Effectiveness and safety of filgotinib in rheumatoid arthritis: a real-life multicentre experience.

OBJECTIVES: We investigated the effectiveness and safety of filgotinib in a real-life multicentre cohort of rheumatoid arthritis (RA) patients. METHODS: RA patients were evaluated at baseline and after 12 and 24 weeks and were stratified based on previous treatments as biologic disease-modifying anti-rheumatic drug (bDMARD)-naive and bDMARD-insufficient responders (IR). Concomitant usage of methotrexate (MTX) and oral glucocorticoids (GC) was recorded. At each timepoint we recorded disease activity, laboratory parameters and adverse events. RESULTS: 126 patients were enrolled. 15.8% were bDMARD-naive (G0), while 84% were bDMARD-IR (G1). In G0, 45% of patients were in monotherapy (G2) and 55% were taken MTX (G3). In G1, 50% of patients were in monotherapy (G4) and 50% used MTX (G5).A significant reduction in all parameters at 12 weeks was observed; in the extension to 24 weeks the significant reduction was maintained for patient global assessment (PGA), examiner global assessment (EGA), visual analogue scale (VAS) pain, VAS fatigue, disease activity score (DAS)28- C-reactive protein (CRP) and CRP values. Filgotinib in monotherapy showed better outcomes in bDMARD-naive patients, with significant differences for patient reported outcomes (PROs) and DAS28-CRP. At 12 weeks, low disease activity (LDA) and remission were achieved in a percentage of 37.2 % and 10.7 % by simplified disease activity index (SDAI), 42.6 % and 5.7 % by clinical disease activity index (CDAI), 26.8 % and 25.2 % by DAS28-CRP, respectively. A significant decrease in steroid dose was evidenced in all patients. We observed a major adverse cardiovascular event in one patient and an increase in transaminase in another. No infections from Herpes Zoster were reported. CONCLUSIONS: Our real-world data confirm the effectiveness and safety of filgotinib in the management of RA, especially in bDMARD-naive patients.

Mortality Attributable to Bloodstream Infections Caused by Different Carbapenem-Resistant Gram-Negative Bacilli: Results From a Nationwide Study in Italy (ALARICO Network).

BACKGROUND: Our aim was to analyze mortality attributable to carbapenem-resistant (CR) gram-negative bacilli (GNB) in patients with bloodstream infections (BSIs). METHODS: Prospective multicentric study including patients with GNB-BSI from 19 Italian hospitals (June 2018-January 2020). Patients were followed-up to 30 days. Primary outcomes were 30-day mortality and attributable mortality. Attributable mortality was calculated in the following groups: Klebsiella pneumoniae carbapenemase (KPC)-producing Enterobacterales, metallo-ß-lactamases (MBL)-producing Enterobacterales, CR-Pseudomonas aeruginosa (CRPA), CR-Acinetobacter baumannii (CRAB). A multivariable analysis with hospital fixed-effect was built to identify factors associated with 30-day mortality. Adjusted OR (aORs) were reported. Attributable mortality was calculated according to the DRIVE-AB Consortium. RESULTS: Overall, 1276 patients with monomicrobial GNB BSI were included: 723/1276 (56.7%) carbapenem-susceptible (CS)-GNB, 304/1276 (23.8%) KPC-, 77/1276 (6%) MBL-producing CRE, 61/1276 (4.8%) CRPA, and 111/1276 (8.7%) CRAB BSI. Thirty-day mortality in patients with CS-GNB BSI was 13.7% compared to 26.6%, 36.4%, 32.8% and 43.2% in patients with BSI by KPC-CRE, MBL-CRE, CRPA and CRAB, respectively (P < .001). On multivariable analysis, age, ward of hospitalization, SOFA score, and Charlson Index were factors associated with 30-day mortality, while urinary source of infection and early appropriate therapy resulted protective factors. Compared to CS-GNB, MBL-producing CRE (aOR 5.86, 95% CI 2.72-12.76), CRPA (aOR 1.99, 95% CI 1.48-5.95) and CRAB (aOR 2.65, 95% CI 1.52-4.61) were significantly associated with 30-day mortality. Attributable mortality rates were 5% for KPC-, 35% for MBL, 19% for CRPA, and 16% for CRAB. CONCLUSIONS: In patients with BSIs, carbapenem-resistance is associated with an excess of mortality, with MBL-producing CRE carrying the highest risk of death.

The Role of Vitamin D and Its Molecular Bases in Insulin Resistance, Diabetes, Metabolic Syndrome, and Cardiovascular Disease: State of the Art.

In the last decade, an increasing awareness was directed to the role of Vitamin D in non-skeletal and preventive roles for chronic diseases. Vitamin D is an essential hormone in regulating calcium/phosphorous balance and in the pathogenesis of inflammation, insulin resistance, and obesity. The main forms of vitamin D, Cholecalciferol (Vitamin D3) and Ergocalciferol (Vitamin D2) are converted into the active form (1,25-dihydroxyvitamin D) thanks to two hydroxylations in the liver, kidney, pancreas, and immune cells. Some anti-inflammatory cytokines are produced at higher levels by vitamin D, while some pro-inflammatory cytokines are released at lower levels. Toll-Like Receptor (TLR) expression is increased, and a pro-inflammatory state is also linked to low levels of vitamin D. Regardless of how it affects inflammation, various pathways suggest that vitamin D directly improves insulin sensitivity and secretion. The level of vitamin D in the body may change the ratio of pro- to anti-inflammatory cytokines, which would impact insulin action, lipid metabolism, and the development and function of adipose tissue. Many studies have demonstrated an inverse relationship between vitamin D concentrations and pro-inflammatory markers, insulin resistance, glucose intolerance, metabolic syndrome, obesity, and cardiovascular disease. It is interesting to note that several long-term studies also revealed an inverse correlation between vitamin D levels and the occurrence of diabetes mellitus. Vitamin D supplementation in people has controversial effects. While some studies demonstrated improvements in insulin sensitivity, glucose, and lipid metabolism, others revealed no significant effect on glycemic homeostasis and inflammation. This review aims to provide insight into the molecular basis of the relationship between vitamin D, insulin resistance, metabolic syndrome, type 1 and 2 diabetes, gestational diabetes, and cardiovascular diseases.

Real-world evidence of biologic treatments in moderate-severe psoriasis in Italy: Results of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional longitudinal study of real-life clinical practice) study.

EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: An obserVAtional (CANOVA) study was aimed at providing real-world evidence of the effectiveness of biologics in Italian patients with moderate-severe psoriasis. It was an observational, retro-prospective cohort study conducted in 17 Italian dermatology clinics. Adult patients with moderate-severe plaque psoriasis, who started a biologic treatment between 24 weeks and 24 months before enrolment, were included. With a follow-up visit at 6 months after enrolment, each patient had at least 12 months of observation. The primary objective was to describe the clinical response rates (PASI 75) after 16/24/52 weeks from biologic treatment start. Secondary outcomes were sustained response, quality of life, and treatment satisfaction. Of the 669 eligible patients (64% males), 52% were naïve to biologics, though a mean duration of psoriasis since first diagnosis of 18.6 years (SD 13.2). The most frequently prescribed biologics were secukinumab (41%), ustekinumab (25%), TNF-inhibitors (22%) and ixekizumab (12%). PASI 75 was achieved by 86% of patients (95% CI: 82%-89%) at 16 weeks, 90% (87%-93%) at 24 weeks, and 91% (89%-94%) at 52 weeks. Patients achieving PASI 90 and PASI 100 at 52 weeks were 75% (71%-79%) and 53% (49%-57%), respectively. Sustained PASI 75 response after 1 year from treatment start was achieved by 78% (74%-82%) of patients. Mean DLQI total score was 2.3 (SD 3.9) at enrollment and decreased at the final visit to 1.8 (3.6). A high level of treatment satisfaction was expressed by patients over the study period. This large real-world study confirms in the clinical practice the good effectiveness and acceptability of biologics in psoriasis patients.

Clinical complexity and diabetes: a multidimensional approach for the management of cardiorenal metabolic syndrome.

Diabetes mellitus (DM) is one of the fastest-growing health emergencies of the 21st century, and one of the chronic diseases with the highest socio-economic impact on health care systems. DM is the main cause of chronic kidney disease, and is associated with a significant increase in cardiovascular risk and clinical and care complexity. The presence of a constellation of cardiac, metabolic, and renal diseases, in a complex patient with DM, constitutes the CardioRenal Metabolic Syndrome (CRMS). The management of these patients should include a paradigm shift from a reactive strategy to a proactive approach, and the integration of territorial, hospital and social assistance services according to the Chronic Care Model (CCM). Complexity science suggests an alternative model in which disease and health arise from complex, dynamic, and unique interactions among the different components of the overall system. The hospital should be viewed as a highly specialized hub of the chronic care system, which interacts with the outpatient specialist and primary care. In order to create effective communication among territorial care units and highly specialized hospitals, levels of clinical complexity are here proposed and included in a multidimensional management model for the complex patient with diabetes and cardiorenal comorbidity.

An Overview of Systematic Reviews of the Role of Vitamin D on Inflammation in Patients with Diabetes and the Potentiality of Its Application on Diabetic Patients with COVID-19.

Almost two years have passed since the outbreak reported for the first time in Wuhan of coronavirus disease 2019 (COVID-19), due to severe acute respiratory syndrome (SARS)-CoV-2 coronavirus, rapidly evolved into a pandemic. This infectious disease has stressed global health care systems. The mortality rate is higher, particularly in elderly population and in patients with comorbidities such as hypertension, diabetes mellitus, cardiovascular disease, chronic lung disease, chronic renal disease, and malignancy. Among them, subjects with diabetes have a high risk of developing severe form of COVID-19 and show increased mortality. How diabetes contributes to COVID-19 severity remains unclear. It has been hypothesized that it may be correlated with the effects of hyperglycemia on systemic inflammatory responses and immune system dysfunction. Vitamin D (VD) is a modulator of immune-response. Data from literature showed that vitamin D deficiency in COVID-19 patients increases COVID-19 severity, likely because of its negative impact on immune and inflammatory responses. Therefore, the use of vitamin D might play a role in some aspects of the infection, particularly the inflammatory state and the immune system function of patients. Moreover, a piece of evidence highlighted a link among vitamin D deficiency, obesity and diabetes, all factors associated with COVID-19 severity. Given this background, we performed an overview of the systematic reviews to assess the association between vitamin D supplementation and inflammatory markers in patients with diabetes; furthermore, vitamin D's possible role in COVID-19 patients was assessed as well. Three databases, namely MEDLINE, PubMed Central and the Cochrane Library of Systematic Reviews, were reviewed to retrieve the pertinent data. The aim of this review is to provide insight into the recent advances about the molecular basis of the relationship between vitamin D, immune response, inflammation, diabetes and COVID-19.

Clinical profiles and quality of care of subjects with type 2 diabetes according to their cardiovascular risk: an observational, retrospective study.

BACKGROUND: The European Society of Cardiology (ESC) recently defined cardiovascular risk classes for subjects with diabetes. Aim of this study was to explore the distribution of subjects with type 2 diabetes (T2D) by cardiovascular risk groups according to the ESC classification and to describe the quality indicators of care, with particular regard to cardiovascular risk factors. METHODS: The study is based on data extracted from electronic medical records of patients treated at the 258 Italian diabetes centers participating in the AMD Annals initiative. Patients with T2D were stratified by cardiovascular risk. General descriptive indicators, measures of intermediate outcomes, intensity/appropriateness of pharmacological treatment for diabetes and cardiovascular risk factors, presence of other complications and overall quality of care were evaluated. RESULTS: Overall, 473,740 subjects with type 2 diabetes (78.5% at very high cardiovascular risk, 20.9% at high risk and 0.6% at moderate risk) were evaluated. Among people with T2D at very high risk: 26.4% had retinopathy, 39.5% had albuminuria, 18.7% had a previous major cardiovascular event, 39.0% had organ damage, 89.1% had three or more risk factors. The use of DPP4-i markedly increased as cardiovascular risk increased. The prescription of secretagogues also increased and that of GLP1-RAs tended to increase. The use of SGLT2-i was still limited, and only slightly higher in subjects with very high cardiovascular risk. The overall quality of care, as summarized by the Q score, tended to be lower as the level of cardiovascular risk increased. CONCLUSIONS: A large proportion of subjects with T2D is at high or very high risk. Glucose-lowering drug therapies seem not to be adequately used with respect to their potential advantages in terms of cardiovascular risk reduction. Several actions are necessary to improve the quality of care.

A real-world economic analysis of biologic therapies for moderate-to-severe plaque psoriasis in Italy: results of the CANOVA observational longitudinal study.

BACKGROUND: Psoriasis is a chronic immune-mediated inflammatory skin disease which can also involve joints. It is often associated with burdensome comorbidities which negatively impact prognosis and quality of life (QoL). Biologic agents have been shown to be effective in controlling disease progression, but their use is associated with higher costs compared with traditional systemic treatments. The economic analysis of the CANOVA (EffeCtiveness of biologic treAtmeNts for plaque psOriasis in Italy: an obserVAtional longitudinal study of real-life clinical practice) study aims to assess the costs and cost-effectiveness of biologics in a real-world context in Italy. METHODS: The annualised overall direct costs of moderate-to-severe plaque psoriasis management, the annualised cost of biologic drugs and the cost per responder in the Italian National Health System perspective were assessed. More specifically, the cost per response and cost per sustained response of the most prescribed biologic therapies for the treatment of moderate-to-severe plaque psoriasis within the CANOVA study were assessed using the Psoriasis Area Severity Index (PASI) at several score levels (75, 90 and 100%). RESULTS: The most frequently used biologic therapies for plaque psoriasis were secukinumab, ustekinumab, adalimumab originator, and ixekizumab. Cost of biologics was the driver of expenditure, accounting for about 98% of total costs. Adalimumab originator was the biologic with the lowest cost per responder ratio (range: €7848 - €31,378), followed by secukinumab (range: €9015 - €33,419). Ustekinumab (range: €11,689 - €39,280) and ixekizumab (range: €11,092 - €34,289) ranked respectively third and fourth, in terms of cost-effectiveness ratio. As concerns the cost per sustained response analysis, secukinumab showed the lowest value observed (€21,375) over the other options, because of its high response rate (86% vs. 60-80%), which was achieved early in time. CONCLUSION: Biologic therapy is a valuable asset for the treatment of moderate-to-severe plaque psoriasis. Concomitant assessment of treatment costs against the expected therapeutic response over time can provide physicians and payers additional insights which can complement the traditional risk-benefit profile assessment and drive treatment decisions.

Evaluation of Hypertension, Proteinuria, and Abnormalities of Body Weight in Italian Adolescents Participating in the World Kidney Days.

INTRODUCTION: World Kidney Day (WKD) was promoted by the Italian Kidney Foundation and the Italian Society of Nephrology for raising awareness, detection, prevention, and treatment of kidney diseases. The Italian WKD focused on the "School Project" by screening students attending the fifth year of high school. The main goal of the "School Project" was to assess in healthy adolescents the presence of hypertension (HTN) and proteinuria; as well as to evaluate potential interrelations between overweight, obesity (both measured with different anthropometric methods), blood pressure (BP) levels, and proteinuria. The ancillary goal was to have an estimate of awareness on some nephrology topics. METHODS: The study population consisted of 17- to 19-year-old students. HTN was defined as systolic BP (SBP) ≥140 mm Hg and/or diastolic BP (DBP) ≥90 mm Hg. Isolated systolic hypertension (ISH) was defined as SBP ≥140 mm Hg and DBP <90 mm Hg; isolated diastolic hypertension as SBP <140 mm Hg and DBP ≥90 mm Hg; systolic and diastolic hypertension as SBP ≥140 mm Hg and DBP ≥90 mm Hg; pre-hypertension as SBP >120 mm Hg but <140 mm Hg or DBP >80 mm Hg but <90 mm Hg; and optimal BP as SBP ≤120 mm Hg and DBP ≤80 mm Hg. Urine tests were performed with a dipstick; the subjects were regarded as proteinuric when the urine dipstick was positive (proteinuria ≥30 mg/dL). Body weight, height, and waist circumference (WC) were measured; body mass index (BMI), waist-to-height ratio (WHtR), and conicity index (Ci) were calculated. According to the BMI, the following classifications were adopted: underweight (<18.5 kg/m2), normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), class-I obesity (30-34.9 kg/m2), class-II obesity (35-39.9 kg/m2), class-III obesity (≥40 kg/m2). RESULTS: Data from 12,125 students (45.6% males) were evaluated. HTN was found in 1,349 participants (11.1%; 61.1% male), and ISH was present in 7.4%. Overweight (24.1%) and class-I (6%), -II (3.6%), and -III (1%) obesity were present in hypertensive participants. Compared to participants with normal BP, hypertensive participants had a higher BMI (p < 0.001), WC (p < 0.001), and WHtR (p < 0.001); whereas the Ci was not different (p = 0.527). Multivariate linear regression analysis showed that both WC and BMI were predictors of abnormal SBP and DBP (p < 0.001) both in males and females. Proteinuria was present in 14.8, 13.8, 14.7, and 14.7% of all normal weight, overweight, obese, and all subjects, respectively. In addition, no association was found between body weight, proteinuria, and BP. CONCLUSION: This study shows that overweight and obesity were significantly associated to HTN in Italian adolescents. BMI and WC were predictors of SBP and DBP. The occurrence of proteinuria was quite similar to that of HTN, but it was not associated with anthropometric indicators or HTN.

Mutual relationship between heart failure and atrial fibrillation.

Atrial fibrillation (AF) and heart failure (HF) are evolving epidemies, together responsible for substantial human suffering and health-care expenditure. The simultaneous co-hexistence of the two conditions is associated with mortality rates higher than those observed in individuals with only one or none of them. Patients with concomitant HF and AF suffer from even worse symptoms and poorer prognosis, yet evidence-based evaluation and management of this group of patients is lacking. In this review, we evaluate the common mechanisms for the development of AF in HF patients and vice versa, focusing on the evidence for potential treatment strategies. Recent data have suggested that these patients may respond differently if compared to those with HF or AF alone. These results highlight the clear clinical need to identify and treat these diseases according to best evidence, in order to prevent adverse outcomes and reduce the huge burden that HF and AF are expected to have on global healthcare systems in the future.

Education and hypertension: impact on global cardiovascular risk.

BACKGROUND: Improving cardiovascular risk prediction continues to be a major challenge and effective prevention of cardiovascular disease. Accordingly, several studies have recently reported on the role of cardiovascular risk education. This study was designed to evaluate the impact of education on global cardiovascular risk in hypertensive patients. SUBJECTS AND METHODS: The study population consisted of 223 consecutive hypertensive outpatients. Their educational status was categorized according to the number of years of formal education as follows: (1) low education (less than 10 years) and (2) medium-high education (10-15 years). RESULTS: In both groups, cardiometabolic comorbidities, global cardiovascular risk and echocardiographic measurements were analysed. Less educated hypertensive subjects were characterized by a significantly higher prevalence of patients with metabolic syndrome (MetS) (p < .01), greater global cardiovascular risk (p < .001), and a higher consumption of antihypertensive drugs (p < .01) rather than medium-high educated hypertensive subjects. In the same subjects, a significant increase in microalbuminuria (MA) (p < .01) and a significant decrease in E/A (p < .001) ratio was found. Univariate analysis indicated that global cardiovascular risk correlated directly with waist-hip ratio, mean blood pressure, MA, left ventricular mass index, MetS and inversely with education (r = -0.45; p < .001). Education was independently (p < .001) associated with global CV risk. CONCLUSIONS: Our data suggest that education may be considered the best predictor of global cardiovascular risk in hypertensives and thus has to be evaluated in the strategies of hypertension and cardiovascular risk management.

Antipsychotic prescription and mortality in hospitalized older persons.

BACKGROUND: Recent scientific reports have shown that older persons treated with antipsychotics for dementia-related behavioural symptoms have increased mortality. However, the impact of these drugs prescribed during hospitalization has rarely been assessed. We aimed to investigate whether antipsychotics are associated with an increased risk of mortality during hospitalization and at 3-month follow-up in elderly inpatients. METHODS: We analyzed data gathered during two waves (2010 and 2012) by the REPOSI (Registro Politerapie Società Italiana Medicina Interna). All new prescriptions of antipsychotic drugs during hospitalization, whether maintained or discontinued at discharge, were collected, and logistic regression models were used to analyze their association with in-hospital and 3-month mortality. Covariates were age, sex, the Short Blessed Test (SBT) score, and the Cumulative Illness Rating Scale. RESULTS: Among 2703 patients included in the study, 135 (5%) received new prescriptions for antipsychotic drugs. The most frequently prescribed antipsychotic during hospitalization and eventually maintained at discharge was haloperidol (38% and 36% of cases, respectively). Patients newly prescribed with antipsychotics were older and had a higher Cumulative Illness Rating Scale comorbidity index both at admission and at discharge compared to those who did not receive a prescription. Of those prescribed antipsychotics, 71% had an SBT score ≥10 (indicative of dementia), 12% had an SBT score of 5-9 (indicative of questionable dementia); and 17% had an SBT score <5 (indicative of normal cognition). In-hospital mortality was slightly higher in patients prescribed antipsychotic drugs (14.3% vs 9.4%; P = 0.109), but in multivariate analysis only male sex, older age, and higher SBT scores were significantly related to mortality during hospitalization. At 3-month follow-up, only male sex, older age, and higher SBT scores were associated with mortality. CONCLUSION: We found that the prescription of antipsychotic drugs during hospitalization was not associated with in-hospital or follow-up mortality. Short-term antipsychotic prescriptions (for acutely ill patients) may have a different effect than long-term, repeated prescriptions.

Circulating adiponectin: a cardiometabolic marker associated with global cardiovascular risk.

OBJECTIVE: This study was designed to evaluate the relationship among circulating adiponectin (ADPN), left ventricular mass (LVM) and cardio-metabolic comorbidities in subjects at higher global cardiovascular risk (score of"Cuore Project"). METHODS: 115 consecutive subjects were grouped according to normal or low ADPN levels. Left ventricular internal diameter (LVID/h), total LV mass (LVM), LVM index (LVMI), relative wall thickness (RWT), LV ejection fraction by echocardiography and diastolic parameters, by pulsed-wave Doppler were calculated. RESULTS: Low-ADPN subjects were characterized by a significantly higher prevalence of some cardiometabolic comorbidities (obesity, visceral obesity, diabetes and insulin resistance, LVH, metabolic syndrome (MetS), coronary artery syndrome (CAD). BMI (P < 0.0001), WHR (P < 0.03), trigly cerides (P < 0.001), HOMA-IR (P < 0.001), LVM, LVMI, IVST and RWT (P < 0.0001) were significantly higher and HDL-C (P < 0.001) and LVEF were significantly lower in low-ADPN than in normal-ADPN subjects. LVMI correlated directly with BMI (P < 0.001), WHR (P < 0.001) MBP (P < 0.001), MetS (P < 0.001) and inversely with ADPN (P < 0.0001). Multiple regres- sion analysis indicated that ADPN was independently associated with LVMI. CONCLUSIONS: ADPN might be considered a key component mediating the cross-talk between adipose tissue, cardiac cells and the vasculature. Accordingly, its routine measurement might become a new target in the management of global CV risk.

Plasma adiponectin: a contributing factor for cardiac changes in visceral obesity-associated hypertension.

This study has been designed to evaluate the impact of adiponectin levels on left ventricular geometry and function in visceral obesity-associated hypertension. 94 consecutive subjects, 53 of them were hypertensives and 41 normotensives with age ≤ 65 years, subgrouped according to the presence or absence of visceral obesity, were studied. Total adiponectin levels were measured by a validated competitive radioimmunoassay. Left ventricular telediastolic internal diameter, interventricular septum, posterior wall thickness, total left ventricular mass (LVM) and normalized for height to the 2.7 power (LVM/h(2.7)), relative wall thickness, left ventricular ejection fraction by echocardiography and isovolumic relaxation time, E/A ratio and deceleration time of E velocity, by pulsed-wave Doppler, were calculated. Plasma adiponectin levels were significantly lower in visceral obesity-associated hypertensives than lean hypertensives (p < 0.001) and in lean normotensives (p < 0.001). LVM and LVM/h(2.7) were significantly (p < 0.05) higher in both hypertensive groups, and in visceral obesity-associated normotensives in comparison with lean normotensives. Adiponectin levels correlated inversely with LVM/h(2.7) but only in normotensives (adjusted R squared 0.77, p < 0.0001) and hypertensives (0.67, p < 0.0001) subjects with visceral obesity. Multiple regression analysis indicated that adiponectin levels remain significantly associated (p < 0.001) to LVM/h(2.7) also when adjusted for age, gender, body mass index, waist to hip ratio and mean blood pressure. Our data suggest an important role of adiponectin in increased LVM/h(2.7) in visceral obesity-associated normotensive and hypertensive subjects. In this last group, adiponectin, more than blood pressure, may be able to explain the development of cardiac damage.

What Is the Role of Basal Weekly Insulin in Clinical Practice? The State of the Art.

Despite the advent of innovative therapies in the treatment of diabetes, ever-increasing awareness is still directed to the role of insulin since it has continued to be at the centre of diabetes therapy for decades, as a therapeutic integration of innovative agents in type 2 diabetes mellitus (T2DM), as the only replacement therapy in type 1 diabetes mellitus (T1DM) and also in gestational diabetes. In this context, the study of molecules such as weekly basal insulins, both for their technological and pharmacodynamic innovation and their manageability and undoubted benefits in compliance with drug therapy, can only be a turning point in diabetes and for all its phenotypes. This review aims to provide insight into the knowledge of basal weekly insulins and their use in type 1 and 2 diabetes mellitus by examining their safety, efficacy, manageability and increased therapeutic compliance.

Tirzepatide against obesity and insulin-resistance: pathophysiological aspects and clinical evidence.

Obesity is a chronic, multifactorial disease in which accumulated excess body fat has a negative impact on health. Obesity continues to rise among the general population, resulting in an epidemic that shows no significant signs of decline. It is directly involved in development of cardiometabolic diseases, ischemic coronary heart disease peripheral arterial disease, heart failure, and arterial hypertension, producing global morbidity and mortality. Mainly, abdominal obesity represents a crucial factor for cardiovascular illness and also the most frequent component of metabolic syndrome. Recent evidence showed that Tirzepatide (TZP), a new drug including both Glucagon Like Peptide 1 (GLP-1) and Glucose-dependent Insulinotropic Polypeptide (GIP) receptor agonism, is effective in subjects with type 2 diabetes (T2D), lowering body weight, fat mass and glycated hemoglobin (HbA1c) also in obese or overweight adults without T2D. This review discusses the pathophysiological mechanisms and clinical aspects of TZP in treating obesity.