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Background and Aims: Phenylketonuria (PKU)-affected women may become pregnant, and dietary phenylalanine (Phe) intake must be adjusted according to Phe tolerance. We report our experience with maternal PKU in relation to genotype PKU heterogeneity., Methods and Results: A total of 10 pregnancies in 7 PKU women (7 different genotypes) were followed up as part of personalized care. Phe tolerance during preconception and pregnancy was assessed by strict dietary control and weekly Phe measurement (blood spots) in relation to genotype. Most women had stopped PKU diet during childhood or adolescence and six pregnancies were unplanned; a phenylalanine-restricted diet was reinstituted soon after conception. Women were classified according to their Phe levels at birth screening and genotype. Phe tolerance increased systematically in the course of pregnancy in all cases, but the increase was different in subjects with classic PKU (cPKU) when compared with cases with mild hyperphenylalaninemia (mHPA), both on average (+297 mg/day in cPKU vs. 597 in mHPA; P = 0.017) and as percentage (+107% in cPKU vs. +17% in mHPA). Notably, Phe tolerance also varied in the same women in the course of different pregnancies, when body weight gain was also different. Two newborns from the same cPKU mother (unplanned pregnancies on free diet) were affected by congenital alterations., Conclusions: Several factors influence metabolic phenotype in maternal PKU, to an unpredictable extent even in the same woman. The number of maternal PKU cases is growing in dedicated Nutrition Units, and the burden associated with careful management of this condition for the health care system should be adequately considered., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2020 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Aldosterone is a mineralocorticoid hormone with a well-known effect on the renal tubule leading to water retention and potassium reabsorption. Other major effects of the hormone include the induction of proinflammatory activity that leads to progressive fibrotic damage of the target organs, heart and kidney. Blocking the aldosterone receptor therefore represents an important pharmacological strategy to avoid the clinical conditions deriving from heart failure (CHF) and chronic kidney disease (CKD). However, steroidal mineralocorticoid receptor antagonists (MRA) have a low safety profile, especially in CKD patients due to the high incidence of hyperkalemia. A new generation of nonsteroidal MRA has recently been developed to obtain a selective receptor block avoiding side-effects like hyperkalemia and thereby making the drugs suitable for administration to CKD patients. This review summarizes the results of published preclinical and clinical studies on the nonsteroidal MRA, apararenone esaxerenone and finerenone. The trials showed a better safety profile with maintained drug efficacy compared with steroidal MRA. For this reason, nonsteroidal MRA represent an interesting new therapeutic approach for the prevention of CHF and CKD progression. Some basic research findings also yielded interesting results in acute clinical settings such as myocardial infarction and acute kidney injury.

Objectives: To describe the video-polysomnographic (VPSG) features of the night eating syndrome (NES), exploring the existence of potential subtypes., Methods: In this study, 20 consecutive patients with NES according to the most recent diagnostic criteria underwent an overnight VPSG. None of them presented with a sleep-related eating disorder (SRED). VPSG recordings were reviewed identifying all eating episodes. For each episode, eating latency (time delay from awakening to food intake), eating duration (time between eating onset to eating offset) and sleep latency after eating offset (time delay from eating offset to sleep) were calculated. Total episode duration was considered as the time between awakening and sleep latency after eating offset., Results: Ten patients fulfilled the A1 core criterion for NES (evening hyperphagia with consumption of at least 25% of the daily caloric intake after the evening meal); within this group, eight patients also fulfilled the A2 criterion (at least two episodes of nocturnal eating per week) and were thus included in the evening hyperphagia (EH) subgroup. The remaining 10 patients satisfied only the A2 core criterion for NES, constituting the nocturnal ingestion (NI) subgroup. We recorded 20 eating episodes, seven in the EH group and 13 in the NI group. In the EH subgroup, three eating episodes occurred before sleep onset, one after an awakening from non-rapid eye movement (NREM) stage 1 sleep, two from NREM stage 2 and one from REM sleep. All 13 NI episodes occurred after an awakening from sleep (1 from NREM stage 1 sleep, 8 from NREM stage 2 and four from NREM stage 3). In EH patients, eating latency, total episode duration and sleep latency after eating offset were significantly longer than in NI patients., Conclusion: Our VPSG data from a case series of 20 patients referred to our center for nocturnal eating indicate potential different NES subtypes. This distinction may have an impact on patients' treatment and follow-up., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background and Aims: Dysfunctional eating might impact on the management and metabolic control of type 2 diabetes (T2DM), modifying adherence to healthy diet and food choices., Methods and Results: In a multicenter study, we assessed the prevalence of dysfunctional eating in 895 adult outpatients with T2DM (51% males, median age 67, median BMI 30.3 kg/m 2 ). Socio-demographic and clinical characteristics were recorded; dysfunctional eating was tested by validated questionnaires (Eating Attitude Test-EAT-26, Binge Eating Scale-BES; Night Eating Questionnaire-NEQ); food intake and adherence to Mediterranean diet were also measured (in-house developed questionnaire and Mediterranean Diet Score-MDS). Obesity was present in 52% of cases (10% obesity class III), with higher rates in women; 22% had HbA1c ≥ 8%. The EAT-26 was positive in 19.6% of women vs. 10.2% of men; BES scores outside the normal range were recorded in 9.4% of women and 4.4% of men, with 3.0% and 1.5% suggestive of binge eating disorder, respectively. Night eating (NEQ) was only present in 3.2% of women and 0.4% of men. Critical EAT and BES values were associated with higher BMI, and all NEQ + ve cases, but one, were clustered among BES + ve individuals. Calorie intake increased with BES, NEQ, and BMI, and decreased with age and with higher adherence to Mediterranean diet. In multivariable logistic regression analysis, female sex, and younger age were associated with increase risk of dysfunctional eating., Conclusion: Dysfunctional eating is present across the whole spectrum of T2DM and significantly impacts on adherence to dietary restriction and food choices., (Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Aims: Intensification of type 2 diabetes (T2DM) treatment with GLP-1 receptor agonists (GLP-1RAs) promotes weight loss. We aimed to determine the synergistic effect of behavioural programmes on body weight on top of GLP-1RA treatment., Materials and Methods: We retrospectively analysed the time course of 328 individuals with T2DM starting GLP-1RA treatment because of insufficient metabolic control. In 29, a structured programme of elementary nutritional counselling was also implemented (elementary nutritional education [ENE]-5 group sessions), whereas 53 entered a programme of cognitive-behavioural treatment (CBT-12 group sessions). Both programmes were completed within 6 months of switching to GLP-1RAs. Data of body weight and metabolic control were followed up to 2 years as part of regular follow-up. Weight loss targets (≥10% and ≥5%) and metabolic target (HbA1c < 7%) were analysed by Cox regression model in comparison with standard care (SC, N = 244)., Results: Body weight remarkably decreased following both behavioural programmes, with significant differences compared with SC at 2 years (CBT, 8.5 ± 5.9% vs 6.3 ± 6.9 in ENE and only 3.1 ± 5.7 in SC; P  < 0.001 and P  = 0.045 vs CBT and ENE, respectively). The 10% weight loss was achieved and maintained in approximately 30% of cases during follow-up, and an additional 35% of cases lost between 5% and 10%. Data were consistent between behavioural programmes, after adjustment for confounders, including initial body weight (logreg Mantel-Cox: ENE vs SC, P  < 0.01; CBT vs SC, P  < 0.001). No differences in metabolic control were detected between groups., Conclusions: Initiation of GLP-1RA treatment provides an opportunity for addressing patients' needs of weight control. By producing initial weight loss, patients' motivation and self-efficacy are expected to increase and adherence to long-term lifestyle changes might be more easily attained., Competing Interests: All authors declare no conflict of interest in relation to the material presented in this study., (© 2019 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Aims: Progressive chronic kidney disease represents a dreadful complication of type 2 diabetes mellitus (T2DM). We tested the pattern of use and the renal effects of old glucose-lowering drugs in T2DM patients cared for by Italian general practitioners (GPs)., Methods: Data of 2606 T2DM patients were extracted from the databases of GPs, who do not have access to the most recent glucose-lowering drugs in Italy. The rate of kidney function decline was calculated by CKD-EPI cr , based on two consecutive creatinine values., Results: Metformin was used in 55% of cases, either alone or with sulfonylureas/repaglinide, across the whole spectrum of CKD (from 66% in stage G1 to only 8% in G4). Sulfonylurea use peaked at 21-22% in stage G2-G3a, whereas repaglinide use significantly increased from 8% in G1 to 22% in G4. The median rate of CKD decline was - 1.64 mL/min/1.73 m 2 per year; it was higher in G1 (- 3.22 per year) and progressively lower with CKD severity. 826 cases (31.7%) were classified as fast progressors (eGFR decline more negative than - 5 mL/min/1.73 m 2 per year). The risk of fast progressing CKD was associated with increasing BMI, albuminuria, and sulfonylurea use, alone (OR, 1.47; 95% confidence interval, 1.16-1.85), or in association with metformin (OR, 1.40; 95% CI 1.04-1.88). No associations were demonstrated for metformin, cardiovascular and lipid lowering drug use., Conclusion: In the setting of Italian family practice, sulfonylurea use is associated with progressive CKD in patients with T2DM. Metformin, at doses progressively reduced according to CKD stages, as recommended by guidelines, is not associated with fast progression.

Sarcopenic obesity (SO) is referred to as the combination of obesity with low skeletal muscle mass and function. However, its definition and diagnosis is debated. SO represents a sizable risk factor for the development of disability, possibly with a worse prognosis in women. The present narrative review summarizes the current evidence on pharmacological, nutrition and exercise strategies on the prevention and/or treatment of SO in middle-aged and older-aged women. A literature search was carried out in Medline and Google Scholar between 29th January and 14th March 2019. Only controlled intervention studies on mid-age and older women whose focus was on the prevention and/or treatment of sarcopenia associated with obesity were included. Resistance training (RT) appears effective in the prevention of all components of SO in women, resulting in significant improvements in muscular mass, strength, and functional capacity plus loss of fat mass, especially when coupled with hypocaloric diets containing at least 0.8 g/kg body weight protein. Correction of vitamin D deficit has a favorable effect on muscle mass. Treatment of SO already established is yet unsatisfactory, although intense and prolonged RT, diets with higher (1.2 g/kg body weight) protein content, and soy isoflavones all look promising. However, further confirmatory research and trials combining different approaches are required., Competing Interests: The authors declare no conflict of interest.

Background & Aims: Interventions aimed at lifestyle changes are pivotal for the treatment of non-alcoholic fatty liver disease (NAFLD), and web-based programs might help remove barriers in both patients and therapists., Methods: In the period 2010-15, 716 consecutive NAFLD cases (mean age, 52; type 2 diabetes, 33%) were treated in our Department with structured programs. The usual protocol included motivational interviewing and a group-based intervention (GBI), chaired by physicians, dietitians and psychologists (five weekly meetings, n = 438). Individuals who could not attend GBI entered a web-based intervention (WBI, n = 278) derived from GBI, with interactive games, learning tests, motivational tests, and mail contacts with the center. The primary outcome was weight loss ≥10%; secondary outcomes were alanine aminotransferase within normal limits, changes in lifestyle, weight, alanine aminotransferase, and surrogate markers of steatosis and fibrosis., Results: GBI and WBI cohorts had similar body mass index (mean, 33 kg/m 2 ), with more males (67% vs. 45%), younger age, higher education, and more physical activity in the WBI group. The two-year attrition rate was higher in the WBI group. Healthy lifestyle changes were observed in both groups and body mass index decreased by almost two points;the 10% weight target was reached in 20% of WBI cases vs. 15% in GBI (not significant). In logistic regression analysis, after adjustment for confounders and attrition rates, WBI was not associated with a reduction of patients reaching short- and long-term 10% weight targets. Liver enzymes decreased in both groups, and normalized more frequently in WBI. Fatty liver index was reduced, whereas fibrosis remained stable (NAFLD fibrosis score) or similarly decreased (Fib-4)., Conclusion: WBI is not less effective than common lifestyle programs, as measured by significant clinical outcomes associated with improved histological outcomes in NAFLD. eHealth programs may effectively contribute to NAFLD control., Lay Summary: In patients with non-alcoholic fatty liver disease, participation in structured lifestyle programs may be jeopardized by job and time constraints. A web-based intervention may be better suited for young, busy patients, and for those living far from liver units. The study shows that, following a structured motivational approach, a web-based, interactive intervention coupled with six-month face-to-face meetings is not inferior to a standard group-based intervention with respect to weight loss, adherence to healthy diet and habitual physical activity, normalization of liver enzymes, and stable surrogate markers of fibrosis., (Copyright © 2018 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Despite intensive training, a few individuals with Type 1 diabetes mellitus (T1DM) fail to reach the desired metabolic targets., Aim: To evaluate the association between disease-related emotional and cognitive aspects and metabolic control in subjects with T1DM., Subjects and Methods: Health locus of control (HLOC), sense of coherence (SOC), and self-esteem were assessed in T1DM subjects using validated questionnaires. Sixty-seven consecutive subjects who did not attain the desired HbA1c target (mean HbA1c, 8.3% [67 mmol/mol]) were compared with 30 cases in satisfactory metabolic control (HbA1c levels <7%-53 mmol/mol)., Results: In the overall population, SOC was negatively associated with BMI and average HbA1c, as was the association of self-esteem with HbA1c. Subjects attaining the desired metabolic target were characterized by higher SOC scores, higher Internal HLOC and prevalent Internal vs. Powerful-others HLOC. Compared to subjects in good metabolic control, subjects with unsatisfactory control had lower scores of SOC, Internal HLOC and Self-esteem, with no difference in Powerful others, or Chance HLOC. In the same group, SOC in the upper tertile was significantly associated with self-esteem (OR 1.35; 95% CI 1.08-1.69) and PHLOC (OR 1.24; 95% CI 1.03-1.49), after adjustment for age, sex, educational level, and comorbidities., Conclusions: Patients who fail to reach a satisfactory metabolic control tend to rely on significant others, trusting in the physicians' skills or on the efficiency of the health-care system. Strategies aimed at increasing self-efficacy and SOC, based on personal ability, are eagerly awaited to help patients improve diabetes care.

Introduction: Following lifestyle intervention programs based on dietary restriction and habitual physical activity, weight loss, however large, is reported to peak within six months. Despite maintenance protocols, only few cases continue to lose weight thereafter. The majority of cases regain weight and adherence to lifestyle changes are fostered by long-term contact with a supportive team. In general, surgical procedures are reported to produce much larger weight loss and to impact more favorably on long-term weight loss maintenance. Areas covered: We performed a PubMed search on lifestyle modification studies, focusing on the role of behavior programs for the long-term management of obesity in comparison with surgical procedures. Behaviorally-achieved weight loss outcomes can be improved by integrating standard behavior therapy with self-regulation cognitive skills, motivational interviewing and/or phone/internet-based recall systems. Expert commentary: Clinically-important long-term weight loss is achievable by behavior therapy in a small proportion of subjects with obesity, however severe, through personalized programs associating lifestyle modification interventions, with procedures aimed at developing commitment and responsibility skills. A new area of research is the integration of cognitive-behavior therapy with bariatric (metabolic) surgery, either pre- or post-operatively, to exploit long-term adherence to healthy diet and habitual physical activity.

Type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD) are highly prevalent in the community, and share common pathogenic mechanisms. There is also evidence that T2DM may be favored by hepatic fat accumulation; in turn the presence of T2DM is a risk factor for liver disease progression. The treatment of T2DM has considerably changed in the past few years; new drug classes, promoting glucose-lowering through mechanisms different from classical insulin-sensitizing or insulin-secreting action, have been added to continuing lifestyle intervention. Metformin and pioglitazone may be safely used in the presence of liver fat, whereas sulfonylureas and insulin itself have been associated with NAFLD progression and adverse outcome. Drugs acting on the incretin axis and on Na-glucose co-transport at renal tubular level offer new hopes for a tailored treatment able to reduce the burden of hepatic triglyceride accumulation and liver disease progression., (Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Hypnic jerks (HJs) are sudden contractions of one or more body segments occurring mostly at sleep onset. They are highly sporadic and affect all ages and both sexes with prevalence between 60% and 70% in the general population., Study Objectives: This study describes the frequency and the neurophysiological characteristics of HJs in a population of patients with parkinsonism by means of nocturnal video-polysomnographic recordings., Methods: This is a prospective cohort study and is reported following the STROBE guidelines. We analyzed the clinical and video-polysomnographic data of the first 66 consecutive patients recruited in the ongoing prospective study "Bologna motor and non-motor Prospective study on Parkinsonism at onset" (BoProPark). Each patient underwent a full neurological workup including a whole-night video- polysomnography. Neurophysiological characteristics including the propagation patterns of the HJs were studied with an extended muscle montage polysomnography., Results: We recorded a total of 62 HJs in 16 patients out of 66 (24%). Sleep parameters were not statistically different between patients with and without HJs. All HJs were spontaneous and occurred randomly throughout the night. Electromyographic analysis showed that muscle activity arose from different muscles with no prevalence of one over the other and without any ordered propagation. No recurring motor pattern of the jerks was detected., Discussion and Conclusions: Our findings demonstrated that HJs are a frequent, underestimated, sleep-related motor phenomenon in patients with parkinsonism. As they may represent a further cause of sleep disruption and insomnia, HJs should be actively examined. Neurophysiological analysis suggests a subcortical origin of HJs as shown previously for a healthy subject., (Copyright © 2016 Elsevier B.V. All rights reserved.)

On a worldwide scale, the total number of migrants exceeds 200 million and is not expected to reduce, fuelled by the economic crisis, terrorism and wars, generating increasing clinical and administrative problems to National Health Systems. Chronic non-communicable diseases (NCD), and specifically diabetes, are on the front-line, due to the high number of cases at risk, duration and cost of diseases, and availability of effective measures of prevention and treatment. We reviewed the documents of International Agencies on migration and performed a PubMed search of existing literature, focusing on the differences in the prevalence of diabetes between migrants and native people, the prevalence of NCD in migrants vs rates in the countries of origin, diabetes convergence, risk of diabetes progression and standard of care in migrants. Even in universalistic healthcare systems, differences in socioeconomic status and barriers generated by the present culture of biomedicine make high-risk ethnic minorities under-treated and not protected against inequalities. Underutilization of drugs and primary care services in specific ethnic groups are far from being money-saving, and might produce higher hospitalization rates due to disease progression and complications. Efforts should be made to favor screening and treatment programs, to adapt education programs to specific cultures, and to develop community partnerships.

Background: The accumulation of fat droplets in the hepatic parenchyma is driven by several factors, synergistically acting to increase triglyceride flow to the liver (diet and metabolic factors, endotoxemia from gut microbiota, genetic factors)., Key Messages: In the presence of unhealthy lifestyles and behavioral factors, leading to enlarged adipose tissue and insulin resistance (IR), both lipolysis and de novo lipogenesis are expected to increase the risk of hepatic lipid depots, in association with high calorie (either high-fat or high-carbohydrate) diets. The gut microbiota may also be involved via obesity, IR and hepatic inflammation generated by gut-derived toxic factors. Finally, several data also support a primary role of genetic factors. A few gene polymorphisms have also been associated with the risk of nonalcoholic fatty liver disease development and nonalcoholic steatohepatitis progression to more fibrosis and advanced liver disease. In a few cases (e.g., patatin-like phospholipase domain-containing 3/adiponutrin), steatosis carries a high risk of both liver disease and cardiovascular morbidity/mortality; in other cases (e.g., transmembrane 6 superfamily 2 human gene), dissociation has been observed between the increased risk of liver disease versus cardiovascular disease., Conclusions: A variable interplay between the genetic background and the metabolic milieu is the likely physiopathologic mechanism involved in individual cases, which must be considered for implementing effective treatment strategies., (© 2016 S. Karger AG, Basel.)

Opinion Statement: Sleep-related eating disorder (SRED) is classified as an NREM-related parasomnia characterized by recurrent episodes of dysfunctional eating that occur after an arousal from the main sleep period with partial or complete amnesia for the event, resulting in weight gain from eating high calorie foods and causing various injuries due to consumption of inedible or toxic items. SRED can be idiopathic or commonly associated with other primary sleep disorders such as sleepwalking, restless legs syndrome (RLS), obstructive sleep apnea syndrome (OSAS), other clinical conditions, or use of sedative-hypnotic medications. First-line treatment of idiopathic SRED includes selective serotonin reuptake inhibitors (SSRIs) at mean dosages of 20 to 30 mg/day. Topiramate at 100-300 mg/day and clonazepam at 0.5-2.0 mg/day can be valid alternative options. SRED related to other parasomnias or sleep disturbances that cause sleep fragmentation benefit most from treatment of the associated sleep disorder. In particular, RLS-related SRED is best treated with dopamine agonists such as pramipexole, while sleepwalking-related SRED benefits from low-dose benzodiazepines such as clonazepam. Different kinds of drug associations have been proposed in a limited number of cases, especially in the past. We strongly recommend that all patients suffering from SRED should undergo consistent and regular follow-up about 2-3 times per year or otherwise according to the physician's judgment, in order to assess the evolution of symptom severity and frequency and re-evaluate treatment efficacy and any side effects that may arise.