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SommarioLa chirurgia metabolica è oggi considerata la terapia a lungo termine più efficace per la cura dell’obesità e il suo utilizzo è raccomandato dalle linee guida internazionali. I pazienti sottoposti a intervento bariatrico possono andare incontro a nuovi specifici problemi: le abitudini alimentari devono adattarsi alla nuova fisiologia gastrointestinale; possono insorgere deficit nutrizionali a seconda del tipo di procedura; può cambiare la gestione di altre malattie associate all’obesità; durante la gravidanza possono insorgere problemi specifici; i pazienti possono sperimentare alcune difficoltà psicologiche nell’adattarsi ai cambiamenti del comportamento alimentare e dell’immagine corporea; il recupero del peso necessita di programmi di prevenzione e gestione. Per tutte queste ragioni, il paziente sottoposto a chirurgia metabolica necessita di una gestione multidisciplinare a lungo termine.

BACKGROUND: Vibration controlled transient elastography (VCTE) and controlled attenuation parameter (CAP™) have shown reliable performance predicting fibrosis and steatosis in normal- to overweight patients but have not been validated in severe to morbid obesity. This study aimed at determining the accuracy of VCTE, CAP™ and the composite score FibroScan-AST (FAST) in patients with a body mass index (BMI) of ≥35 kg/m(2). METHODS: Patients scheduled for bariatric-metabolic surgery underwent preoperative VCTE/CAP™ measurement, and intraoperative liver biopsy. The feasibility and accuracy of VCTE, CAP™ and the composite score FAST were retrospectively analysed to evaluate fibrosis, steatosis and active fibrotic non-alcoholic steatohepatitis [NASH + non-alcoholic fatty liver disease (NAFLD) activity score ≥4 + fibrosis grade ≥2] using per protocol (PP) and intent to diagnose (ITD) calculation. RESULTS: In total, 170 patients (median BMI 44.4 kg/m(2)) were included in the study. Liver biopsy showed NASH, simple steatosis, and normal livers in 60.6% (n=103), 28.8% (n=49), and 10.6% (n=18), respectively. VCTE and CAP™ delivered reliable results in 90.6% (n=154/170) and 90.5% (n=134/148). The AUC (PP) of VCTE, CAP™, and FAST were 0.687 (≥F2), 0.786 (≥F3), 0.703 (≥S2), 0.738 (S3), and 0.780 (active fibrotic NASH). The AUC increased to 0.742 (≥F2), 0.842 (≥F3), 0.712 (≥S2), 0.780 (S3), and 0.836 (active fibrotic NASH) in patients below the median BMI of 44.4 kg/m(2). CONCLUSIONS: VCTE, CAP™ and FAST show acceptable accuracy for the detection of fibrosis, steatosis and NASH in a real-life cohort of patients with obesity. Accuracy improves in patients with a BMI

Background and aim Obese subjects are at high risk of nonalcoholic fatty liver disease (NAFLD) and diabetes (T2D) due to insulin resistance (IR). Since high glucose levels are as toxic as lipids for hepatic metabolism, we hypothesize that altered response to oral glucose tolerance test (OGTT) is associated to more severe NAFLD with significant/advanced liver damage. Methods and results We studied 90 subjects with morbid obesity (73F/17M, BMI = 43.2 ± 5,9 kg/m2) undergoing bariatric surgery and intraoperative liver biopsy, and measured HbA1c, HOMA-IR (fasting Glucose x Insulin/22.5), OGTT glucose and insulin profile, and calculated OGIS (muscle insulin sensitivity), hepatic-IR (glucose [AUC0-30] x insulin [AUC0-30]) during OGTT, insulin response as (insulin [dAUC0-120]/glucose [dAUC0-120] or Insulinogenic Index (IGI = (I30–I0)/(G30-G0)). Patients were divided in 3 groups according to liver biopsy: A (no-NAFLD, 23%), B (simple steatosis (SS), 53%) and C (NASH, 24%) with similar age, gender and BMI. Diabetes was 0% in no-NAFLD, 13% in SS, 35% in NASH. During OGTT, OGIS decreased from A to C (422 vs 360 vs 338, p Conclusions In morbid obesity indexes of IR, and not of insulin response, are markers of histological severity of liver disease.

Introduction: gut microbiota (GM) seems to be involved in the pathophysiology and progression of both metabolic syndrome (MS) and obesity. The aim was to investigate GM's composition in patients with severe obesity, candidates for bariatric/metabolic surgery BMS. Materials and Methods: Multicentre, prospective, cohort study, enrolling 84 patients with BMI 40–55 kg/m2, divided by metabolic status (MS) in healthy (group A), pre-MS (B), or MS (C). Results: No differences were found regarding anthropometric, nutritional parameters, except for vitamin D. As a whole the alpha and beta diversity examinations showed no statistical differences in GM profile. A total of 5/7 phyla with relative frequencies were identified above 0.1% (Actinobacteria, Bacteroidetes, Firmicutes, Proteobacteria, Verrucomicrobia). Fusobacteria and Patescibacteria represented the less abundant. There were no significant differences in the top ten genera. Data on Bacteroidetes (inversely related to triglycerides and LDL and directly related to HDL levels) and on Firmicutes (opposite trend) relative abundances suggest no differences among the three conditions. No correlation between the relative abundance of the main phyla and plasmatic glucose levels was observed. Conclusions: In a selected cohort of patients with obesity, MS did not affect the preoperative GM's profile. Severe obesity, per se, seems to be an independent condition affecting GM.

Purpose: to study the possible association of CT-derived quantitative Epicardial Adipose Tissue (EAT) and glycemia at the admission, with severe outcomes in patients with COVID-19.Methods: 229 patients consecutively hospitalized for COVID-19 from March 1st to June 30th2020 were studied.Non contrast chest CT scans, to confirm diagnosis of pneumonia, were performed. EAT volume (cm3) and attenuation (Hounsfield units) were measured using a CT post-processing software. The primary outcome was acute respiratory distress syndrome (ARDS) or in-hospital death.Results: The primary outcome occurred in 56,8% patients. Fasting blood glucose was significantly higher in the group ARDS/death than in the group with better prognosis [114 (98-144) vs 101 (91-118) mg/dl, p=0,001]. EAT volume was higher in patients with vs without the primary outcome [103 (69,25;129,75) vs 78,95 (50,7;100,25) cm3, p Conclusions: Our findings suggest that both blood glucose and EAT, measurable and modifiable targets, could allow the early identification of subjects at greater risk of developing severe complications.

BACKGROUND: Obesity represents a risk factor for COVID-19 infection. Therefore, in order to reduce COVID-19 related comorbidities in obese population a continuation of obesity treatment is needed. However, bariatric procedures were postponed because of COVID-19 restrictions, delaying treatment for obese patients seeking for surgery. This study aimed to test the feasibility of a telematics pre-operative psychological and nutritional assessment as an alternative tool during COVID-19 outbreak. METHODS: Twenty-six patients were contacted. The pre-operative assessment consisted in 3-weekly one-to-one online sessions and a final in-person multidisciplinary session. The protocol feasibility has been evaluated on the following outcome: rejection rate (%), dropout rate (%), compliance and satisfaction's degree. RESULTS: Eighteen participants completed the whole protocol and 10% dropped-out. Seventy-two percent of participants obtained an excess weight loss ≥5%. All participants were satisfied of the telematics assessment. CONCLUSIONS: COVID-19 emergency has changed standard hospital procedures and this study could represent a landmark for an online pre-operative assessment method to adopt in case of new restrictions.

Biliverdin reductase A (BVR-A) is an enzyme involved in the regulation of insulin signalling. Knockout (KO) mice for hepatic BVR-A, on a high-fat diet, develop more severe glucose impairment and hepato-steatosis than the wild type, whereas loss of adipocyte BVR-A is associated with increased visceral adipose tissue (VAT) inflammation and adipocyte size. However, BVR-A expression in human VAT has not been investigated. We evaluated BVR-A mRNA expression levels by real-time PCR in the intra-operative omental biopsy of 38 obese subjects and investigated the association with metabolic impairment, VAT dysfunction, and biopsy-proven non-alcoholic fatty liver disease (NAFLD). Individuals with lower VAT BVR-A mRNA levels had significantly greater VAT IL-8 and Caspase 3 expression than those with higher BVR-A. Lower VAT BVR-A mRNA levels were associated with an increased adipocytes&rsquo, size. An association between lower VAT BVR-A expression and higher plasma gamma-glutamyl transpeptidase was also observed. Reduced VAT BVR-A was associated with NAFLD with an odds ratio of 1.38 (95% confidence interval: 1.02&ndash, 1.9, &chi, 2 test) and with AUROC = 0.89 (p = 0.002, 95% CI = 0.76&ndash, 1.0). In conclusion, reduced BVR-A expression in omental adipose tissue is associated with VAT dysfunction and NAFLD, suggesting a possible involvement of BVR-A in the regulation of VAT homeostasis in presence of obesity.

AIMS Experimental data suggest that visceral adipose tissue (VAT) dysfunction contributes to non-alcoholic fatty liver disease (NAFLD) development in obesity, however, data on humans are limited. Aims of this study were to investigate the relationship between NAFLD and VAT morphofunctional impairment and to determine whether the extent of VAT remodelling is associated with liver damage and metabolic alterations in obesity. METHODS We analysed data from 40 obese individuals candidate to bariatric surgery in whom paired intraoperative liver and omental biopsies were performed for diagnosing NAFLD and VAT inflammation by immunohistochemistry and mRNA expression studies. RESULTS Within our study population, NAFLD was significantly associated with greater VAT CD68+ macrophages infiltration (P = .04), fibrosis (P = .04) and impaired microvascular density (P = .03) as well as increased expression of markers of local hypoxia, apoptosis and inflammation (UNC5B, CASP7, HIF1-α, IL-8, MIP2, WISP-1, all P

Background & aims Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide and an independent risk factor for cardiovascular mortality. Angiopoietin-like proteins (ANGPTLs) are targets for vitamin D receptor (VDR)-mediated gene transcription and this axis may promote NAFLD. ANGPTL3 is a hepatokine which inhibits lipoprotein lipase and its experimentally induced inactivation reduces hepatosteatosis. Little is known on ANGPTL3 in human NAFLD and no data exist on its relationship with hepatic VDR/VD-related genes. The aim of this research was to investigate hepatic ANGPTLs and VDR/VD-related gene expression in human obesity in relation to NAFLD. Methods We conducted a cross-sectional investigation on forty obese subjects with/without NAFLD. We evaluated hepatic ANGPTL3, ANGPTL4, ANGPTL8, LPL, VDR, CYP27A1 and CYP2R1 mRNA expression in liver biopsies by RT-PCR; VDR expression was further investigated by immunohistochemistry; circulating ANGPTL3 was measured by Milliplex assay. Results Compared to non-NAFLD, NAFLD individuals had significantly higher hepatic VDR, ANGPTL3 and LPL expression. ANGPTL3 correlated with steatosis grade, LPL, VDR, CYP27A1 and CYP2R1 expression. Plasma ANGPTL3 concentrations were positively associated with clinical/histological markers of NAFLD/NASH and with hepatic ANGPTL3 expression. Greater hepatic VDR expression was the main determinant of hepatic ANGPTL3 after adjusting for multiple confounders. Conclusions Hepatic ANGPTL3 expression correlates with greater VDR expression, presence and severity of NAFLD and translates in increased circulating ANGPTL3, likely as a result of its modulation by up-regulated hepatic VDR in NAFLD. This study provides novel insights to potential mechanisms underlying ANGPTLs-mediated ectopic fat accumulation and NAFLD development in obesity.

Objective ANGPTL4 inhibits lipoprotein lipase in adipose tissue, regulating plasma triglycerides levels. In persons with obesity plasma ANGPTL4 levels have been positively correlated with body fat mass, TG levels and low HDL. A loss-of-function E40K mutation in ANGPTL4 prevents LPL inhibition, resulting in lower TGs and higher HDLc in the general population. Since obesity determines metabolic alterations and consequently is a major risk factor for cardiovascular disease, the aim was to explore if obesity-related metabolic abnormalities are modified by the ANGPTL4-E40K mutation. Methods ANGPTL4-E40K was screened in 1206 Italian participants, of which 863 (71.5%) with obesity. All subjects without diabetes underwent OGTT with calculation of indices of insulin-sensitivity. Results Participants with obesity carrying the E40K variant had significantly lower TG (p = 0.001) and higher HDLc levels (p = 0.024). Also in the whole population low TGs and high HDLc were confirmed in E40K carriers. In the obese subpopulation it was observed that almost all E40K carriers were within the lowest quartile of TGs (p = 1.1 × 10-9). E40K had no substantial effect of on glucose metabolism. Finally, none of the obese E40K carriers had T2D, and together with the favourable lipid profile, they resemble a metabolically healthy obese (MHO) phenotype, compared to 38% of E40E wild-type obese that had diabetes and/or dyslipidaemia (p = 0.0106). Conclusions In participants with obesity the ANGPTL4-E40K variant protects against dyslipidemia. The phenotype of obese E40K carriers is that of a patient with obesity without metabolic alterations, similar to the phenotype described as metabolic healthy obesity.

Vitamin D acts through the binding to the vitamin D receptor (VDR). Several polymorphisms in VDR gene have been studied. Among these, the rs2228570 CT (FokI) variant has been demonstrated to be functional, leading to a protein with a different size and activity. So far, genetic studies on the association between VDR gene rs2228570 single nucleotide polymorphism (SNP) and type 2 diabetes mellitus (T2DM) showed contradictory results. Thus, we performed an association study in a large cohort of adult Italian subjects with T2DM and in nondiabetic controls.For this study, 1713 subjects, 883 T2DM patients and 830 controls, were genotyped for the polymorphism. All participants without a diagnosis of diabetes underwent oral glucose tolerance test (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance (Homeostatic model assessment of insulin resistance, insulin sensitivity index), secretion (homeostatic model assessment for beta-cell, corrected insulin response at 30 minutes) and disposition index were calculated.Genotype distributions and allele frequencies did not show difference between T2DM subjects and controls. We did not find significant differences among the three genotypes regarding gender, age, BMI, waist, hip, waist-to-hip ratio, and blood pressure. There were also no significant differences in lipid parameters, aspartate aminotransferase, and alanine aminotransferase levels. We tested for association with OGTT-derived data and surrogate indices of insulin resistance and secretion. We did not find significant differences among the genotypes in any of above-mentioned parameters. Furthermore, vitamin D levels were measured in a subgroup of subjects. We did not find significant differences among the genotypes.Our study does not provide evidence for the association of the rs2228570 polymorphism with T2DM in a Caucasian population.

A number of meta-analyses have demonstrated the effectiveness of bariatric surgery in improving morbid obesity and its associated co-morbidities. The aim of the study was to evaluate at long term a cohort of obese patients with type 2 diabetes (T2DM) submitted to laparoscopic sleeve gastrectomy (LSG) analyzing the incidence of weight regain (WR) and the impact of the WR on T2DM evolution. Seventy-eight morbid obese patients (54 females) with T2DM, aged 49.6 ± 8.7 years, weight 121.1 ± 24.4 kg, BMI 44.1 ± 7.2 kg/m2, underwent primary LSG. The trend over time of T2DM after LSG was analyzed in the different groups, subdivided on the basis of the absence or presence of WR and of its different degrees: no regain (NR), mild regain (MR), and severe regain (SR) groups. In the NR group, 54% show complete remission, 46% persistence, and no case of diabetes relapse; in the MR group, 59% show complete remission, 36% persistence, and 5% relapse; in the SR group, 61% show complete remission, 22% persistence, and 17% relapse. A statistically significant difference concerns the preoperative values of fasting glucose, glycosylated hemoglobin, and duration of diabetes, major in the group with diabetes relapse (respectively, p = 0.002, p = 0.001, and p

In morbid obesity nonalcoholic fatty liver disease (NAFLD) is endemic. Aim of this study is to evaluate the diagnostic accuracy of the most common noninvasive methods for identify NAFLD and fibrosis in a cohort of morbid obese population. Ninety morbid obese patients undergoing bariatric surgery (BS) and intraoperative liver biopsy were evaluated preoperatively with Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and serum biomarkers for steatosis and fibrosis and liver stiffness measurement (LSM) using acoustic radiation force impulse (ARFI) elastography. All nondiabetic patient (n = 77) underwent OGTT and calculation of Oral Glucose Insulin Sensitivity index (OGIS). In the entire cohort prevalence of NAFLD was 77%, NASH 24%, moderate/severe steatosis 50%, and significant fibrosis 14%. New cut-offs were evaluated for all steatosis score assessed in this population. In all patients with moderate/severe steatosis HOMA IR was significantly greater than 3.5. ALT, GGT, Triglycerides, HOMA IR, and ARFI increased with fibrosis grade (p 0.03, p 0.008, p 0.04, p 0.05, respectively) and AST to Platelet ratio (APRI) was the only noninvasive fibrosis score significantly increased in significant fibrosis (p 0.04). A combination of 1/OGIS and VAI was able to discriminate NASH from simple steatosis (NAFL) (p 0.02). In morbid obese subjects, we calculated new cut-offs of the most common steatosis indexes and found that a score based on insulin resistance (1/OGIS) and abdominal obesity (VAI) could represent a way to identify morbid obese subjects at risk of NASH.

Introduction Copeptin is the stable surrogate marker of vasopressin (VP), which is released in response to elevated plasma osmolality or low blood pressure. Elevated plasma copeptin levels are associated with higher risk of insulin resistance-related disorders, such as type 2 diabetes (T2DM), metabolic syndrome (MS), and cardiovascular disease, and experimental reduction of circulating VP levels is shown to significantly decrease hepatic fat content in obese rats, independently from body adiposity. However, the association between copeptin and non-alcoholic fatty liver disease and steatohepatitis (NAFLD/NASH) in humans has not been explored yet. The aim of this study was to explore the relationship between plasma copeptin and the presence/severity of NAFLD/NASH. Methods For this study, we recruited 60 obese patients candidate to bariatric surgery for clinical purposes in which intraoperative liver biopsies were performed for diagnosing NAFLD/NASH. Circulating copeptin levels were also assessed in 60 age- and sex-comparable non-obese individuals without NAFLD at liver ultrasonography. Plasma copeptin was measured by sandwich immunoluminometric assay (Thermo Fisher Scientific). Results Obese patients with biopsy-proven NAFLD (53%) had significantly higher copeptin levels than both obese individuals without NAFLD and non-obese subjects (ob/NAFLD+ 9.5 ± 4.9; ob/NAFLD− 6.4 ± 2.6; and non-ob/NAFLD− 7.4 ± 5.1 pmol/L; p = 0.004 and p = 0.01 respectively). Plasma copeptin concentration positively correlated with hepatic macro- and micro-vesicular steatosis (r = 0.36, p = 0.026; r = 0.31, p = 0.05), lobular inflammation (r = 0.37, p = 0.024) and significantly increased throughout degrees of NASH severity, as expressed as absence, borderline, and overt NASH at the liver biopsy (r = 0.35, p = 0.01). Greater circulating copeptin predicted the presence of NASH with OR = 1.73 (95% CI = 1.02–2.93) after multivariate adjustment for age, sex, renal function and presence of T2DM and MS components. Conclusions Increased plasma copeptin is independently associated with the presence and severity of NAFLD and NASH, pointing to a novel mechanism behind human fatty liver disease potentially modifiable by pharmacological treatment and lifestyle intervention. Electronic supplementary material The online version of this article (10.1186/s12916-019-1319-4) contains supplementary material, which is available to authorized users.

Biliverdin reductase-A (BVR-A) is a serine/threonine/tyrosine kinase involved in the regulation of insulin signaling. In vitro studies have demonstrated that BVR-A is a substrate of the insulin receptor and regulates IRS1 by avoiding its aberrant activation, and in animal model of obesity the loss of hepatic BVR-A has been associated with glucose/insulin alterations and fatty liver disease. However, no studies exist in humans. Here, we evaluated BVR-A expression levels and activation in peripheral blood mononuclear cells (PBMC) from obese subjects and matched lean controls and we investigated the related molecular alterations of the insulin along with clinical correlates. We showed that BVR-A levels are significantly reduced in obese subjects and associated with a hyper-activation of the IR/IRS1/Akt/GSK-3β/AS160/GLUT4 pathway. Low BVR-A levels also associate with the presence of obesity, metabolic syndrome, NASH and visceral adipose tissue inflammation. These data suggest that the reduction of BVR-A may be responsible for early alterations of the insulin signaling pathway in obesity and in this context may represent a novel molecular target to be investigated for the comprehension of the process of insulin resistance development in obesity.

Background and aims 1α,25-dihydroxyvitamin-D3, the biologically active vitamin D, plays a central role in several metabolic pathways through the binding to the vitamin D receptor (VDR). VDR has been shown to be involved in cardiovascular diseases, cancer, autoimmunity and type 2 diabetes mellitus (T2DM). Several polymorphisms in the VDR gene have been described. Among these, the rs11568820 G-to-A nucleotide substitution was found to be functional, modulating the transcription of the VDR gene. Objective of this study was to perform an association study between rs11568820 polymorphism and T2DM in a cohort of Italian adults with T2DM and in non-diabetic controls. To add further insight into the role of VDR gene we explored whether this association begins early in life in overweight/obese children, or becomes manifest only in adulthood. Methods and results As many as 1788 adults and 878 children were genotyped for the rs11568820 polymorphism. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin-resistance and secretion were also calculated. The AA genotype was significantly more frequent in adults with T2DM compared to controls (7.5% vs. 4.6%, P = 0.037), and conferred a higher risk of T2DM (OR Hom = 1.69C.I. = [1.13–2.53], P = 0.011). In the adult cohort, rs11568820 was also associated with reduced indices of β-cell insulin secretion. In children, the AA genotype was associated with 2 h high-normal glucose, a marker of cardio-metabolic risk. Conclusions Our study demonstrates for the first time that VDR gene AA carriers have higher risk of T2DM and impaired insulin secretion. In children, the association between AA homozygous and high-normal 2h glucose suggests that mild alterations associated with this genotype may appear early in life.

Neurotensin (NT) is a 13-amino acid peptide localized in the neuroendocrine cells of the small intestine, which promotes fat absorption and fatty acids translocation in response to lipid ingestion. NT-knock-out mice fed with a high-fat diet are protected from obesity, fatty liver, and the development of insulin-resistance. In humans, higher plasma levels of pro-NT, which is the stable circulating precursor of NT, predict obesity, type 2 diabetes (T2D), and cardiovascular disease. In obesity, the presence of visceral adipose tissue (VAT) inflammation leads to unfavorable metabolic outcomes and is associated with the development of T2D and non-alcoholic fatty liver disease (NAFLD). In this study, we investigated the relationship between plasma pro-NT levels and the presence of VAT inflammation in biopsies from 40 morbidly obese subjects undergoing bariatric surgery. We demonstrated that higher proNT levels are significantly associated with greater macrophages infiltration, HIF-1α, WISP-1, and UNC5B expression in VAT (all p < 0.01) due to the diagnosis of T2D and NAFLD. The overall results show that, in obesity, pro-NT is a biomarker of VAT inflammation and insulin-resistance. Additionally, NT may be involved in the development of dysmetabolic conditions likely mediated by increased gut fat absorption and the presence of a proinflammatory milieu in the adipose tissue.

Background Recently, significant attention has been paid to the possible activation of an autoimmune response in the presence of obesity. The aim of this study was to evaluate and compare the frequencies of autoantibodies typical of autoimmune diabetes in obese patients with normal glucose tolerance (NGT), obese patients with type 2 diabetes (T2D) and controls. We also evaluated the presence of immunoreactivity to Hashimoto's thyroiditis and autoimmune gastritis. Materials and methods Consecutive sera from obese patients, 444 with NGT, 322 with T2D, and 212 controls were analysed by radioimmunoassay or enzyme-linked immunosorbent assay for glutamic acid decarboxylase, protein tyrosine phosphatase islet antigen-2 (IA-2)IC and IA-2(256-760) , islet beta-cell zinc cation transporter (ZnT8), thyroid peroxidase, and anti-parietal cell autoantibodies. Results Altogether the presence of organ-specific autoantibodies was significantly more frequent in obese patients with NGT (128/444, 28.5%) and obese with T2D (79/322, 24.5%) than in controls (36/212, 17%; P = 0.002). Thyroid peroxidase immunoreactivity was prevalent in all groups of subjects investigated. The frequencies of diabetes-specific autoantibodies were slightly higher in obese patients with NGT (20/444, 4.5%) than in obese with T2D (12/322, 3.7%) and controls (4/212, 1.9%). The anti IA-2(256-760) was the most frequent islet autoantibody in obese subjects with NGT (14/20, 70%). Conclusions We observed significant evidence of immunoreactivity specific to diabetes, thyroid, and gastric-parietal cells in obese patients with NGT. The relatively higher frequency of the diabetes-related IA-2(256-760) autoantibodies in obese patients with NGT may suggest that this autoantibody could be associated with obesity the presence of obesity itself.

Obesity is one of the major health challenges throughout the world. The association between obesity and diabetes is well established because 90% of patients with type 2 diabetes mellitus (T2DM) show excess body weight. The aim of the study was to evaluate the effect of laparoscopic sleeve gastrectomy (LSG) on morbid obesity and type 2 diabetes (T2DM) in the long-term follow-up. One hundred ninety-five obese patients, 78 with T2DM, were evaluated before and after LSG up to 10 years, to identify complete diabetes remission (FPG 5 years) follow-up respectively. Furthermore, 45.2% maintained complete remission for at least 5 years and about 36% showed a persistent but improved diabetes. None of the patients cured from diabetes had a duration disease greater than 8 years and a glycemic control requiring insulin. The prevalence of hypertension and dyslipidemia significantly decreased from 49 to 35% and from 51 to 40% respectively. LSG significantly improves body weight, diabetes, hypertension, and dyslipidemia in long-term follow-up.

Background Perilipin 2 (PLIN2), a member of the family of perilipin lipid droplets coating proteins, is very widely expressed. The Ser251Pro (rs35568725) missense mutation in exon 6 of PLIN2 gene was previously associated with increased lipid accumulation, decreased lipolysis and increased number of small lipid droplets per cell. Furthermore, the Pro251 mutation was associated with decreased plasma triglyceride and very low density lipoprotein concentrations in population studies. The aim of this study was to evaluate the effect of the Ser251Pro mutation of PLIN2 gene in a cohort with a higher predisposition to obesity-associated metabolic alterations, such as insulin resistance, decreased insulin-secretion, hyperglycaemia, and dyslipidaemia. Methods A large cohort (N = 1692) of Italian obese subjects (mean body mass index = 41 kg/m2) was genotyped for the Ser251Pro mutation. All participants underwent oral glucose tolerance tests (OGTT), with measurement of glucose and insulin levels. Indices of insulin resistance and of insulin secretion were also calculated. Clinical and biochemical parameters were collected for all participants. Results We observed that insulin concentration was significantly reduced at 120 min after the administration of glucose in Pro251 allele carriers, whereas glucose levels were similar in Pro251 allele carriers and non-carriers throughout the OGTT. Furthermore, the CIR120 index of insulin secretion was significantly lower (P

Context Neurotensin (NT), an intestinal peptide released by fat ingestion, promotes lipid absorption; higher circulating NT levels are associated with type 2 diabetes (T2D), obesity, and cardiovascular disease. Whether NT is related to nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) has not been fully investigated. Objective To study the relationship between plasma proneurotensin 1 to 117 (pro-NT), a stable fragment of the NT precursor hormone, and the presence/severity of NAFLD/NASH and to unravel correlates of increased pro-NT levels. Design/Setting/Participants For this cross-sectional study, 60 obese individuals undergoing bariatric surgery for clinical purposes were recruited. The association between pro-NT and NAFLD was further investigated in 260 consecutive subjects referred to our outpatient clinics for metabolic evaluations, including liver ultrasonography. The study population underwent complete metabolic characterization; in the obese cohort, liver biopsies were performed during surgery. Main Outcome Measures Plasma pro-NT levels in relation to NAFLD/NASH. Results Obese subjects with biopsy-proven NAFLD (53%) had significantly higher plasma pro-NT than those without NAFLD (183.6 ± 81.4 vs 86.7 ± 56.8 pmol/L, P < 0.001). Greater pro-NT correlated with NAFLD presence (P < 0.001) and severity (P < 0.001), age, female sex, insulin resistance, and T2D. Higher pro-NT predicted NAFLD with an area under receiver operating characteristic curve of 0.836 [95% confidence interval (CI), 0.73 to 0.94; P < 0.001]. Belonging to the highest pro-NT quartile correlated with increased NAFLD risk (odds ratio, 2.62; 95% CI, 1.08 to 6.40) after adjustment for confounders. The association between higher pro-NT and NAFLD was confirmed in the second cohort independently from confounders. Conclusions Increased plasma pro-NT levels identify the presence/severity of NAFLD; in dysmetabolic individuals, NT may specifically promote hepatic fat accumulation through mechanisms likely related to increased insulin resistance.

Context: Wnt1-inducible signaling pathway protein 1 (WISP1) is a novel adipokine participating in adipose tissue (AT) dysfunction; so far, no data on WISP1 in diabetes are available. Objectives: To evaluate plasma WISP1 in subjects with type 2 diabetes (T2D) and its correlates linked to AT inflammation. Design and Participants: For this cross-sectional study, 97 consecutive dysmetabolic patients were recruited at the diabetes outpatient clinics of Sapienza University in Rome; 71 of them had T2D, with (n = 35) or without (n = 36) obesity, and 26 were obese patients without diabetes. Twenty-one normal-weight nondiabetic individuals were enrolled as a control group. Study participants underwent clinical workup and blood sampling for metabolic/inflammatory characterization; magnetic resonance imaging (MRI) data on subcutaneous AT and visceral AT (VAT) area, hepatic fat content, and VAT homogeneity were available for most diabetic patients. Results: Plasma WISP1 significantly increased throughout classes of obesity and correlated with greater VAT area, interleukin-8 (IL-8), and lower adiponectin levels, without differing between diabetic and nondiabetic participants. Higher IL-8 was the main determinant of increased WISP1. MRI-assessed VAT inhomogeneity was associated with higher WISP1, IL-8 and C-reactive protein levels, independent of obesity; high WISP1 strongly predicted VAT inhomogeneity (P < 0.001). Conclusions: WISP1 levels are increased in obese persons and are directly related to adiposity, independent of glycemic status or insulin resistance; moreover, they are strongly associated with increased plasma IL-8 and signal abnormalities of VAT. The overall data add insights to the mechanisms underlying metabolic alterations and may open a scenario for innovative therapeutic approaches for diabetes prevention and care., This study of plasma Wnt1-inducible signaling pathway protein 1 (WISP1) in dysmetabolic patients and controls found that higher WISP1 levels strongly correlated with obesity and adipose tissue dysfunction, independent of diabetes.

Background: The aim of this study was to evaluate the long-term effects of laparoscopic sleeve gastrectomy (LSG) on type 2 diabetes mellitus (T2DM) and other related co-morbidities in severely obese patients. Methods: From May 2003 to July 2008, 33 morbidly obese diabetic patients (20 with body mass index [BMI] 450 kg/m 2 ) underwent LSG. A total of 23 females and 10 males participated, with a mean age of 49.3 8 years, mean preoperative BMI of 52.1 8.5 kg/m 2 , mean fasting plasma glucose (FPG) of 143.2 47.9 mg/dL, mean glycosylated hemoglobin (HbA1c) of 7.3% 1.4%, and a mean T2DM duration of 7 years. All patients had a 36-month follow-up, and 13 had a 60month follow-up. Results: Twenty-nine patients (87.8%) discontinued antidiabetic medications 3 months after LSG, (mean BMI of 42.8 7.8 kg/m 2 ; FPG of 104.5 22.1 mg/dL; HbA1c of 5.3% .4%). At 36 months, 22 of 26 LSG patients (84.6%) had normal FPG and HbA1c values without antidiabetic therapy. At the 60-month follow-up, 10 of 13 patients (76.9%) had normal FPG and HbA1c values without antidiabetic therapy. The Framingham risk score decreased significantly from 9.7% preoperatively to 4.7% postoperatively. No new diabetic retinopathy occurred during the whole period of observation. Conclusions: This study confirms the efficacy of LSG in the treatment of T2DM and indicates that, at both 36- and 60-month follow-ups, LSG can provide a significant percentage of treated patients with a prolonged remission of T2DM, with diminished cardiac risk factors and no development of diabetic retinopathy. These results compare favorably with those reported after standard medical therapy. (Surg Obes Relat Dis 2013;9:498–502.) r 2013 American Society for Metabolic and Bariatric Surgery. All rights reserved.

Apelin is a peptide produced and secreted by white adipose tissue. It is synthesized as preproapelin, a protein containing 77 aminoacids which is then cleaved to shorter active fragments. As an adipokine, apelin plays a role in the regulation of many biological functions, including body energy homeostasis and glucose metabolism, water balance, and immunity. We have recently demonstrated that subjects with type 2 diabetes (T2D) have significantly higher serum apelin levels compared with controls, and that these levels associate with fasting glucose, basal disposition index, age, and diagnosis of T2D. The first aim of this study was to search for sequence variants in the apelin gene (APLN), located on chromosome Xq25-q26.1 that may associate with serum levels of apelin. The second aim was to analyze the possible association between diabetes and diabetes-related traits and APLN variants.We designed a two-step genetic association study. Step one consisted of an initial screen of 100 individuals selected from the extremes of the apelin distribution levels wherein we sequenced the APLN gene to identify common variants. In step two, the rs181301686 with a minor allele frequency0.2 was genotyped in 917 individuals to explore its association with T2D and diabetes-related traits.Five sequence variations were found across the APLN gene. To test for association with apelin levels, the rs181301686 and rs2281069 single-nucleotide polymorphisms were genotyped in 256 subjects for whom serum apelin levels were available. No significant differences were observed in apelin levels between genotypes. Association analysis in 917 individuals did not show significant differences between APLN genotypes and diabetes and diabetes-related traits.Resequencing of the apelin gene in subjects stratified by low or high apelin levels identified five APLN variants in an European population. No association was found between the most frequent variant, diabetes, and metabolic parameters.

AIM To evaluate whether obesity represents a risk factor for the onset of ovarian cancer. PATIENTS AND METHODS One hundred and sixty-three patients with a body mass index (BMI) >30 kg/m2 (group 1) and 130 women with a BMI of 13%) was found in 24.5% of group 1 patients, whereas a high ROMA score was identified in 5.3% of group 2 women. During the study, 13 out of 40 group 1 patients with ROMA >13% were deemed eligible for bariatric surgery. After bariatric surgery and decrease of BMI, eight out of these 13 obese women had a ROMA index

Background and aims The rate of mortality in diabetic patients, especially of cardiovascular origin, is about twice as much that of nondiabetic individuals. Thus, the pathogenic factors shaping the risk of mortality in such patients must be unraveled in order to target intensive prevention and treatment strategies. The "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes" is aimed at identifying new molecular promoters of mortality and major vascular events in patients with type 2 diabetes mellitus (T2DM). Methods/design The "SUMMER study in diabetes" is an observational, prospective, and collaborative study conducted on at least 5000 consecutive patients with T2DM, recruited from several diabetes clinics of Central–Southern Italy and followed up for a minimum of 5 years. The primary outcome is all-cause mortality; the secondary outcomes are cardiovascular mortality, acute myocardial infarction, stroke, and dialysis. A biobank will be created for genomic, transcriptomic, and metabolomic analysis, in order to unravel new molecular predictors of mortality and vascular morbidity. Discussion The "SUMMER study in diabetes" is aimed at identifying new molecular promoters of mortality and major vascular events in patients with T2DM. These novel pathogenic factors will most likely be instrumental in unraveling new pathways underlying such dramatic events. In addition, they will also be used as additional markers to increase the performance of the already existing risk-scoring models for predicting the above-mentioned outcomes in T2DM, as well as for setting up new preventive and treatment strategies, possibly tailored to specific pathogenic backgrounds. Trial registration ClinicalTrials.gov, NCT02311244; URL https://clinicaltrials.gov/ct2/show/NCT02311244?term=SUMMER&rank=5.

Background. Laparoscopic gastric sleeve (LGS) has been recently introduced as a stand-alone, restrictive bariatric surgery. Theoretically, LGS attenuates micronutrients deficiencies and associated complications that were typically observed following malabsorptive procedures. The aim of this study was to assess some micronutrients and mineral deficiencies in patients undergoing LGS. Methods. In the period between July 2008 and April 2010, 138 obese patients (110 females and 28 males) with mean BMI 44.4 kg/m2 ± 6.5, mean age 4 3 . 9 ± 1 0 . 9 years were enrolled and underwent LGS. Patients were followed up with routine laboratory tests and anthropometric measurements and assessed for nutritional status, as regards vitamin B12, folic acid, iron, hemoglobin, calcium, and vitamin D, every three months throughout 12 months. Results. 12 months after sleeve, patients did not show iron deficiency and/or anemia; plasma calcium levels were in the normal range without supplementation from the sixth month after the operation. Vitamin B12 and folic acid were adequately supplemented for all the follow-up period. Vitamin D was in suboptimal levels, despite daily multivitamin supplementation. Conclusion. In this study, we showed that LGS is an effective surgery for the management of morbid obesity. An adequate supplementation is important to avoid micronutrients deficiencies and greater weight loss does not require higher dosage of multivitamins.

Le ipoglicemie funzionali possono costituire un primo passo verso la malattia diabetica oppure essere una conseguenza di un intervento chirurgico sul tratto gastrointestinale superiore. Nell’ambito di quest’ultima categoria, accanto agli interventi di gastrectomia che in passato venivano fatti, spesso in urgenza, per la presenza di una patologia ulcerosa, si sta delineando una forma di ipoglicemia associata ad alcuni interventi di chirurgia bariatrica, effettuati per favorire la perdita di peso in pazienti obesi. Al di la di queste condizioni rimangono le forme cosiddette “reattive idiopatiche” che costituiscono un’alterazione del ricambio glucidico controversa. Alcuni studiosi, infatti, arrivano addirittura a negarne l’esistenza, quando e noto che nella comune pratica clinica spesso i pazienti ci riferiscono una sintomatologia suggestiva per la presenza di ipoglicemia in particolare a meta mattina, piu o meno a distanza di 3–4 ore dalla prima colazione. Tuttavia, l’ipoglicemia e spesso un’autodiagnosi, intendendo con questo che spesso il paziente si reca dal medico accusando una mancanza di zuccheri e di sentirsi immediatamente meglio assumendo qualcosa di dolce. Addirittura si possono trovare articoli sulle riviste non mediche che confortano le persone e aiutano a fortificare la convinzione di andare spesso in ipoglicemia. Va da se che il rimedio a questa autodiagnosi e normalmente molto ben accetto dalle persone che si sentono “costrette” ad assumere quando stanno male bibite zuccherate se non proprio caramelle, cioccolatini e altri dolci. Questo atteggiamento contrasta totalmente con le prescrizioni del medico che, laddove ravvisi veramente la presenza di una sindrome ipoglicemica funzionale, dovra prescrivere proprio l’abolizione di carboidrati raffinati nella dieta e in questo articolo cercheremo di capirne il perche.

We evaluated the effectiveness of a sequential diet regimen termed the obese preoperative diet (OPOD) in morbidly obese patients with and without type 2 diabetes mellitus (T2DM) scheduled for laparoscopic bariatric surgery. Fifty patients (body mass index 53.5 ± 8.4 kg/m2) scheduled for bariatric surgery, including 14 with T2DM, were prospectively enrolled and followed the OPOD regimen: a very low-calorie ketogenic diet for 10 days, followed by a very low-calorie diet for 10 days, and then a low-calorie diet for 10 days. Patients were evaluated at baseline (T0) and after 10 days (T1), 20 days (T2), and 30 days (T3). Body weight, body mass index, waist circumference, and neck circumference were significantly lower at T1, T2, and T3 than at T0 in the 48 patients who completed the OPOD. Two patients discontinued the OPOD after 4–7 days. In patients with T2DM, fasting plasma glucose levels decreased significantly, enabling reduction of diabetic medications. Plasma and urine ketone levels increased at T1 but were all

The study was carried out on type 2 diabetic obese patients who underwent laparoscopic sleeve gastrectomy (LSG). Patients underwent regular glycemic controls throughout 3 years and all patients were defined cured from diabetes according to conventional criteria defined as normalization of fasting glucose levels and glycated hemoglobin in absence of antidiabetic therapy. After 3 years of follow-up, Continuous Glucose Monitoring (CGM) was performed in each patient to better clarify the remission of diabetes. In this study, we found that the diabetes resolution after LSG occurred in 40% of patients; in the other 60%, even if they showed a normal fasting glycemia and A1c, patients spent a lot of time in hyperglycemia. During the oral glucose tolerance test (OGTT), we found that 2 h postload glucose determinations revealed overt diabetes only in a small group of patients and might be insufficient to exclude the diagnosis of diabetes in the other patients who spent a lot of time in hyperglycemia, even if they showed a normal glycemia (

BACKGROUND: Metabolic syndrome (MS) and hypovitaminosis D represent two of the most diffuse condition worldwide, reaching pandemic proportions in industrialized countries, and are both strongly associated with obesity. This study set out to evaluate the presence of an independent association between hypovitaminosis D and MS in an adult population of obese subjects with/without MS. METHODS: We recruited 107 consecutive obese subjects, 61 with MS (age(mean±SD) 45.3±13.3 years, BMI(mean±SD): 43.1±8.3 kg/m(2)) and 46 without MS (age: 41.8±11.5, p = n.s., BMI:41.6±6.5 kg/m(2), p = n.s.) comparable for sex, BMI, waist circumference and body fat mass, evaluated by bioimpedentiometry. 25(OH) vitamin D3 levels were measured by colorimetric method. Insulin resistance was estimated by fasting blood insulin, HOMA-IR and ISI. RESULTS: Serum 25(OH)D3 levels were significantly lower in MS obese patients than in obese subjects without MS (median(range) 13.5(3.3-32) vs 17.4(5.1-37.4), p

Objective To compare the effect of sleeve gastrectomy vs medical therapy on type 2 diabetes mellitus and other obesity-related comorbidities (obstructive sleep apnea syndrome, hypertension, and dyslipidemia) in prospectively enrolled and matched obese patients with type 2 diabetes. Design A prospective cohort study. Morbidly obese patients with type 2 diabetes who either underwent sleeve gastrectomy or conventional therapy were followed up and assessed for their diabetic state and other comorbidities every 3 months for 18 months. Setting Centre for the Surgical-Medical Treatment of Morbid Obesity, Policlinico “Umberto I,” University of Rome “Sapienza,” Italy. Patients A total of 30 morbidly obese patients with type 2 diabetes who underwent sleeve gastrectomy (group A) and a total of 30 morbidly obese patients with type 2 diabetes who underwent conventional therapy (group B). Results In group A, the preoperative mean (SD) body mass index, fasting plasma glucose level, and hemoglobin A 1c level were 41.3 (6.0), 166.6 (68.1) mg/dL, and 7.9% (2.1%), respectively, and, at 18 months, these values were 28.3 (5.4), 96.2 (29.4) mg/dL, and 6.0% (1.5%), respectively. For 80% of patients, diabetes was resolved. With regard to other comorbidities, the prevalence of obstructive sleep apnea syndrome dropped from 50% to 10%, and patients reduced significantly their use of medication for hypertension and dyslipidemia. In group B, the preoperative mean (SD) body mass index, fasting plasma glucose level, and hemoglobin A 1c level were 39.0 (5.5), 183.7 (63.5) mg/dL, and 8.1% (1.7%), respectively, and, at 18 months, these values were 39.8 (5.0), 150 (48) mg/dL, and 7.1% (1.3%), respectively. All patients remained diabetic and continued or increased their level of hypoglycemic therapy. With regard to other comorbidities, we observed an increase in the use of medication for hypertension and dyslipidemia, and the prevalence of obstructive sleep apnea syndrome did not change. Conclusions This study confirms the efficacy of sleeve gastrectomy in the treatment of morbidly obese type 2 diabetic patients when compared with conventional medical treatment.

Obesity is recognized as a major health problem worldwide. Genetic factors play a major role in obesity, and genomewide association studies have provided evidence that several common variants within the fat mass- and obesity-associated (FTO) gene are significantly associated with obesity. Very limited data is available onFTOin the Italian population. Aims of our study are to investigate: (1) the association ofFTOgene SNPs rs9939609 and rs9930506 with body mass index (BMI) and obesity-related parameters in a large cohort (n=752) of Italian obese subjects; (2) the association between the twoFTOSNPs and age of onset of obesity. Our results demonstrate a strong association betweenFTOSNPs rs9939609 (P<0.043) and rs9930506 (P<0.029) with BMI in the Italian population.FTOrs9930506 was significantly associated with higher BMI in a G allele dose-dependent manner (BMI+1.4 kg/m2per G allele). We also observed that the association with BMI of the twoFTOvariants varied with age, with the carriers of the risk alleles developing an increase in body weight earlier in life. In conclusion, our study further demonstrates a role of the genetic variability inFTOon BMI in a large Italian population.

Background Type 2 diabetes mellitus (T2DM) and obesity are diseases of epidemic proportions. Long-term realistic weight loss by nonsurgical methods has a variable effect on glycemic control, and only a proportion of patients with T2DM have a worthwhile response. Laparoscopic sleeve gastrectomy (LSG) has been proposed as an advantageous bariatric procedure for patients with a lower body mass index (BMI). Our objective was to compare the effects of LSG and medical therapy on patients with T2DM and a BMI of 2 . Methods A total of 18 nonmorbidly obese patients with T2DM, diagnosed according to the American Diabetes Association guidelines, were consecutively enrolled. Of these patients, 9 underwent LSG (group A) and 9 underwent conventional medical therapy (group B). The 2 groups were matched for BMI, glycated hemoglobin (HbA1c) and C-peptide levels, pretrial therapy type, and number of patients with a T2DM duration of >10 years. Results In group A, T2DM resolution was achieved in 8 (88.8%) of the 9 patients (T2DM duration 5.2 yr). Hypertension was controlled in all 8 of 9 patients. Dyslipidemia was corrected. In 1 patient, obstructive sleep apnea syndrome improved. In group B, all 9 patients continued to have T2DM and required hypertensive and hypolipemic therapies throughout the observation period. At baseline, 3 patients were affected by obstructive sleep apnea syndrome and remained affected 1 year later. Conclusion The results of the present study have confirmed the efficacy of LSG in the treatment of nonmorbidly obese T2DM patients, with a remission rate of 88.8% without undesirable excessive weight loss. The results in this group of patients add to those obtained by us in patients with a BMI >35 kg/m 2 .

Several studies have demonstrated a high rate of type 2 diabetes mellitus (T2DM) resolution after sleeve gastrectomy. Different prognostic factors have been hypothesized for T2DM remission after bariatric surgery. Our objectives were to analyze the role of T2DM duration as an independent prognostic factor for remission.From January 2008 to September 2010, 56 obese patients with T2DM underwent sleeve gastrectomy. Group A consisted of 16 patients who had lived with T2DM for10 years (12 women and 4 men, mean body mass index 42.7 kg/m2). Group B included 40 obese patients who had lived with T2DM for10 years (29 women and 11 men, mean body mass index 44.9 kg/m2).In group A, 43.7% were treated with oral hypoglycemics, 6.3% with insulin, and 50% with oral hypoglycemics and insulin. In group B, 87.5% were treated with oral hypoglycemics, 5% with dietary therapy, and 7.5% with insulin. The preoperative average glycemia, glycosylated hemoglobin, and C-peptide value was 206.2 mg/dL, 9.5%, and 2.8 μg/L in group A and 134 mg/dL, 7.1%, and 4.5 μg/L in group B, respectively (P.05 for all). The T2DM remission rate in all 56 patients was 80.3%. However, in group B, the resolution rate was 100%, but in group A, the resolution rate was 31%. Patients without complete remission were more sensitive to lower doses of antidiabetic drugs.Sleeve gastrectomy is effective in the treatment of obese patients with T2DM. The duration of T2DM seems to be of paramount importance as a prognostic factor, with 10 years representing a cutoff between a 100% rate of remission and significantly lower rates of remission.

Background This study aimed to compare the efficacy of laparoscopic sleeve gastrectomy (SG) with that of laparoscopic gastric bypass (GBP) and laparoscopic adjustable gastric banding (AGB) for glucose homeostasis in morbidly obese subjects with type 2 diabetes mellitus (T2DM) at a 3-year follow-up assessment and to elucidate the role of weight loss in the T2DM resolution after SG. Methods For this study, 60 morbidly obese T2DM patients (44 females and 16 males) who underwent AGB (24 patients), GBP (16 patients), or SG (20 patients) between 1996 and 2008 were retrospectively analyzed. Age, sex, body mass index (BMI), estimated weight loss (EWL), fasting glycemia, HbA1c, euglycemic hyperinsulinemic clamp, discontinuation of diabetes treatment, and time until interruption of therapy were evaluated. Results In the study, 54 patients received oral hypoglycemic agents for at least 12 months before surgery, and 6 patients received insulin. The mean follow-up period was 36 months. The resolution rate was 60.8% for the AGB patients, 81.2% for the GBP patients, and 80.9% for the SG patients. The postoperative time until interruption of therapy was 12.6 months for the AGB patients, 3.2 months for the GBP patients, and 3.3 months for the SG patients. The hyperinsulinemic euglycemic clamp test was performed 12 months after surgery for the cured patients. Insulin resistance was restored to normal values in all the patients. The greatest improvement from preoperative values occurred in the SG group. For the not-cured GBP and SG patients, an improvement of 120 mg/dl in fasting plasma glucose was observed 3 months after the surgery, suggesting an enhancement in insulin sensitivity, which determines better medical control. The resolution rate remained constant at the 36-month follow-up evaluation in both the GBP and SG groups. Conclusions All three bariatric procedures are effective in treating diabetes, with a 3-year follow-up evaluation showing an effect that lasts. The AGB procedure was the least effective. The antidiabetic effect was similarly precocious after GBP and SG compared with AGB. This difference may indicate that a hormonal mechanism may be involved, independent of weight loss.

The PNPLA3 I148M variant (rs738409) is robustly associated with hepatic steatosis. Intriguingly, initial findings in cohorts with a mean body mass index (BMI) of 30 kg m(-2) also suggested that it is associated with elevated liver enzymes but not with insulin resistance and dyslipidaemia.To determine whether the PNPLA3 variant alters the susceptibility of morbidly obese subjects to develop liver injury and metabolic sequelae.The study was carried out in 678 obese Italians (mean BMI = 41 kg m(-2)) who were genotyped for the I148M variant. All participants provided fasting blood samples and then underwent oral glucose tolerance tests.Indices of liver injury (alanine transaminase (ALT), aspartate transaminase (AST)), glucose tolerance and insulin resistance were measured.Markers of hepatic injury such as ALT and AST were significantly higher in carriers of the 148M allele (P = 2.2 x 10(-5) and 0.001, respectively). In all, 50% of 148M risk allele homozygotes had pathological levels of ALT (40 U l(-1)) compared with 25% of 148I allele homozygotes (P = 0.005). Glucose tolerance and insulin sensitivity were similar in all three genotypes.Obese Southern Europeans carrying the 148M allele have increased indices of liver damage uncoupled from proxy measures of insulin resistance.

Background The influence of gastritis patterns in Helicobacter pylori eradication rates has been poorly investigated. Aims To compare the efficacy of bismuth or proton pump inhibitors triple therapy for H. pylori eradication in pangastritis. Patients and methods One hundred and eight patients with pangastritis were assigned to either lansoprazole 30 mg once a day ( n = 54) or bismuth 240 mg bis in die ( n = 54) for 14 days combined, for the first week, with amoxicillin 1 g plus metronidazole 250 mg tris in die . Eradication was confirmed by 13 C-urea breath test. Results With bismuth, successful eradication was observed in 75.9% (41/54) in the intention-to-treat analysis and 78.8% (41/52) in the per-protocol analysis. With lansoprazole, the eradication rates were respectively 46.3% (25/54) and 51.0% (25/49). Bismuth had a significant higher efficacy according to both intention-to-treat analysis ( p = 0.0029) and per-protocol analysis ( p = 0.0038) with OR of 3.66 (95% CI: 1.61–8.32) and 3.58 (95% CI: 1.50–8.54) respectively. At regression analysis, the only independent variable affecting eradication was the type of regimen ( p = 0.026) with an OR of 3.31 (95% CI: 1.16–9.44). Conclusions In pangastritis patients, bismuth is more effective than PPI in first-line eradication. For improving the overall eradication rates, an evaluation of gastritis extent might need to be considered.

Bariatric surgeons often advocate preoperative Helicobacter pylori (H. pylori) testing and eradication because of the increased risk of postoperative ulcers and foregut symptoms in H. pylori-positive patients. The aim of this pilot study was to evaluate whether body mass index (BMI) might influence the success rate of eradication. Eighty one nondiabetic naive H. pylori-positive patients were divided into two groups according to their BMI, with 41 in the control group (normal BMI) and 40 in the overweight/obese group (BMI ≥25). Gastroscopy was performed and multiple biopsies were obtained from the antrum and corpus. Both groups were given a triple therapy consisting of pantoprazole 40 mg for 2 weeks plus amoxicillin 1 g tris in die (t.i.d), and clarithromycin 250 mg t.i.d, for the first week of treatment. Eradication was confirmed by the 13C-urea breath test at 3 months. Successful eradication was observed in 55.0% of the overweight/obese group compared with 85.4% [p