Beneficial effects of the ketogenic diet on nonalcoholic fatty liver disease: A comprehensive review of the literature

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

Nickel sensitivity is associated with GH-IGF1 axis impairment and pituitary abnormalities on MRI in overweight and obese subjects

Nickel (Ni) is a ubiquitous metal, the exposure of which is implied in the development of contact dermatitis (nickel allergic contact dermatitis (Ni-ACD)) and Systemic Ni Allergy Syndrome (SNAS), very common among overweight/obese patients. Preclinical studies have linked Ni exposure to abnormal production/release of Growth Hormone (GH), and we previously found an association between Ni-ACD/SNAS and GH-Insulin-like growth factor 1 (IGF1) axis dysregulation in obese individuals, altogether suggesting a role for this metal as a pituitary disruptor. We herein aimed to directly evaluate the pituitary gland in overweight/obese patients with signs/symptoms suggestive of Ni allergy, exploring the link with GH secretion; 859 subjects with overweight/obesity and suspected of Ni allergy underwent Ni patch tests. Among these, 106 were also suspected of GH deficiency (GHD) and underwent dynamic testing as well as magnetic resonance imaging for routine follow up of benign diseases or following GHD diagnosis. We report that subjects with Ni allergies show a greater GH-IGF1 axis impairment, a higher prevalence of Empty Sella (ES), a reduced pituitary volume and a higher normalized T2 pituitary intensity compared to nonallergic ones. We hypothesize that Ni may be detrimental to the pituitary gland, through increased inflammation, thus contributing to GH-IGF1 axis dysregulation

Application of a Machine Learning Technology in the Definition of Metabolically Healthy and Unhealthy Status: A Retrospective Study of 2567 Subjects Suffering from Obesity with or without Metabolic Syndrome.

The key factors playing a role in the pathogenesis of metabolic alterations observed in many patients with obesity have not been fully characterized. Their identification is crucial, and it would represent a fundamental step towards better management of this urgent public health issue. This aim could be accomplished by exploiting the potential of machine learning (ML) technology. In a single-centre study (n = 2567), we used an ML analysis to cluster patients with metabolically healthy (MHO) or metabolically unhealthy (MUO) obesity, based on several clinical and biochemical variables. The first model provided by ML was able to predict the presence/absence of MHO with an accuracy of 66.67% and 72.15%, respectively, and included the following parameters: HOMA-IR, upper body fat/lower body fat, glycosylated haemoglobin, red blood cells, age, alanine aminotransferase, uric acid, white blood cells, insulin-like growth factor 1 (IGF-1) and gamma-glutamyl transferase. For each of these parameters, ML provided threshold values identifying either MUO or MHO. A second model including IGF-1 zSDS, a surrogate marker of IGF-1 normalized by age and sex, was even more accurate with a 71.84% and 72.3% precision, respectively. Our results demonstrated high IGF-1 levels in MHO patients, thus highlighting a possible role of IGF-1 as a novel metabolic health parameter to effectively predict the development of MUO using ML technology

Implantação de Unidade Psiquiátrica livre de tabaco em um hospital geral

19719

Predictors of weight loss in patients with obesity treated with a Very Low-Calorie Ketogenic Diet

IntroductionThe 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.MethodsWe 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.ResultsWe 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).DiscussionVLCKD 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

Bone density and genomic analysis unfold cold adaptation mechanisms of ancient inhabitants of Tierra del Fuego

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

Letter to the Editor: "Our Response to COVID-19 as Endocrinologists and Diabetologists"

We read with interest the article by Kaiser et al highlighting some relevant aspects about the management of patients with endocrine conditions who are simultaneously infected with the 2019 novel coronavirus (SARS-CoV-2) (1). As far as we are concerned, understanding the evidence of the role played by corticosteroids in SARS-CoV-2 infection is of immediate clinical importance. The existing literature does not currently provide conclusive evidence regarding their administration for the treatment of COVID-19 (2). There have been a number of reports stating generally positive outcomes upon corticosteroid use, especially in the early acute phase of infection, as they are capable of reducing immune-mediated damage (3). In this regard, Fu Y et al suggest to adopt steroids in combination with the use of intravenous immunoglobulin to block Fc receptors (FcR) activation in order to prevent severe lung injury. However, such treatment remains to be clinically tested for effectiveness (4). On the other hand, patients taking supraphysiologic doses of glucocorticoids may have increased susceptibility to COVID-19 because of the immunosuppressive effects of steroids, which can be ultimately responsible for severe lymphocytopenia, thus promoting a viral rebound. Moreover, steroids have also been associated with higher risk of acute respiratory distress syndrome (ARDS) (5) and may therefore determine exaggerated pro-inflammatory responses and even worsen the clinical condition of the patients. However, in the event of COVID-19, patients on long-term steroids, or suffering from adrenal insufficiency and uncontrolled Cushing syndrome may be unable to develop a normal stress response, thus requiring a rescue dose of glucocorticoids (1). In our opinion, this evidence by Kaiser and colleagues should be extended to those patients with chronic pain on therapy with opioids. Long-term use of opioids has been associated with suppression of the hypothalamic-pituitary-adrenal (HPA) axis through the inhibition of corticotrophin-releasing hormone (CRH) and antidiuretic hormone (ADH) secretion, resulting in decreased adrenocorticotropic hormone (ACTH) release (6) and central hypocortisolism (defined as stimulated cortisol concentration of <18 μg/dL [500 nmol/L] in an insulin tolerance test) (7, 8). Further investigations on the balanced use of corticosteroids therapy in COVID-19 patients with alteration of the HPA axis due to long-term opioids or steroid treatment are necessary, since these patients represent a frail population at major risk

Liver disease in obesity and underweight: the two sides of the coin. A narrative review

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

Beneficial effects of the ketogenic diet on nonalcoholic fatty liver disease: A comprehensive review of the literature

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