Dynamics of Gut Microbiota and Clinical Variables after Ketogenic and Mediterranean Diets in Drug-Naïve Patients with Type 2 Diabetes Mellitus and Obesity.

Type 2 diabetes mellitus (T2DM), the most common form of diabetes, is a progressive chronic metabolic disease that has increasingly spread worldwide, enhancing the mortality rate, particularly from cardiovascular diseases (CVD). Lifestyle improvement through diet and physical activity is, together with drug treatment, the cornerstone of T2DM management. The Mediterranean diet (MD), which favors a prevalence of unprocessed vegetable foods and a reduction in red meats and industrial foods, without excluding any food category, is usually recommended. Recently, scientific societies have promoted a very low-calorie ketogenic diet (VLCKD), a multiphasic protocol that limits carbohydrates and then gradually re-introduces them, with a favorable outcome on body weight and metabolic parameters. Indeed, gut microbiota (GM) modifications have been linked to overweight/obesity and metabolic alterations typical of T2DM. Diet is known to affect GM largely, but only a few studies have investigated the effects of VLCKD on GM, especially in T2DM. In this study, we have compared anthropometric, biochemical, lifestyle parameters, the quality of life, and the GM of eleven patients with recently diagnosed T2DM and overweight or obesity, randomly assigned to two groups of six and five patients who followed the VLCKD (KETO) or hypocaloric MD (MEDI) respectively; parameters were recorded at baseline (T0) and after two (T2) and three months (T3). The results showed that VLCKD had more significant beneficial effects than MD on anthropometric parameters, while biochemical improvements did not statistically differ. As for the GM, despite the lack of significant results regarding the alpha and beta diversity, and the Firmicutes/Bacteroidota ratio between the two groups, in the KETO group, a significant increase in beneficial microbial taxa such as Verrucomicrobiota phylum with its members Verrucomicrobiae, Verrucomicrobiales, Akkermansiaceae, and Akkermansia, Christensenellaceae family, Eubacterium spp., and a reduction in microbial taxa previously associated with obesity (Firmicutes and Actinobacteriota) or other diseases (Alistipes) was observed both at T2 and T3. With regards to the MEDI group, variations were limited to a significant increase in Actinobacteroidota phylum at T2 and T3 and Firmicutes phylum at T3. Moreover, a metagenomic alteration linked to some metabolic pathways was found exclusively in the KETO group. In conclusion, both dietary approaches allowed patients to improve their state of health, but VLCKD has shown better results on body composition as well as on GM profile.

Association between High Normal TSH Levels and Obesity in Women with Anti-Thyroid Autoantibodies (ATAs).

A positive correlation between Thyroid-Stimulating Hormone (TSH) and Body Mass Index (BMI) has been reported in many studies, but data on this topic remain controversial, especially when TSH values are in the normal range. Moreover, few studies have evaluated the co-existence of thyroid autoimmunity. This study investigated the role of thyroid autoimmunity in the interconnection between TSH, BMI, and waist circumference (WC) in euthyroid patients with overweight or obesity. We enrolled 902 patients (213 males; mean age ± SD: 45 ± 14 years; mean BMI ± SD: 35.8 ± 6.5 kg/m2), with normal serum TSH concentration; anti-thyroid autoantibodies (ATAs) were evaluated in 752 patients (186 males). Patients were divided into four BMI classes, based on WHO criteria, and the relationship between BMI, WC, and TSH was evaluated in the whole sample and compared to ATAs positivity, observed in 235 patients (44 males). No significant difference was found between TSH levels in the BMI classes. A statistically significant correlation between TSH and BMI was found only in ATAs-positive females (N = 191, Spearman rho: 0.149; p-value: 0.040). However, this finding was not confirmed when considering the WC. Our study shows a positive correlation only between TSH and BMI in obese women with positive ATAs, suggesting that in these patients, the high normal levels of TSH could be attributed to a mild thyroid failure with a possible worsening obesity-related effect, and both need a careful evaluation.

Effect of a Low-Moderate Exercise Program on Dysmetabolism in Older Adults: Results of a Randomized Controlled Trial.

Physical exercise has been shown to improve dysmetabolism in older adults, reducing cardiovascular risk, while its role in preventing dysmetabolism is less known. Moreover, most of the trials use exercise programs that are difficult to put into daily practice. The purpose of this Randomized Controlled Trial (RCT) was to evaluate the effectiveness of a 3-month moderate exercise program in improving or preventing dysmetabolism in 120 older adults, randomly selected for the exercise program (experimental group) or cultural activities (control group). None of the subjects were following a hypocaloric diet, and all of them reported healthy eating habits. Anthropometric (Body Mass Index (BMI) and Waist Circumference (WC)) and metabolic variables (fasting plasma glucose (FPG), High-Density Lipoprotein Cholesterol (HDL-C), and triglycerides (TG)) were assessed at baseline (T0) and at the end of the trial (T1). Dysmetabolism was defined by the presence of an increased WC plus at least two metabolic alterations. At T0, the two groups did not differ by sex, age, education, BMI, WC, FPG, HDL-C levels, and prevalence of dysmetabolism. The mean BMI value indicated overweight, and WC values were higher than the cut-off. At T1, a slight reduction in the number of people with dysmetabolism was found only in the experimental group. However, none of the individuals without dysmetabolism at T0 in the experimental group developed it at T1, while 11.4% developed it in the control group (p = 0.032). This study highlights that a moderate exercise program, accessible in daily practice, can prevent dysmetabolism in older adults, even while being overweight, while if dysmetabolism is already present, more prolonged combined nutritional and exercise interventions will be needed.

Depression in Diabetic Patients: What Is the Link With Eating Disorders? Results of a Study in a Representative Sample of Patients With Type 1 Diabetes.

Background and Purpose: Comorbidity between diabetes and depression, and diabetes and eating disorders (ED) conveys significant diagnostic, clinical and therapeutic implications. The present study was conducted on a sample of adult outpatients affected by Type 1 Diabetes (T1DM) to assess lifetime prevalence of ED; current prevalence of depression and Disturbed Eating Behaviors (DEB) and their impact on glycemic control. We hypothesized that patients with depression would have higher rates of lifetime ED and current DEB. We hypothesized a significant and independent association between DEB and the prevalence of depression. Materials and Methods: The study was carried out using a cross-sectional design in a sample of 172 diabetic patients with T1DM aged from 17 to 55 years. Lifetime prevalence of ED according to DSM-5 criteria was assessed by means of the Module H modified of the Structured Clinical Interview for DSM-IV Axis I Disorder (SCID-I). The following questionnaires were used: Beck Depression Inventory-IA version (BDI-IA) and Diabetes Eating Problems Survey-Revised (DEPS-R), to assess respectively the current presence of depression and DEB. Socio-demographic, clinical, and laboratory data were also collected. Results: High rates of depression (35.5%) and DEB (19.2%) were observed in our sample of 172 adult outpatients with T1DM. Lifetime history of ED was present in 20.9% of the sample and was more frequently diagnosed in patients with current depression (34.4% vs. 13.9%, p = 0.002). Higher levels of DEB at DEPS-R significantly increased the odds of depression (adjOR: 1.09; 95% CI: 1.03-1.15; p = 0.003). The presence of DEB was associated with poor glycemic control. On the other hand, no association was found between depression and metabolic compensation. Conclusion: Adult patients with T1DM and depression should be screened for ED and DEB. Treating DEB could positively impact both mood and glycemic control in this population. Further studies should be carried out on a larger patient population using a longitudinal design and an accurate method of evaluation to explore the complex relationship between diabetes, depression, ED, and DEB. Future research should investigate treatment strategies for DEB in T1DM patients and their impact on both psychopathological and metabolic outcomes.

Gut Microbiota Markers and Dietary Habits Associated with Extreme Longevity in Healthy Sardinian Centenarians.

This study was aimed at characterizing the gut microbiota (GM) and its functional profile in two groups of Sardinian subjects with a long healthy life expectancy, overall named Long-Lived Subjects (LLS) [17 centenarians (CENT) and 29 nonagenarians (NON)] by comparing them to 46 healthy younger controls (CTLs). In addition, the contribution of genetics and environmental factors to the GM phenotype was assessed by comparing a subgroup of seven centenarian parents (CPAR) with a paired cohort of centenarians' offspring (COFF). The analysis was performed through Next Generation Sequencing (NGS) of the V3 and V4 hypervariable region of the 16S rRNA gene on the MiSeq Illumina platform. The Verrucomicrobia phylum was identified as the main biomarker in CENT, together with its members Verrucomicrobiaceae, Akkermansia and Akkermansia muciniphila. In NON, the strongest associations concern Actinobacteria phylum, Bifidobacteriaceae and Bifidobacterium, while in CTLs were related to the Bacteroidetes phylum, Bacteroidaceae, Bacteroides and Bacteroides spp. Intestinal microbiota of CPAR and COFF did not differ significantly from each other. Significant correlations between bacterial taxa and clinical and lifestyle data, especially with Mediterranean diet adherence, were observed. We observed a harmonically balanced intestinal community structure in which the increase in taxa associated with intestinal health would limit and counteract the action of potentially pathogenic bacterial species in centenarians. The GM of long-lived individuals showed an intrinsic ability to adapt to changing environmental conditions, as confirmed by functional analysis. The GM analysis of centenarians' offspring suggest that genetics and environmental factors act synergistically as a multifactorial cause in the modulation of GM towards a phenotype similar to that of centenarians, although these findings need to be confirmed by larger study cohorts and by prospective studies.

Weight Maintenance after Dietary Weight Loss: Systematic Review and Meta-Analysis on the Effectiveness of Behavioural Intensive Intervention.

After a low-calorie diet, only 25% of patients succeed in maintaining the result of weight loss for a long time. This systematic review and meta-analysis aims to explore whether patients undergoing intensive intervention during the maintenance phase have a greater preservation of the weight achieved during the previous slimming phase than controls. A bibliographic search was conducted using PubMed, Scopus, and Cochrane databases for clinical trials and randomised, controlled trials investigating the role of choice in weight-loss-maintenance strategies. Only studies with a follow-up of at least 12 months were considered. A total of eight studies, for a total of 1454 patients, was identified, each comparing a group that followed a more intensive protocol to a control group. Our metanalysis highlighted that an intensive approach even in the maintenance phase could be important to ensure greater success in the phase following the weight-loss period. However, it should be pointed out that the improvement was not so different from the trend of the respective controls, with a non-statistically significant mean difference of the effect size (0.087; 95% CI -0.016 to 0.190 p = 0.098). This finding, along with the observation of a weight regain in half of the selected studies, suggests this is a long work that has to be started within the weight-loss phase and reinforced during the maintenance phase. The problem of weight control in patients with obesity should be understood as a process of education to a healthy lifestyle and a balanced diet to be integrated in the context of a multidisciplinary approach.

Relationship between Olfactory Function and BMI in Normal Weight Healthy Subjects and Patients with Overweight or Obesity.

Smell plays a critical role in food choice and intake by influencing energy balance and body weight. Malnutrition problems or modified eating behaviors have been associated with olfactory impairment or loss. The obesity epidemic is a serious health problem associated with an increased risk of mortality and major physical comorbidities. The etiopathogenesis of obesity is complex and multifactorial, and one of the main factors contributing to the rapid increase in its incidence is the environment in which we live, which encourages the overconsumption of foods rich in energy, such as saturated fats and sugars. By means of the "Sniffin' Sticks" test, we measured the olfactory threshold, discrimination and identification score (TDI score) in patients of the Obesity Center of the University Hospital (OC; n = 70) and we compared them with that of healthy normal weight controls (HC; n = 65). OC patients demonstrated a significantly lower olfactory function than HC subjects both general and specific for the ability to discriminate and identify odors, even when they were considered separately as females and males. For OC patients, a negative correlation was found between body mass index (BMI) and olfactory scores obtained by each subject, both when they were divided according to gender and when they were considered all together. Besides, normosmic OC patients showed a significantly lower BMI than hyposmic ones. A reduced sense of smell may contribute to obesity involving the responses of the cephalic phase, with a delay in the achievement of satiety and an excessive intake of high-energy foods and drinks.

Moderate Exercise Improves Cognitive Function in Healthy Elderly People: Results of a Randomized Controlled Trial.

BACKGROUND: Physical activity in the elderly is recommended by international guidelines to protect against cognitive decline and functional impairment. OBJECTIVE: This Randomized Controlled Trial (RCT) was set up to verify whether medium-intensity physical activity in elderly people living in the community is effective in improving cognitive performance. DESIGN: RCT with parallel and balanced large groups. SETTING: Academic university hospital and Olympic gyms. SUBJECTS: People aged 65 years old and older of both genders living at home holding a medical certificate for suitability in non-competitive physical activity. METHODS: Participants were randomized to a 12-week, 3 sessions per week moderate physical activity program or to a control condition focused on cultural and recreational activities in groups of the same size and timing as the active intervention group. The active phase integrated a mixture of aerobic and anaerobic exercises, including drills of "life movements", strength and balance. The primary outcome was: any change in Addenbrooke's Cognitive Examination Revised (ACE-R) and its subscales. RESULTS: At the end of the trial, 52 people completed the active intervention, and 53 people completed the control condition. People in the active intervention improved on the ACE-R (ANOVA: F(1;102)=4.32, p=0.040), and also showed better performances on the memory (F(1;102)=5.40 p=0.022) and visual-space skills subscales of the ACE-R (F(1;102)=4.09 p=0.046). CONCLUSION: A moderate-intensity exercise administered for a relatively short period of 12 weeks is capable of improving cognitive performance in a sample of elderly people who live independently in their homes.Clinical Trials Registration No: NCT03858114.

Nutritional Management in Bariatric Surgery Patients.

The obesity epidemic, mainly due to lifestyle changes in recent decades, leads to serious comorbidities that reduce life expectancy. This situation is affecting the health policies of many nations around the world. Traditional measures such as diet, physical activity, and drugs are often not enough to achieve weight loss goals and to maintain the results over time. Bariatric surgery (BS) includes various techniques, which favor rapid and sustained weight loss. BS is a useful and, in most cases, the best treatment in severe and complicated obesity. In addition, it has a greater benefit/risk ratio than non-surgical traditional therapies. BS can allow the obese patient to lose weight quickly compared with traditional lifestyle changes, and with a greater probability of maintaining the results. Moreover, BS promotes improvements in metabolic parameters, even diabetes remission, and in the quality of life. These changes can lead to an increase of life expectancy by over 6 years on average. The nutrition of people before and after BS must be the subject of indications from a trained staff, and patients must be followed in the subsequent years to reduce the risk of malnutrition and the associated problems. In particular, it is still debated whether it is necessary to lose weight prior to surgery, a procedure that can facilitate the surgeon's work reducing the surgical risk, but at the same time, lengthens preparation times increasing the risks associated with concomitant pathologies. Furthermore, preventing nutritional deficiencies prior to the intervention can improve the results and reduce short- and long-term mortality.

Active elderly and health-can moderate exercise improve health and wellbeing in older adults? Protocol for a randomized controlled trial.

BACKGROUND: Aging is marked by a progressive rise in chronic diseases with an impact on social and healthcare costs. Physical activity (PA) may soothe the inconveniences related to chronic diseases, has positive effects on the quality of life and biological rhythms, and can prevent the decline in motor functions and the consequent falls, which are associated with early death and disability in older adults. METHODS: We randomized 120 over-65 males and females into groups of similar size and timing and will give each either moderate physical activity or cultural and recreational activities. Being younger than 65 years, inability to participate in physical activity for any medical reason, and involvement in a massive program of physical exercise are the exclusion criteria. The primary outcome measures are: quality of life, walking speed, and postural sway. Participants are tested at baseline, post-treatment, and 6-month (24 weeks) and 12-month (48 weeks) follow-ups. DISCUSSION: This study aims at improving the quality of life, wellness, and cognitive functioning in the elderly through a low-cost affordable program of moderate physical activity. Given the growing aging of the world population and the social and economic burden of disability in the elderly, our results might have a major impact on future practices. TRIAL REGISTRATION: ClinicalTrials.gov NCT03858114 . Registered on 28 February 2019.

Gut microbiota markers associated with obesity and overweight in Italian adults.

In the present study, we characterized the distinctive signatures of the gut microbiota (GM) from overweight/obese patients (OB), and normal-weight controls (NW), both of Sardinian origin. Fecal bacterial composition of 46 OB patients (BMI = 36.6 ± 6.0; F/M = 40/6) was analyzed and compared to that of 46 NW subjects (BMI = 21.6 ± 2.1; F/M = 41/5), matched for sex, age and smoking status, by using 16S rRNA gene sequencing on MiSeq Illumina platform. The gut microbial community of OB patients exhibited a significant decrease in the relative abundance of several Bacteroidetes taxa (i.e. Flavobacteriaceae, Porphyromonadaceae, Sphingobacteriaceae, Flavobacterium, Rikenella spp., Pedobacter spp., Parabacteroides spp., Bacteroides spp.) when compared to NW; instead, several Firmicutes taxa were significantly increased in the same subjects (Lachnospiraceae, Gemellaceae, Paenibacillaceae, Streptococcaceae, Thermicanaceae, Gemella, Mitsuokella, Streptococcus, Acidaminococcus spp., Eubacterium spp., Ruminococcus spp., Megamonas spp., Streptococcus, Thermicanus, Megasphaera spp. and Veillonella spp.). Correlation analysis indicated that body fatness and waist circumference negatively correlated with Bacteroidetes taxa, while Firmicutes taxa positively correlated with body fat and negatively with muscle mass and/or physical activity level. Furthermore, the relative abundance of several bacterial taxa belonging to Enterobacteriaceae family, known to exhibit endotoxic activity, was increased in the OB group compared to NW. The results extend our knowledge on the GM profiles in Italian OB, identifying novel taxa linking obesity and intestine.

Diabetes insipidus secondary to nivolumab-induced neurohypophysitis and pituitary metastasis.

SUMMARY: A 62-year-old patient with metastatic hypopharyngeal carcinoma underwent treatment with nivolumab, following which he developed symptoms suggestive of diabetes insipidus. Nivolumab was stopped and therapy with methylprednisolone was started. During corticosteroid therapy, the patient presented himself in poor health condition with fungal infection and glycemic decompensation. Methylprednisolone dose was tapered off, leading to the resolution of mycosis and the restoration of glycemic compensation, nevertheless polyuria and polydipsia persisted. Increase in urine osmolarity after desmopressin administration was made diagnosing central diabetes insipidus as a possibility. The neuroradiological data by pituitary MRI scan with gadolinium was compatible with coexistence of metastatic localization and infundibulo-neurohypophysitis secondary to therapy with nivolumab. To define the exact etiology of the pituitary pathology, histological confirmation would have been necessary; however, unfortunately, it was not possible. In the absence of histological confirmation, we believe it is likely that both pathologies coexisted. LEARNING POINTS: A remarkable risk of endocrine immune-related adverse events (irAEs) during therapy with checkpoint inhibitors exsists. In order to ensure maximum efficiency in the recognition and treatment of endocrine iRAes related to immune checkpoint inhibitors, multidisciplinary management of oncological patients is critical. The pituitary syndrome in oncological patients who underwent immunotherapy represents a challenge in the differential diagnosis between pituitary metastasis and drug-induced hypophysitis. This is the first case, described in the literature of diabetes insipidus in a patient suffering from nivolumab-induced infundibulo-neurohypophysitis and anterohypophyseal metastasis.

Impact of a Moderately Hypocaloric Mediterranean Diet on the Gut Microbiota Composition of Italian Obese Patients.

Although it is known that the gut microbiota (GM) can be modulated by diet, the efficacy of specific dietary interventions in determining its composition and diversity in obese patients remains to be ascertained. The present work aims to evaluate the impact of a moderately hypocaloric Mediterranean diet on the GM of obese and overweight patients (OB). The GM of 23 OB patients (F/M = 20/3) was compared before (T0) and after 3 months (T3) of nutritional intervention (NI). Fecal samples were analyzed by Illumina MiSeq sequencing of the 16S rRNA gene. At baseline, GM characterization confirmed typical obesity-associated dysbiosis. After 3 months of NI, patients presented a statistically significant reduction in body weight and fat mass, along with changes in the relative abundance of many microbial patterns. In fact, an increase in the abundance of several Bacteroidetes taxa (i.e., Sphingobacteriaceae, Sphingobacterium, Bacteroides spp., Prevotella stercorea) and a depletion of many Firmicutes taxa (i.e., Lachnospiraceae members, Ruminococcaceae and Ruminococcus, Veillonellaceae, Catenibacterium, Megamonas) were observed. In addition, the phylum Proteobacteria showed an increased abundance, while the genus Sutterella, within the same phylum, decreased after the intervention. Metabolic pathways, predicted by bioinformatic analyses, showed a decrease in membrane transport and cell motility after NI. The present study extends our knowledge of the GM profiles in OB, highlighting the potential benefit of moderate caloric restriction in counteracting the gut dysbiosis.

Validity of Accelerometers for the Evaluation of Energy Expenditure in Obese and Overweight Individuals: A Systematic Review.

OBJECTIVE: Even though the validity of accelerometers for the measurement of energy expenditure (EE) has been demonstrated for normal-weight individuals, the applicability of this instrument in obese individuals remains controversial. This review aims to summarize the level of agreement between accelerometers and the gold standards (indirect calorimetry and doubly labelled water) for the measurement of energy expenditure (EE) in obese or overweight individuals. METHODS: The literature search was limited to comparison studies assessing agreement in EE determination between accelerometers and indirect calorimetry (IC) or doubly labelled water (DLW). We searched in PubMed and in Scopus until March 1, 2019. The analysis was restricted to obese or overweight adult individuals. The following descriptive information was extracted for each study: sample size, characteristics of participants (sex, age, BMI, fat mass percentage, any pathological conditions, modality of recruitment in the study, and exclusion criteria), accelerometer description (model, type and body position), and type of gold standard and validity protocol (duration, conditions, and requirements during and before the experiment). Three review authors independently screened the obtained results, and the quality of the selected articles was assessed by the QUADAS-2 tool. RESULTS: We obtained seventeen eligible articles, thirteen of which showed concerns for the applicability section, due to the patient selection. Regarding the accelerometers, nine devices were validated in the included studies with the BodyMedia SenseWear® (SWA) being the most frequently validated. Although correlations between accelerometers and the gold standard were high in some studies, agreement between the two methods was low, as shown by the Bland-Altman plots. CONCLUSIONS: Most accelerometer estimations of EE were inaccurate for obese/overweight subjects, and authors advise to improve the accuracy of algorithms for SWA software, or the predicted equations for estimating EE from other accelerometers.

Circulating antithyroid antibodies contribute to the decrease of glomerular filtration rate in lithium-treated patients: a longitudinal study.

BACKGROUND: Concerns about the adverse effects of long-term treatment with lithium include reduced renal function. In the present study, we examined comorbidities which may be associated with chronic kidney disease in a cohort of patients treated with lithium for up to 41 years. METHODS: We studied 394 patients who were treated with lithium for ≥ 5 years. The potential role of comorbidities (diabetes, concurrent antihypertensive medication, treatment with L-thyroxine, and presence of antithyroid peroxidase/microsomes, anti-thyroglobulin, and/or anti-thyrotropin-receptor antibodies) was analysed. We focused on the categories of patients with an estimated glomerular filtration rate (eGFR) lower than 60 or 45 mL/min/1.73 m2 as calculated from serum creatinine according to the Modification of Diet in Renal Disease Study Group. We applied multivariate regression analysis and Cox survival analysis to study the effects exerted by sex, age, duration of lithium treatment, and comorbidities using eGFR categories as the dependent variable. Kaplan-Meier curves were generated to measure the time to decline to an eGFR lower than 45 mL/min/1.73 m2 in patients with positive or negative thyroid antibodies. RESULTS: Age was associated with a decline to an eGFR lower than 60 mL/min/1.73 m2 after controlling for sex, duration of lithium treatment, and comorbidities. Circulating thyroid antibodies were associated with a decline to an eGFR lower than 45 mL/min/1.73 m2. CONCLUSIONS: The present study is the first to suggest a potential role of circulating thyroid antibodies in the severe decline of eGFR in lithium-treated patients.

Psychopathology, psychosocial factors and obesity.

AIMS: The aims of this study were to evaluate the association between obesity and socio-demographic and psychopathological variables in a clinical sample of patients referred to a center for the diagnosis and treatment of obesity, compared with a homogeneous sample of normal-weight subjects. METHODS: In the context of a research project regarding obesity and psychopathology, a multivariate logistic regression analysis was used to examine the association between obesity and the demographic and clinical variables, on the basis of the dataset of a consecutive sample of 293 obese patients (48 males, 245 females, mean age: 45.41±13.55, mean body mass index [BMI] 35.6±6.2)compared with a control group of 293 non-obese subjects (48 males, 245 females, mean age 45.66±13.86, mean BMI 21.8±2.06). All subjects were assessed by structured clinical interview, the Structured Clinical Interview for Diagnosis for axis I DSM-IV (SCID-I) and for axis II DSM-IV(SCID-II). RESULTS: Multivariate statistical analysis showed that the status of housewife and the presence of lifetime axis I and II psychiatric diagnosis in general, and of depressive, anxiety, eating and some personality disorders in particular, significantly increased the likelihood of being overweight/obese. The likelihood for different combinations of risk factors increased from a value of 32.3% for an individual not exposed to any risk factor, to a value of 86.7% for those exposed to all risk factors considered. CONCLUSIONS: The presence of an axis I and/or II diagnosis and housewife status are both independently associated with an increased likelihood of being overweight/obese. The interaction of these factors increases this likelihood. Even taking into account the limits of the study, in particular of its cross-sectional nature, these findings may have important implications in both prevention and treatment of obesity.

Bipolar disorder and antithyroid antibodies: review and case series.

Mood disorders and circulating thyroid antibodies are very prevalent in the population and their concomitant occurrence may be due to chance. However, thyroid antibodies have been repeatedly hypothesized to play a role in specific forms of mood disorders. Potentially related forms include treatment-refractory cases, severe or atypical depression, and depression at specific phases of a woman's life (early gestation, postpartum depression, perimenopausal). With regard to bipolar disorder, studies of specific subgroups (rapid cycling, mixed, or depressive bipolar) have reported associations with thyroid antibodies. Offspring of bipolar subjects were found more vulnerable to develop thyroid antibodies independently from the vulnerability to develop psychiatric disorders. A twin study suggested thyroid antibodies among possible endophenotypes for bipolar disorder. Severe encephalopathies have been reported in association with Hashimoto's thyroiditis. Cases with pure psychiatric presentation are being reported, the antithyroid antibodies being probably markers of some other autoimmune disorders affecting the brain. Vasculitis resulting in abnormalities in cortical perfusion is one of the possible mechanisms.

Prediction of type 1 diabetes in Sardinian schoolchildren using islet cell autoantibodies: 10-year follow-up of the Sardinian schoolchildren type 1 diabetes prediction study.

AIMS: Stable genetic background makes individuals from the Mediterranean island of Sardinia ideal to define the predictive power of islet-related autoantibodies (IRAs): glutamic acid decarboxylase antibodies (GADA), tyrosine phosphatase-like antibodies (IA-2A), islet cell antibodies (ICA) to identify T1DM progressors. The aims of the present study were: (1) determination of IRAs reference limits in healthy non-diabetic Sardinian schoolchildren (SSc). (2) Predictive power evaluation of IRAs as single or combined determination to identify islet to identify T1DM progressors. METHODS: Between 1986 and 1994, 8448 SSc were tested for IRAs. All were followed up for 10 years. The predictive power of single or combination of IRAs was determined as hazard ratio (HR), sensitivity, specificity, area under the ROC curve, negative and positive predictive value (NPV, PPV). RESULTS: All 43 progressors to T1DM, but three showed at least one autoantibody positivity. HR for any single-autoantibody positivity was 55.3 times greater when compared to SSc negative for all IRAs. Any single autoantibody performed at least 64.9 % sensitivity with PPV always lower than 16 %. The best performing combination was ICA, plus IA-2A (showing 52.6 % sensitivity, 99.8 % specificity, 0.76 area under the ROC curve, 51.3 % PPV and 99.8 % NPV. CONCLUSIONS: Determination of IRAs reference limits in healthy SSc by standard statistical methods is crucial to establish the power of IRAs as progression markers to T1DM. Our data offer a solid rationale for future testing of ICA and IA-2A as routine laboratory markers to identify individuals at high risk of T1DM in the general population.

Nervous Facilitation in Cardiodynamic Response of Exercising Athletes to Superimposed Mental Tasks: Implications in Depressive Disorder.

INTRODUCTION: Motor commands to perform exercise tasks may also induce activation of cardiovascular centres to supply the energy needs of the contracting muscles. Mental stressors per se may also influence cardiovascular homeostasis. We investigated the cardiovascular response of trained runners simultaneously engaged in mental and physical tasks to establish if aerobically trained subjects could develop, differently from untrained ones, nervous facilitation in the brain cardiovascular centre. Methods : Cardiovascular responses of 8 male middle-distance runners (MDR), simultaneously engaged in mental (colour-word interference test) and physical (cycle ergometer exercise) tasks, were compared with those of 8 untrained subjects. Heart rate, cardiac (CI) and stroke indexes were assessed by impedance cardiography while arterial blood pressures were assessed with a brachial sphygmomanometer. Results : Only in MDR simultaneous engagement in mental and physical tasks induced a significant CI increase which was higher (p<0.05) than that obtained on summing CI values from each task separately performed. Conclusion : Aerobic training, when performed together with a mental effort, induced a CI oversupply which allowed a redundant oxygen delivery to satisfy a sudden fuel demand from exercising muscles by utilizing aerobic sources of ATP, thus shifting the anaerobic threshold towards a higher work load. From data of this study it may also be indirectly stated that, in patients with major depressive disorder, the promotion of regular low-intensity exercise together with mental engagement could ameliorate the perceived physical quality of life, thus reducing their heart risk associated with physical stress.

Differences in hemodynamic response to metaboreflex activation between obese patients with metabolic syndrome and healthy subjects with obese phenotype.

Patients suffering from obesity and metabolic syndrome (OMS) manifest a dysregulation in hemodynamic response during exercise, with an exaggerated systemic vascular increase. However, it is not clear whether this is the consequence of metabolic syndrome per se or whether it is due to concomitant obesity. The aim of the present investigation was to discover whether OMS and noncomplicated obesity resulted in different hemodynamic responses during the metaboreflex. Twelve metabolically healthy but obese subjects (MHO; 7 women), 13 OMS patients (5 women), and 12 normal age-matched controls (CTL; 6 women) took part in this study. All participants underwent a postexercise muscle ischemia protocol to evaluate the metaboreflex activity. Central hemodynamics were evaluated by impedance cardiography. The main result shows an exaggerated increase in systemic vascular resistance from baseline during the metaboreflex in the OMS patients as compared with the other groups (481.6 ± 180.3, -0.52 ± 177.6, and -60.5 ± 58.6 dynes·s(-1)·cm(-5) for the OMS, the MHO, and the CTL groups, respectively; P < 0.05). Moreover, the MHO subjects and the CTL group showed an increase in cardiac output during the metaboreflex (288.7 ± 325.8 and 703.8 ± 276.2 ml/m increase with respect to baseline), whereas this parameter tended to decrease in the OMS group (-350 ± 236.5 ml/m). However, the blood pressure response, which tended to be higher in the OMS patients, was not statistically different between groups. The results of the present investigation suggest that OMS patients have an exaggerated vasoconstriction in response to metaboreflex activation and that this fact is not due to obesity per se.