Ketogenic nutritional therapy (KeNuT)-a multi-step dietary model with meal replacements for the management of obesity and its related metabolic disorders: a consensus statement from the working group of the Club of the Italian Society of Endocrinology (SIE)-diet therapies in endocrinology and metabolism.

PURPOSE: The ketogenic nutritional therapy (KeNuT) is an effective dietary treatment for patients with obesity and obesity-related comorbidities, including type 2 diabetes, dyslipidaemia, hypertension, coronary artery disease, and some type of cancers. However, to date an official document on the correct prescription of the ketogenic diet, validated by authoritative societies in nutrition or endocrine sciences, is missing. It is important to emphasize that the ketogenic nutritional therapy requires proper medical supervision for patient selection, due to the complex biochemical implications of ketosis and the need for a strict therapeutic compliance, and an experienced nutritionist for proper personalization of the whole nutritional protocol. METHODS: This practical guide provides an update of main clinical indications and contraindications of ketogenic nutritional therapy with meal replacements and its mechanisms of action. In addition, the various phases of the protocol involving meal replacements, its monitoring, clinical management and potential side effects, are also discussed. CONCLUSION: This practical guide will help the healthcare provider to acquire the necessary skills to provide a comprehensive care of patients with overweight, obesity and obesity-related diseases, using a multistep ketogenic dietary treatment, recognized by the Club of the Italian Society of Endocrinology (SIE)-Diet Therapies in Endocrinology and Metabolism.

Role of Mediterranean diet in endocrine diseases: a joint overview by the endocrinologist and the nutritionist.

PURPOSE: The purpose of this review is to examine the current evidence on the potential role of Mediterranean diet (MD) in the prevention and management of endocrine disorders and to highlight the importance of interdisciplinary collaboration between endocrinologists and nutritionists. METHODS: A literature search was conducted using PubMed and Google Scholar databases to identify relevant studies published in English. Studies were selected based on their relevance to the role of MD in the prevention and management of endocrine disorders. The search terms included "Mediterranean diet," "endocrine disorders," "thyroid disorders," "gonadal disorders," and "neuroendocrine tumors". RESULTS: The studies reviewed suggest that MD may have a beneficial effect in the prevention and management of various endocrine disorders, including thyroid disorders, gonadal disorders, and neuroendocrine tumors. MD has been associated with decreased risk of nodular thyroid disease and thyroid cancer, improved male and female reproductive health, and a potential role in the management of neuroendocrine tumors. MD's anti-inflammatory and antioxidant properties, as well as its high levels of phytochemicals, may play a role in its beneficial effects. CONCLUSION: Interdisciplinary collaboration between endocrinologists and nutritionists is essential for the optimal management of endocrine disorders, including the potential role of MD in their prevention and management. While further research is needed, the current evidence suggests that MD may have a protective effect against endocrine disorders, and its incorporation into dietary recommendations may be beneficial.

Obesity: a gender-view.

PURPOSE: There is a growing awareness of the importance of understanding gender differences in obesity. The aim of this short review was to revise the current evidence on anthropometric characteristics and nutritional and pharmacological aspects of obesity from a gender perspective. METHODS: A literature search within PubMed was performed. Selected publications related to obesity and gender differences were reviewed. RESULTS: The prevalence of obesity among men is higher than in women, but women have a higher percentage of body fat content compared to men, and gender appears to be an important factor in the manifestation of central (android) or peripheral (gynoid) obesity. In addition, while in most clinical trials, women are still underrepresented, in clinical registration trials of anti-obesity drugs, women are commonly up-represented and gender-specific analysis is uncommon. Considering that adipose tissue is one of the factors affecting the volume of distribution of many drugs, mainly lipophilic drugs, gender differences might be expected in the pharmacokinetics and pharmacodynamics of anti-obesity drugs. Indeed, although Liraglutide 3 mg, a long-acting glucagon-like peptide-1 receptor agonist, and naltrexone/bupropion display lipophilic properties, currently, a gender-dose adjustment for both these drugs administration is not recommended. In addition, despite that predicted responders to treatment offer substantial opportunities for efficient use, especially of expensive new therapies, such as anti-obesity drugs, data on gender differences to identify early responders to both these have not yet been investigated. Finally, bariatric surgery gender disparity reflects healthcare practices. Weight loss similar, but differing effects: women need more correction and face psychology challenges; men have worse physiology and fewer comorbidity improvements. CONCLUSION: Gender differences exist in obesity prevalence and phenotype, body fat distribution, drug efficacy, clinical trial representation, and different secondary effects of bariatric surgery. Gender is an important variable in obesity analysis.

Effects of very low-calorie ketogenic diet on hypothalamic-pituitary-adrenal axis and renin-angiotensin-aldosterone system.

BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system involved in controlling stress responses in humans under physiological and pathological conditions; cortisol is the main hormone produced by the HPA axis. It is known that calorie restriction acts as a stressor and can lead to an increase in cortisol production. Renin-angiotensin-aldosterone system (RAAS) is a complex endocrine network regulating blood pressure and hydrosaline metabolism, whose final hormonal effector is aldosterone. RAAS activation is linked to cardiometabolic diseases, such as heart failure and obesity. Obesity has become a leading worldwide pandemic, associated with serious health outcomes. Calorie restriction represents a pivotal strategy to tackle obesity. On the other hand, it is well known that an increased activity of the HPA may favour visceral adipose tissue expansion, which may jeopardize a successful diet-induced weight loss. Very low-calorie ketogenic diet (VLCKD) is a normoprotein diet with a drastic reduction of the carbohydrate content and total calorie intake. Thanks to its sustained protein content, VLCKD is extremely effective to reduce adipose tissue while preserving lean body mass and resting metabolic rate. PURPOSE: The purpose of this narrative review is to gain more insights on the effects of VLCKD on the HPA axis and RAAS, in different phases of weight loss and in different clinical settings.

Liraglutide and polycystic ovary syndrome: is it only a matter of body weight?

Despite Polycystic Ovary Syndrome (PCOS) is a very prevalent disorder among women of reproductive age, there is widespread agreement that until now, no pharmacological options are available to tackle the entire spectrum of clinical manifestations encountered in the clinical practice. Obesity and insulin resistance, which commonly characterized this syndrome, prompted the design of studies investigating the effects of glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1RA) in PCOS. Indeed, a very impressive number of randomized controlled clinical trials (RCTs) and systematic reviews provided robust evidence on the effectiveness of GLP-1RA in PCOS as a new, appealing approach, producing both satisfactory and permanent weight loss, and improvement of insulin resistance at the same time. However, most of the subjects included in the RCTs are PCOS patients with obesity/overweight, whereas a portion of PCOS women, which can even reach 50%, might present a lean phenotype. Moreover, some benefits on clinical and metabolic features of PCOS may not have fully emerged due to the low or medium doses employed in the vast majority of the current studies. Thus, pitfalls in the methodology of these studies have led sometimes to misleading results. In addition, some aspects of GLP-1 beyond weight loss, such as preclinical evidence on GLP-1 effects in directly modulating the hypothalamus-pituitary-gonadal axis, or the effects of GLP-1RA on clinical and biochemical expression of hyperandrogenism, still deserve a greater insight, especially in light of a possible therapeutic use in PCOS women independently of obesity. Aim of this review is to further unravel the possible role of GLP-1 in PCOS pathogenesis, tempting to provide additional supports to the rationale of treatment with GLP-1RA in the management of PCOS also independent of weight loss. For this purpose, the outcomes of RCTs investigating in PCOS the anthropometric and metabolic changes have been treated separately to better underpin the effects of GLP-1 RA, in particular liraglutide, beyond weight loss.

Vitamin D and chronotype: is there any relationship in individuals with obesity?

PURPOSE: Chronotype is the attitude to perform most of the daily activities in the morning ("morning chronotype", MC) or in the evening ("evening chronotype", EC). The latter, as well as vitamin D deficiency, has been associated with an increased risk of obesity-related complications, likely through the promotion of insulin resistance. Therefore, we aimed to investigate whether there is any relationship between vitamin D (25-OH-D) and chronotype in individuals with obesity. METHODS: In this cross-sectional study, we enrolled 59 individuals (43.1 ± 13 years; 17M/42F) with obesity. Anthropometric parameters, lifestyle habits, personal medical history, chronotype, insulin resistance, and 25-OH-D were assessed. RESULTS: Individuals with EC presented significantly higher BMI than MC (p < 0.001), greater waist (p = 0.012), and hip circumferences (p = 0.001). Individuals with EC showed significantly lower insulin sensitivity (p = 0.017) and 25-OH-D than MC. In addition, the prevalence of vitamin D deficiency and impaired fasting glucose was significantly higher in EC than in MC. 25-OH-D directly correlated with chronotype score (r = 0.351; p = 0.019) whereas inversely with BMI (r = - 0.363; p = 0.016). The regression analysis showed that BMI was most tightly associated with 25-OH-D concentrations (ß = - 0.323, p = 0.032), followed by chronotype score (ß = 0.340, p = 0.042). Using chronotype score as the dependent variable, BMI significantly predicted a lower chronotype score (ß = - 0.586, p < 0.001). CONCLUSION: The present study showed that 25-OH-D, as well as chronotype, correlate independently with obesity.

Weight stigma speaks Italian, too.

PURPOSE: Weight stigma is the negative weight related attitudes and beliefs towards individuals because of their overweight or obesity. Subjects with obesity are often victim of weight-related stigma resulting in a significant negative social consequence. As obesity epidemic is growing so fast, there is urgency to act on weight-stigma related social consequences being potentially serious and pervasive. This study investigated experiences, interpersonal sources, and context of weight stigma in Italy in a sample of adult subjects with obesity. METHODS: An online questionnaire was distributed to respondents via a snowball sampling method among subjects with obesity belonging to Italian Associations for people living with obesity aged 18 years and above. RESULTS: Four hundred and three respondents (47.18 ± 9.44 years; body mass index (BMI) 33.2 ± 8.48 kg/m2) participated to the study. Most respondents were females (94.8%). The age first dieted was 15.82 ± 7.12 years. The mean period of obesity was 27.49 ± 11.41 years. Frequency analyses reported that stigmatizing situations were experienced by 98% of participants: 94.82% during adulthood, 89.88% during adolescence and 75.39% during childhood. Verbal mistreatments (92.43%) was the most reported stigmatizing situation, strangers (92.43%) were the most common interpersonal sources of stigma and public settings (88.08%) were the most common location of stigma. CONCLUSIONS: Identifying strategies acting on the identified weight stigma targets could contribute to reduce weight stigma and thus to result in important implications for obesity treatment in Italy.

Body composition and obstructive sleep apnoea assessment in adult patients with Prader-Willi syndrome: a case control study.

INTRODUCTION: In Prader-Willi syndrome (PWS) adult patients, sleep-breathing disorders, especially obstructive sleep apnoea syndrome (OSAS), are very common, whose missed or delayed diagnosis can contribute to further increase cardiovascular morbidity and mortality. PURPOSE: The aim of this cross-sectional study was to evaluate differences in sleep-breathing parameters obtained by overnight cardiorespiratory polygraphy in 13 adult PWS patients and 13 individuals with non-syndromic obesity as controls matched by age, sex, and BMI. METHODS: In all subjects' anthropometric parameters, body composition using bioimpedance analysis and overnight cardiorespiratory monitoring parameters were obtained. RESULTS: Ten (76.9%) PWS patients were diagnosed with OSAS, most notably nine (69.2%) and one PWS (7.7%) with mild and severe OSAS, respectively. Compared with the control group, PWS patients had evidence of higher apnoea-hypopnea index (AHI) (p = 0.04) and oxyhaemoglobin desaturation index (ODI) (p = 0.009). However, no differences were found between the two groups regarding OSAS categories or diagnosis of nocturnal respiratory failure. In the PWS group, there were no significant correlations among AHI, ODI and hypoxemia index (T90) and anthropometric measurements, fat mass (FM), and FM percentage (%). Conversely, in the control group, the sleep-related respiratory indices evaluated correlated positively with BMI, waist circumference, FM and FM%. CONCLUSIONS: This study confirmed that AHI and ODI indices were worse in PWS than in age, sex and BMI-matched controls. The lack of their significant association with the anthropometric parameters and FM supported the existence of PWS-related mechanisms in OSAS pathophysiology that are independent of visceral obesity and FM.

Obesity in Prader-Willi syndrome: physiopathological mechanisms, nutritional and pharmacological approaches.

Prader-Willi syndrome (PWS) is a genetic disorder caused by the lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region. The three main genetic subtypes are represented by paternal 15q11-q13 deletion, maternal uniparental disomy 15, and imprinting defect. Clinical picture of PWS changes across life stages. The main clinical characteristics are represented by short stature, developmental delay, cognitive disability and behavioral diseases. Hypotonia and poor suck resulting in failure to thrive are typical of infancy. As the subjects with PWS age, clinical manifestations such as hyperphagia, temperature instability, high pain threshold, hypersomnia and multiple endocrine abnormalities including growth hormone and thyroid-stimulating hormone deficiencies, hypogonadism and central adrenal insufficiency due to hypothalamic dysfunction occur. Obesity and its complications are the most common causes of morbidity and mortality in PWS. Several mechanisms for the aetiology of obesity in PWS have been hypothesized, which include aberration in hypothalamic pathways of satiety control resulting in hyperphagia, disruption in hormones regulating appetite and satiety and reduced energy expenditure. However, despite the advancement in the research field of the genetic basis of obesity in PWS, there are contradictory data on the management. Although it is mandatory to adopt obesity strategy prevention from infancy, there is promising evidence regarding the management of obesity in adulthood with current obesity drugs along with lifestyle interventions, although the data are limited. Therefore, the current manuscript provides a review of the current evidence on obesity and PWS, covering physiopathological aspects, obesity-related complications and conservative management.

Is there any gender difference in epidemiology, clinical presentation and co-morbidities of non-functioning pituitary adenomas? A prospective survey of a National Referral Center and review of the literature.

PURPOSE: Gender differences in patients diagnosed with non-functioning Pituitary Adenomas (NFPA) in a National Referral Center for Pituitary Tumors at the Federico II University of Naples, Italy. METHODS: Patients newly diagnosed with non-functioning sellar masses found on pituitary Magnetic Resonance Imaging from January 1st 2016 to December 31th 2018 underwent anthropometric measurements, basal evaluation of pituitary function, and metabolic assessment. Fatty live index (FLI) and visceral adiposity index (VAI) were calculated. RESULTS: Seventy-three patients (35 males, 51.1 ± 17.0 years; 38 females, 41.8 ± 18.1 years) presented with NFPA. Lesions > 1 cm (85.7% vs. 47.3%; χ2 = 10.26, p = 0.001) and hypopituitarism (77.1% vs. 7.9%; χ2 = 33.29, p = 0.001) were more frequent in males than females. The highest sizes of pituitary adenomas were significantly associated with male gender (OR = 1.05, p = 0.049; R2 = 0.060; IC 1.00-1.10). Headache (62.8% vs. 31.6%; χ2 = 5.96, p = 0.015) and visual field deficits (57.1% vs. 26.3%; χ2 = 5.93, p = 0.015) were significantly more frequent in males than in females. There was no sex difference in obesity prevalence, but the metabolic syndrome was more common among males than females (60.6% vs. 26.3%; χ2 = 7.14, p = 0.001). FLI was also higher in males (69.6 ± 27.3 vs. 49.2 ± 31.3; p < 0.001), while there were no differences in VAI. CONCLUSIONS: Apart from the possible delay in the diagnosis induced by the gender differences in symptom presentation, the higher prevalence of macroadenomas amongst NFPA in males compared with females let to hypothesize a key role of the sex hormone profile as predictive factors of their biological behavior and metabolic profile. Further studies are, however, mandatory to better support the influence of gender differences on onset, progression, and metabolic consequences of NFPA.

An Approach to Prevent Frailty in Community Dwelling Older Adults: a pilot study performed in Campania region in the framework of the PERSSILAA project.

We developed and tested an innovative physical training method in older adults that embeds the gym program into everyday life in the most conservative way possible. Physical training was included in the activities of local parishes where older women from Southern Italy spend most of their free time and was delivered by trained physical therapists with the support of an ICT tool known as CoCo. 113 older women (aged 72.0 [69.0-75.0] years) noncompliant to conventional exercise programs participated to the study. 57 of them underwent the final anthropometric assessment and 50 the final physical tests. In study completers handgrip strength and physical performance evaluated with the chair-stand, the two minutes step and the chair-sit and -reach tests significantly improved. Quality of life as evaluated with the EuroQol-5dimension (EQ-5D) questionnaire improved as well. In conclusion, a training program designed to minimally impact on life habits of older people is effective in improving fitness in patients noncompliant to other to physical exercise programs.

Nutrition and Osteoporosis: Preliminary data of Campania Region of European PERsonalised ICT Supported Service for Independent Living and Active Ageing.

BACKGROUND: Bone impairment and malnutrition are associated with significant disability and mortality. PERSSILAA is an European project developing health services to detect and prevent frailty in older adults by addressing cognitive, physical and nutritional. METHODS: Subjects underwent anthropometric measurements, calcaneal quantitative ultrasound (QUS) scan and PREDIMED (PREvención con DIeta MEDiterránea) questionnaire. AIM: To investigate the association between adherence to the Mediterranean Diet (MD) and bone health. RESULTS: 87 subjects (4 males and 83 females) 70.1±4.9 aged, were examined. Mean Body Mass Index (BMI) was 28.7±4.7(kg/m(2)): in particular 28 subjects (32.2%) resulted obese, 42 (48.3%) overweight, and only 17 (19.5%) with normal weight. Mean T score was -1.2±1.2: in particular 13 subjects (14.9%) resulted osteoporotic; 43 (49.5%) osteopenic; and 31 (35.6%) with normal bone mineral density. Regarding adherence to MD, 9 subjects (10.3%) were poorly adherent; 41 (47.2%) average adherent; 37 (42.5%) highly adherent. T-score was associated with PREDIMED score and osteoporotic subjects presented the lowest PREDIMED score (5.8±2.2). CONCLUSIONS: These preliminary data show a significant correlation between the adherence to the MD and bone health parameters. The association between MD and bone health highlights the potential beneficial effects of nutritional interventions promoting a Mediterranean food pattern, as safe adjuvant treatment in ageing.

Beyond waist circumference in an adult male population of Southern Italy: Is there any role for subscapular skinfold thickness in the relationship between insulin-like growth factor-I system and metabolic parameters?

BACKGROUND: Apart from waist circumference, other adiposity measures, such as subscapular skin fold (SST), arouse growing interest due to their relationship to metabolic complications and cardiovascular risk. The IGF-I system is deregulated in obese subjects in proportion to their degree of visceral adiposity. AIM: To examine the association among IGF-I, IGF-binding protein (BP)-1 and -3 levels and different measures of adiposity in a sample of adult male population in Southern Italy. MATERIALS AND METHODS: A complete database for this analysis was available for 229 (age range 50-82 yr) participating at 2002-2004 Olivetti Heart Study follow-up. RESULTS: After adjustment for age, IGF-I was inversely associated with body mass index (BMI) and waist circumference (p<0.05). IGFBP-1 was inversely associated with BMI, waist circumference, SST, homeostasis model assessment (HOMA) index, fat mass. HOMA index, age, and SST significantly predicted the IGFBP-1 plasma levels, with 24% of IGFBP-1 variability explained at a linear regression analysis. CONCLUSIONS: IGFBP-1 inversely correlated to adiposity and HOMA index. Among adiposity indexes, SST was the best predictor of IGFBP-1 levels. The evaluation of some components of the IGF system, and simple measures of body adiposity, such as SST, may represent a further tool to better evidence phenotype profiles associated to the pathogenetic mechanism of cardiovascular risk factor clustering in male adults.