Blood glucose and epicardial adipose tissue at the hospital admission as possible predictors for COVID-19 severity.

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: Two hundred and twenty-nine patients consecutively hospitalized for COVID-19 from March 1st to June 30th 2020 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 < 0.001] and it was positively correlated with glycemia, PCR, fibrinogen, P/F ratio. In the multivariable logistic regression analysis, age and EAT volume were independently associated with ARDS/death. Glycemia and EAT attenuation would appear to be factors involved in ARDS/death with a trend of statistical significance. CONCLUSIONS: Our findings suggest that both blood glucose and EAT, easily measurable and modifiable targets, could be important predisposing factors for severe Covid-19 complications.

Weight Regain and Diabetes Evolution After Sleeve Gastrectomy: a Cohort Study with over 5 Years of Follow-Up.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.0001). CONCLUSIONS: The results of this study showed no significant difference regarding the trend of diabetes remission comparing the "no regain," "mild regain," and "severe regain" groups and confirmed the importance of the duration of the illness and an early intervention towards surgical therapy.

ANGPTL4 gene E40K variation protects against obesity-associated dyslipidemia in participants with 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.

The vitamin D receptor (VDR) gene rs11568820 variant is associated with type 2 diabetes and impaired insulin secretion in Italian adult subjects, and associates with increased cardio-metabolic risk in children.

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 (ORHom = 1.69C.I. = [1.13-2.53], P = 0.011). In the adult cohort, rs11568820 was also associated with reduced indices of ß-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.

Assessing the association between 25-OH vitamin D levels and ROMA score in a population of obese women.

The “Risk of Malignancy Algorithm” (ROMA) combines the diagnostic power of the CA125 and HE4 markers with menopausal status to predict the risk for developing epithelial ovarian cancer (EOC). The aim of this study was to evaluate the association between 25-OH vitamin D levels and ROMA score in obese women. One hundred and eighteen patients with a Body Mass Index (BMI) > 30 kg/m2 (Group 1) and 80 women with a BMI less than 25 kg / m² (Group 2) were studied. The 25-OH vitamin D was quantified with LUMIPULSE® G 1200. As a threshold value, identified by ROC curve analysis, 20.2 ng/ mL (sensitivity 73.3%, specificity 84%) was chosen corresponding to the limit between sufficient and insufficient 25-OH vitamin D according to the World Health Organization (WHO). Low 25-OH vitamin D levels were observed in 64% of obese women and in 11% of normal-weight women (p less than 0.001). ROMA score above 13% was detected only in obese women (19%). An association between low levels of 25-OH vitamin D and ROMA score was observed. Indeed, 64% of obese women with ROMA score >13% had concomitant insufficient levels of 25-OH vitamin D, while only 36% of obese women with ROMA score >13% had sufficient 25-OH vitamin D levels (p less than 0.0001). This study suggests that the deficiency of 25- OH vitamin D in obese women has a possible correlation with high ROMA score.

The "Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes": Study protocol.

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.

Axis II disorders, body image and childhood abuse in bariatric surgery candidates.

BACKGROUND AND AIMS: Psychiatric disorders are common in obese patients and they are often considered contraindications for bariatric surgery. In this patients Axis I profile has been widely investigated, while only few studies on Axis II profile are reported. Aim of the study was to examine the prevalence of Axis II psychopathology, to describe the typical body image and to evaluate the prevalence of childhood abuse in bariatric surgery candidates. MATERIALS AND METHODS: A total of 102 consecutive obese patients (77 females) were evaluated by the Structured Clinical Interview for DSM IV which assessed Axis I Disorders. After the exclusion of Axis I Disorders, 50 patients (36 females, BMI: 44.68 ± 9.48 Kg/m2, age: 44.5 ± 11.7 years) were enrolled. All 50 patients received a psychiatric assessment including the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID-II); the Body Uneasiness Test, part a (BUT-A), which assesses body image disorders; the Childhood Trauma Questionnaire (CTQ) as a screening test of childhood maltreatment histories. RESULTS: Nineteen patients (38%) were affected by Axis II disorders. Cluster C disorders, including avoidant, dependent and obsessive-compulsive personality disorders, represented the most common diagnosis (24%). Moreover, 34 patients (68%) showed body image disorders (BID), with a GSI score ≥1.2 and 24 (48%) referred an abuse during childhood. Patients with Axis II disorder or a body image uneasiness or a history of maltreatment during childhood, showed higher BMI in adulthood. CONCLUSIONS: Psychiatric comorbidities in obese patients were not only represented by depression or anxiety (Axis I disorders), but also by personality disorders (Axis II), body image disorders and childhood abuse. The identification of these conditions could improve outcomes of bariatric surgery and represent an indication for a most important psychiatric support before, during and after surgery.

Is type 2 diabetes really resolved after laparoscopic sleeve gastrectomy? Glucose variability studied by continuous glucose monitoring.

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 (<140 mg/dL) at 120 minutes OGTT. These interesting data could help clinicians to better individualize patients in which diabetes is not resolved and who could need more attention in order to prevent chronic complications of diabetes.

Laparoscopic gastric sleeve and micronutrients supplementation: our experience.

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/m(2) ± 6.5, mean age 43.9 ± 10.9 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.

First-phase insulin secretion, insulin sensitivity, ghrelin, GLP-1, and PYY changes 72 h after sleeve gastrectomy in obese diabetic patients: the gastric hypothesis.

BACKGROUND: The aim of this study was to evaluate the possible role of sleeve gastrectomy (SG) per se in the reversibility of diabetes. METHODS: Insulin secretion and peripheral insulin sensitivity using the intravenous glucose tolerance test (IVGTT) were assessed in 18 obese type 2 diabetic patients and in 10 nondiabetic obese patients before and 3 days after SG, before any food intake and any weight change occurrence. At the same time, ghrelin, GLP-1, and PYY levels were determined. RESULTS: In diabetic patients who had the disease less than 10.5 years, the first phase of insulin secretion promptly improved after SG. The early insulin area under the curve (AUC) significantly increased at the postoperative IVGTT, indicating an increased glucose-induced insulin secretion. The second phase of insulin secretion (late AUC) significantly decreased after SG in all groups, indicating an improved insulin peripheral sensitivity. In all groups, pre- and postoperatively, intravenous glucose stimulation determined a decrease in ghrelin values and an increase in GLP-1 and PYY values. However, in the group of patients with disease duration >10.5 years, the differences were not significant except for the late insulin AUC. Postoperative basal and intravenous glucose-stimulated ghrelin levels were lower than preoperative levels in all groups of patients. Basal and intravenous stimulated GLP-1 and PYY postoperative values were higher than preoperative levels in all groups. CONCLUSIONS: Restoration of the first phase of insulin secretion and improved insulin sensitivity in diabetic obese patients immediately after SG, before any food passage through the gastrointestinal tract and before any weight loss, seem to be related to ghrelin, GLP-1, and PYY hormonal changes of possible gastric origin and was neither meal- nor weight-change-related. Duration of the disease up to 10.5 years seems to be a major cut off in the pathophysiological changes induced by SG. A "gastric" hypothesis may be put forward to explain the antidiabetes effect of SG.

Prediction of QTc length as function of BMI: a clinical tool to establish arrhythmias risk in obesity.

AIMS: Among the electrocardiographic alterations used for stratifying the cardiovascular risk of life threatening arrhythmias (LFA) and sudden death (SD) there is the increment of the corrected QT(QTc). This increment is usually observable in obese patients (OP). Therefore, a study has been planned to investigate the possibility to predict QTc values in OP simply by detecting the best fitting regression method that represents the relationship between QTc and Body Mass Index (BMI). MATERIALS AND METHODS: The study has been carried on 144 individuals classified as a function of their BMI in normoponderal subjects (NPS, No. 24; F/M=15/9; BMI=21.8± 1.7 kg/m(2)), Class I OP (No. 24; F/M=17/7; BMI=32.5± 1.1 kg/m(2)); Class II OP (No. 24; F/M=17/7; BMI=37.7± 1.5 kg/m(2)). Class IIIa (No. 24, F/M=15/9; BMI=44.4± 27 kg/m(2)), Class IIIb (No. 24; F/M=14/10; BMI 54.3± 2.7 kg/m(2)); Class IIIc (No. 24; F/M=14/10; BMI=63.3± 4.5 kg/m(2)). Both linear and non-linear fitting modes have been tested. RESULTS: While the BMI progressively increases in classified OP, the QTc shows an intergroup difference that is not only not constant but also declining in Class IIIc obesity. The optimal regressive model was found to be the following fourth order degree polynomial: QTc=317,15+(7,47xBMI)+(-0,28*BMI(2))+(0,005xBMI(3))+ (-0,00003xBMI(4)). CONCLUSION: By entering the BMI of a given OP into the above-cited formula, the QTc can be easily predicted and compared to that of NPS. Importantly, to have the possibility for a pre-electrocardiographic estimation of QTc allows all the medical and paramedical personnel, involved in the multidisciplinary treatment of obesity, to immediately establish the cardiovascular risk in the OP under observation.

Morbid obesity exposes the association between PNPLA3 I148M (rs738409) and indices of hepatic injury in individuals of European descent.

CONTEXT: 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. OBJECTIVE: To determine whether the PNPLA3 variant alters the susceptibility of morbidly obese subjects to develop liver injury and metabolic sequelae. PARTICIPANTS AND METHODS: 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. MAIN OUTCOME MEASURES: Indices of liver injury (alanine transaminase (ALT), aspartate transaminase (AST)), glucose tolerance and insulin resistance were measured. RESULTS: 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. CONCLUSION: Obese Southern Europeans carrying the 148M allele have increased indices of liver damage uncoupled from proxy measures of insulin resistance.

Long-term effects of laparoscopic sleeve gastrectomy, gastric bypass, and adjustable gastric banding on type 2 diabetes.

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.

High efficacy of bismuth subcitrate for Helicobacter pylori eradication in pangastritis.

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 1g 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.

Metabolic syndrome and adipose tissue: new clinical aspects and therapeutic targets.

The metabolic syndrome is a long-term process, explained by the interaction of genetic and environmental factors, that starts early in life and is involved in the pathophysiology of a large percentage of cases with type 2 diabetes and atherosclerosis. A number of clinical studies have demonstrated the importance of fat distribution and especially the contribution of visceral fat accumulation to the development of metabolic disorders. Visceral adipose tissue can be studied through different imaging techniques. The accumulation of visceral adipose tissue, as opposed to subcutaneous fat, increases the risk of developing metabolic disease and cardiovascular diseases (CVD). Visceral adipocytes secrete a variety of cytokines known as adipocytokines suggesting that adipose tissue is an endocrine organ that may affect the function of other organs. Weight loss, particularly a reduction in waist circumference, improves insulin sensitivity, lipid profile, and serum adipocytokines, reducing the risk of developing chronic disease and CVD. Waist circumference is a required component of metabolic syndrome under the International Diabetes Federation (IDF) criteria, rather than an optional component as used by other previous classifications. Studies have shown that using a lower waist circumference threshold within the context of metabolic syndrome increases the prevalence, but decreases the risk of mortality and type 2 diabetes. It is possible that waist circumference acts as a marker for other risk factors. These findings reinforce the notion that reductions in visceral adipose tissue should be a primary aim of strategies designed to reduce health risks associated with metabolic syndrome.

[Diseases associated with Ménière's disease]. / Associazioni morbose della malattia di Ménière.

The object of the present paper was to investigate the presence of other diseases in patients suffering from Menière's disease and to identify any common etiopathogenetic factors. In a group of 100 patients there was a high incidence of three pathological associations: 1) anxiety and depression; 2) dyspepsia; and 3) vasomotor headache. The percentages were then compared with the data found in the literature and with the non menieric population. The association of dyspepsia proved statistically significant. The relationship between anxiety and vasomotor headache remains suspect while awaiting more precise definition of these diseases and findings more comparable with the total population.