Eicosapentaenoic Acid: between Cardiovascular Benefits and the Risk of Atrial Fibrillation.

In recent years, scientific research has increasingly focused on the cardiovascular benefits of omega-3 polyunsaturated fatty acids (n-3 PUFAs) supplements. The most promising results emerged from the new trials on a high-dose eicosapentaenoic acid (EPA)-only approach, instead of the previously prescribed therapy with EPA + docosahexaenoic acid (DHA). The evidence of the reduction of cardiovascular events in patients at high cardiovascular risk with EPA is intriguing. However, physicians have expressed concern about the potential high risk of atrial fibrillation (AF) occurrence due to such an approach. This study aims to investigate the current evidence on the cardiovascular benefits of EPA and its association with atrial arrhythmogenesis. Current guidelines consider EPA (as IPE) treatment for selected patients but with no specific indication regarding AF risk evaluation. We propose a flowchart that could be a starting point for the future development of an algorithm to help clinicians to prescribe EPA safely and effectively, especially in patients at high risk of incipient AF.

The Effects of Omega 3 and Omega 6 Fatty Acids on Glucose Metabolism: An Updated Review.

Massive changes have occurred in our diet. A growing consumption of vegetal oils rich in omega-6 (ω-6) and a depletion of omega-3 (ω-3) fatty acids (FAs) in our food has led to an imbalance between ω-3 and ω-6. In particular, eicosapentaenoic (EPA)/arachidonic acid (AA) ratio seems to be an indicator of this derangement, whose reduction is associated to the development of metabolic diseases, such as diabetes mellitus. Our aim was therefore to investigate the literature on the effects of ω-3 and ω-6 FAs on glucose metabolism. We discussed emerging evidence from pre-clinical studies and from clinical trials. Notably, conflicting results emerged. Source of ω-3, sample size, ethnicity, study duration and food cooking method may be responsible for the lack of univocal results. High EPA/AA ratio seems to be a promising indicator of better glycemic control and reduced inflammation. On the other hand, linoleic acid (LA) appears to be also associated to a minor incidence of type 2 diabetes mellitus, although it is still not clear if the outcome is related to a reduced production of AA or to its intrinsic effect. More data derived from multicenter, prospective randomized clinical trials are needed.

Predicting Glycated Hemoglobin Through Continuous Glucose Monitoring in Real-Life Conditions: Improved Estimation Methods.

BACKGROUND: The adoption of continuous glucose monitoring (CGM) already helps to improve glycemic control in diabetes. When coupled with appropriate data analysis techniques, CGM also provides dependable estimates for significant metrics, like glycated hemoglobin (HbA1c). Findings from the REALISM-T1D study can boost HbA1c estimation methods in diabetes care and stimulate their use in clinical practice. METHODS: Continuous glucose monitoring data of 27 adults affected by type-1 diabetes were acquired by means of G6 (Dexcom, San Diego, CA) sensors for a time span of 120 days. Glycated hemoglobin laboratory assays were performed during the concluding follow-up visits. Data were then analyzed to derive estimates of assay results, taken as the gold standard. RESULTS: Bland-Altman (BA) plots show that smart interpolation to patch missing data and a wise choice of interstitial glucose (IG) weighting function, besides a proper mean interstitial glucose (MIG) to HbA1c regression equation, improve HbA1c estimation quality with respect to methods relying on MIG alone. A decrease in the BA plot-related variance of differences with respect to the gold standard confirms the improvement. Wilcoxon signed-rank tests on the bias-compensated mean squared error (MSE) with respect to conventional MIG-based methods show that the improvement is statistically significant with a confidence level better than 95% (P = .0179). CONCLUSIONS: Improved HbA1c estimation methods result in better HbA1c prediction quality with respect to those based on MIG alone, thus providing quick, but still relatively accurate feedback to diabetologists. They alleviate the discordances reported in literature and, with further improvements, may become a viable complement/alternative to HbA1c assays.

The Role of the Person Focused IARA Model in Reducing Anxiety and Improving Body Awareness and Illness Management in Diabetics with Acquired Lipodystrophy: A Mixed-Method Study.

Background: Lipodystrophy is one of the most frequent complications in people with diabetes following subcutaneous insulin therapy, and poor management can lead to several problems, such as impaired glycemic control and adherence to therapy, anxiety, and depression. Poor injection technique represents the main risk factor for lipodystrophies. In order to enhance the patient's insulin injection technique to heal lipodystrophy, improve psychological indices, and promote involvement in their health and care, the efficacy of emerging person-centered care called the IARA model was tested. Methods: A total of 49 patients were randomly allocated to the IARA group (Experimental; n = 25) or standard education (Control; n = 24). The following questionnaires were used in a mixed-method design: (i) State Anxiety Scale; (ii) Beck Depression Inventory; (iii) Italian Summary of Diabetes Self-Care Activities. An ad hoc open-ended questionnaire was structured for the qualitative analysis. Finally, photos were taken in order to verify if injection sites were changed until the follow-up at 12 months. The number of patients who participated until the completion of the study was 17 in the IARA and 11 in the Control group. Results: State anxiety was significantly reduced in people who followed IARA to follow-up at 3 and 6 months (p < 0.05). The IARA group also demonstrated better compliance in blood glucose monitoring and foot-care compared to Control at follow-up at 12 months. The management of insulin injections dramatically improved in participants who received IARA intervention. Conclusions: IARA could be considered an effective strategy to improve well-being and compliance in people affected with diabetes mellitus and lipodystrophy complications.

In Patients with Obesity, Are Affective Temperaments Associated with Attrition? An Evaluation during and before the SARS-CoV-2 Pandemic.

Timely data on attrition from weight loss programs for patients with obesity during the SARS-CoV-2 pandemic are lacking, so we aimed to contribute to filling this gap in the literature by comparing attrition during or outside of the SARS-CoV-2 pandemic and its possible association with patients' affective temperaments, psychopathology, and clinical variables. Two-hundred and eleven outpatients with obesity were recruited and completed the Temperament Evaluation of Memphis, Pisa, and San Diego Auto-questionnaire, Binge Eating Scale, Beck Depression Inventory, and State-Trait Anxiety Inventory. Those who dropped out during the pandemic period were mostly men, with younger age of weight gain, and with a larger waist circumference than completers. Patients with obesity who dropped out outside of the SARS-CoV-2 pandemic showed marked levels of depression, anxiety, binge eating episodes, and higher affective temperaments (but the hyperthymic one) when compared to their counterparts. The cyclothymic temperament slightly increased attrition (OR = 1.13, 95% CI 1.00-1.27 p = 0.05) outside the pandemic, while during the pandemic, male gender (OR = 3.50, 1.04-11.7, p = 0.04) was associated with attrition. These findings suggested that male patients with obesity are at particular risk of drop-out from weight-loss treatment during the SARS-CoV-2 pandemic; contrariwise, outside the pandemic, affective temperaments could be a useful baseline assessment for defining the attrition risk in these patients.

A New Clinical Model to Estimate the Pre-Test Probability of Cushing's Syndrome: The Cushing Score.

Background: Hypercortisolism accounts for relevant morbidity and mortality and is often a diagnostic challenge for clinicians. A prompt diagnosis is necessary to treat Cushing's syndrome as early as possible. Objective: The aim of this study was to develop and validate a clinical model for the estimation of pre-test probability of hypercortisolism in an at-risk population. Design: We conducted a retrospective multicenter case-control study, involving five Italian referral centers for Endocrinology (Turin, Messina, Naples, Padua and Rome). One hundred and fifty patients affected by Cushing's syndrome and 300 patients in which hypercortisolism was excluded were enrolled. All patients were evaluated, according to current guidelines, for the suspicion of hypercortisolism. Results: The Cushing score was built by multivariable logistic regression, considering all main features associated with a clinical suspicion of hypercortisolism as possible predictors. A stepwise backward selection algorithm was used (final model AUC=0.873), then an internal validation was performed through ten-fold cross-validation. Final estimation of the model performance showed an average AUC=0.841, thus reassuring about a small overfitting effect. The retrieved score was structured on a 17.5-point scale: low-risk class (score value: ≤5.5, probability of disease=0.8%); intermediate-low-risk class (score value: 6-8.5, probability of disease=2.7%); intermediate-high-risk class (score value: 9-11.5, probability of disease=18.5%) and finally, high-risk class (score value: ≥12, probability of disease=72.5%). Conclusions: We developed and internally validated a simple tool to determine pre-test probability of hypercortisolism, the Cushing score, that showed a remarkable predictive power for the discrimination between subjects with and without a final diagnosis of Cushing's syndrome.

Affective temperaments and obesity: Is there an association with binge eating episodes and multiple weight cycling?

BACKGROUND: affective temperaments have been so far understudied in the field of obesity. Therefore, we aimed to assess affective temperaments in outpatients with obesity reporting symptoms of binge eating (BE) and multiple weight cycling (MWC) and to investigate the likelihood of an association between affective temperaments and risk of both conditions. METHODS: A total of 300 individuals with obesity seeking treatment at the Obesity Unit of an academic hospital were asked to complete self-report measures of affective temperaments, BE, depressive and anxiety symptoms, and quality of life. RESULTS: Even in the absence of full-blown mental disorders, symptoms of anxiety and depression emerged in the sample; 197 individuals (65.6%) reported BE and 162 (54%) MWC. The most frequent affective temperament was the depressive one. Depression symptoms and cyclothymic scores (directly), and age and hyperthymic score (inversely) were significantly associated with BE risk, while being an active smoker (directly) and hyperthymic score (inversely) were significantly associated with MWC risk, after controlling for confounders in a multiple logistic regression. LIMITATIONS: sample size was small, the study was limited to a single center, no formal definition of weight cycling exists and MWC was self-reported. CONCLUSIONS: A substantial number of outpatients with obesity reported BE and MWC notwithstanding the absence of a formal psychiatric diagnosis. Cyclothymic scores were positively associated with BE while the hyperthymic temperament showed a protective effect on both BE and MWC. These findings suggest the need for multidisciplinary treatments for people with obesity enhancing research on temperament-based psychological interventions.

Predictors of attrition from a weight loss program. A study of adult patients with obesity in a community setting.

PURPOSE: Obesity unit attrition is frequent and contributes to treatment failure. Many studies evaluating attrition predictors were part of randomized trials, and different terminology and criteria were used in the engagement field. We aimed to investigate the factors potentially implicated in early (< 12 weeks) and late (> 12 weeks) attrition from an obesity unit in a community setting METHODS: This was a retrospective cohort study of 250 patients with obesity who were followed-up at our obesity unit. Our program included at least 6 meetings in 12 months. Sociodemographic and anthropometric data, and psychometric questionnaires were collected from all participants. RESULTS: One-hundred thirty-four (53.6%) participants dropped out. Those individuals showed lower BMI, lower overall health status, and increased depression scores. In a multiple regression model, BMI (inversely; OR = 0.90; 95%CI 0.84-0.96) and depression score (directly, OR = 1.05; 1.00-1.10) were associated with attrition risk. Early dropouts (n = 47) had lower weights, smaller waist circumferences and worse mental health scores than late dropouts (n = 87) and more frequently lived alone. When compared to completers, early dropouts had lower weights, BMIs, waist circumferences, overall health and mental status scores, increased depression scores and percentage of individuals living alone. In a multiple regression, lower BMI (OR = 0.83; 0.75-0.92), lower mental status score (OR = 3.17; 1.17-8.59) and living alone (OR = 2.25; 1.02-4.97) were associated with early attrition risk. CONCLUSION: Lower BMI and increased depression score were associated with attrition. Early attrition was associated with lower weight, decreased mental well-being, and living alone. Individuals with these characteristics might need tailored approaches to enhance their engagement. LEVEL OF EVIDENCE: Level V, retrospective descriptive study.

Changes in Weight and Nutritional Habits in Adults with Obesity during the "Lockdown" Period Caused by the COVID-19 Virus Emergency.

Our aim is evaluating the changes in weight and dietary habits in a sample of outpatients with obesity after 1 month of enforced lockdown during the COVID-19 pandemic in Northern Italy. In this observational retrospective study, the patients of our Obesity Unit were invited to answer to a 12-question multiple-choice questionnaire relative to weight changes, working activity, exercise, dietary habits, and conditions potentially impacting on nutritional choices. A multivariate regression analysis was performed to evaluate the associations among weight/BMI changes and the analyzed variables. A total of 150 subjects (91.5%) completed the questionnaire. Mean self-reported weight gain was ≈1.5 kg (p < 0.001). Lower exercise, self-reported boredom/solitude, anxiety/depression, enhanced eating, consumption of snacks, unhealthy foods, cereals, and sweets were correlated with a significantly higher weight gain. Multiple regression analyses showed that increased education (inversely, ß = -1.15; 95%CI -2.13, -0.17, p = 0.022), self-reported anxiety/depression (ß = 1.61; 0.53, 2.69, p = 0.004), and not consuming healthy foods (ß = 1.48; 0.19, 2.77, p = 0.026) were significantly associated with increased weight gain. The estimated direct effect of self-reported anxiety/depression on weight was 2.07 kg (1.07, 3.07, p < 0.001). Individuals with obesity significantly gained weight 1 month after the beginning of the quarantine. The adverse mental burden linked to the COVID-19 pandemic was greatly associated with increased weight gain.

Is HDL cholesterol protective in patients with type 2 diabetes? A retrospective population-based cohort study.

BACKGROUND: The protective role of high HDL cholesterol levels against cardiovascular diseases has been recently questioned. Limited data are available on this specific topic in patients with type 2 diabetes mellitus (T2DM). We aimed to evaluate the association of HDL cholesterol concentrations with all-cause and cause-specific mortality in a historical cohort of T2DM patients with 14 years of follow-up. METHODS: This is a retrospective population-based cohort study involving 2113 T2DM patients attending the Diabetic Clinic of Asti. Survival analyses were performed to assess hazard ratios for overall and specific-cause mortality by HDL cholesterol tertiles, using the middle HDL cholesterol tertile as a reference. RESULTS: The mean age was 66 ± 11 years; 51.4% of patients had low HDL-cholesterol levels. After a 14-year follow-up, 973/2112 patients had died (46.1%). The HDL cholesterol tertile cut-off points were 37.5 and 47.5 mg/dL (males) and 41.5 and 52.0 mg/dL (females). No associations between lower and upper HDL cholesterol tertiles respectively and all-cause (HR = 1.12; 95% CI 0.96-1.32; HR = 1.11; 0.95-1.30), cardiovascular (HR = 0.97; 0.77-1.23; HR = 0.94; 0.75-1.18) or cancer (HR = 0.92; 0.67-1.25; HR = 0.89; 0.66-1.21) mortality were found. A significantly increased risk for infectious disease death was found both in the lower (HR = 2.62; 1.44-4.74) and the upper HDL-cholesterol tertiles (HR = 2.05; 1.09-3.85) when compared to the reference. Individuals in the upper tertile showed an increased risk for mortality due to diabetes-related causes (HR = 1.87; 1.10-3.15). CONCLUSIONS: Our results corroborate the hypothesis that HDL cholesterol levels are nonprotective in T2DM patients. The U-shaped association between HDL-cholesterol levels and mortality associated with infectious diseases should be verified by further studies.

Incidence of hospitalization and mortality in patients with diabetic foot regardless of amputation: a population study.

AIMS: The aim of our study was to estimate the overall rate of first hospitalizations for diabetic foot (DF) regardless of the outcome in amputations, as well as the mortality rate with their determinants in the period 2012-2016 in Piedmont Region in Italy. METHODS: The study included all the subjects registered in the Regional Diabetes Registry and alive as at January 1, 2012. DF cases were identified by record linkage with the regional hospital discharge database. Incident cases of diabetic foot were followed up for mortality. RESULTS: The 5-year rates were 1762, 324, and 343 × 100,000 patients for first hospitalization without amputations, with major amputations, and with minor amputations, respectively. Patients not undergoing amputations were more than 70% of the cohort. Patients with the more severe stages of diabetes and those with low education were at higher risk of each type of hospitalization. The risk of death during a mean follow-up of 2.5 years was about 16, 18, and 30% among patients without amputations, with major amputations, and with minor amputations, respectively. Males, insulin-treated patients, those affected with severe diabetes complications, particularly on dialysis, and those with lower levels of education were at higher risk. CONCLUSIONS: The heavier burden of DF on hospitalizations is due to cases without amputation, a condition that is seldom considered in the diabetes literature. The severity of diabetes, preexisting complications, and low educational levels are associated with both first hospitalization and subsequent survival at any level of severity of DF.

Coping strategies in people with type 1 diabetes on insulin pump treatment.

BACKGROUND: In stressed people with diabetes (PWD) glycemia varies idiosyncratically. Coping is a relatively stable personality trait that assesses how individual deals with stress. Insulin pumps are considered the best insulin delivery system but require more attention from PWD, virtually increasing stress levels. Aim of our study was to evaluate the coping strategies adopted by a pool of participants with type 1 diabetes mellitus (T1DM) on continuous subcutaneous insulin infusion (CSII) therapy. METHODS: We collected data from 158 people with T1DM on CSII. COPE-NVI Test was administered and we also collected: hemoglobin A1c (HbA1c), 30 days of self-monitoring of blood glucose (SMBG) and continuous glucose monitoring (CGM) records (the most recent). From SMBG and CGM records we computed Kovatchev indexes. We investigated bivariate correlations between HbA1c, indexes and the results of the COPE-NVI Test; the analysis was performed on the total sample and on two sub-groups: men and women. The participants were then divided into clusters and non-parametric tests were performed. RESULTS: Regarding bivariate correlation, at a level of significance of 95%, several statistically significant correlations were found in the total sample and in both men and women sub-groups. Regarding non-parametric tests, we observed statistically significant results in clusters of the total sample and clusters of the sub-group formed by men, divided according to Low Blood Glucose Index (LBGI) risk, showing a different use of certain coping strategies. CONCLUSIONS: Assessing coping strategies preferably used by PWD is useful to select PWD in need of counseling and empowerment-oriented training in order to improve glycemic outcomes and decrease severe hypo/hyperglycemic events.

Risk of Erythrocytosis During Concomitant Testosterone and SGLT2-Inhibitor Treatment: A Warning From Two Clinical Cases.

Context: Erythrocytosis is one of the most common side effects occurring during testosterone replacement therapy (TRT) in male hypogonadism. It is well known that all testosterone formulations may cause Hb and hematocrit increase, especially with short-acting injectable formulations. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a new class of glucose-lowering agents that reduce hyperglycemia in patients with type 2 diabetes mellitus (T2DM) by inhibition of renal glucose reabsorption, leading to increased urinary glucose excretion. The co-occurrence of T2DM and hypogonadism is known to be increasingly frequent. However, to date, no adverse events with the concomitant use of TRT and SGLT2is are reported. Case Description: We report two cases of erythrocytosis during testosterone treatment and SGLT2i in patients with hypogonadism and T2DM. Conclusion: Considering that hypogonadism and T2DM are frequently associated, clinicians should carefully monitor the risk of occurrence of erythrocytosis when prescribing TRT and SGLT2i together.

Effects of Self-Conditioning Techniques (Self-Hypnosis) in Promoting Weight Loss in Patients with Severe Obesity: A Randomized Controlled Trial.

OBJECTIVE: The usefulness of the rapid-induction techniques of hypnosis as an adjunctive weight-loss treatment has not been defined. This randomized controlled trial evaluated whether self-conditioning techniques (self-hypnosis) added to lifestyle interventions contributed to weight loss (primary outcome), changes in metabolic and inflammatory variables, and quality of life (QoL) improvement (secondary outcomes) in severe obesity. METHODS: Individuals (with BMI = 35-50 kg/m2 ) without organic or psychiatric comorbidity were randomly assigned to the intervention (n = 60) or control arm (n = 60). All received exercise and behavioral recommendations and individualized diets. The intervention consisted of three hypnosis sessions, during which self-hypnosis was taught to increase self-control before eating. Diet, exercise, satiety, QoL, anthropometric measurements, and blood variables were collected and measured at enrollment and at 1 year (trial end). RESULTS: A similar weight loss was observed in the intervention (-6.5 kg) and control (-5.6 kg) arms (ß = -0.45; 95% CI: -3.78 to 2.88; P = 0.79). However, habitual hypnosis users lost more weight (-9.6 kg; ß = -10.2; 95% CI: -14.2 to -6.18; P < 0.001) and greatly reduced their caloric intake (-682.5 kcal; ß = -643.6; 95% CI: -1064.0 to -223.2; P = 0.005) in linear regression models. At trial end, the intervention arm showed lower C-reactive protein values (ß = -2.55; 95% CI: -3.80 to -1.31; P < 0.001), higher satiety (ß = 19.2; 95% CI: 7.71-30.6; P = 0.001), and better QoL (ß = 0.09; 95% CI: 0.02-0.16; P = 0.01). CONCLUSIONS: Self-hypnosis was not associated with differences in weight change but was associated with improved satiety, QoL, and inflammation. Indeed, habitual hypnosis users showed a greater weight loss.

Changes in the gut microbiota composition during pregnancy in patients with gestational diabetes mellitus (GDM).

Gestational diabetes mellitus (GDM), a common pregnancy complication, is associated with an increased risk of maternal/perinatal outcomes. We performed a prospective observational explorative study in 41 GDM patients to evaluate their microbiota changes during pregnancy and the associations between the gut microbiota and variations in nutrient intakes, anthropometric and laboratory variables. GDM patients routinely received nutritional recommendations according to guidelines. The fecal microbiota (by 16S amplicon-based sequencing), was assessed at enrolment (24-28 weeks) and at 38 weeks of gestational age. At the study end, the microbiota α-diversity significantly increased (P < 0.001), with increase of Firmicutes and reduction of Bacteroidetes and Actinobacteria. Patients who were adherent to the dietary recommendations showed a better metabolic and inflammatory pattern at the study-end and a significant decrease in Bacteroides. In multiple regression models, Faecalibacterium was significantly associated with fasting glucose; Collinsella (directly) and Blautia (inversely) with insulin, and with Homeostasis-Model Assessment Insulin-Resistance, while Sutterella with C-reactive protein levels. Consistent with this latter association, the predicted metagenomes showed a correlation between those taxa and inferred KEGG genes associated with lipopolysaccharide biosynthesis. A higher bacterial richness and strong correlations between pro-inflammatory taxa and metabolic/inflammatory variables were detected in GDM patients across pregnancy. Collectively these findings suggest that the development of strategies to modulate the gut microbiota might be a potentially useful tool to impact on maternal metabolic health.

Effects of meal timing on changes in circulating epinephrine, norepinephrine, and acylated ghrelin concentrations: a pilot study.

BACKGROUND: Timing of food intake impacts on metabolic diseases. Few data are available about post-meal changes in epinephrine (E), norepinephrine (NE), and acylated ghrelin (AG) at different times of the day. SUBJECTS AND METHODS: This randomized cross-over trial investigated E/NE/AG concentrations after identical meals consumed at 0800 or 2000 hours in 20 healthy volunteers, by standardizing diet, exercise, duration of fast, and resting. Participants randomly received the test meal at 0800 or 2000 hours, and vice versa after 1 week. Blood samples were collected before and up to 180-min post-meal, every 30 min, with participants supine, motionless, but awake. RESULTS: Median E levels increased at 30-60 min, then declined and rose again at 150 min; values at 60 min (19.0 vs. 15.0 ng/l, p = 0.03) and 180 min (25.0 vs. 11.0 ng/l, p < 0.001) were higher after the morning meals. NE rose at 30-60 min and then progressively declined; median values at 60 min (235.3 vs. 206.3 ng/l, p = 0.02) and 120 min (208.8 vs. 142.0 ng/l, p = 0.04) increased more after morning meals. AG progressively declined to increase again at 90 min after meal; median AG area-under-the-curve (AUC) values were lower at morning (7206.8 vs. 8828.3 pg/mL×h). AG-AUC was inversely associated with diet-induced thermogenesis (ß = -121.6; 95% CI -201.0 to 42.2; p = 0.009 for each unit increase), while log NE-AUC was inversely associated with log-triglyceride AUC (ß = -0.57; 95% CI -0.98 to 0.16; p = 0.015) in a multiple regression model, after multiple adjustments. CONCLUSIONS: In conclusion, E/NE concentrations were higher after the morning meal, while AG showed an opposite behavior. These data, although requiring confirmation in larger samples, suggest an adjunctive possible mechanism explaining the unfavorable effects of evening eating on metabolic risk.

Timing of food intake: Sounding the alarm about metabolic impairments? A systematic review.

Growing evidence points to an association between timing of food intake and obesity in humans, raising the question if when to eat matters as much as what and how much to eat. Based on the new definition of obesity as a chronobiological disease, an unusual or late meal timing represent a circadian chronodisruption, leading to metabolic impairments. Preliminary data from cross-sectional and experimental studies suggest that changes in meal timing can influence obesity and success of weight loss therapy, independently from total energy intake, dietary composition and estimated energy expenditure. A systematic review of observational and experimental studies in humans was conducted to explore the link between time of food ingestion, obesity and metabolic alterations. Results confirm that eating time is relevant for obesity and metabolism: observational and experimental studies found an association between meal timing, weight gain, hyperglycemia and diabetes mellitus with benefits deriving from an early intake of food in the day in a wide range of individuals. Herein clinical, future perspectives of chronoprevention and chronotherapy of obesity and type 2 diabetes are also provided. In conclusion, meal timing appears as a new potential target in weight control strategies, and therapeutic strategies should consider this contributor in the prevention of obesity.

Beneficial effect of lixisenatide after 76 weeks of treatment in patients with type 2 diabetes mellitus: A meta-analysis from the GetGoal programme.

AIMS: To evaluate the long-term efficacy and safety of lixisenatide, a short-acting, prandial glucagon-like peptide-1 receptor agonists (GLP-1 RA) as add-on therapy in type 2 diabetes mellitus. METHODS: A meta-analysis of 76-week results of 5 placebo-controlled clinical trials from the GetGoal programme was performed, including 3000 inadequately controlled adult diabetic patients where lixisenatide 20 µg once-daily was administered in combination with metformin (GetGoal-M and GetGoal-F1), sulphonylurea ± metformin (GetGoal-S), basal insulin ± metformin (GetGoal-L) or pioglitazone ± metformin (GetGoal-P). RESULTS: A significant reduction in HbA1c at 76 weeks was observed in the intervention arm compared to placebo (LSM difference: -0.41%, 95%CI: -0.51, -0.32, P < .00001). Compared to placebo, lixisenatide induced a larger decrease in fasting plasma glucose (LSM difference -0.49 mmol/L, 95% CI -0.71, -0.27, P < .0001) and postprandial glucose excursion after a standard test meal (LSM difference -3.29 mmol/L, 95% CI -4.17, -2.42, P < .00001). A bodyweight reduction was observed in the lixisenatide arm (LSM difference -0.40 kg, 95%CI: -0.8, -0.01, P = .05). The risk of hypoglycaemia was slightly higher with lixisenatide vs placebo (risk difference +0.02, 95% CI: 0, 0.04, P = .04). The most commonly observed non-severe adverse events were nausea and vomiting, which after week 16 and week 8, were steadily <4% and <1% in the lixisenatide arm, respectively. CONCLUSIONS: Lixisenatide, a once-daily prandial GLP-1 RA, provides long-term glycaemic control, a sustained beneficial effect on weight and with a good safety profile.

Predictive role of the Mediterranean diet on mortality in individuals at low cardiovascular risk: a 12-year follow-up population-based cohort study.

BACKGROUND: Adherence to the Mediterranean diet reduces the risk of all-cause and cardiovascular (CV) mortality and the incidence of CV events. However, most previous studies were performed in high-risk individuals. Our objective was to assess whether the adherence to the Mediterranean diet, evaluated by the MED score, was associated with all-cause and CV mortality and incidence of CV events in individuals at low CV risk from a population-based cohort, after a 12-year mean follow-up. METHODS: A cohort of 1658 individuals completed a validated food-frequency questionnaire in 2001-2003. The MED score was calculated by a 0-9 scale. Anthropometric, laboratory measurements, and the vital status were collected at baseline and during 2014. The baseline CV risk was estimated by the Framingham risk score. Participants were divided into two groups: individuals at low risk (CV < 10) and individuals with CV risk ≥ 10. RESULTS: During a 12-year mean follow-up, 220 deaths, 84 due to CV diseases, and 125 incident CV events occurred. The adherence to the Mediterranean diet was low in 768 (score 0-2), medium in 685 (score 4-5) and high in 205 (score > 6) individuals. Values of BMI, waist circumference, fasting glucose and insulin significantly decreased from low to high diet adherence only in participants with CV risk ≥ 10. In a Cox-regression model, the hazard ratios (HRs) in low-risk individuals per unit of MED score were: HR = 0.83 (95 % CI 0.72-0.96) for all-cause mortality, HR = 0.75 (95 % CI 0.58-0.96) for CV mortality, and HR = 0.79 (95 % CI 0.65-0.97) for CV events, after multiple adjustments. In individuals with CV risk ≥ 10, the MED score predicted incident CV events (HR = 0.85; 95 % CI 0.72-0.99), while the associations with all-cause (HR = 1.02; 95 % CI 0.90-1.15) and CV mortality (0.94; 95 % CI 0.76-1.15) were not significant. CONCLUSIONS: Greater adherence to the Mediterranean diet was associated with reduced fatal and non fatal CV events, especially in individuals at low CV risk, thus suggesting the usefulness of promoting this nutritional pattern in particular in healthier individuals.