2D at dual risk of severe hypoglycaemia and cardiovascular outcomes show features of "frailty." Many of such patients may be better treated by the use of GLP-1 receptor agonists or SGLT2 inhibitors rather than insulin. Continuous glucose monitoring (CGM) should be considered for all individuals with increased risk for hypoglycaemia, impaired hypoglycaemia awareness, frequent nocturnal hypoglycaemia and with history of severe hypoglycaemia. Patients with impaired awareness of hypoglycaemia benefit from real-time CGM. The diabetes educator is an invaluable resource and can devote the time needed to thoroughly educate the individual to reduce the risk of hypoglycaemia and integrate the information within the entire construct of diabetes self-management. Conversations about hypoglycaemia facilitated by a healthcare professional may reduce the burden and fear of hypoglycaemia among patients with diabetes and their family members. Optimizing insulin doses and carbohydrate intake, in addition to a short warm up before or after the physical activity sessions may help avoiding hypoglycaemia. Several therapeutic considerations are important to reduce hypoglycaemia risk during pregnancy including administration of rapid-acting insulin analogues rather than human insulin, pre-conception initiation of insulin analogues, and immediate postpartum insulin dose reduction., (© 2020 John Wiley & Sons Ltd.)

Background: Obesity was recently identified as a major risk factor for worse COVID-19 severity, especially among the young. The reason why its impact seems to be less pronounced in the elderly may be due to the concomitant presence of other comorbidities. However, all reports only focus on BMI, an indirect marker of body fat., Aim: To explore the impact on COVID-19 severity of abdominal fat as a marker of body composition easily collected in patients undergoing a chest CT scan., Methods: Patients included in this retrospective study were consecutively enrolled among those admitted to an Emergency Department in Rome, Italy, who tested positive for SARS-Cov-2 and underwent a chest CT scan in March 2020. Data were extracted from electronic medical records., Results: 150 patients were included (64.7% male, mean age 64 ± 16 years). Visceral fat (VAT) was significantly higher in patients requiring intensive care (p = 0.032), together with age (p = 0.009), inflammation markers CRP and LDH (p < 0.0001, p = 0.003, respectively), and interstitial pneumonia severity as assessed by a Lung Severity Score (LSS) (p < 0.0001). Increasing age, lymphocytes, CRP, LDH, D-Dimer, LSS, total abdominal fat as well as VAT were found to have a significant univariate association with the need of intensive care. A multivariate analysis showed that LSS and VAT were independently associated with the need of intensive care (OR: 1.262; 95%CI: 1.0171-1.488; p = 0.005 and OR: 2.474; 95%CI: 1.017-6.019; p = 0.046, respectively)., Conclusions: VAT is a marker of worse clinical outcomes in patients with COVID-19. Given the exploratory nature of our study, further investigation is needed to confirm our findings and elucidate the mechanisms underlying such association., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Evidence has lately emerged regarding an increased risk of SARS-CoV-2 with worse prognosis in patients with obesity, especially among the young. Weight excess is a well-established respiratory disease risk factor, and the newly reported correlation is therefore unsurprising. The underlying pathophysiology is likely multi-stranded, ranging from complement system hyperactivation, increased Interleukin-6 secretion, chronic inflammation, presence of comorbidities such as diabetes and hypertension, and a possible local, detrimental effect within the lung. Further understanding the link between obesity and SARS-CoV-2 is crucial, as this could aid proper tailoring of immunomodulatory treatments, together with improving stratification among those possibly requiring critical care., (© 2020 John Wiley & Sons Ltd.)

First identified as a feasible treatment for intractable epilepsy, the ketogenic diet (KD) has recently gained popularity thanks to growing evidence on applications such as weight loss, most importantly, but also NAFLD, cancer, neurologic conditions and chronic pain. As with any treatment, whether pharmacologic or not, the KD might not be an appropriate intervention for every individual, and a number of contraindications have been proposed, now deeply rooted into clinical practice, excluding de facto many patients that could benefit from its use. However, many of these concerns were expressed due to the absence of clinical studies conducted on fragile populations, and an assessment of lately emerged evidence relative to KD safety is currently lacking and much needed. We herein provide a critical revision of the literature behind each safety alert, in order to guide through the treatment options in the case of subjects with an indication to the KD and a borderline safe situation. Based on available evidence, the possible use of this diet as a therapeutic intervention should be assessed on a patient-to-patient basis by adequately skilled medical doctors, keeping in mind current recommendations, but reading them through the knowledge of the current state of the art., (© 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

The use of food supplements for weight loss purposes has rapidly gained popularity as the prevalence of obesity increases. Navigating through the vast, often low quality, literature available is challenging, as is providing informed advice to those asking for it. Herein, we provide a comprehensive literature revision focusing on most currently marketed dietary supplements claimed to favor weight loss, classifying them by their purported mechanism of action. We conclude by proposing a combination of supplements most supported by current evidence, that leverages all mechanisms of action possibly leading to a synergistic effect and greater weight loss in the foreseen absence of adverse events. Further studies will be needed to confirm the weight loss and metabolic improvement that may be obtained through the use of the proposed combination.

Nonalcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease, characterized by hepatic fat accumulation and possible development of inflammation, fibrosis, and cancer. The ketogenic diet (KD), with its drastic carbohydrate reduction, is a now popular weight loss intervention, despite safety concerns on a possible association with fatty liver. However, KDs were also reported to be beneficial on hepatic pathology, with ketone bodies recently proposed as effective modulators of inflammation and fibrosis. If the beneficial impact of weight loss on NAFLD is established, less is known on the effect of macronutrient distribution on such outcome. In a hypocaloric regimen, the latter seems not to be crucial, whereas at higher calorie intake, macronutrient ratio and, theoretically, ketosis, may become important. KDs could positively impact NAFLD for their very low carbohydrate content, and whether ketosis plays an additional role is unknown. Indeed, several mechanisms may directly link ketosis and NAFLD improvement, and elucidating these aspects would pave the way for new therapeutic strategies. We herein aimed at providing an accurate revision of current literature on KDs and NAFLD, focusing on clinical evidence, metabolic pathways involved, and strict categorization of dietary interventions., (© 2020 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Background: Non-alcoholic fatty liver disease (NAFLD) is a major cause of liver disease. Very low-calorie ketogenic diets (VLCKD) represent a feasible treatment as they induce profound weight loss and insulin resistance (IR) improvement. Despite the recognized benefits on NAFLD deriving from pharmacological administration of fibroblast growth factor 21 (FGF21), whose endogenous counterpart is a marker of liver injury, little is known about its physiology in humans., Aim: To identify predictors of NAFLD improvement as reflected by the reduction of the non-invasive screening tool hepatic steatosis index (HSI) in obese patients undergoing a weight loss program., Methods: Sixty-five obese patients underwent a 90-day dietary program consisting of a VLCKD followed by a hypocaloric low carbohydrate diet (LCD). Anthropometric parameters, body composition, and blood and urine chemistry were assessed., Results: Unlike most parameters improving mainly during the VLCKD, the deepest HSI change was observed after the LCD ( p = 0.02 and p < 0.0001, respectively). Baseline HOMA-IR and serum FGF21 were found to be positive (R = 0.414, p = 0009) and negative (R = 0.364, p = 0.04) independent predictors of HSI reduction, respectively., Conclusions: We suggest that patients with IR and NAFLD derive greater benefit from a VLCKD, and we propose a possible role of human FGF21 in mediating NAFLD amelioration following nutritional manipulation.

Growing evidence suggested that Sleep Disorders (SD) could increase the risk of developing obesity and could contribute to worsen obesity-related cardiovascular risk. Further, obesity per se has been reported to blunt sleep homeostasis. This happens through several mechanisms. First of all, the excessive adipose tissue at neck and chest levels could represent a mechanical obstacle to breathe. Moreover, the visceral adipose tissue is known to release cytokines contributing to low-grade chronic inflammation that could impair the circadian rhythm. Also, nutrition plays an important role in sleep homeostasis. High fat and/or high carbohydrate diets are known to have a negative impact on both sleep quality and duration. In addition, obesity predisposes to a condition called " obstructive sleep apnea " that has a detrimental effect on sleep. SD could increase the risk and/or could contribute to worsen cardiovascular risk usually associated with obesity. The chronic low grade inflammation associated with obesity has been reported to increase the risk of developing hypertension, type 2 diabetes and dyslipidemia. In turn, improving quality of sleep has been reported to improve the management of these cardiovascular risk factors. Thus, the aim of this manuscript is to provide evidence on the association of obesity and SD and on how they could contribute to the risk of developing cardiovascular risk factors such as hypertension, dyslipidemia and type 2 diabetes in obesity., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Nature Limited 2020.)

Very low-calorie ketogenic diets (VLCKD) are an effective and increasingly used tool for weight loss. Traditionally considered high protein, ketogenic diets are often looked at with concern by clinicians due to the potential harm they pose to kidney function. We herein evaluated the efficacy and safety of a VLCKD in patients with obesity and mild kidney failure. A prospective observational real-life study was conducted on ninety-two patients following a VLCKD for approximately 3 months. Thirty-eight had mild kidney failure and fifty-four had no renal condition and were therefore designated as control. Anthropometric parameters, bioelectrical impedance and biochemistry data were collected before and at the end of the dietary intervention. The average weight loss was nearly 20% of initial weight, with a significant reduction in fat mass. We report an improvement of metabolic parameters and no clinically relevant variation regarding liver and kidney function. Upon stratification based on kidney function, no differences in the efficacy and safety outcomes were found. Interestingly, 27.7% of patients with mild renal failure reported normalization of glomerular filtrate after dietary intervention. We conclude that, when conducted under the supervision of healthcare professionals, a VLCKD is an effective and safe treatment for weight loss in patients with obesity, including those affected by mild kidney failure., Competing Interests: All other authors declare no conflict of interest and have approved the final manuscript.

Background: Diabetic patients with on-treatment high platelet reactivity (HPR) show an increased risk of thrombotic events. Whether measuring glycated haemoglobin (HbA1c) levels and/or glycaemic variability (GV) may help identifying diabetic patients at higher risk deserving tailored antiplatelet and/or glucose lowering strategies is unknown. We aimed to investigate the relationship between GV, HbA1c levels and platelet reactivity in patients with type 2 diabetes mellitus (DM) undergoing percutaneous coronary intervention (PCI)., Methods: Platelet reactivity was measured in type 2 DM patients using VerifyNow P2Y12 assay. HPR was defined as P2Y12 Reaction Unit (PRU) > 240. GV was expressed through mean amplitude of glycaemic excursions (MAGE) and coefficient of variance (CV) by using the iPro™ continuous glucose recorder., Results: Thirty-five patients (age 70 ± 9 years, 86% male, mean HbA1c 7.2 ± 1.0%) on clopidogrel therapy were enrolled. HbA1c was independently associated with HPR (OR 7.25, 95% CI 1.55-33.86, p = 0.012). Furthermore, when factored into the model, GV indexes provided independent (OR 1.094, 95% CI 1.007-1.188, p < 0.034) and additional (p < 0.001) diagnostic significance in identifying diabetic patients with HPR., Conclusions: Glyco-metabolic state significantly correlates with HPR in well-controlled type 2 DM patients on clopidogrel therapy. HbA1c identifies patients at higher thrombotic risk but the highest diagnostic accuracy is achieved by combining GV and HbA1c. Whether individualized antithrombotic and glucose-lowering therapies based on the assessment of these parameters may reduce the incidence of thrombotic events in patients undergoing PCI should be further investigated.

Aims: To assess the effects of walnuts on cardiometabolic outcomes in obese people and to explore the underlying mechanisms using novel methods including metabolomic, lipidomic, glycomic and microbiome analysis, integrated with lipid particle fractionation, appetite-regulating hormones and haemodynamic measurements., Materials and Methods: A total of 10 obese individuals were enrolled in this cross-over, randomized, double-blind, placebo-controlled clinical trial. The participants had two 5-day inpatient stays, during which they consumed a smoothie containing 48 g walnuts or a macronutrient-matched placebo smoothie without nuts, with a 1-month washout period between the two visits., Results: Walnut consumption improved aspects of the lipid profile; it reduced fasting small and dense LDL particles (P < 0.02) and increased postprandial large HDL particles (P < 0.01). Lipoprotein insulin resistance score, glucose and the insulin area under the curve (AUC) decreased significantly after walnut consumption (P < 0.01, P < 0.02 and P < 0.04, respectively). Consuming walnuts significantly increased 10 N-glycans, with eight of them carrying a fucose core. Lipidomic analysis showed a robust reduction in harmful ceramides, hexosylceramides and sphingomyelins, which have been shown to mediate effects on cardiometabolic risk. The peptide YY AUC significantly increased after walnut consumption (P < 0.03). No major significant changes in haemodynamic or metabolomic analysis or in microbiome host health-promoting bacteria such as Faecalibacterium were found., Conclusions: These data provide a more comprehensive mechanistic perspective of the effect of dietary walnut consumption on cardiometabolic variables. Lipidomic and lipid nuclear magnetic resonance spectroscopy analysis showed an early but significant reduction in ceramides and other atherogenic lipids with walnut consumption, which may explain the longer-term benefits of walnuts or other nuts on insulin resistance, cardiovascular risk and mortality., (Published 2019. This article is a U.S. Government work and is in the public domain in the USA.)

Lorcaserin is a serotonin 2c receptor agonist that promotes weight loss while contributing to the prevention and improvement of type 2 diabetes and improvement of atherogenic lipid profiles, without higher rates of major cardiovascular events. The full spectrum of possible lorcaserin-induced improvements in cardiometabolic health remains to be clarified. Thus, we investigated the way in which lorcaserin treatment may alter cardiovascular disease risk, either independently or through changes in body weight. We measured, for the first time, lipid particle quantification, lipid peroxidation, appetite-regulating hormones and mRNA expression of the 5-hydroxytryptamine 2c receptor (5-HT2c receptor). A total of 48 obese participants were enrolled in this six-month, randomized (1:1), placebo-controlled, double-blinded clinical trial. Lorcaserin treatment reduced fat mass (P < 0.001), the fatty liver index (P < 0.0001) and energy intake (P < 0.03) without affecting energy expenditure or lean mass. Total low-density lipoprotein (LDL) (P < 0.04) and small LDL particles (P < 0.03) decreased, while total high-density lipoprotein (HDL) P < 0.02) increased and heart rate significantly decreased with lorcaserin treatment. No mRNA expression of the 5-HT2c receptor was observed in peripheral organs. These data suggest that lorcaserin treatment for six months improves cardiometabolic health in obese individuals, acting mainly through the brain., (© 2019 John Wiley & Sons Ltd.)

Obesity is a multifactorial disease resulting in excessive accumulation of adipose tissue. Over the last decade, growing evidence has identified the gut microbiota as a potential factor in the pathophysiology of both obesity and the related metabolic disorders. The gut microbiota is known to protect gastrointestinal mucosa permeability and to regulate the fermentation and absorption of dietary polysaccharides, perhaps explaining its importance in the regulation of fat accumulation and the resultant obesity. The proposed mechanisms by which the gut microbiota could contribute to the pathogenesis of obesity and the related metabolic diseases include: (a) a high abundance of bacteria that ferment carbohydrates, leading to increased rates of short-chain fatty acid (SCFA) biosynthesis, providing an extra source of energy for the host, that is eventually stored as lipids or glucose; (b) increased intestinal permeability to bacterial lipopolysaccharides (LPS), resulting in elevated systemic LPS levels that aggravate low-grade inflammation and insulin resistance; (c) increased activity of the gut endocannabinoid system. Fecal transplantation studies in germ-free mice have provided crucial insights into the potential causative role of the gut microbiota in the development of obesity and obesity-related disorders. Diet +/- bariatric surgery have been reported to modulate the gut microbiota, leading to lean host phenotype body composition. This review aims to report clinical evidence for a link of the gut microbiota with human obesity and obesity-related diseases, to provide molecular insights into these associations, and to address the effect of diet and bariatric surgery on the gut microbiota, including colonic microbiota, as a potential mechanism for promoting weight loss., Competing Interests: Conflict of interestThe authors declare that they have no conflict of interest.