STEATOEPATITE NON ALCOLICA E FIBROSI EPATICA IN UNA CASISTICA DI PAZIENTI OBESI SOTTOPOSTI A CHIRURGIA BARIATRICA

Obiettivi dello studio: Valutare la prevalenza di epatopatia steatosica non alcolica (NAFLD) ed in particolare di steatoepatite non alcolica (NASH) e fibrosi epatica in pazienti con obesit\ue0 grave, che sono candidati ad intervento di chirurgia bariatrica. E\u2019 stato inoltre valutato l\u2019andamento delle transaminasi plasmatiche, adiponectina e di alcuni scores non invasivi di fibrosi epatica avanzata dopo 6 e 12 mesi dall\u2019intervento chirurgico.Popolazione e Metodi: Abbiamo studiato un campione di 28 pazienti affetti da obesit\ue0 grave (75% donne, et\ue0 mediana 41 anni, BMI mediano 45 kg/m\ub2), che sono stati sottoposti ad intervento in elezione di sleeve gastrectomy (19 pazienti) o bypass gastrico (9 pazienti). In tutti i pazienti sono stati eseguiti accertamenti metabolici (incluso 2-h clamp euglicemico iperinsulinemico) al baseline ed \ue8 stata eseguita una biopsia epatica durante l\u2019intervento chirurgico. Nessuno di questi pazienti aveva un eccessivo consumo di alcoolici n\ue9 una precedente storia di cirrosi e/o altre epatopatie croniche note.Risultati: Dei 28 pazienti inclusi nello studio, 16 (57%) hanno soddisfatto i criteri istologici per una diagnosi di NASH, mentre i restanti 12 (43%) pazienti non avevano NASH al baseline. Di questi 12 pazienti privi di NASH alla biopsia, 8 pazienti avevano steatosi macrovescicolare di grado lieve o severo (NAFL), mentre solo 4 pazienti (pari al 14.3% del campione totale) erano esenti da NAFLD alla biopsia epatica. Per quanto riguarda il grado di fibrosi epatica, 4 pazienti (14.3%) non avevano fibrosi (stadio F0), 14 (50%) pazienti avevano fibrosi moderata (F2) e 10 (35.7%) avevano \u201cbridging fibrosis\u201d (F3). Nessuno dei pazienti aveva cirrosi epatica precedentemente misconosciuta (F4). Quando i pazienti venivano suddivisi sulla base della presenza/assenza di NASH e/o della severit\ue0 di fibrosi epatica (F3 vs. F0-2), i due gruppi di pazienti erano comparabili per et\ue0, sesso e le principali variabili biochimiche esaminate, incluso transaminasi, APRI index, FIB-4 score e sensibilit\ue0 insulinica (M-clamp). L\u2019intervento chirurgico induceva, sia dopo 6 che 12 mesi, un marcato calo ponderale ed una significativa riduzione dei livelli circolanti di adiponectina in entrambi i gruppi. Al contrario, i valori di transaminasi e gli scores non invasivi di fibrosi epatica avanzata non hanno mostrato alcuna significativa variazione dopo 6 e 12 mesi dall\u2019intervento chirurgico in nessuno dei gruppi di pazienti considerati (NASH vs. no-NASH e F3 vs. F0-2).Conclusioni: Nei nostri pazienti con obesit\ue0 grave, candidati a chururgia bariatrica, la NAFLD \ue8 una patologia assai comune (essendo presente in circa 85% del campione) ed \ue8 gi\ue0 presente anche nelle sue forme istologiche pi\uf9 severe (NASH nel 57% dei casi e fibrosi avanzata nel 35.7% dei casi), pur rimanendo queste forme spesso clinicamente silenti (o pauci-sintomatiche) e senza accompagnarsi a significative alterazioni delle transaminasi circolanti e degli scores non-invasivi di fibrosi avanzata. Questi dati suggeriscono la necessit\ue0 di una diagnosi precoce e tempestiva delle forme pi\uf9 severe della NAFLD (che sono quelle associate ad un maggior rischio di progressione verso la cirrosi e l\u2019epatocarcinoma) in tutti i soggetti obesi che vengono sottoposti a chirurgia bariatrica (da eseguirsi almeno in fase intra-operatoria)

Prevalence and risk factors of glomerular hyperfiltration in adults with type 2 diabetes: A population-based study

Aims: Glomerular hyperfiltration characterises the earliest stage of diabetic nephropathy and predicts adverse kidney and cardiovascular outcomes. We aimed to assess the prevalence and risk factors of glomerular hyperfiltration in a population-based contemporary cohort of individuals with type 2 diabetes (T2D). Materials and methods: The prevalence of unequivocal glomerular hyperfiltration (defined by an estimated glomerular filtration rate >120 mL/min/1.73 m(2) ) and its associated risk factors were identified in a cohort of 202,068 adult patients with T2D receiving specialist care in 2021-2022, whose center-aggregated data were automatically extracted from electronic medical records of 75 diabetes clinics in Italy. Results: Glomerular hyperfiltration was identified in 1262 (0.6%) participants. The prevalence of glomerular hyperfiltration varied widely across centers (0%-3.4%) and correlated with mean center age, HbA(1c) , body mass index (BMI), and low-density lipoprotein cholesterol. Patients in centers with high glomerular hyperfiltration prevalence (>0.8%) were more often men and had lower age and BMI, but more frequent albuminuria and worse glucose, lipid, and blood pressure control, compared with low-normal prevalence centers. Conclusions: Unequivocal glomerular hyperfiltration can be identified in up to 3.4% of patients receiving up-to-date specialist diabetes care. Glomerular hyperfiltration prevalence varies across centers and substantially increases with suboptimal control of metabolic risk factors, which would require improved management to mitigate the negative health consequences of this pathological condition

Clinical Features, Cardiovascular Risk Profile, and Therapeutic Trajectories of Patients with Type 2 Diabetes Candidate for Oral Semaglutide Therapy in the Italian Specialist Care

Introduction: This study aimed to address therapeutic inertia in the management of type 2 diabetes (T2D) by investigating the potential of early treatment with oral semaglutide. Methods: A cross-sectional survey was conducted between October 2021 and April 2022 among specialists treating individuals with T2D. A scientific committee designed a data collection form covering demographics, cardiovascular risk, glucose control metrics, ongoing therapies, and physician judgments on treatment appropriateness. Participants completed anonymous patient questionnaires reflecting routine clinical encounters. The preferred therapeutic regimen for each patient was also identified. Results: The analysis was conducted on 4449 patients initiating oral semaglutide. The population had a relatively short disease duration (42%  60% of patients, and more often than sitagliptin or empagliflozin. Conclusion: The study supports the potential of early implementation of oral semaglutide as a strategy to overcome therapeutic inertia and enhance T2D management

Association between specific plasma ceramides and high-sensitivity C-reactive protein levels in postmenopausal women with type 2 diabetes

AIM: Emerging evidence suggests that specific plasma ceramides are involved in the pathophysiology of cardiovascular disease (CVD) and other inflammation-associated diseases. However, only scanty information is currently available on the association between distinct plasma ceramides (those associated with increased cardiovascular morbidity and mortality) and plasma high-sensitivity C-reactive protein (hs-CRP) concentrations in patients with type 2 diabetes mellitus (T2DM), a group at high risk of developing CVD and other chronic inflammation-related conditions. METHODS: Previously, six high-risk plasma ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), Cer(d18:1/24:1)] were identified in 92 postmenopausal women with T2DM attending a diabetes outpatients service over a 3-month period. Plasma ceramide levels were measured using targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay. RESULTS: Plasma hs-CRP levels were positively associated with all measured ceramides on univariable linear regression analyses, but only plasma Cer(d18:1/16:0) (standard \u3b2 coefficient: 0.27, P = 0.015), Cer(d18:1/22:0) (standard \u3b2 coefficient: 0.25, P = 0.032) and Cer(d18:1/24:1) (standard \u3b2 coefficient: 0.30, P = 0.007) remained significantly associated with increased plasma hs-CRP levels after adjusting for age, adiposity measures, diabetes duration, HbA1c, insulin resistance, smoking, hypertension, plasma LDL cholesterol, estimated glomerular filtration rate, preexisting ischaemic heart disease and use of lipid-lowering, antihypertensive, antiplatelet or hypoglycaemic drugs. CONCLUSION: In postmenopausal women with T2DM, elevated levels of specific plasma ceramides are associated with higher plasma hs-CRP levels independent of established cardiovascular risk factors, diabetes-related variables and other potential confounding factors

From lipoprotein apheresis to proprotein convertase subtilisin/kexin type 9 inhibitors: Impact on low-density lipoprotein cholesterol and C-reactive protein levels in cardiovascular disease patients

In this observational study, we compared the effect of lipoprotein apheresis and evolocumab or alirocumab on levels of lipoprotein cholesterol, triglycerides and inflammatory markers (C reactive protein and interleukin 6) in cardiovascular patients ( n\u2009=\u20099). Patients were monitored during the last year of lipoprotein apheresis followed by six months of treatment with proprotein convertase subtilisin/kexin type 9 inhibitors. The biochemical parameters were determined pre- and post- every apheresis procedure for 12 months and then after one, three and six months of treatment with evolocumab (140\u2009mg every two weeks [Q2W]) or alirocumab (75\u2009mg or 150\u2009mg every two weeks [Q2W]). Lipoprotein apheresis significantly reduced low-density lipoprotein cholesterol levels from 138\u2009\ub1\u200932\u2009mg/dl to 46\u2009\ub1\u200916\u2009mg/dl ( p\u2009<\u20090.001), with an inter-apheresis level of 114\u2009\ub1\u200926\u2009mg/dl. Lipoprotein(a) was also reduced from a median of 42\u2009mg/dl to 17\u2009mg/dl ( p\u2009<\u20090.01). Upon anti-proprotein convertase subtilisin/kexin type 9 therapy, low-density lipoprotein cholesterol levels were similar to post-apheresis (59\u2009\ub1\u200925, 41\u2009\ub1\u200922 and 42\u2009\ub1\u200921mg/dl at one, three and six months, respectively) as well as those of lipoprotein(a) (18\u2009mg/dl). However, an opposite effect was observed on high-density lipoprotein cholesterol levels: -16.0% from pre- to post-apheresis and +34.0% between pre-apheresis and proprotein convertase subtilisin/kexin type 9 inhibitors. Apheresis significantly reduced high-sensitivity C-reactive protein levels (1.5\u2009\ub1\u20091.2\u2009mg/l pre-apheresis to 0.6\u2009\ub1\u20090.6\u2009mg/l post-apheresis), while no changes were found upon proprotein convertase subtilisin/kexin type 9\u2009mAbs administration. In conclusion, our study demonstrated that, by switching from lipoprotein apheresis to anti-proprotein convertase subtilisin/kexin type 9 therapies, patients reached similar low-density lipoprotein cholesterol and lipoprotein(a) levels, increased those of high-density lipoprotein cholesterol, and showed no changes on high-sensitivity C-reactive protein

442-P: Excess Burden of Adverse In-Hospital Outcomes in Patients with Diabetes Hospitalized for Stroke

Cerebrovascular accidents (CVA) represent a major complication in diabetes (DM). Real-life evidence as to whether modern management of CVA and DM have softened this relationship is currently limited. We assessed the prevalence of DM, previously known or newly-diagnosed, in all patients (N=542, males 51.5%) admitted for CVA at the Stroke Unit (SU) of Verona University Hospital from 1/1/2015 to 12/31/2016. DM was ascertained by previous diagnosis, glucose-lowering therapy at admission/discharge or admittance plasma glucose (PG) ≥11.1 mmol/L. Prevalence of DM was 21.03% (78.1% known-DM; 21.9% new-DM). In-hospital death rate was 10.5%. Compared to non-DM, patients with DM showed an increased risk of death (15.8 vs. 9.1%; OR 1.87 95% CI, 1.03-3.41) and complications (48.2 vs. 33.3%; 1.87, 1.22-2.86) with similar duration of hospitalization (mean±SEM, 9.14±1.06 vs. 8.80±0.39 days, p=0.72). All deaths occurred in the SU. The “survivors” with DM transferred to non-intensive ward had an out-of-SU hospital stay twice as longer than non-DM (2.32±1.02 vs. 0.98±0.19 days, p=0.038). After multivariable adjustment, DM remained predictor of complications (adj-OR 1.87, 1.22-2.86) but not mortality (1.79, 0.92-3.46). Patients in the highest PG quartile (≥6.55 mmol/L) displayed the highest risk of death (7.89, 2.73-22.79; PG&amp;lt;4.77 mmol/L, ref.) and complications (2.30, 1.24-4.23), independent of diabetes status, glucose-lowering medications, CVA treatment and established CVA risk factors. Individuals in the older age tertile (≥81 years) were at increased risk of death (3.25, 1.40-7.54; age &amp;lt;72 years, ref.), while risk of infectious/cardiorespiratory complications was higher at younger age (3.13, 1.42-6.9). No difference was observed in new-DM vs. known-DM. In conclusion, these data highlight that DM frequently occurs in patients admitted for CVA and adds an excess burden of adverse clinical outcomes that urgently calls for strategies to anticipate DM diagnosis in high-risk individuals. Disclosure M. Dauriz: None. E. Tregnaghi: None. L. Santi: None. T. Lucianer: None. A. Altomari: None. E. Rinaldi: None. S. Tardivo: None. C. Bovo: None. E. Bonora: None. </jats:sec

Association between helicobacter pylori infection and risk of nonalcoholic fatty liver disease: an updated meta-analysis

Although clinical studies have shown possible links of Helicobacter pylori infection with the development of nonalcoholic fatty liver disease (NAFLD), the results remain controversial. The aim of this meta-analysis is to investigate the association between H. pylori infection and NAFLD. A comprehensive search of relevant studies was performed up to November 2018. Data on H. pylori infection in NAFLD patients and controls were extracted. Odds ratio (OR) and 95% confidence interval (CI) were calculated using a random-effects model. Twelve studies involving 27 400 NAFLD patients and 60 347 controls were included. The pooled overall OR of H. pylori infection in NAFLD patients compared with controls was 1.36 (95% CI: 1.22–1.53, I2=89.6%, P=0.000). Meta-regression and subgroup analysis showed that the sample size and the case–control ratio may have accounted for some of the heterogeneity. When stratified by publication year, the diagnostic method used for H. pylori, and Newcastle–Ottawa Scale scores, the OR remained significant. However, possible publication bias was observed. Of the 12 studies, six had carried out multivariable analysis after adjusting for potential confounders. The pooled results from these studies still indicated a higher risk of NAFLD in patients infected with H. pylori (OR=1.17, 95% CI: 1.01–1.36, I2=72.4%, P=0.003). There is a 36% increased risk of NAFLD in patients with H. pylori infection. Further studies are warranted to investigate whether eradication of H. pylori is useful in the prevention and treatment of NAFLD

Diabetes mellitus in stroke unit: prevalence and outcomes-the Verona acute coronary syndrome and stroke in diabetes outcome (VASD-OUTCOME) study

Background: Cerebrovascular accidents (CVA) represent a major complication in diabetes (DM). Real-life evidence as to whether modern management of CVA and DM have softened this relationship is limited. Therefore, we estimated prevalence and impact of DM on in-hospital survival and complications in a contemporary cohort of subjects with CVA. Methods: We retrospectively evaluated the records of 937 patients admitted for CVA at the Stroke Unit of Verona University Hospital during a 3-year period. Pre-existing or de novo DM was ascertained by prior diagnosis, glucose-lowering therapy at admission/discharge or admittance plasma glucose ≥ 200&nbsp;mg/dL. Multiple regressions were applied to test DM as predictor of in-hospital mortality, complications (composite of infections, cardio- and cerebrovascular complications, major bleeding and pulmonary complications), duration and costs of hospitalization. Results: Diabetes prevalence was 21%, of which 22% de novo diagnoses. Compared to non-DM, diabetic individuals were older and carried an increased burden of cardiovascular risk factors. Compared to known DM, de novo DM individuals were younger, had higher admittance plasma glucose and poorer cardiovascular comorbidities. Overall, DM versus non-DM individuals did not show significantly increased risk of death (14.0 vs. 9.3%; crude-OR 1.59 95% CI 0.99-2.56). Controlling for confounders did not improve significance. DM resulted independent predictor for in-hospital complications (36.2% vs. 26.9%; adj-OR 1.49, 1.04-2.13), but not for duration and costs of hospitalization. Conclusion: DM frequently occurs in patients admitted for stroke and carries an excess burden of adverse in-hospital complications, urgently calling for strategies to anticipate DM diagnosis and tailored treatment in high-risk individuals