Editorial for the Special Issue "Effects of COVID-19 on Lifestyle Behaviors in Children with Obesity".

During the last four decades, the prevalence of obesity has increased dramatically worldwide; concomitantly, a progressive rise in the prevalence of obesity, diabetes, and other nutrition-related chronic diseases has also been observed in childhood [...].

Association of erectile dysfunction with diabetic foot and its outcomes in type 2 diabetic men.

PURPOSE: Erectile dysfunction (ED) and diabetic foot (DF) are common complications in patients with diabetes. However, the relationship between ED and DF has been little studied. In particular, no study has evaluated whether ED is associated with the outcomes of DF. The aim of this retrospective cohort study was to investigate whether ED is a predictor of the outcomes of DF in a large population of men with DF. METHODS: Three hundred and twenty-six consecutive men with type 2 diabetes and a recent and single DF ulcer were recruited and followed up for 41.7 ± 22.7 months. RESULTS: Among men with DF, 56.1% had ED (ED group) and 43.9% did not (NO ED group). Wound healing rate was significantly higher in the NO ED than in the ED group (90.2 versus 73.3%; p = 0.0001). Minor amputation rate (13.7 versus 4.8%; p = 0.007) and mortality (25.7 versus 0.7%; p < 0.001) were significantly greater in the ED than in the NO ED group. Among 263 patients with healed ulcers, recurrence rate was significantly higher in the ED than in the NO ED group (51.5 versus 26.3%; p < 0.001). Multivariate analysis showed that the absence of ED was associated with wound healing (OR: 0.459; 95% CI: 0.213-0.993; p = 0.048), while the presence of ED predicted mortality (OR: 22.644; 95% CI: 2.976-34.271; p = 0.002) and DF recurrence (OR: 3.498; 95% CI: 1.882-6.499; p < 0.001). CONCLUSIONS: Our data show that among men with DF the prevalence of ED is very high. Moreover, ED may be a strong predictor of wound healing, mortality, and ulcer recurrence.

Eating Habits and Body Weight Changes Induced by Variation in Smell and Taste in Patients with Previous SARS-CoV-2 Infection.

Olfactory and gustatory dysfunction are recognized as common symptoms in patients with COVID-19, with a prevalence ranging, respectively, between 41-61% and 38.2-49%. This review focused on relating the variations in dietary habits with the reduction/loss of smell and/or taste in patients who contracted the COVID-19 infection. Primarily, we reviewed the main pathological mechanisms involved in COVID 19-induced anosmia/dysosmia and ageusia/dysgeusia. Then, we explored and summarized the behavioural changes in food intake and body weight during the COVID-19 pandemic in relation to sensory impairment and the underlying mechanisms. Most studies on this topic argue that the altered chemosensory perception (taste and smell) mainly induces reduced appetite, leading to a faster fullness sensation during the consumption of a meal and, therefore, to a decrease in body weight. On the other hand, a reduced perception of the food's sensory properties may trigger compensatory responses that lead some individuals to increase food intake with a different effect on body weight. Regarding body weight, most studies evaluated malnutrition in patients hospitalized for COVID-19; more studies are warranted to investigate nutritional status specifically in non-hospitalized patients with olfactory and gustatory dysfunctions caused by COVID-19 infection.

Chrono-communication and cardiometabolic health: The intrinsic relationship and therapeutic nutritional promises.

Circadian rhythm, an innate 24-h biological clock, regulates several mammalian physiological activities anticipating daily environmental variations and optimizing available energetic resources. The circadian machinery is a complex neuronal and endocrinological network primarily organized into a central clock, suprachiasmatic nucleus (SCN), and peripheral clocks. Several small molecules generate daily circadian fluctuations ensuring inter-organ communication and coordination between external stimuli, i.e., light, food, and exercise, and body metabolism. As an orchestra, this complex network can be out of tone. Circadian disruption is often associated with obesity development and, above all, with diabetes and cardiovascular disease onset. Moreover, accumulating data highlight a bidirectional relationship between circadian misalignment and cardiometabolic disease severity. Food intake abnormalities, especially timing and composition of meal, are crucial cause of circadian disruption, but evidence from preclinical and clinical studies has shown that food could represent a unique therapeutic approach to promote circadian resynchronization. In this review, we briefly summarize the structure of circadian system and discuss the role playing by different molecules [from leptin to ghrelin, incretins, fibroblast growth factor 21 (FGF-21), growth differentiation factor 15 (GDF15)] to guarantee circadian homeostasis. Based on the recent data, we discuss the innovative nutritional interventions aimed at circadian re-synchronization and, consequently, improvement of cardiometabolic health.

Lower miR-21/ROS/HNE levels associate with lower glycemia after habit-intervention: DIAPASON study 1-year later.

BACKGROUND: The prevalence of prediabetes is increasing in the global population and its metabolic derangements may expose to a higher risk to develop type 2 diabetes (T2D) and its cardiovascular burden. Lifestyle modifications might have considerable benefits on ameliorating metabolic status. Alternative biomarkers, such as circulating miR-21, has been recently discovered associated with dysglycemia. Here we evaluated, in a longitudinal cohort of dysglycemic population the relation between the circulating miR-21/ROS/HNE levels and the habit-intervention (HI) after 1 year of follow-up. METHODS: 1506 subjects from DIAPASON study were screened based on the Findrisc score. Of them, 531 subjects with Findrisc ≥ 9 were selected for dysglycemia (ADA criteria) and tested for circulating miR-21, ROS and HNE levels, as damaging-axis. 207 subjects with dysglycemia were re-evaluated after 1-year of habit intervention (HI). Repeated measures tests were used to evaluate changes from baseline to 1-year of follow-up. The associations between glycemic parameters and miR-21/ROS/HNE were implemented by linear regression and logistic regression models. RESULTS: After HI, we observed a significant reduction of miR-21/ROS/HNE axis in dysglycemic subjects, concomitantly with ameliorating of metabolic parameters, including insulin resistance, BMI, microalbuminuria, reactive hyperemia index and skin fluorescence. Significant positive interaction was observed between miR-21 axis with glycaemic parameters after HI. Lower miR-21 levels after HI, strongly associated with a reduction of glycemic damaging-axis, in particular, within-subjects with values of 2hPG < 200 mg/dL. CONCLUSIONS: Our findings demonstrated that HI influenced the epigenetic changes related to miR-21 axis, and sustain the concept of reversibility from dysglycemia. These data support the usefulness of novel biological approaches for monitoring glycemia as well as provide a screening tool for preventive programmes.

Turning the clock forward: New pharmacological and non pharmacological targets for the treatment of obesity.

AIMS: Obesity and its main metabolic complication, type 2 diabetes, have attained the status of a global pandemic; there is need for novel strategies aimed at treating obesity and preventing the development of diabetes. A healthy diet and exercise are basic for treatment of obesity but often not enough. Pharmacotherapy can be helpful in maintaining compliance, ameliorating obesity-related health risks, and improving quality of life. In the last two decades, the knowledge of central and peripheral mechanisms underlying homeostatic and hedonic aspects of food intake has significantly increased. Dysregulation of one or more of these components could lead to obesity. DATA SYNTHESIS: In order to better understand how potential innovative treatment options can affect obesity, homeostatic and reward mechanisms that regulate energy balance has been firstly illustrated. Then, an overview of potential therapeutic targets for obesity, distinguished according to the level of regulation of feeding behavior, has been provided. Moreover, several non-drug therapies have been recently tested in obesity, such as non-invasive neurostimulation: Transcranial Magnetic Stimulation or Transcranial Direct Current Stimulation. All of them are promising for obesity treatment and are almost devoid of side effects, constituting a potential resource for the prevention of metabolic diseases. CONCLUSIONS: The plethora of current anti-obesity therapies creates the unique challenge for physicians to customize the intervention, according to the specific obesity characteristics and the intervention side effect profiles; moreover, it allows multimodal approaches addressed to treat obesity and metabolic adaptation with complementary mechanisms.

Deep transcranial magnetic stimulation in combination with skin thermography in obesity: a window on sympathetic nervous system.

AIMS: Obesity is known to be associated with an altered thermoregulation as well as a dysregulation of sympathetic nervous system (SNS). Considering the ability of deep transcranial magnetic stimulation (dTMS) to modulate the SNS, we hypothesized a potential role of dTMS in affecting thermoregulation in obesity. Aims of the study were to monitor the effect of a single session of dTMS on body temperature in subjects with obesity, and to correlate the dTMS-induced changes in body temperature with activation of the SNS (epinephrine and norepinephrine release). METHODS: Twenty-nine subjects with obesity [5 M, 24 F; age 50 (IQR: 58, 38) yrs; BMI 36.1 (IQR: 33.9, 38.7) kg/m2] were randomized into 2 groups receiving a single session of high frequency stimulation (HF) or sham stimulation. Under neutral thermal conditions, infrared thermography was utilized to assess bilateral fingernail-beds and abdominal temperature. RESULTS: During a single session HF, the average temperature of both fingernail-beds decreased. Right-hand temperature difference was statistically greater in HF vs Sham: median = - 1.45 (IQR: - 2.0, - 1.0)  °C for HF, p = 0.009. While temperature variation in the fingernail-bed of left hand was not statistically significant in HF compared to Sham: median = - 1.26 (IQR: - 1.6, -0.5) °C, p = 0.064. Concurrently, when estimating the effect of norepinephrine variation on temperature change of fingernail-bed of left hand, a borderline significant positive association was estimated (beta = 1.09, p = 0.067) in HF. CONCLUSIONS: Deep TMS revealed to be effective in modulating temperature in subjects with obesity, partially reversing obesity-induced alterations in heat production and dissipation with a potential SNS-mediated mechanism.

Olfactory disfunction and diabetic complications in type 2 diabetic patients: a pilot study.

PURPOSE: Scarce information on the prevalence and characteristics of olfactory disfunction (OD) in type 2 diabetic (T2D) patients are available. The aims of this study were (1) to assess the olfactory function in T2D patients and to compare it with a control group of individuals without T2D, and (2) to evaluate the differences in OD within T2D patients according to the presence of diabetic complications. METHODS: A group of 39 T2D patients and a control group of 39 healthy individuals were enrolled. Each subject underwent an evaluation of the olfactory performance using the Sniffing Olfactory Screening Test (SOST) and completed a questionnaire assessing the subjective perception of olfaction. According to the presence of diabetic complications, the group of T2D patients was divided into two subgroups. Non-parametric tests and regression analysis were used for statistical analysis. RESULTS: No differences in the subjective perception of olfaction were demonstrated among T2D patients (with and without complications) and controls. A significant difference for the SOST score was demonstrated among the different groups. In particular, OD was more frequent in T2D patients than in controls. In addition, OD was far more frequent in T2D patients with complications. Regression analysis did not demonstrate any significant association between OD and clinical/demographic characteristics of T2D patients. CONCLUSION: T2D patients were more frequently affected by OD. The subgroup analysis suggested a possible relationship between OD and diabetic complications since patients with T2D diabetic complications demonstrated lower olfactory abilities than controls subjects and T2D patients without diabetic complications.

Diabetes Mellitus and Cardiovascular Diseases: Nutraceutical Interventions Related to Caloric Restriction.

Type 2 diabetes (T2DM) and cardiovascular disease (CVD) are closely associated and represent a key public health problem worldwide. An excess of adipose tissue, NAFLD, and gut dysbiosis establish a vicious circle that leads to chronic inflammation and oxidative stress. Caloric restriction (CR) is the most promising nutritional approach capable of improving cardiometabolic health. However, adherence to CR represents a barrier to patients and is the primary cause of therapeutic failure. To overcome this problem, many different nutraceutical strategies have been designed. Based on several data that have shown that CR action is mediated by AMPK/SIRT1 activation, several nutraceutical compounds capable of activating AMPK/SIRT1 signaling have been identified. In this review, we summarize recent data on the possible role of berberine, resveratrol, quercetin, and L-carnitine as CR-related nutrients. Additionally, we discuss the limitations related to the use of these nutrients in the management of T2DM and CVD.

Physical activity as a proxy to ameliorate inflammation in patients with type 2 diabetes and periodontal disease at high cardiovascular risk.

While the beneficial impact of physical activity has been ascertained in a variety of pathological scenarios, including diabetes and low-grade systemic inflammation, its potential remains still putative for periodontal health. Periodontal disease has been associated with inflammatory systemic alterations, which share a common denominator with type 2 diabetes mellitus and cardiovascular disease. Physical exercise, along with nutritional counseling, is a cornerstone in the treatment and prevention of type 2 diabetes, also able to reduce the prevalence of periodontal disease and cardiovascular risk. In addition, considering the higher incidence of periodontitis in patients with type 2 diabetes compared to healthy controls, the fascinating research question would be whether physical activity could relieve the inflammatory pressure exerted by the combination of these two diseases. This multi-disciplinary viewpoint discusses available literature in order to argument the hypothesis of a "three-way relationship" linking diabetes, periodontitis, and physical activity.

Reduction of impulsivity in patients receiving deep transcranial magnetic stimulation treatment for obesity.

PURPOSE: Aims of the present study were to investigate a wide array of psychological symptoms through validated psychometric tests, before and after 5 weeks of deep Transcranial Magnetic Stimulation (dTMS) in individuals with obesity, and to identify possible relationships with neuroendocrine parameters. METHODS: Forty-five patients with obesity (33 F, 12 M; age 48.8 ± 9.9 years; body wt 97.6 ± 14.2 Kg; BMI 36.2 ± 4.2) were randomized into two groups: 26 received high frequency (HF) dTMS and 19 Sham stimulation for 5 weeks. At baseline and after the 5-week treatment, all patients underwent the following psychometric evaluations: Food Cravings Questionnaire-Trait (FCQ-T) and its subscales, Barratt Impulsiveness Scale-11 (BIS-11), State and Trait Anxiety Inventory (STAI-y1 and STAI-y2), and Beck Depression Inventory (BDI). Hormonal and neuroendocrine markers were assessed at the first and last dTMS session. RESULTS: By adjusting for baseline variables and treatment arms, a significant decrease in body wt and BMI was found in HF group, both with univariate (p = 0.019) and multivariate analyses (p = 0.012). Impulsivity significantly decreased in HF group, both with univariate (p = 0.031) and multivariate analyses (p = 0.011). A positive association between the impulsivity score change and the leptin level variation (p = 0.031) was found. CONCLUSION: The decrease of impulsivity together with the BMI reduction in individuals with obesity, treated with real stimulation, suggests that impulsivity may be a risk factor for obesity. Treatment with dTMS revealed to be effective in reducing both BMI and impulsivity by enhancing inhibitory capacity of Pre-Frontal Cortex (PFC), and modulating neuroendocrine system, especially leptin.

Playing around the anaerobic threshold during COVID-19 pandemic: advantages and disadvantages of adding bouts of anaerobic work to aerobic activity in physical treatment of individuals with obesity.

INTRODUCTION: Obesity is a condition that generally limits work capacity and predisposes to a number of comorbidities and related diseases, the last being COVID-19 and its complications and sequelae. Physical exercise, together with diet, is a milestone in its management and rehabilitation, although there is still a debate on intensity and duration of training. Anaerobic threshold (AT) is a broad term often used either as ventilatory threshold or as lactate threshold, respectively, detected by respiratory ventilation and/or respiratory gases (VCO2 and VO2), and by blood lactic acid. AIMS AND METHODOLOGY: This review outlines the role of AT and of the different variations of growth hormone and catecholamine, in subjects with obesity vs normal weight individuals below and beyond AT, during a progressive increase in exercise training. We present a re-evaluation of the effects of physical activity on body mass and metabolism of individuals with obesity in light of potential benefits and pitfalls during COVID-19 pandemic. Comparison of a training program at moderate-intensity exercise (< AT) with training performed at moderate intensity (< AT) plus a final bout of high-intensity (> AT) exercise at the end of the aerobic session will be discussed. RESULTS: Based on our data and considerations, a tailored strategy for individuals with obesity concerning the most appropriate intensity of training in the context of rehabilitation is proposed, with special regard to potential benefits of work program above AT. CONCLUSION: Adding bouts of exercise above AT may improve lactic acid and H+ disposal and improve growth hormone. Long-term aerobic exercise may improve leptin reduction. In this way, the propensity of subjects with obesity to encounter a serious prognosis of COVID-19 may be counteracted and the systemic and cardiorespiratory sequelae that may ensue after COVID-19, can be overcome. Individuals with serious comorbidities associated with obesity should avoid excessive exercise intensity.

Deep Transcranial Magnetic Stimulation Affects Gut Microbiota Composition in Obesity: Results of Randomized Clinical Trial.

Growing evidence highlights the crucial role of gut microbiota in affecting different aspects of obesity. Considering the ability of deep transcranial magnetic stimulation (dTMS) to modulate the cortical excitability, the reward system, and, indirectly, the autonomic nervous system (ANS), we hypothesized a potential role of dTMS in affecting the brain-gut communication pathways, and the gut microbiota composition in obesity. In a hospital setting, 22 subjects with obesity (5 M, 17 F; 44.9 ± 2.2 years; BMI 37.5 ± 1.0 kg/m2) were randomized into three groups receiving 15 sessions (3 per week for 5 weeks) of high frequency (HF), low frequency (LF) dTMS, or sham stimulation. Fecal samples were collected at baseline and after 5 weeks of treatment. Total bacterial DNA was extracted from fecal samples using the QIAamp DNA Stool Mini Kit (Qiagen, Italy) and analyzed by a metagenomics approach (Ion Torrent Personal Genome Machine). After 5 weeks, a significant weight loss was found in HF (HF: -4.1 ± 0.8%, LF: -1.9 ± 0.8%, sham: -1.3 ± 0.6%, p = 0.042) compared to LF and sham groups, associated with a decrease in norepinephrine compared to baseline (HF: -61.5 ± 15.2%, p < 0.01; LF: -31.8 ± 17.1%, p < 0.05; sham: -35.8 ± 21.0%, p > 0.05). Furthermore, an increase in Faecalibacterium (+154.3% vs. baseline, p < 0.05) and Alistipes (+153.4% vs. baseline, p < 0.05) genera, and a significant decrease in Lactobacillus (-77.1% vs. baseline, p < 0.05) were found in HF. Faecalibacterium variations were not significant compared to baseline in the other two groups (LF: +106.6%, sham: +27.6%; p > 0.05) as well as Alistipes (LF: -54.9%, sham: -15.1%; p > 0.05) and Lactobacillus (LF: -26.0%, sham: +228.3%; p > 0.05) variations. Norepinephrine change significantly correlated with Bacteroides (r2 = 0.734; p < 0.05), Eubacterium (r2 = 0.734; p < 0.05), and Parasutterella (r2 = 0.618; p < 0.05) abundance variations in HF. In conclusion, HF dTMS treatment revealed to be effective in modulating gut microbiota composition in subjects with obesity, reversing obesity-associated microbiota variations, and promoting bacterial species representative of healthy subjects with anti-inflammatory properties.

Obesity and COVID-19: the ominous duet affecting the renin-angiotensin system.

The world population is facing a health challenge never seen since the Spanish influenza of one hundred years ago. During the last months, the scientific community has been debating on the potential harmful effect of angiotensin-converting-enzyme inhibitors (ACEi) or angiotensin II receptor type 1 receptor blockers (AT1-receptor blockers, ARBs) during the COVID-19 pandemic. That is because the S spike protein of SARS-CoV viruses utilizes the angiotensin-converting enzyme 2 (ACE2) as a receptor to enter alveolar epithelial cells. Obesity, often associated to type 2 Diabetes, was shown to worsen the prognosis of SARS-CoV-2 infection. Herein we discuss the complex interaction between the renin-angiotensin-aldosterone system (RAAS), its receptors, and the interaction with the Kallikrein-Kinin-system (KKS) and the potential activation of the coagulation cascade. Alteration of the equilibrium between the RAAS system and the KKS cascade may explain the frequent thromboembolic complications of COVID-19 mainly seen in obese and diabetic-obese patients. In contrast, angiotensin (1-7) contributes to maintaining a correct balance between RAAS and KKS system. Our conclusion is that the higher mortality rate in patients with obesity is linked to the alteration of RAS and RAS-KKS interaction consequent to SARS-CoV-2-cell entrance. At present, no data support the necessity of modifying ACEi or ARBs treatment in hypertensive patients.

Adipokines, Myokines, and Cardiokines: The Role of Nutritional Interventions.

It is now established that adipose tissue, skeletal muscle, and heart are endocrine organs and secrete in normal and in pathological conditions several molecules, called, respectively, adipokines, myokines, and cardiokines. These secretory proteins constitute a closed network that plays a crucial role in obesity and above all in cardiac diseases associated with obesity. In particular, the interaction between adipokines, myokines, and cardiokines is mainly involved in inflammatory and oxidative damage characterized obesity condition. Identifying new therapeutic agents or treatment having a positive action on the expression of these molecules could have a key positive effect on the management of obesity and its cardiac complications. Results from recent studies indicate that several nutritional interventions, including nutraceutical supplements, could represent new therapeutic agents on the adipo-myo-cardiokines network. This review focuses the biological action on the main adipokines, myokines and cardiokines involved in obesity and cardiovascular diseases and describe the principal nutraceutical approaches able to regulate leptin, adiponectin, apelin, irisin, natriuretic peptides, and follistatin-like 1 expression.

Does intestinal dysbiosis contribute to an aberrant inflammatory response to severe acute respiratory syndrome coronavirus 2 in frail patients?

In a few months, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has become the main health problem worldwide. Epidemiologic studies revealed that populations have different vulnerabilities to SARS-CoV-2. Severe outcomes of the coronavirus disease 2019 (COVID-19) with an increased risk of death are observed in patients with metabolic syndrome, as well as diabetic and heart conditions (frail population). Excessive proinflammatory cytokine storm could be the main cause of increased vulnerability in this frail population. In patients with diabetes and/or heart disease, a low inflammatory state is often associated with gut dysbiosis. The increase amount of microbial metabolites (i.e., trimethylamine N-oxide and lipopolysaccharide), which generate an inflammatory microenvironment, is probably associated with an improved risk of severe illness from COVID-19. Nutritional interventions aimed at restoring the gut microbial balance could represent preventive strategies to protect the frail population from COVID-19. This narrative review presents the possible molecular mechanisms by which intestinal dysbiosis that enhances the inflammatory state could promote the spread of SARS-CoV-2 infection. Some nutritional strategies to counteract inflammation in frail patients are also analyzed.

L-carnitine supplementation attenuates NAFLD progression and cardiac dysfunction in a mouse model fed with methionine and choline-deficient diet.

Non-alcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disorder. NAFLD, associated lipotoxicity, fibrosis, oxidative stress, and altered mitochondrial metabolism, is responsible for systemic inflammation, which contributes to organ dysfunction in extrahepatic tissues, including the heart. We investigated the ability of L-carnitine (LC) to oppose the pathogenic mechanisms underlying NAFLD progression and associated heart dysfunction, in a mouse model of methionine-choline-deficient diet (MCDD). Mice were divided into three groups: namely, the control group (CONTR) fed with a regular diet and two groups fed with MCDD for 6 weeks. In the last 3 weeks, one of the MCDD groups received LC (200 mg/kg each day) through drinking water (MCDD + LC). The hepatic lipid accumulation and oxidative stress decreased after LC supplementation, which also reduced hepatic fibrosis via modulation of α-smooth muscle actin (αSMA), peroxisome-activated receptor gamma (PPARγ), and nuclear factor kappa B (NfƙB) expression. LC ameliorated systemic inflammation, mitigated cardiac reactive oxygen species (ROS) production, and prevented fibrosis progression by acting on signal transducer and activator of transcription 3 (STAT3), extracellular signal-regulated kinase 1-2 (ERK1-2), and αSMA. This study confirms the existence of a relationship between fatty liver disease and cardiac abnormalities and highlights the role of LC in controlling liver oxidative stress, steatosis, fibrosis, and NAFLD-associated cardiac dysfunction.