Dysfunctional eating in type 2 diabetes mellitus: A multicenter Italian study of socio-demographic and clinical associations.

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/m2). 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.

Predictors of the transition from metabolically healthy obesity to unhealthy obesity.

PURPOSE: Evidence that metabolically healthy obesity (MHO) is a stable benign condition is unclear. The aim of this study was to estimate the transition of MHO subjects to unhealthy obesity (occurrence of cardio-metabolic events and/or risk factors) and its predictors. METHODS: We conducted an explorative follow-up study in a subset of MHO patients > 40 years without any cardio-metabolic risk factors and with normal LDL cholesterol (LDLc) levels, identified among 1530 obese patients. Due to the low sample size, a bootstrap approach was applied to identify the variables to be included in the final multivariate discrete-time logit model. RESULTS: The prevalence of MHO was 3.7%. During the follow-up (mean 6.1 years, SD 2.0), none of the MHO reported cardiovascular events, diabetes or prediabetes; 26 subjects developed risk factors (53% high LDLc and 50% hypertension). At the 6 and 12-year of follow-up, the cumulative incidence of transition to unhealthy obesity was 44% (95% CI 31-59%) and 62% (95% CI 45-79%), the incidence of high LDLc was 23% (95% CI 13-37%) and 40% (95% CI 25-59%) and that of hypertension was 20% (95% CI 11-33%) and 30% (95% CI 17-48%). LDLc and duration of follow-up were independent predictors of the transition from MHO to unhealthy obesity [OR 1.038 (1.005-1.072) and 1.360 (1.115-1.659)]. CONCLUSIONS: Results suggest that (a) MHO individuals do not move over time forward diabetes/prediabetes but develop risk factors, such as hypertension and higher LDL c that worsen the cardiovascular prognosis; (b) LDLc and the flow of time independently predict the transition to unhealthy status. LEVEL OF EVIDENCE: Level III, cohort study.

Cross-modal interactions for custard desserts differ in obese and normal weight Italian women.

The effects of variation in odors and thickening agents on sensory properties and acceptability of a model custard dessert were investigated in normal weight and obese women. Subjects rated their liking and the intensity of sensory properties (sweetness, vanilla and butter flavors, and creaminess) of 3 block samples (the first varied in vanilla aroma, the second varied in butter aroma and the third varied in xanthan gum). Significant differences were found in acceptability and intensity ratings in relation to body mass index. The addition of butter aroma in the custard was the most effective way to elicit odor-taste, odor-flavor and odor-texture interactions in obese women. In this group, butter aroma, signaling energy dense products, increased the perception of sweetness, vanilla flavor and creaminess, which are all desirable properties in a custard, while maintaining a high liking degree. Understanding cross-modal interactions in relation to nutritional status is interesting in order to develop new food products with reduced sugar and fat, that are still satisfying for the consumer. This could have important implications to reduce caloric intake and tackle the obesity epidemic.

Effects of Greenselect Phytosome® on weight maintenance after weight loss in obese women: a randomized placebo-controlled study.

BACKGROUND: Most subjects regain weight after weight loss due to compensatory adaptations finalized to maintain stable body energy stores. Green tea (GT) preparations, which help maintain energy expenditure while dieting could be a useful strategy to facilitate weight maintenance. The usefulness of GT preparations in weight maintenance has been poorly studied so far with conflicting results. This study evaluated if a supplement of GSP and piperine helps obese women to maintain the weight loss obtained with a 3-month lifestyle intervention. METHODS: In a randomized placebo-controlled study, we examined whether a highly bioavailable GT extract may counteract weight regain after weight loss. Forty obese women (age 50.1 ± 10.1 years, Body Mass Index (BMI) 36.3 ± 2.7 kg/m(2)) underwent a 3-month lifestyle intervention. At the end of the intervention, the women were randomized in two groups for the weight-maintenance phase: 20 of them were prescribed twice a day, for 3 months, with a formula containing 150 mg/dose of Greenselect Phytosome® and 15 mg/dose of pure piperine (GSP group), and 20 were given placebo (P group). Anthropometric measures and body composition were measured before (V-3) and after lifestyle intervention (V0), 1 (V1), 2 (V2), and 3 (V3) months after prescribing supplements and 3 months following the discontinuation of supplements (V6). RESULTS: Lifestyle intervention induced a significant weight reduction in both groups with similar weight change (-6.2 ± 2.6 in GSP group vs. -4.8 ± 3.1 % in P group). In the GSP group, V1 in comparison to V0, had further reduction in weight and fat mass, which remained stable at V2 and V3 and increased at V6. In the P group, weight and fat mass increased from V2 onwards. Weight changes in GSP group and P group from V0 to V3 were -1.0 kg (95 % CI -2.5 to +0.5) and + 0.3 kg (95 % CI -0.9 to +1.6), respectively. The proportion of women with weight loss ≥ 5 % was greater in the GSP group than in the P group (75 % vs. 45 % at V1, and 60 % vs. 30 % at V6, p < 0.05 for both groups). CONCLUSIONS: Greenselect Phytosome® devoid of caffeine may have a clinical potential for the maintenance of weight after intentional weight loss. TRIAL REGISTRATION: Clinicaltrials.gov NCT02542449 (September 2015).

Visceral adipocytes: old actors in obesity and new protagonists in Crohn's disease?

OBJECTIVE: Crohn's disease (CD) is a chronic inflammatory bowel disease characterised by a peculiar accumulation of mesenteric adipose tissue covering the inflamed intestinal wall. METHODS: The authors characterised different adipose tissue compartments of patients with CD using morphological and molecular techniques and compared them to those of subjects with obesity (OB) and healthy subjects with normal weight (N). Adipose tissue samples were taken from subcutaneous adipose tissue, omental visceral adipose tissue (VAT) and healthy mesenteric depot (hMES), as well as from fat wrapping the affected (unhealthy) intestinal tracts (uhMES). Microarray analyses, validated by real-time quantitative PCR technique, were performed in whole adipose tissue and in isolated adipocytes. RESULTS: The morphology of subcutaneous adipose tissue was similar in subjects with CD and those with N. In patients with CD, VAT adipocytes were smaller than those derived from uhMES and hMES and were smaller than VAT adipocytes of subjects with N. The molecular profiles of CD, VAT and uhMES were characterised by upregulation of genes related to inflammation and downregulation of those involved in lipid metabolism. Adipocytes isolated from VAT of subjects with CD and those with OB exhibited similar upregulation of genes involved in inflammation and immunity. VAT adipocytes of patients with CD compared to those of patients with OB also showed a greater upregulation of several anti-inflammatory genes. CONCLUSION: In patients with CD, VAT distant from uhMES is affected by inflammation and displays features similar to those of VAT of patients with severe OB. The small diameter of VAT adipocytes of CD, together with their high expression of anti-inflammatory genes, suggests a potentially protective role for this tissue. VAT adipocytes may play an important role in the pathophysiology and/or activity of CD.

Rationale and design of the CV-PREVITAL study: an Italian multiple cohort randomised controlled trial investigating innovative digital strategies in primary cardiovascular prevention.

INTRODUCTION: Prevention of cardiovascular disease (CVD) is of key importance in reducing morbidity, disability and mortality worldwide. Observational studies suggest that digital health interventions can be an effective strategy to reduce cardiovascular (CV) risk. However, evidence from large randomised clinical trials is lacking. METHODS AND ANALYSIS: The CV-PREVITAL study is a multicentre, prospective, randomised, controlled, open-label interventional trial designed to compare the effectiveness of an educational and motivational mobile health (mHealth) intervention versus usual care in reducing CV risk. The intervention aims at improving diet, physical activity, sleep quality, psycho-behavioural aspects, as well as promoting smoking cessation and adherence to pharmacological treatment for CV risk factors. The trial aims to enrol approximately 80 000 subjects without overt CVDs referring to general practitioners' offices, community pharmacies or clinics of Scientific Institute for Research, Hospitalization and Health Care (Italian acronym IRCCS) affiliated with the Italian Cardiology Network. All participants are evaluated at baseline and after 12 months to assess the effectiveness of the intervention on short-term endpoints, namely improvement in CV risk score and reduction of major CV risk factors. Beyond the funded life of the study, a long-term (7 years) follow-up is also planned to assess the effectiveness of the intervention on the incidence of major adverse CV events. A series of ancillary studies designed to evaluate the effect of the mHealth intervention on additional risk biomarkers are also performed. ETHICS AND DISSEMINATION: This study received ethics approval from the ethics committee of the coordinating centre (Monzino Cardiology Center; R1256/20-CCM 1319) and from all other relevant IRBs and ethics committees. Findings are disseminated through scientific meetings and peer-reviewed journals and via social media. Partners are informed about the study's course and findings through regular meetings. TRIAL REGISTRATION NUMBER: NCT05339841.

Nutrition knowledge is associated with greater weight loss in obese patients following a multidisciplinary rehabilitation program.

BACKGROUND: A major objective of the metabolic-nutritional-psychological multidisciplinary rehabilitation of obese subjects is providing a nutritional education aimed at achieving a weight loss and the improvement of obesity-related cardio-metabolic diseases. The impact of nutrition knowledge in healthy eating patterns and weight loss is still debated. The aim of this study was to identify whether the increase in nutrition knowledge is associated with weight loss. METHODS: Two hundred fifty-six obese patients (80% women, mean age 57.5±12.4 years) were consecutively recruited among those referred for a three-month metabolic-nutritional-psychologic rehabilitation program. Education level and time of the onset of obesity were collected. Before and at the end of the intervention, anthropometric measures and body composition were assessed and the Moynihan Questionnaire (MQ) and the International Physical Activity Questionnaire administered. The weight loss maintenance was evaluated in patients who attended the 6-month follow-up visit. RESULTS: Nutrition knowledge was poor/sufficient in 97 out of 256 obese patients. The MQ Score was associated with the education level but not with age, gender and Body Mass Index. After rehabilitation, there was an increase in nutrition knowledge (mean score change -12±10.5%, P<0.0001) in the whole group of patients as well as in those with poor knowledge, 77% of whom reached a good/high level of knowledge on healthy diet. The improvement in knowledge was greater in patients with a weight loss ≥5% (P<0.05 vs. patients with a lower weight loss). Weight maintenance at follow-up, was associated with a better improvement in the nutritional knowledge during the previous rehabilitation. CONCLUSIONS: Weight-management programs should include a strong component of nutrition education to alleviate knowledge inequalities and promote more effective weight loss and control. The MQ may be a useful tool to verify the nutritional education carried out during the rehabilitation of obese subjects.

A High Protein Diet Is More Effective in Improving Insulin Resistance and Glycemic Variability Compared to a Mediterranean Diet-A Cross-Over Controlled Inpatient Dietary Study.

The optimal dietary pattern to improve metabolic function remains elusive. In a 21-day randomized controlled inpatient crossover feeding trial of 20 insulin-resistant obese women, we assessed the extent to which two isocaloric dietary interventions-Mediterranean (M) and high protein (HP)-improved metabolic parameters. Obese women were assigned to one of the following dietary sequences: M-HP or HP-M. Cardiometabolic parameters, body weight, glucose monitoring and gut microbiome composition were assessed. Sixteen women completed the study. Compared to the M diet, the HP diet was more effective in (i) reducing insulin resistance (insulin: Beta (95% CI) = -6.98 (-12.30, -1.65) µIU/mL, p = 0.01; HOMA-IR: -1.78 (95% CI: -3.03, -0.52), p = 9 × 10-3); and (ii) improving glycemic variability (-3.13 (-4.60, -1.67) mg/dL, p = 4 × 10-4), a risk factor for T2D development. We then identified a panel of 10 microbial genera predictive of the difference in glycemic variability between the two diets. These include the genera Coprococcus and Lachnoclostridium, previously associated with glucose homeostasis and insulin resistance. Our results suggest that morbidly obese women with insulin resistance can achieve better control of insulin resistance and glycemic variability on a high HP diet compared to an M diet.

Cushing's disease due to double pituitary ACTH-secreting adenomas: the first case report.

Double pituitary adenomas are rare occurrences in autoptical, surgical and neuroradiological series and are mostly due to non-functioning pituitary adenomas, GH-secreting and prolactin-secreting adenomas. ACTH secreting tumours are more rare and, to our knowledge, two distinct ACTH-producing adenomas within the same pituitary have never been reported. We herewith describe a 56 year old woman with Cushing' s disease due to two clearly distinct ACTH-secreting pituitary adenomas. She presented with signs and symptoms of hypercortisolism and hormonal testing was indicative for pituitary-dependent Cushing' s syndrome. Sellar MRI visualized an asymmetric pituitary gland with suspect lesions in both the right and the left pituitary lobes. Both lesions were removed during transsphenoidal surgery and remission of hypercortisolism ensued. Pathology confirmed the existence of two distinct adenomas located in different sites in the gland. Both presented ACTH immunoreactivity but displayed distinct morphological features. Our case indicates that double ACTH-secreting pituitary adenomas may occur in patients with Cushing' s disease. Careful radiological, surgical and pathological examination is necessary to recognize this condition and avoid surgical failure.

Determinants of the Lifestyle Changes during COVID-19 Pandemic in the Residents of Northern Italy.

BACKGROUND: The confinement recommended during COVID-19 pandemic could affect behavior and health. METHODS: We conducted a self-reported survey in northern Italy to observe the lockdown effects on lifestyle changes and to assess their determinants. Prevalence Odds Ratio and Prevalence Risk Ratio were determined. RESULTS: 490 adults (84% female) completed the survey: 13% and 43% reported improved and unchanged sleep quality, respectively, while 43% had insomnia symptoms. Among the 272 active subjects in pre-lockdown, 14% continued habitual exercising, 18% increased it and 68% reduced it; 27% of sedentary subjects started physical exercise; 34% reported an improvement in diet quality; 42% increased food intake and 13% decreased it; and 38% of the smokers increased cigarette consumption. Age and the pre-lockdown habit of regular physical exercising were the mainly determinants of lifestyle changes whereas BMI, gender, and the presence of chronic diseases did not. Living with other people increased the likelihood of increasing the food intake (p = 0.002). CONCLUSIONS: More than a third of people were able to positively reorganize their lives during the forced home confinement. It is worth to disseminate information to preserve a healthy lifestyle even when confined at home.

Expanding the role of bitter taste receptor in extra oral tissues: TAS2R38 is expressed in human adipocytes.

Increasing evidence indicates that taste receptors mediate a variety of functions in extra-oral tissues. The present study investigated the expression of bitter taste receptor TAS2R38 in human adipocytes, the possible link with genetic background and the role of TAS2R38 in cell delipidation and lipid accumulation rate in vitro. Subcutaneous (SAT) and visceral (VAT) adipose tissues were collected in 32 obese and 18 lean subjects. The TAS2R38 gene expression and protein content were examined in whole tissues, differentiated adipocytes and stroma-vascular fraction cells (SVF). The P49A SNP of TAS2R38 gene was determined in each collected sample. The effect of two bitter agonists (6-n-propylthiouracil and quinine) was tested. TAS2R38 mRNA was more expressed in SAT and VAT of obese than lean subjects and the expression/protein content was greater in mature adipocytes. The expression levels were not linked to P49A variants. In in vitro differentiated adipocytes, bitter agonists induced a significant delipidation. Incubation with 6-n-propylthiouracil induced an inhibition of lipid accumulation rate together with an increase in TAS2R38 and a decrease in genes involved in adipocyte differentiation. In conclusion, TAS2R38 is more expressed in adipocytes of obese than lean subjects and is involved in differentiation and delipidation processes.

Cardiovascular Risk Factors Associated With the Metabolically Healthy Obese (MHO) Phenotype Compared to the Metabolically Unhealthy Obese (MUO) Phenotype in Children.

Background: In pediatric age the prevalence of obesity is high. Obese children who do not have other risk factors than excess weight have been defined as "metabolically healthy obese" (MHO). Aim: The aim of this study is to evaluate, in a population of obese children, the prevalence of the MHO and "metabolically unhealthy obese" (MUO) phenotype. Furthermore, we evaluated the distribution of Uric Acid, HOMA index and Waist-Height ratio (W-Hr) in the MHO and MUO sub-groups and the impact of these non-traditional risk factors on the probability to be MUO. Methods: In 1201 obese children and adolescents [54% males, age (±SD) 11.9 (±3.0) years] weight, height, waist circumference, systolic (SBP) and diastolic (DBP) blood pressure, pubertal status, glucose, insulin, HDL cholesterol, triglycerides and Uric Acid serum values were assessed. MUO phenotype was defined as the presence of at least one of the following risk factors: SBP or DBP ≥ 90th percentile, glycaemia ≥ 100 mg/dl, HDL cholesterol <40 mg/dl, triglycerides ≥100 mg/dl (children <10 years) or ≥130 mg/dl (children ≥10 years). A multivariate logistic regression analysis was used to estimate the association between MUO phenotype and non-traditional cardiovascular risk factors. Results: The prevalence of the MUO status was high (61%). MUO subjects were more often male, older and pubertal (p < 0.001). The levels of the three non-traditional risk factors were significantly higher in MUO children compared to MHO children (p < 0.001) and all of them were independent predictors of the fact of being MUO [OR 1.41 (95% CI 1.24-1.69); 1.15 (95% CI 1.06-1.23) and 1.03 (95% CI1.01-1.05) for Uric Acid, HOMA index and W-Hr, respectively]. About 15% of MHO subjects had serum Uric Acid, HOMA index and W-Hr values within the highest quartile of the study population. Conclusion: The prevalence of MUO subjects in a large pediatric population is high and serum Uric Acid, HOMA index and W-Hr values are independent predictors of the probability of being MUO. A non-negligible percentage of subjects MHO has high values of all three non-traditional risk factors.

Ambient Odor Exposure Affects Food Intake and Sensory Specific Appetite in Obese Women.

Food odors are important in food perception not only during consumption, but also in anticipation of food. Even though it is well established that smell is involved in eating behavior, its role in affecting actual food consumption is still unclear, especially in morbidly obese subjects, who are reported to be more affected by sensory cues than lean subjects. The aim of the present study was to investigate the influence of ambient odor exposure on ad libitum food intake and on sensory specific appetite in obese women. Thirty obese women (BMI: 34.9 ± 0.8 kg m-2; age: 50.8 ± 1.8) attended two sessions in which they were exposed to a bread odor dispersed, in a detectable but mild concentration, in the test room ("scented" condition) and to a control condition ("unscented" condition). Participants filled out a questionnaire on general appetite before entering the test room and completed a sensory specific appetite questionnaire (including 12 specific products) about 10 min after entering the test room. After approximately 15 min of exposure, the ad libitum intake of a low energy dense food product (vegetable soup) was measured. The "scented" condition significantly (p < 0.01) increased the amount of soup eaten compared to the "unscented" condition (466.4 ± 33.1 g; 368.9 ± 33.2 g, respectively). Moreover, the odor exposure induced sensory specific appetite for congruent food products in term of taste and energy density, as well as a significant increase in general appetite scores (p < 0.001). In conclusion, ambient odor exposure to a food odor affected the intake of a low energy food in obese women and stimulated appetite for congruent products. This could have important implications for influencing energy intake of individuals.

Effect of Short-Term Dietary Intervention and Probiotic Mix Supplementation on the Gut Microbiota of Elderly Obese Women.

Accumulating literature is providing evidence that the gut microbiota is involved in metabolic disorders, but the question of how to effectively modulate it to restore homeostasis, especially in the elderly, is still under debate. In this study, we profiled the intestinal microbiota of 20 elderly obese women (EO) at the baseline (T0), after 15 days of hypocaloric Mediterranean diet administered as part of a nutritional-metabolic rehabilitation program for obesity (T1), and after a further 15 days of the same diet supplemented with a probiotic mix (T2). Fecal samples were characterized by Illumina MiSeq sequencing of the 16S rRNA gene. The EO microbiota showed the typical alterations found in obesity, namely, an increase in potential pro-inflammatory components (i.e., Collinsella) and a decrease in health-promoting, short-chain fatty acid producers (i.e., Lachnospiraceae and Ruminococcaceae members), with a tendency to reduced biodiversity. After 15 days of the rehabilitation program, weight decreased by (2.7 ± 1.5)% and the gut microbiota dysbiosis was partially reversed, with a decline of Collinsella and an increase in leanness-related taxa. During the next 15 days of diet and probiotics, weight dropped further by (1.2 ± 1.1)%, markers of oxidative stress improved, and Akkermansia, a mucin degrader with beneficial effects on host metabolism, increased significantly. These findings support the relevant role of a correct dietetic approach, even in the short term, to modulate the EO gut microbiota towards a metabolic health-related configuration, counteracting the increased risk of morbidity in these patients.

Impact of the 2017 Blood Pressure Guidelines by the American Academy of Pediatrics in overweight/obese youth.

OBJECTIVES: The aim of this study was to compare the impact of the European Society of Hypertension Guidelines 2016 (ESHG2016) and the American Academy of Pediatrics Guidelines 2017 (AAPG2017) on the screening of hypertension and classification of abnormal left ventricular geometry (ALVG) in overweight/obese youth. METHODS: This study included 6137 overweight/obese youth; 437 had echocardiographic assessment. Hypertension was defined using either ESHG2016 or AAPG2017. ALVG was defined using 95th percentile for age and sex of left ventricular mass index (LVMi) and/or relative wall thickness (RWT) more than 0.38 (juvenile cut-offs) according to ESHG2016 or LVMi more than 51 g/h and/or RWT more than 0.42 (adult cut-offs) according to AAPG2017. RESULTS: Prevalence of youth at a high risk of hypertension was 13% higher using AAPG2017 than ESHG2016. The increase was larger in overweight youth at least 13 years of age (+43%). Using the juvenile cut-offs for ALVG, youth at a high risk of hypertension by ESHG2016 had an odds ratio [95% confidence interval (95% CI)] of 3.03 (1.31-7.05) for left ventricular concentric remodelling (LVcr) and 2.53 (1.43-4.47) for concentric left ventricular hypertrophy (cLVH) as compared with youth with normal LVG. Similarly, in youth at a high risk of hypertension by AAPG2017, the odds ratio for LVcr was 3.28 (1.45-7.41, P < 0.001) and 3.02 (95% CI: 1.73-5.27, P < 0.001) for cLVH. Using the adult cut-offs, no significant difference in ALVG was found with both guidelines. CONCLUSION: The prevalence of overweight/obese youth at a high risk of hypertension increased by 13% comparing AAPG2017 vs. ESHG2016. The juvenile cut-offs for ALVG were more effective than the adult criteria in intercepting individuals with a potentially higher cardiovascular risk.

Ten years of experience with DPP-4 inhibitors for the treatment of type 2 diabetes mellitus.

Achieving and maintaining recommended glycemic targets without causing adverse e ffects, including hypoglycemia, is challenging, especially in older patients with type 2 diabetes mellitus (T2DM). The introduction of dipeptidyl peptidase-4 (DPP-4) inhibitors, more than 10 years ago, has provided an alternative to conventional medications for the intensification of glucose-lowering treatment after failure of metformin monotherapy, and therefore, marked an important advance in the management of T2DM. By prolonging the activity of incretin hormones, DPP-4 inhibitors induce insulin release and decrease glucagon secretion in a glucose-dependent manner. This results in a more physiologic glycemic control as compared to that ensured by insulin secretagogues (sulfonylureas and glinides). Overall, DPP-4 inhibitors have a favorable safety profile and can be used without dose adjustments in older adults and in patients with mild renal impairment; they have a neutral effect on body weight and do not cause hypoglycemia by themselves. Safety issues, reported mainly in post-marketing surveillance programs and including cardiovascular outcomes and the risk of acute pancreatitis, are being extensively investigated. The aim of this review is to discuss the impact of DPP-4 inhibitors on the treatment of T2DM, after 10 years of experience, with an emphasis on diabetes care in Italy. We will first describe T2DM treatment in Italy and then provide an overview of the main findings from randomized controlled trials, real-world studies and post-marketing surveillance programs with DPP-4 inhibitors.

Analysis of Predictive Equations for Estimating Resting Energy Expenditure in a Large Cohort of Morbidly Obese Patients.

The treatment of obesity requires creating an energy deficit through caloric restriction and physical activity. Energy needs are estimated assessing the resting energy expenditure (REE) that in the clinical practice is estimated using predictive equations. In the present cross sectional study, we compared, in a large cohort of morbidly obese patients, the accuracy of REE predictive equations recommended by current obesity guidelines [Harris-Benedict, WHO/FAO/ONU and Mifflin-St Jeor (MJ)] and/or developed for obese patients (Muller, Muller BC, Lazzer, Lazzer BC), focusing on the effect of comorbidities on the accuracy of the equations. Data on REE measured by indirect calorimetry and body composition were collected in 4,247 obese patients (69% women, mean age 48 ± 19 years, mean BMI 44 ± 7 Kg/m2) admitted to the Istituto Auxologico Italiano from 1999 to 2014. The performance of the equations was assessed in the whole cohort, in 4 groups with 0, 1, 2, or ≥ 3 comorbidities and in a subgroup of 1,598 patients with 1 comorbidity (47.1% hypertension, 16.7% psychiatric disorders, 13.3% binge eating disorders, 6.1% endocrine disorders, 6.4% type 2 diabetes, 3.5% sleep apnoea, 3.1% dyslipidemia, 2.5% coronary disease). In the whole cohort of obese patients, as well as in each stratum of comorbidity number, the MJ equation had the highest performance for agreement measures and bias. The MJ equation had the best performance in obese patients with ≥3 comorbidities (accuracy of 61.1%, bias of -89.87) and in patients with type 2 diabetes and sleep apnoea (accuracy/bias 69%/-19.17 and 66%/-21.67 respectively), who also have the highest levels of measured REE. In conclusion, MJ equation should be preferred to other equations to estimate the energy needs of Caucasian morbidly obese patients when measurement of the REE cannot be performed. As even MJ equation does not precisely predict REE, it should be better to plan the diet intervention by measuring rather than estimating REE. Future studies focusing on the clinical differences that determine the high inter-individual variability of the precision of the REE predictive equations (e.g., on the organ-tissue metabolic rate), could help to develop predictive equations with a better performance.

Effect of continuous positive airway pressure in hypertensive patients with obstructive sleep apnea and high urinary metanephrines.

OBJECTIVE: Some cases of pseudopheochromocytoma have been described among hypertensive patients with obstructive sleep apnea (OSA). This study examined whether a pathological rise of urinary metanephrines is a common feature in hypertensive OSA patients and, in such a case, whether the ventilation treatment during sleep (continuous or biphasic positive airway pressure) may normalize high metanephrines levels. METHODS: Patients with endocrine diseases, drug abuse, therapy with TCA and cardiovascular events in the previous 6 months were excluded. Thirty-four hypertensive patients with OSA (BMI 40.6 ±â€Š8.7 kg/m(2)) performed three 24-h urine collections for metanephrine assessment, before and after 1 month of ventilation therapy. RESULTS: Urinary normetanephrine (uNMT) was above the normal limit in 21 of 34 of the patients. In the 16 to 21 patients with high uNMT who were compliant to ventilation treatment, uNMT decreased in 13 by 26% and normalized in six of 13. uNMT levels were associated with apnea hypopnea index (AHI) (r = 0.799, P < 0.0001) and minimal SaO2 (r = -0.700, P < 0.01). The ventilation therapy-induced changes in AHI were associated with those in uNMT (r = 0.689, P < 0.005). In the multivariate analysis with uNMT changes as dependent variable and changes in AHI, BMI, SBP as independent variables, only AHI changes were independently associated with uNMT changes (ß = 0.738, P < 0.01). CONCLUSION: Two-thirds of OSA hypertensive patients have uNMT values above the normal limit. The early identification of these patients is important as ventilation therapy can correct the pathological sympathoadrenal activation. Patients who do not normalize uNMT with ventilation therapy deserve a strict follow-up as this lack of normalization may indicate insufficient ventilation therapy or resistance of sympathetic hyperactivity to this treatment, not excluding an early stage of a chromaffin tumor.

Adiponectin is a candidate marker of metabolic syndrome in obese children and adolescents.

The aim of this study was to compare the use of several biomarkers to identify obese children and adolescents with increased metabolic risk. One hundred sixty-two Caucasian obese children and adolescents (41% males, 9-18 years old) referred to the Istituto Auxologico Italiano between 2003 and 2004 underwent an oral glucose tolerance test. Circulating levels of adiponectin (AD), plasminogen activator inhibitor 1 (PAI-1), interleukin 18 (IL-18), C-reactive protein (CRP), fibrinogen, uric acid, lipids and insulin were measured. Twenty five percent of obese children had the MS defined using World Health Organization-derived child specific criteria. MS subjects had significantly lower AD (p<0.01) and higher log-PAI-1 (p<0.001), uric acid (p<0.0001), and IL-18 (p<0.001). Subjects with AD levels

The impact of the degree of obesity on the discrepancies between office and ambulatory blood pressure values in youth.

OBJECTIVES: Obesity is an increasingly frequent problem among children and adolescents, and may lead to blood pressure (BP) increase. The aim of the present study was to assess the prevalence of hypertension, white-coat and masked hypertension in obese adolescents making systematic use of both office BP and 24-h ambulatory BP measurement. The impact of different degrees of obesity on BP and heart rate variability was also investigated. METHODS: Office and ambulatory BP were obtained in 285 overweight and obese Caucasian adolescents (11-18 years old) and in 180 age- and sex-matched controls. The extent of obesity was quantified using body mass index z score. RESULTS: A significant positive relationship between body mass index z score and both office and ambulatory systolic BP was found after adjusting for age and height in both boys and girls. Obese youths had not only higher BP levels, but also higher BP variability compared with controls. Among obese youths, 20.8% had abnormal BP conditions, 6.6% were white-coat hypertensives, 9.2% were masked hypertensives and 5% were sustained hypertensives. CONCLUSIONS: The prevalence of these abnormal BP conditions, which can be identified thanks to ambulatory BP monitoring, further emphasizes the usefulness of this diagnostic tool in obese youths.