Turning the clock forward: New pharmacological and non pharmacological targets for the treatment of obesity.

AIMS: Obesity and its main metabolic complication, type 2 diabetes, have attained the status of a global pandemic; there is need for novel strategies aimed at treating obesity and preventing the development of diabetes. A healthy diet and exercise are basic for treatment of obesity but often not enough. Pharmacotherapy can be helpful in maintaining compliance, ameliorating obesity-related health risks, and improving quality of life. In the last two decades, the knowledge of central and peripheral mechanisms underlying homeostatic and hedonic aspects of food intake has significantly increased. Dysregulation of one or more of these components could lead to obesity. DATA SYNTHESIS: In order to better understand how potential innovative treatment options can affect obesity, homeostatic and reward mechanisms that regulate energy balance has been firstly illustrated. Then, an overview of potential therapeutic targets for obesity, distinguished according to the level of regulation of feeding behavior, has been provided. Moreover, several non-drug therapies have been recently tested in obesity, such as non-invasive neurostimulation: Transcranial Magnetic Stimulation or Transcranial Direct Current Stimulation. All of them are promising for obesity treatment and are almost devoid of side effects, constituting a potential resource for the prevention of metabolic diseases. CONCLUSIONS: The plethora of current anti-obesity therapies creates the unique challenge for physicians to customize the intervention, according to the specific obesity characteristics and the intervention side effect profiles; moreover, it allows multimodal approaches addressed to treat obesity and metabolic adaptation with complementary mechanisms.

The impact of short-term hyperglycemia and obesity on biventricular and biatrial myocardial function assessed by speckle tracking echocardiography in a population of women with gestational diabetes mellitus.

BACKGROUND AND AIMS: To compare biventricular and biatrial myocardial strain indices assessed by two-dimensional speckle tracking echocardiography (2D-STE) in women with gestational diabetes mellitus (GDM) and those with uncomplicated pregnancy at the third trimester of pregnancy and in post-partum. METHODS AND RESULTS: 30 consecutive GDM women and 30 age-, ethnicity- and gestational week-matched controls without any comorbidity were examined in this prospective case-control study. All women underwent obstetric visit, blood tests and transthoracic echocardiography (TTE) implemented with 2D-STE analysis of all cardiac chambers at 36-38 weeks' gestation. TTE and 2D-STE were repeated at 6-10 weeks after delivery. At 36-38 weeks' gestation, GDM women, compared to controls, had significantly higher body mass index (BMI), blood pressure values and inflammatory markers. TTE showed increased left ventricular (LV) mass and impaired LV diastolic function in GDM women, whereas there was no significant difference between the groups in ejection fraction. 2D-STE revealed that biventricular global longitudinal strain (GLS) and biatrial reservoir strain indices were significantly lower in GDM women than controls. Third trimester BMI was inversely correlated with LV-GLS (r = -0.86) and was independently associated with reduced LV-GLS (less negative than -20%) in GDM women in post-partum (OR 1.81, 95%CI 1.14-2.89). A BMI value ≥ 30 kg/m2 had 100% sensitivity and 99.5% specificity for identifying GDM women with impaired LV-GLS in post-partum (AUC = 0.97). CONCLUSION: Women with GDM, compared to women with uncomplicated pregnancy, have significantly lower biventricular and biatrial myocardial deformation indices. These abnormalities may be persistent in post-partum in GDM women with obesity.

Repetitive deep TMS for the reduction of body weight: Bimodal effect on the functional brain connectivity in "diabesity".

BACKGROUND AND AIMS: Deep repetitive Transcranial Magnetic Stimulation (deep rTMS) over the bilateral insula and prefrontal cortex (PFC) can promote weight-loss in obesity, preventing cardiometabolic complications as Type 2 Diabetes (T2D). To investigate the changes in the functional brain integration after dTMS, we conducted a resting-state functional connectivity (rsFC) study in obesity. METHODS AND RESULTS: This preliminary study was designed as a randomized, double-blind, sham-controlled study: 9 participants were treated with high-frequency stimulation (realTMS group), 8 were sham-treated (shamTMS group). Out of the 17 enrolled patients, 6 were affected by T2D. Resting-state fMRI scans were acquired at baseline (T0) and after the 5-week intervention (T1). Body weight was measured at three time points [T0, T1, 1-month follow-up visit (FU1)]. A mixed-model analysis showed a significant group-by-time interaction for body weight (p = .04), with a significant decrease (p < .001) in the realTMS group. The rsFC data revealed a significant increase of degree centrality for the realTMS group in the medial orbitofrontal cortex (mOFC) and a significant decrease in the occipital pole. CONCLUSION: An increase of whole-brain functional connections of the mOFC, together with the decrease of whole-brain functional connections with the occipital pole, may reflect a brain mechanism behind weight-loss through a diminished reactivity to bottom-up visual-sensory processes in favor of increased reliance on top-down decision-making processes. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03009695.

Diabetes Mellitus and Cardiovascular Diseases: Nutraceutical Interventions Related to Caloric Restriction.

Type 2 diabetes (T2DM) and cardiovascular disease (CVD) are closely associated and represent a key public health problem worldwide. An excess of adipose tissue, NAFLD, and gut dysbiosis establish a vicious circle that leads to chronic inflammation and oxidative stress. Caloric restriction (CR) is the most promising nutritional approach capable of improving cardiometabolic health. However, adherence to CR represents a barrier to patients and is the primary cause of therapeutic failure. To overcome this problem, many different nutraceutical strategies have been designed. Based on several data that have shown that CR action is mediated by AMPK/SIRT1 activation, several nutraceutical compounds capable of activating AMPK/SIRT1 signaling have been identified. In this review, we summarize recent data on the possible role of berberine, resveratrol, quercetin, and L-carnitine as CR-related nutrients. Additionally, we discuss the limitations related to the use of these nutrients in the management of T2DM and CVD.

Deep Transcranial Magnetic Stimulation Affects Gut Microbiota Composition in Obesity: Results of Randomized Clinical Trial.

Growing evidence highlights the crucial role of gut microbiota in affecting different aspects of obesity. Considering the ability of deep transcranial magnetic stimulation (dTMS) to modulate the cortical excitability, the reward system, and, indirectly, the autonomic nervous system (ANS), we hypothesized a potential role of dTMS in affecting the brain-gut communication pathways, and the gut microbiota composition in obesity. In a hospital setting, 22 subjects with obesity (5 M, 17 F; 44.9 ± 2.2 years; BMI 37.5 ± 1.0 kg/m2) were randomized into three groups receiving 15 sessions (3 per week for 5 weeks) of high frequency (HF), low frequency (LF) dTMS, or sham stimulation. Fecal samples were collected at baseline and after 5 weeks of treatment. Total bacterial DNA was extracted from fecal samples using the QIAamp DNA Stool Mini Kit (Qiagen, Italy) and analyzed by a metagenomics approach (Ion Torrent Personal Genome Machine). After 5 weeks, a significant weight loss was found in HF (HF: -4.1 ± 0.8%, LF: -1.9 ± 0.8%, sham: -1.3 ± 0.6%, p = 0.042) compared to LF and sham groups, associated with a decrease in norepinephrine compared to baseline (HF: -61.5 ± 15.2%, p < 0.01; LF: -31.8 ± 17.1%, p < 0.05; sham: -35.8 ± 21.0%, p > 0.05). Furthermore, an increase in Faecalibacterium (+154.3% vs. baseline, p < 0.05) and Alistipes (+153.4% vs. baseline, p < 0.05) genera, and a significant decrease in Lactobacillus (-77.1% vs. baseline, p < 0.05) were found in HF. Faecalibacterium variations were not significant compared to baseline in the other two groups (LF: +106.6%, sham: +27.6%; p > 0.05) as well as Alistipes (LF: -54.9%, sham: -15.1%; p > 0.05) and Lactobacillus (LF: -26.0%, sham: +228.3%; p > 0.05) variations. Norepinephrine change significantly correlated with Bacteroides (r2 = 0.734; p < 0.05), Eubacterium (r2 = 0.734; p < 0.05), and Parasutterella (r2 = 0.618; p < 0.05) abundance variations in HF. In conclusion, HF dTMS treatment revealed to be effective in modulating gut microbiota composition in subjects with obesity, reversing obesity-associated microbiota variations, and promoting bacterial species representative of healthy subjects with anti-inflammatory properties.

Weight loss induced by deep transcranial magnetic stimulation in obesity: A randomized, double-blind, sham-controlled study.

AIM: To test the hypothesis that deep transcranial magnetic stimulation (dTMS) reduces food craving and causes weight loss via neuromodulation. MATERIALS AND METHODS: This pilot study was designed as a randomized, double-blind, sham-controlled study. A total of 33 obese people (nine men, 24 women, mean age 48.1 ± 10.6 years, body mass index [BMI] 36.9 ± 4.7 kg/m2 ) were randomized and completed the study: 13 participants underwent a 5-week treatment with high-frequency (HF) dTMS (18 Hz; HF group), 10 were treated with low-frequency (LF) dTMS (1 Hz; LF group), and 10 were sham-treated (sham group). Food craving, and metabolic and neuro-endocrine variables were evaluated at baseline, after the 5-week treatment, and at follow-up visits (1 month, 6 months, 1 year after the end of treatment). RESULTS: The mixed-model analysis for repeated measures showed a significant interaction of time and groups for body weight (P = 0.001) and BMI (P = 0.001), with a significant body weight (-7.83 ± 2.28 kg; P = 0.0009) and BMI (-2.83 ± 0.83, P = 0.0009) decrease in the HF versus the sham group. A decreasing trend in food craving in the HF versus the LF and sham groups (P = 0.073) was observed. A significant improvement of metabolic and physical activity variables was found (P < 0.05) in the HF group. CONCLUSIONS: We demonstrated the safety and efficacy of dTMS, in addition to physical exercise and a hypocaloric diet, in reducing body weight for up to 1 year in obese people. We hypothesize that a possible mechanism of HF dTMS treatment is modulation of the dopaminergic pathway and stimulation of physical activity.

Effects of hazelnuts and cocoa on vascular reactivity in healthy subjects: a randomised study.

Cocoa helps maintain endothelium-dependent vasodilation; consumption of hazelnuts has been associated with reduced cardiovascular disease risk. This study assesses the effects of hazelnuts and cocoa on vascular reactivity and metabolic profile. Sixty-one healthy volunteers, examined in a randomised, controlled, two-week intervention, received one of six breakfast integrations containing either hazelnuts, cocoa, both or none. Consumption of unpeeled hazelnuts improved HDL-cholesterol (+7.3%, p = .01 vs. baseline, p = .02 vs. control). Brachial artery peak systolic velocities (PSV) at rest increased with hazelnut integrations by 43.4% (p = .04 vs. control) and hazelnut-cocoa integrations by 26.4% (p = .01 vs. control). PSV after 3-min cuff occlusion increased by 60.7% (p = .002 vs. control) with a peeled hazelnut snack and by 64.7% with a hazelnut-cocoa integration (p = .04 vs. control). The combination hazelnut-cocoa may act in a synergic and protective way on cardiovascular system.

The Influence of Anthropometrics on Cardiac Mechanics in Healthy Women With Opposite Obesity Phenotypes (Android vs Gynoid).

BACKGROUND: The possible influence exerted by mechanical factors and/or compressive phenomena on myocardial strain parameters in healthy individuals with opposite obesity phenotypes (android vs gynoid) has never been previously investigated. Accordingly, we aimed at evaluating the relationship between anthropometrics, such as the waist-to-hip ratio (WHR), modified Haller index (MHI, the ratio of chest transverse diameter over the distance between sternum and spine), and epicardial adipose tissue (EAT), and left ventricular (LV)-global longitudinal strain (GLS), in healthy women with opposite obesity phenotypes (android vs gynoid). METHODS: Forty healthy women with obesity (body mass index (BMI) ≥30 Kg/m2) and WHR ≥0.85 ("android group") (52.5±13.2 yrs), 40 age- and BMI-matched healthy women with obesityand WHR <0.78 ("gynoid group") (49.8±13.4 yrs) and 40 age-matched healthy women without obesity (BMI <30 Kg/m2) (controls) (50.3±12.5 yrs) were retrospectively analyzed. All women underwent transthoracic echocardiography implemented with echocardiographic strain analysis of all cardiac chambers. Correlation between LV-GLS and anthropometrics (WHR, MHI, and EAT) was assessed in both groups of obese women. Age, WHR, homeostasis model assessment for insulin resistance (HOMA-IR), and left ventricular mass index (LVMi) were included in the logistic regression analysis performed for evaluating the independent predictors of reduced LV-GLS magnitude (less negative than -20%) in women with android obesity. RESULTS: Compared to the other groups of women, those with android obesity were found with significantly greater LVMi, higher LV filling pressures, and lower biventricular and biatrial deformation indices. A strong inverse correlation between LV-GLS and all anthropometrics (WHR, MHI, and EAT) was demonstrated in both groups of women with obesity. Univariate logistic regression analysis revealed that WHR (OR 1.58, 95%CI 1.22-2.03, p<0.001) and LVMi (OR 1.09, 95%CI 1.02-1.16, p=0.006) were independently correlated with LV-GLS impairment in women with android obesity. On multivariate logistic regression analysis, the WHR maintained a statistically significant association with the above-mentioned outcome (OR 1.68, 95%CI 1.14-2.48, p=0.009). Receiver operating characteristic (ROC) curve analysis showed that a WHR value ≥1.01 had 93% sensitivity and 100% specificity for detecting LV-GLS impairment in women with android obesity (AUC=0.98; 95%CI 0.96-1.00). CONCLUSIONS: Anthropometrics may strongly influence cardiac mechanics in healthy women with obesity. The WHR is associated with reduced LV-GLS magnitude in healthy women with android obesity, independent of age, glycometabolic status, and LV size.

Post-surgical Persistent Hyperparathyroidism Successfully Treated with Parathyroid Radiofrequency Ablation: A Case Report.

BACKGROUND: Currently, parathyroidectomy is the standard treatment for Primary Hyperparathyroidism (PHPT). Surgical treatment is often effective, although not free of complications and relapses. Minimally invasive techniques, such as Microwave Ablation (MWA) and Radiofrequency Ablation (RFA), are an alternative to surgery in selected patients. We have, herein, reported on the successful use of RFA in a patient with post-surgical persistent hyperparathyroidism. CASE PRESENTATION: A 54-year-old woman was referred to our Center for mild hypercalcemia with exams revealing Primary Hyperparathyroidism (PHPT). Neck ultrasound and Technetium- 99 Methoxy-isobutyl-isonitrile (99mTc-MIBI) scintigraphy scanning revealed a suspicious right parathyroid hyperplasia/adenoma. She underwent parathyroidectomy and histological examination showed a parathyroid nodular hyperplasia. During the follow-up, she suffered from persistent hyperparathyroidism due to the treatment of left parathyroid hypoplasia with RFA. Blood tests after the procedure showed the remission of the disease 7 months post-treatment. CONCLUSION: A minimally invasive technique for PHPT may represent a valid alternative to surgery, especially in patients with an elevated surgery-related risk. More studies are necessary to investigate the benefit of RFA as a first-line treatment in PHPT.

The effect of gestational diabetes mellitus on carotid artery intima-media thickness in and after pregnancy: a systematic review and meta-analysis.

AIMS: The association between gestational diabetes mellitus (GDM) and common carotid artery (CCA) intima-media thickness (IMT) is still controversial. This systematic review and meta-analysis was performed to assess the correlation between GDM and CCA-IMT in and after pregnancy. METHODS: PubMed and EMBASE databases were systematically reviewed on April 2023. Studies measuring CCA-IMT in both pregnant women with GDM and women with previous history of GDM (pGDM) vs. healthy controls were included. The subtotal and overall standardized mean differences (SMDs) of CCA-IMT were calculated using the random-effect model. RESULTS: Nineteen studies with a total of 302 GDM and 861 pGDM women were analyzed. The average value of CCA-IMT measured in GDM/pGDM (0.59 ± 0.12 mm) was slightly increased in comparison to the accepted reference limits of IMT according to age classes. Substantial heterogeneity was detected for the studies involving both GDM and pGDM women, with an overall statistic I2 of 86.0% (p < 0.001). Large SMDs were obtained for the studies conducted on both GDM and pGDM women, with an overall SMD of 0.89 (95%CI 0.63-1.15, p < 0.001). Egger's test for a regression intercept gave a p-value of 0.37, indicating no publication bias. On meta-regression analysis, all potential confounders (number of patients, age at pregnancy, body mass index, measuring time, follow-up duration and GDM criteria) were not significantly associated with effect modification. CONCLUSIONS: GDM in and after pregnancy is independently associated with subclinical atherosclerosis. The association between GDM and carotid remodeling is potentially mediated by the longstanding underlying risk.

Influence of gestational diabetes mellitus on subclinical myocardial dysfunction during pregnancy: A systematic review and meta-analysis.

OBJECTIVE: The correlation between gestational diabetes mellitus (GDM) and subclinical myocardial dysfunction has been poorly investigated. Accordingly, we performed a meta-analysis to examine the influence of GDM on left ventricular (LV) global longitudinal strain (GLS), assessed by speckle tracking echocardiography (STE), during pregnancy. STUDY DESIGN: All echocardiographic studies assessing conventional echoDoppler parameters and LV-GLS in GDM women vs. healthy controls, selected from PubMed and EMBASE databases, were included. The risk of bias was assessed by using the National Institutes of Health (NIH) Quality Assessment of Case-Control Studies. The subtotal and overall standardized mean differences (SMDs) of LV-GLS were calculated using the random-effect model. RESULTS: The full-texts of 10 studies with 1147 women with GDM and 7706 pregnant women without diabetes were analyzed. GDM women enrolled in the included studies were diagnosed with a small reduction in LV-GLS in comparison to controls (average value -19.4 ± 2.5 vs -21.8 ± 2.5 %, P < 0.001) and to the accepted reference values (more negative than -20 %). Substantial heterogeneity was detected for the included studies, with an overall statistic value I2 of 94.4 % (P < 0.001). Large SMDs were obtained for the included studies, with an overall SMD of -0.97 (95 %CI -1.32, -0.63, P < 0.001). Egger's test for a regression intercept gave a P-value of 0.99, indicating no publication bias. On meta-regression analysis, all moderators and/or potential confounders (age at pregnancy, BMI, systolic blood pressure and ethnicity) were not significantly associated with effect modification (all P < 0.05). CONCLUSIONS: GDM is independently associated with subclinical myocardial dysfunction in pregnancy. STE analysis allows to identify, among GDM women, those who might benefit of targeted non-pharmacological and/or pharmacological interventions, aimed at reducing the risk of developing type 2 diabetes and cardiovascular complications later in life.

Urban diabetes: analysis of diabetes prevalence in cities of the Lombardy region participating in the cities changing diabetes project.

AIM: The urban population increases by about 60 million people/year. Urbanization, unhealthy lifestyle and aging of the population are reflected in a constant growth in the prevalence of diabetes. In 2014, Steno Diabetes Centre in Copenhagen, University College London and Novo Nordisk, launched the Cities Changing Diabetes® program with the aim of creating a unified movement that would stimulate policy-makers to prioritize urban diabetes. METHODS: The socio-demographic data derive from (1) ISTAT (National Institute of Statistics of Italy), (2) ATS Metropolitan City of Milan, (3) ATS Val Padana-Cremona, (4) ATS Insubria-Varese, (5) The unemployment rates of the various municipalities have been extrapolated from an ISTAT-MEF elaboration published by Sole 24 Ore journal. RESULTS: In the different sanitary districts of the Metropolitan City of Milan, a strong linear correlation was found between the prevalence of diabetes and the prevalence of heart disease (R = 0.695, p < 0.001), as well as between the prevalence of diabetes and of nephropathies (R = 0.316, p < 0.001). The analysis concerning the province of Cremona showed a fair correlation between the prevalence of diabetes and cardiovascular disease (R = 0.658, p < 0.001). Even for the municipalities of Varese, the analysis documented a good correlation between the prevalence of diabetes and heart disease (R = 0.419, p < 0.001), but not between diabetes and nephropathies. CONCLUSIONS: Interesting differences in the relationship of diabetes prevalence with several diseases and socio-demographic factors have been found when comparing the metropolitan City of Milan with two smaller size cities as Varese and Cremona. Our present data confirm the hypothesis that urban diabetes will be the challenge for our society during the next decades.

Therapeutic patient education and treatment intensification of diabetes and hypertension in subjects with newly diagnosed type 2 diabetes mellitus: a longitudinal study.

PURPOSE: The aim of this study is to prospectively evaluate whether individual and group Therapeutic Patient Education (TPE) can reduce the need to intensify treatment of diabetes and hypertension in newly diagnosed type 2 diabetic patients. METHODS: A total of 937 patients were recruited and followed-up for 42.7 ± 21.5 months. TPE was a structured comprehensive education delivered by trained nurses: 322 patients received individual TPE (ITPE), 291 underwent group TPE (GTPE), and 324 were in Usual Care (UC). The primary endpoints were intensification of diabetes treatment and intensification of hypertension treatment. RESULTS: The rate of diabetes treatment intensification was 40.1% in patients receiving ITPE, 47.8% in patients undergoing GTPE, and 64.2% in patients in UC (p < 0.001). The rate of hypertension treatment intensification was 24.2% in patients following ITPE, 31.3% in patients receiving GTPE, and 41.0% in patients in UC (p < 0.001). Multivariate analysis showed that both ITPE and GTPE were associated with reduced intensification of diabetes (ITPE: HR:0.51; 95% IC:0.40-0.64; p < 0.001 - GTPE: HR:0.46; 95% IC:0.44-0.70; p < 0.001) and hypertension medication (ITPE: HR:0.45; 95% IC:0.34-0.61; p < 0.001 - GTPE: HR:0.49; 95% IC:0.38-0.65; p < 0.001). The association was independent of age, sex, BMI, HbA1c, and presence of hypertension at baseline. CONCLUSIONS: TPE, delivered as both individual and group sessions, represents an effective tool to reduce the need to intensify treatment of both diabetes and hypertension. Therefore, it can ensure better control of diabetes and hypertension with fewer medications. This could reduce adverse effects and costs and improve quality of life and medication taking in patients with type 2 diabetes.

Liver transplantation in alcoholic patients: impact of an alcohol addiction unit within a liver transplant center.

BACKGROUND: Many concerns about liver transplantation in alcoholic patients are related to the risk of alcohol recidivism. Starting from 2002, an Alcohol Addiction Unit (AAU) was formed within the liver transplant center for the management of alcoholic patients affected by end-stage liver disease and included in the waiting list for transplantation. We evaluated retrospectively the impact of the AAU on alcohol recidivism after transplantation. The relationship between alcohol recidivism and the duration of alcohol abstinence before transplant was evaluated as well. METHODS: Between 1995 and 2010, 92 cirrhotic alcoholic patients underwent liver transplantation. Clinical evaluation and management of alcohol use in these patients was provided by psychiatrists with expertise in addiction medicine not affiliated to the liver transplant center before 2002 (n = 37; group A), or by the clinical staff of the AAU within the liver transplant center starting from 2002 (n = 55; group B). RESULTS: Group B, as compared with group A, showed a significantly lower prevalence of alcohol recidivism (16.4 vs. 35.1%; p = 0.038) and a significantly lower mortality (14.5 vs. 37.8%; p = 0.01). Furthermore, an analysis of group B patients with either ≥6 or <6 months of alcohol abstinence before transplantation showed no difference in the rate of alcohol recidivism (21.1 vs. 15.4%; p = ns). CONCLUSIONS: The presence of an AAU within a liver transplant center reduces the risk of alcohol recidivism after transplantation. A pretransplant abstinence period <6 months might be considered, at least in selected patients managed by an AAU.

Editorial for the Special Issue "Effects of COVID-19 on Lifestyle Behaviors in Children with Obesity".

During the last four decades, the prevalence of obesity has increased dramatically worldwide; concomitantly, a progressive rise in the prevalence of obesity, diabetes, and other nutrition-related chronic diseases has also been observed in childhood [...].

How images of food become cravingly salient in obesity.

OBJECTIVE: This case-control study was aimed at testing two main hypotheses: (i) obesity is characterized by neurofunctional alterations within the mesocorticolimbic reward system, a brain network originating from the midbrain ventral tegmental area (VTA); and (ii) these alterations are associated with a bias for food-related stimuli and craving. METHODS: Normal-weight individuals and individuals with obesity underwent a resting-state functional magnetic resonance imaging scan and the assessment of impulsivity, food craving, appetite, and implicit bias for food and non-food stimuli. The VTA was used as a seed to map, for each participant, the strength of its functional connections with the rest of the brain. The between-group difference in functional connectivity was then computed, and brain-behavior correlations were performed. RESULTS: Individuals with obesity showed hyper-connectivity of the VTA with part of the ventral occipitotemporal cortex, recently found to be specialized for food images, and hypo-connectivity with the left inferior frontal gyrus, devoted to cognitive control. VTA-ventral occipitotemporal cortex connectivity was positively associated with food craving and food-related bias; the reverse correlation was observed for VTA-inferior frontal gyrus connectivity. CONCLUSIONS: These findings reveal that, in obesity, food-related visual stimuli become cravingly salient through an imbalanced connectivity of the reward system with sensory-specific regions and the frontal cortex involved in cognitive control.

A Comprehensive Therapeutic Patient Education May Improve Wound Healing and Reduce Ulcer Recurrence and Mortality in Persons With Type 2 Diabetes.

OBJECTIVES: The impact of a comprehensive therapeutic patient education (TPE) on the prognosis of diabetic foot ulcer (DFU) has not yet been evaluated in the literature. The purpose of this study was to determine whether TPE is a predictor of outcome in type 2 diabetes patients with DFU. METHODS: We evaluated 583 consecutive individuals with a recent and single DFU. They were treated and followed for 42.8±23.3 months. Patients were divided into 2 groups. The TPE group included subjects who had been receiving regular sessions of a comprehensive TPE, including a specific foot care education (FCE), for at least 12 months before DFU occurred (n=129). The non-TPE group comprised the remaining subjects (n=454). All 583 patients received intensive FCE during the treatment period. RESULTS: We identified a significantly higher percentage of healed DFUs (96.0% vs 74.9%; p<0.0001) and a lower percentage of major amputations (0.8% vs 4.4%; p=0.0511), minor amputations (1.6% vs 12.3%; p=0.0003), DFU persistence (1.6% vs 8.4%; p=0.0069) and deaths (1.6% vs 21.4%; p<0.0001) in the TPE group than in the non-TPE group. Among 464 patients with healed ulcers, the proportion of subjects with re-ulceration was greater in the non-TPE group than in the TPE group (48.8% vs 6.5%; p<0.0001). Multivariate analysis showed that TPE can predict healing (odds ratio [OR], 4.202; 95% confidence interval [CI], 1.604 to 11.004; p=0.0035) and may significantly reduce DFU recurrence (OR, 0.093; 95% CI, 0.043 to 0.201; p<0.0001) and mortality (OR, 0.096; 95% CI, 0.022 to 0.410; p=0.0016). CONCLUSION: A comprehensive TPE may have a positive impact on wound healing, ulcer recurrence and mortality in people with DFU.

Impact of microvascular complications on the outcomes of diabetic foot in type 2 diabetic patients with documented peripheral artery disease.

PURPOSE: Microvascular disease (MVD) is associated with amputation linked to peripheral artery disease (PAD) in the general population. No study evaluated the impact of diabetic microvascular complications on the outcomes of vascular diabetic foot ulcers (DFU). The aim of the study was to investigate whether retinopathy, nephropathy, and polyneuropathy can predict the outcomes of DFU in type 2 diabetic patients with PAD. METHODS: Three hundred and thirty-one consecutive patients with vascular DFU were enrolled and followed up for 44.1 ± 23.9 months. RESULTS: The prevalence of retinopathy was significantly higher in subjects with ulcer persistence (45.2%; p < 0.01), minor amputation (48.9%; p < 0.001), and major amputation (57.9%; p < 0.001) than in healed patients (23.3%), and in non-survivors than in survivors (64.9 versus 20.5%; p < 0.001). The prevalence of nephropathy was significantly greater in subjects with ulcer persistence (83.9%; p < 0.01), minor amputation (86.7%; p < 0.001), and major amputation (94.7%; p < 0.001) than in those with healed DFU (64.4%), and in non-survivors than in survivors (88.3 versus 65.7%; p < 0.001). The prevalence of polyneuropathy was significantly higher in non-survivors than in survivors (76.6 versus 61.0%; p = 0.012). Multivariate analysis showed that absence of retinopathy (OR: 0.451; 95% CI: 0.250-0.815; p < 0.001) and nephropathy (OR: 0.450; 95% CI: 0.212-0.951; p = 0.036) were independently associated with healing. Moreover, retinopathy was a predictor both of minor amputation (OR: 2.291; 95% CI: 1.061-4.949; p = 0.034) and mortality (OR: 5.274; 95% CI: 2.524-11.020; p < 0.001). Polyneuropathy never entered the regression model. CONCLUSIONS: Diabetic microvascular complications, in particular retinopathy, may predict the outcomes of vascular DFU. Longitudinal studies should confirm this finding.