Publications by authors named "Giorgio Sesti"

261 Publications

Impact of Sacubitril/Valsartan on Clinical and Echocardiographic Parameters in Heart Failure Patients With Reduced Ejection Fraction: Data From a Real Life 2-year Follow-Up Study.

Front Pharmacol 2021 16;12:733475. Epub 2021 Aug 16.

Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Catanzaro, Italy.

Heart failure (HF) represents a widespread health problem characterized by high morbidity and mortality. Sacubitril/Valsartan (sac/val) has improved clinical prognosis in patients affected by HF with reduced ejection fraction (HFrEF). The aim of this study was to evaluate the effectiveness and durability of sac/val treatment on the clinical, hemodynamic and echocardiographic parameters, in real-life consecutive HFrEF outpatients, evaluated up to 2-years of follow-up. We collected 300 repeated observations over time in 60 patients suffering of HFrEF and symptomatic despite optimal drug therapy. Patients with left ventricular ejection fraction (LVEF) <35 and II-III NYHA functional class were considered. All patients underwent to clinical-instrumental and laboratory determinations and Minnesota Living with HF Questionnaire (MLHFQ) every 6 months until 24 months to evaluate possible clinical benefits and adverse events. During a 2-year follow-up period and through a 6-monthly control of the study variables both clinical, hemodynamic, biochemical and echocardiographic parameters significantly improved, in particular cardiac index (CI), both atrial and ventricular volumes and global longitudinal strain (GLS). Furthermore, there was a reduction of NT-proBNP levels and betterment of renal function and NYHA functional class, demonstrating the efficacy and durability of sac/val treatment. In a multiple linear mixed model the longitudinal evolutions of CI were associated to concomitant changes of GLS and E/e' ratio. Our study, contemplating the collection of 300 repeated observations in 60 patients, provides a complete and detailed demonstration of sac/val effects, showing effectiveness, safety and effect durability of the treatment every 6 months up to 2-years of follow-up with significant improvement of several clinical, hemodynamic and echocardiographic parameters in HFrEF outpatients.
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http://dx.doi.org/10.3389/fphar.2021.733475DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8415264PMC
August 2021

Endothelial progenitor cells predict vascular damage progression in naive hypertensive patients according to sex.

Hypertens Res 2021 Sep 1. Epub 2021 Sep 1.

Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Catanzaro, Italy.

Low levels of endothelial progenitor cells (EPCs) are associated with cardiovascular (CV) morbidity and mortality. Early indicators of vascular damage represent independent predictors of CV prognosis. The aim of this study was to evaluate the possible association of EPCs and circulating cytokine levels with vascular damage markers in naive hypertensive patients according to sex and to evaluate the role of EPCs in vascular damage progression. We enrolled 60 subjects; circulating EPCs were determined by cytometric analysis, and serum cytokines were determined by chemiluminescence microarray technology. Endothelial function was estimated with the measurement of the reactive hyperemia index (RHI), arterial stiffness (AS) was evaluated with the measurement of carotid-femoral pulse wave velocity (PWV) and carotid intima-media thickness (IMT) was determined by a high-resolution ultrasound B-mode system. Patients were evaluated at baseline and after an average follow-up of 3.0 ± 0.6 years. RHI was correlated with EPCs and inversely related to HOMA, TNF-α, IL-6, hs-CRP, and IL-1β. PWV was positively correlated with HOMA, TNF-α, IL-6, IL-1β, and hs-CRP, and it was inversely related to EPCs. An inverse relationship was observed between c-IMT and EPCs and e-GFR. EPCs were the major predictor of the RHI and PWV. After adjustment for vascular index basal values and the other covariates, EPCs explained 17.0%, 27.7%, and 10.6% of the variability in ΔRHI, ΔPWV, and Δc-IMT at follow-up, respectively. Our study results support the hypothesis of an etiological link between circulating EPCs and morphofunctional vascular parameters in hypertensive subjects. Of interest, circulating EPCs, after adjusting for possible confounding factors, may indicate vascular damage progression.
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http://dx.doi.org/10.1038/s41440-021-00716-zDOI Listing
September 2021

Predictors of Renal Function Worsening in Patients with Chronic Obstructive Pulmonary Disease (COPD): A Multicenter Observational Study.

Nutrients 2021 Aug 16;13(8). Epub 2021 Aug 16.

Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, 88100 Catanzaro, Italy.

Background: Chronic obstructive pulmonary disease (COPD) patients have multiple comorbidities which may affect renal function. Chronic kidney disease (CKD) is a risk factor for adverse outcomes in COPD patients. The predictors of CKD in COPD are not well investigated.

Methods: A multicenter observational cohort study including patients affected by COPD (GOLD stages 1 and 2) was carried out. Principal endpoints were the incidence of CKD, as defined by an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m, and the rapid decline of eGFR >5 mL/min/1.73 m/year.

Results: We enrolled 707 outpatients. Overall, 157 (22.2%) patients had CKD at baseline. Patients with CKD were older, with higher serum uric acid (UA) levels, and lower FEV. During a mean follow-up of 52.3 ± 30.2 months, 100 patients developed CKD, and 200 patients showed a rapid reduction of eGFR. Multivariable Cox regression analysis displayed that UA (hazard ratio (HR) 1.148, < 0.0001) and diabetes (HR 1.050, < 0.0001) were predictors of incident CKD. The independent predictors of rapidly declining renal function were represented by an increase of 1 mg/dL in UA (odds ratio (OR) 2.158, < 0.0001)), an increase of 10 mL/min/1.73 m in baseline eGFR (OR 1.054, < 0.0001) and the presence of diabetes (OR 1.100, < 0.009).

Conclusions: This study shows that COPD patients have a significant worsening of renal function over time and that UA and diabetes were the two strongest predictors. Optimal management of these risk factors may reduce the incidence of CKD in this population thus probably improving clinical outcome.
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http://dx.doi.org/10.3390/nu13082811DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400083PMC
August 2021

The effects of the glycaemic control on the severity of the delirium in the advanced phase of Alzheimer's disease.

F1000Res 2020 16;9:1470. Epub 2020 Dec 16.

Sapienza University of Rome, ROMA CAPITALE, RM, 00100, Italy.

Background: Behavioral and psychological symptoms of dementia (BPSD) and delirium are common in advanced phases of Alzheimer's disease (AD).

Methods: Thirty-eight moderate-severe AD patients were enrolled (n=16 affected by type 2 diabetes). Each patient received a comprehensive geriatric assessment (CGA) (including evaluation of BPSD and frailty), and a complete metabolic evaluation (including the measurement of the glycated hemoglobin, HbA1c).

Results: Both the hyper- and hypo-glycemic extremes of the glycemic spectrum worsened BPSD, but delirium was more susceptible to hypoglycemic events. The severity of delirium was significantly related to cognitive function (r = -0.585, p<0.001) and frailty (r = +0.440, p<0.05).

Conclusions: The measurement of HbA1c was useful for evaluating the risk of delirium in relationship to glycemic control and nutritional status.
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http://dx.doi.org/10.12688/f1000research.26022.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278245.2PMC
August 2021

Impaired Clinical Efficacy of Aspirin in Hypoalbuminemic Patients With Diabetes Mellitus.

Front Pharmacol 2021 22;12:695961. Epub 2021 Jun 22.

Department of Clinical, Internal, Anaesthesiological, and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy.

To investigate the impact of albumin levels on the aspirin efficacy, since aspirin inhibits platelet aggregation (PA) by cyclooxygenase one irreversible acetylation that is less effective in patients with type 2 diabetes mellitus (T2DM). A total of 612 aspirin (100 mg/day)-treated T2DM patients were followed-up for 54.4 ± 7.3 months. The primary endpoint, a composite of cardiovascular events (CVEs) including CV death, myocardial infarction, ischemic stroke and coronary revascularization, was analysed according to baseline values of serum albumin (≥ or < 3.5 g/dL). Serum thromboxane (Tx)B was also measured. 250 (40.8%) patients had serum albumin < 3.5 g/dL; these patients were overweight and had higher values of fibrinogen ( = 0.009), high sensitivity C-reactive protein ( = 0.001) and fasting plasma glucose ( < 0.0001) compared to those with albumin ≥ 3.5 g/dL. During follow-up, 86 CVEs were recorded, 49 and 37 in patients with serum albumin < or ≥3.5 g/dL, respectively ( = 0.001). At multivariable Cox regression analysis, serum albumin < 3.5 g/dL (hazard ratio [HR] 1.887, 95% confidence interval [CI] 1.136-3.135, = 0.014), age (HR 1.552 for every 10 years, 95%CI 1.157-2.081, = 0.003), fasting plasma glucose (HR 1.063, 95%CI 1.022-1.105, = 0.002) and beta-blocker use (HR 0.440, 95%CI 0.270-0.717, = 0.001) were associated to CVEs. Serum TxB levels ( = 377) were 0.32 ± 0.12 and 0.24 ± 0.12 ng/ml in patients with albumin < or ≥ 3.5 g/dL, respectively ( < 0.001). In T2DM patients, the efficacy of aspirin varies according to albumin levels. Hypoalbuminemia associated with impaired TxB inhibition and an increased risk of long-term CVEs.
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http://dx.doi.org/10.3389/fphar.2021.695961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8258313PMC
June 2021

Sarcopenia and Appendicular Muscle Mass as Predictors of Impaired Fasting Glucose/Type 2 Diabetes in Elderly Women.

Nutrients 2021 Jun 2;13(6). Epub 2021 Jun 2.

Department of Clinical and Experimental Medicine, University Magna Grecia, 88100 Catanzaro, Italy.

Elderly women exhibit a high risk of type 2 diabetes (T2D), but no definitive data exist about the possible role of postmenopausal increases in visceral adiposity, the loss of lean body mass, or decreases in the sum of the lean mass of arms and legs (appendicular skeletal muscle mass (ASMM)). This retrospective, longitudinal study investigated whether body composition (bioelectrical impedance analysis) predicted the development of impaired fasting glucose (IFG) or T2D in a cohort of 159 elderly women (age: 71 ± 5 years, follow-up: 94 months) from southern Italy (Clinical Nutrition and Geriatric Units of the "Mater Domini" University Hospital in Catanzaro, Calabria region, and the "P. Giaccone "University Hospital in Palermo, Sicily region). Sarcopenia was defined in a subgroup of 128 women according to the EWGSOP criteria as the presence of low muscle strength (handgrip strength <16 kg) plus low muscle mass (reported as appendicular skeletal muscle mass <15 kg). Participants with a low ASMM had a higher IFG/T2D incidence than those with a normal ASMM (17% vs. 6%, p-adjusted = 0.044); this finding was independent of BMI, fat mass, waist circumference, and habitual fat intake (OR = 3.81, = 0.034). A higher incidence of IFG/T2D was observed in the subgroup with sarcopenia than those without sarcopenia (33% vs. 7%, p-adjusted = 0.005) independent of BMI and fat mass (OR = 6.75, = 0.007). In conclusion, this study demonstrates that elderly women with low ASMM had a higher probability of developing IFG/T2D. Further studies are needed to confirm these results in men and in other age groups.
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http://dx.doi.org/10.3390/nu13061909DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8227668PMC
June 2021

Neutrophil degranulation biomarkers characterize restrictive echocardiographic pattern with diastolic dysfunction in patients with diabetes.

Eur J Clin Invest 2021 Jun 15:e13640. Epub 2021 Jun 15.

Department of Internal Medicine, First Clinic of internal Medicine, University of Genoa, Genoa, Italy.

Objective: To investigate the potential association between neutrophil degranulation and patterns of myocardial dysfunction in a cohort of patients with type 2 diabetes mellitus (T2DM).

Background: Two distinct phenotypes of diabetic cardiomyopathy have been described: a restrictive phenotype with diastolic dysfunction (restrictive/DD) and a dilative phenotype with systolic dysfunction (dilative/SD). However, the underlying determinants of these two patterns are not yet recognized.

Methods: In this single-centre, observational, cross-sectional study, 492 patients were recruited. Ultrasonographic measurements were performed by two experienced sonographers, blinded to the clinical data of the participants. Serum biomarkers of neutrophil degranulation were measured by enzyme-linked immunosorbent sandwich assay (ELISA).

Results: After adjustment for confounders, resistin, myeloperoxidase, matrix metalloproteinase 8 and matrix metalloproteinase 9/tissue inhibitor of metalloproteinases 1 complex were positively associated with the restrictive/DD pattern compared with the normal pattern. Similarly, MPO was positively associated with the dilative/SD pattern compared with the normal pattern, and resistin was negatively associated with the dilative/SD pattern compared with the restrictive/DD pattern.

Conclusions: Neutrophil degranulation is associated with the restrictive/DD echocardiographic pattern in patients with T2DM, but not with the normal pattern and dilative/SD patterns. Neutrophils could have a pivotal role in the pathogenesis of myocardial dysfunction, and particularly diastolic dysfunction, in patients with T2DM.
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http://dx.doi.org/10.1111/eci.13640DOI Listing
June 2021

Hyperglycemia at 1h-OGTT in Pregnancy: A Reliable Predictor of Metabolic Outcomes?

Front Endocrinol (Lausanne) 2021 24;12:612829. Epub 2021 May 24.

Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, Italy.

Gestational diabetes mellitus (GDM) is associated with a high risk of developing type 2 diabetes (T2DM) and cardiovascular disease (CVD). Identifying among GDM women those who are at high risk may help prevent T2DM and, possibly CVD. Several studies have shown that in women with GDM, hyperglycemia at 1 h during an oral glucose tolerance test (OGTT) (1-h PG) is not only associated with an increase in adverse maternal and perinatal outcomes but is also an independent predictor of T2DM. Interestingly, also in pregnant women who did not meet the criteria for a GDM diagnosis, 1-h PG was an independent predictor of postpartum impaired insulin sensitivity and beta-cell dysfunction. Moreover, maternal 1- and 2-h PG levels have been found to be independently associated with insulin resistance and impaired insulin secretion also during childhood. There is evidence that hyperglycemia at 1h PG during pregnancy may identify women at high risk of future CVD, due to its association with an unfavorable CV risk profile, inflammation, arterial stiffness and endothelial dysfunction. Overall, hyperglycemia at 1h during an OGTT in pregnancy may be a valuable prediction tool for identifying women at a high risk of future T2DM, who may then benefit from therapeutic strategies aimed at preventing cardiovascular outcomes.
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http://dx.doi.org/10.3389/fendo.2021.612829DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8181723PMC
May 2021

Depressed myocardial mechano-energetic efficiency in subjects with dysglycemia.

Diabetes Res Clin Pract 2021 Jul 1;177:108883. Epub 2021 Jun 1.

Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome 00189, Italy. Electronic address:

Aims: Evidence indicate that 1 h post-load glucose levels (1hPG) ≥ 155 mg/dl identify amongst subjects with normal glucose tolerance (NGT) a new category of prediabetes (NGT 1 h-high). A compromised myocardial mechano-energetic efficiency (MEE) is associated with type 2 diabetes and predicts adverse cardiovascular outcomes. Herein, we explored the association between prediabetes conditions such as NGT 1 h-high, impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) and a decreased MEE.

Methods: MEE was assessed by an echocardiography-derived measure in 1467 non-diabetic individuals subdivided according to their glucose tolerance: NGT and 1-hPG < 155 mg/dl (NGT 1 h-low, n = 617), NGT 1 h-high (n = 210), isolated IFG (n = 237), and IGT (n = 403).

Results: Subjects with NGT 1 h-high, isolated IFG, and IGT displayed a higher myocardial oxygen consumption, and a decreased MEE in comparison to NGT 1 h-low group. MEE was inversely related to male sex, age, body mass index, total cholesterol, triglycerides, fasting and post-load glucose and insulin, C reactive protein, and positively correlated with insulin sensitivity estimated by the Matsuda index. In a stepwise multivariate linear regression model including several cardio-metabolic risk factors, 1hPG was the major predictor of MEE.

Conclusions: Subjects with NGT 1 h-high, isolated IFG, and IGT have a raised myocardial oxygen consumption and a reduced MEE.
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http://dx.doi.org/10.1016/j.diabres.2021.108883DOI Listing
July 2021

The TRIB3 R84 variant is associated with increased left ventricular mass in a sample of 2426 White individuals.

Cardiovasc Diabetol 2021 05 29;20(1):115. Epub 2021 May 29.

Department of Clinical and Molecular Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161, Rome, Italy.

Background: Prior studies in animal models showed that increased cardiac expression of TRIB3 has a pathogenic role in inducing left ventricular mass (LVM). Whether alterations in TRIB3 expression or function have a pathogenic role in inducing LVM increase also in humans is still unsettled. In order to address this issue, we took advantage of a nonsynonymous TRIB3 Q84R polymorphism (rs2295490), a gain-of-function amino acid substitution impairing insulin signalling, and action in primary human endothelial cells which has been associated with insulin resistance, and early vascular atherosclerosis.

Methods: SNP rs2295490 was genotyped in 2426 White adults in whom LVM index (LVMI) was assessed by validated echocardiography-derived measures.

Results: After adjusting for age and sex, LVMI progressively and significantly increased from 108 to 113, to 125 g/m in Q84Q, Q84R, and R84R individuals, respectively (Q84R vs. Q84Q, P = 0.03; R84R vs. Q84Q, P < 0.0001). The association between LVMI and the Q84R and R84R genotype remained significant after adjusting for blood pressure, smoking habit, fasting glucose levels, glucose tolerance status, anti-hypertensive treatments, and lipid-lowering therapy (Q84R vs. Q84Q, P = 0.01; R84R vs. Q84Q, P < 0.0001).

Conclusions: We found that the gain-of-function TRIB3 Q84R variant is significantly associated with left ventricular mass in a large sample of White nondiabetic individual of European ancestry.
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http://dx.doi.org/10.1186/s12933-021-01308-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164223PMC
May 2021

Clinical factors associated with death in 3044 COVID-19 patients managed in internal medicine wards in Italy: results from the SIMI-COVID-19 study of the Italian Society of Internal Medicine (SIMI).

Intern Emerg Med 2021 Jun 24;16(4):1005-1015. Epub 2021 Apr 24.

Internal Medicine Department, San Carlo Hospital, Paderno Dugnano, Milan, Italy.

During the COVID-19 2020 outbreak, a large body of data has been provided on general management and outcomes of hospitalized COVID-19 patients. Yet, relatively little is known on characteristics and outcome of patients managed in Internal Medicine Units (IMU). To address this gap, the Italian Society of Internal Medicine has conducted a nationwide cohort multicentre study on death outcome in adult COVID-19 patients admitted and managed in IMU. This study assessed 3044 COVID-19 patients at 41 referral hospitals across Italy from February 3rd to May 8th 2020. Demographics, comorbidities, organ dysfunction, treatment, and outcomes including death were assessed. During the study period, 697 patients (22.9%) were transferred to intensive care units, and 351 died in IMU (death rate 14.9%). At admission, factors independently associated with in-hospital mortality were age (OR 2.46, p = 0.000), productive cough (OR 2.04, p = 0.000), pre-existing chronic heart failure (OR 1.58, p = 0.017) and chronic obstructive pulmonary disease (OR 1.17, p = 0.048), the number of comorbidities (OR 1.34, p = 0.000) and polypharmacy (OR 1.20, p = 0.000). Of note, up to 40% of elderly patients did not report fever at admission. Decreasing PaO/FiO ratio at admission was strongly inversely associated with survival. The use of conventional oxygen supplementation increased with the number of pre-existing comorbidities, but it did not associate with better survival in patients with PaO/FiO ratio < 100. The latter, significantly benefited by the early use of non-invasive mechanical ventilation. Our study identified PaO/FiO ratio at admission and comorbidity as the main alert signs to inform clinical decisions and resource allocation in non-critically ill COVID-19 patients admitted to IMU.
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http://dx.doi.org/10.1007/s11739-021-02742-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065333PMC
June 2021

COPD significantly increases cerebral and cardiovascular events in hypertensives.

Sci Rep 2021 Apr 12;11(1):7884. Epub 2021 Apr 12.

Department of Medical and Surgical Sciences, University Magna Græcia, Viale Europa-Loc. Germaneto, 88100, Catanzaro, Italy.

Essential hypertension and chronic obstructive pulmonary disease often coexist in the same patient. The aim of this study was to evaluate whether the addition of chronic obstructive pulmonary disease modifies the risk of cardiovascular events in hypertensives. We enrolled 1728 hypertensives. Study outcomes included fatal and non-fatal cardiovascular stroke and myocardial infarction, and cardiovascular death. During a mean follow-up of 57 months there were 205 major adverse cardiovascular events (2.47 per 100 pts/yr): cardiac (n117; 1.41 per 100 pts/yr) and cerebrovascular (n = 77; 0.93 per 100 pts/yr). In hypertensives with chronic obstructive pulmonary disease we observed a greater number of cardiovascular events than in hypertensives without respiratory disease (133 [5.55 per 100 pts/yr) vs 72 [1.22 per 100 pts/yr], respectively. The addition of chronic obstructive pulmonary disease to hypertension increased the incidence of total and non-fatal stroke of more than nine- (2.42 vs 0.32 per 100 pts/yr) and 11-fold (2.09 vs 0.22 per 100 pts/yr), respectively. The same trend was observed for total (2.88 vs 0.81 per 100 pts/yr) and non-fatal (2.67 vs 0.79 per 100 pts/y) myocardial infarction. The presence of chronic obstructive pulmonary disease in hypertensives significantly increases the risk of stroke, myocardial infarction and major adverse cardiovascular events.
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http://dx.doi.org/10.1038/s41598-021-86963-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042020PMC
April 2021

Nox2 up-regulation and hypoalbuminemia in patients with type 2 diabetes mellitus.

Free Radic Biol Med 2021 05 26;168:1-5. Epub 2021 Mar 26.

Mediterranea Cardiocentro, Napoli, Italy; Department of Clinical, Internal, Anaesthesiologic, and Cardiovascular Sciences, Sapienza University of Rome, Rome, Italy. Electronic address:

Type 2 diabetes mellitus (T2DM) is associated with oxidative stress but the underlying mechanisms promoting oxidative stress as well as its relationship with cardiovascular events is still unclear. In 375 T2DM patients who were followed-up for approximately 5 years we measured the serum levels of soluble NOX2-derived peptide (sNOX2-dp), a marker of Nox2 activation, and albumin, a powerful antioxidant protein. In the entire cohort soluble Nox2 and serum albumin were significantly correlated (r = -0.348, P < 0.0001). During the follow-up 49 cardiovascular events (CVE) were registered, of which 45 were non-fatal myocardial infarction (MI); patients with non-fatal MI had significantly higher soluble NOX2/albumin ratio compared to cardiovascular events-free patients. Cox regression analysis showed a significant association between sNox2-dp/serum albumin ratio and the incidental risk of non-fatal MI (HR 1.106, CI95% 1.020-1.198, P = 0.014). The study suggests that redox status imbalance negatively influences vascular outcomes in T2DM.
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http://dx.doi.org/10.1016/j.freeradbiomed.2021.03.026DOI Listing
May 2021

Continuous Positive Airway Pressure Improves Renal Function in Obese Patients With Obstructive Sleep Apnea Syndrome.

Front Med (Lausanne) 2021 3;8:642086. Epub 2021 Mar 3.

Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.

Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for cardiovascular morbidity and mortality, and it has a detrimental effect on renal function. Obesity is the major risk factor for OSAS, and represents a risk factor for chronic kidney disease. Continuous positive airway pressure (CPAP) is the suggested therapy for moderate-to-severe OSAS. We designed this study to evaluate the effect of CPAP on estimated glomerular filtration rate (e-GFR) in a cohort of obese patients with moderate-to-severe OSAS and normal renal function. We enrolled 198 obese subjects, divided into two groups (OSAS+ and OSAS-), on the basis of cardiorespiratory monitoring; mild OSAS patients ( = 33) were excluded from the study, thus the analyses were conducted on 165 patients. Comparisons between groups were made by Student -test or χ test as appropriate. Linear regression analyses were used to assess the relationship between baseline e-GFR and different covariates and, in the OSAS+ group, between Δe-GFR and different covariates. A multivariate regression analysis was performed to determinate the independent predictor of the Δe-GFR. OSAS+ subjects showed significantly increased values of systolic blood pressure, HOMA, pulse wave velocity, high-sensitivity C reactive protein and uric acid compared with OSAS- group. OSAS+ group showed significantly lower values of e-GFR and increased values of microalbuminuria. At linear regression analysis e-GFR resulted significantly and inversely related to AHI in the whole study population and in the two groups. After 6 months of CPAP therapy, OSAS+ subjects showed an improvement in respiratory parameters, as well as a significant increase in e-GFR values (104.2 + 19.0 vs. 84.0 + 13.1 ml/min/1.73 m, < 0.0001). At multiple regression analysis, Δ apnea/hypopnea index (AHIa) resulted the main independent predictor of Δe-GFR explaining 22% of its variation. Obese OSAS patients show significantly lower values of e-GFR, even if in the normal range, compared with obese non-OSAS subjects. After 6 months of CPAP, e-GFR significantly improved (+20 ml/min/1.73 m) and ΔAHIa resulted the most important independent predictor of Δe-GFR.
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http://dx.doi.org/10.3389/fmed.2021.642086DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7965975PMC
March 2021

Accuracy of 1-Hour Plasma Glucose During the Oral Glucose Tolerance Test in Diagnosis of Type 2 Diabetes in Adults: A Meta-analysis.

Diabetes Care 2021 04;44(4):1062-1069

Public Health Promotion Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.

Objective: One-hour plasma glucose (1-h PG) during the oral glucose tolerance test (OGTT) is an accurate predictor of type 2 diabetes. We performed a meta-analysis to determine the optimum cutoff of 1-h PG for detection of type 2 diabetes using 2-h PG as the gold standard.

Research Design And Methods: We included 15 studies with 35,551 participants from multiple ethnic groups (53.8% Caucasian) and 2,705 newly detected cases of diabetes based on 2-h PG during OGTT. We excluded cases identified only by elevated fasting plasma glucose and/or HbA. We determined the optimal 1-h PG threshold and its accuracy at this cutoff for detection of diabetes (2-h PG ≥11.1 mmol/L) using a mixed linear effects regression model with different weights to sensitivity/specificity (2/3, 1/2, and 1/3).

Results: Three cutoffs of 1-h PG, at 10.6 mmol/L, 11.6 mmol/L, and 12.5 mmol/L, had sensitivities of 0.95, 0.92, and 0.87 and specificities of 0.86, 0.91, and 0.94 at weights 2/3, 1/2, and 1/3, respectively. The cutoff of 11.6 mmol/L (95% CI 10.6, 12.6) had a sensitivity of 0.92 (0.87, 0.95), specificity of 0.91 (0.88, 0.93), area under the curve 0.939 (95% confidence region for sensitivity at a given specificity: 0.904, 0.946), and a positive predictive value of 45%.

Conclusions: The 1-h PG of ≥11.6 mmol/L during OGTT has a good sensitivity and specificity for detecting type 2 diabetes. Prescreening with a diabetes-specific risk calculator to identify high-risk individuals is suggested to decrease the proportion of false-positive cases. Studies including other ethnic groups and assessing complication risk are warranted.
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http://dx.doi.org/10.2337/dc20-1688DOI Listing
April 2021

Sex-specific differences in left ventricular mass and myocardial energetic efficiency in non-diabetic, pre-diabetic and newly diagnosed type 2 diabetic subjects.

Cardiovasc Diabetol 2021 03 6;20(1):60. Epub 2021 Mar 6.

Department of Clinical and Molecular Medicine, University of Rome-Sapienza, 00189, Rome, Italy.

Background: Women with type 2 diabetes (T2DM) have a higher excess risk for cardiovascular disease (CVD) than their male counterparts. However, whether the risk for CVD is higher in prediabetic women than men is still debated. We aimed to determine whether sex-related differences exist in left ventricular mass index (LVMI), and myocardial mechano-energetic efficiency (MEEi) in with normal glucose tolerant (NGT), pre-diabetic and newly diagnosed type 2 diabetic subjects.

Methods: Sex-related differences in LVMI and myocardial MEEi, assessed by validated echocardiography-derived measures, were examined among 1562 adults with NGT, prediabetes, and newly diagnosed T2DM, defined according to fasting glucose, 2-h post-load glucose, or HbA1c.

Results: Worsening of glucose tolerance in both men and women was associated with an increase in age-adjusted LVMI and myocardial MEEi. Women with newly diagnosed T2DM exhibited greater relative differences in LVMI and myocardial MEEi than diabetic men when compared with their NGT counterparts. Prediabetic women exhibited greater relative differences in myocardial MEEi, but not in LVMI, than prediabetic men when compared with their NGT counterparts. The statistical test for interaction between sex and glucose tolerance on both LVMI (P < 0.0001), and myocardial MEEi (P < 0.0001) was significant suggesting a sex-specific association.

Conclusions: Left ventricle is subject to maladaptive changes with worsening of glucose tolerance, especially in women with newly diagnosed T2DM. The sex-specific increase in LVM and decrease in MEEi, both being predictors of CVD, may have a role in explaining the stronger impact of T2DM on the excess risk of CVD in women than in men.
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http://dx.doi.org/10.1186/s12933-021-01248-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937311PMC
March 2021

Correspondence on 'Disease activity, cytokines, chemokines and the risk of incident diabetes in rheumatoid arthritis'.

Ann Rheum Dis 2021 Feb 22. Epub 2021 Feb 22.

Unit of Allergology, Immunology, Rheumatology, Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy.

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http://dx.doi.org/10.1136/annrheumdis-2021-220047DOI Listing
February 2021

One Hour-Post-load Plasma Glucose ≥155 mg/dl in Healthy Glucose Normotolerant Subjects Is Associated With Subcortical Brain MRI Alterations and Impaired Cognition: A Pilot Study.

Front Aging Neurosci 2021 4;13:608736. Epub 2021 Feb 4.

Geriatrics Division, Department of Medical and Surgical Sciences, Magna Graecia University, Catanzaro, Italy.

Glucose alterations are associated with impaired cognition. The 1-h-post-load plasma glucose ≥155 mg/dl in non-diabetic subjects confers an increased risk of cardiovascular events and diabetes. This pilot study aimed to investigate whether the 1-h-post-load plasma glucose ≥155 mg/dl negatively affects the subcortical regions of the brain and the cognitive functions. We enrolled 32 non-diabetic subjects. Patients were divided into two groups based on 1-h- post-load plasma glucose value > or < 155 mg/dl: normal glucose tolerance (NGT) 1-h-high and NGT 1-h-low subjects. All subjects underwent 3 Tesla MRI and standard neuropsychological tests. NGT 1-h-high subjects showed significantly lower values of both right (4.9 ± 0.9 vs. 5.1 ± 0.9 ml) and left (4.8 ± 1.1 vs. 5.1 ± 1.1 ml) hippocampal hemisphere volume, while right hemisphere hippocampal diffusivity was lower in the NGT 1-h-high group (10.0 ± 0.6 vs. 10.6 ± 0.5 10 mms). NGT 1-h-high subjects also showed a poorer memory performance. In particular, for both Rey Auditory Verbal Learning Task (RAVLT)-immediate-recall and Free and Cued Selective Reminding Test (FCSRT)-delayed total recall, we found lower cognitive test scores in the NGT-1 h-high group (26.5 ± 6.3 and 10.4 ± 0.3, respectively). One-hour-post-load hyperglycemia is associated with morpho-functional subcortical brain alterations and poor memory performance tests.
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http://dx.doi.org/10.3389/fnagi.2021.608736DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7891177PMC
February 2021

Effects of Alpha-2-HS-glycoprotein on cognitive and emotional assessment in prediabetic and diabetic subjects.

J Affect Disord 2021 03 29;282:700-706. Epub 2020 Dec 29.

Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Viale Europa, Loc. Germaneto, Catanzaro 88100, Italy.

Background: High concentrations of Alpha-2-HS-glycoprotein, also called Fetuin-A (Fet-A), are associated with insulin resistance, obesity, non-alcoholic fatty liver disease, type 2 diabetes and polycystic ovary syndrome. Moreover, Fet-A is able to cross the bloodbrain barrier into ischemic brain tissue in adult humans. Although the brain is an important target of insulin action, there is little evidence associating serum levels of Fet-A with psychiatric conditions such as depression and cognitive decline, and no reports about the presence and degree of anxiety disorders.

Methods: We have examined cognitive and emotional alterations in a Caucasian population of 94 subjects.

Results: Our data confirmed that, irrespective of insulin sensitivity status, circulating Fet-A levels are positively associated with an increased risk of showing signs of depression according to the BDI-II test, and have reported new evidences of a positive association between Fet-A and state- and trait- anxiety, as measured by the STAI questionnaires. In contrast, no association was observed between Fet-A levels and cognitive performance on the MMSE.

Limitations: Although the study includes a well-characterized population, the small sample size and cross sectional nature are important limitations, and this results should not be considered definitive. The data are based only on Caucasian subjects and their generalizability to other ethnic groups should be done with caution.

Conclusion: Overall, these data suggest for the first time a role of Fet-A as an independent risk factor in the development of symptoms of anxiety and depression in prediabetic and diabetic subjects.
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http://dx.doi.org/10.1016/j.jad.2020.12.135DOI Listing
March 2021

Impact of Mediterranean Diet on Disease Activity and Gut Microbiota Composition of Rheumatoid Arthritis Patients.

Microorganisms 2020 Dec 14;8(12). Epub 2020 Dec 14.

Department of Clinical and Molecular Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, 00185 Rome, Italy.

Rheumatoid arthritis (RA) is an autoimmune disorder in which gut and oral microbiota play a crucial role. Diet is a modifiable factor that can influence both microbiota composition and arthritis outcome; previous studies have suggested associations between dietary habits and RA, with contrasting results. We investigate the protective effect of the Mediterranean diet (MD) on disease activity and the gut microbiota profile in RA patients. Sixty consecutive RA patients were enrolled upon filling a validated 14-item questionnaire for the assessment of adherence to the Mediterranean diet (Prevention with Mediterranean Diet-PREDIMED). Then, 16S analysis was employed to explore the gut microbiota within the two cohorts of patients. Patients with high adherence to MD (20) had a significantly lower C-reactive protein ( < 0.037) and disease activity ( < 0.034) than the 40 patients with low/moderate adherence to MD. An inverse association between MD and disease activity was confirmed by multivariate analysis after adjustments for all the different demographic, clinical and serologic variables. A healthier gut microbiota composition was observed in the high adherence group, with a significant decrease in Lactobacillaceae and an almost complete absence of with respect to the low/moderate adherence group. In conclusion, our findings support the protective role of MD on disease activity and microbiota composition in RA patients, and suggest the feasibility of shifting the habitual diet to modulate the gut microbiota and promote the benefits associated with MD.
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http://dx.doi.org/10.3390/microorganisms8121989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764882PMC
December 2020

Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus.

Circ Genom Precis Med 2020 12 13;13(6):e002769. Epub 2020 Aug 13.

The Usher Institute of Population Health Sciences & Informatics (A.D.M.), University of Edinburgh, Edinburgh, U.K.

Background: Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).

Methods: To test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).

Results: None of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.

Conclusions: This study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.
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http://dx.doi.org/10.1161/CIRCGEN.119.002769DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7748049PMC
December 2020

Recurrent COVID-19 pneumonia in the course of chemotherapy: Consequence of a weakened immune system?

J Med Virol 2021 04 17;93(4):1882-1884. Epub 2020 Dec 17.

Emergency Medicine COVID-19 Unit, Department of Clinical and Molecular Medicine, Faculty of Medicine and Psychology, Sant'Andrea University Hospital, Sapienza University, Rome, Italy.

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http://dx.doi.org/10.1002/jmv.26701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753699PMC
April 2021

Endothelial dysfunction and C-reactive protein predict the incidence of heart failure in hypertensive patients.

ESC Heart Fail 2021 02 25;8(1):399-407. Epub 2020 Nov 25.

Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Viale Europa, Catanzaro, 88100, Italy.

Aims: Endothelial dysfunction and heart failure are associated, but no prospective studies demonstrated that impaired endothelium-dependent vasodilation predicts incident heart failure. We designed this study to test whether endothelial dysfunction is associated with incident heart failure in a group of hypertensives.

Methods And Results: We enrolled 735 White never-treated hypertensive outpatients free from heart failure, diabetes, chronic kidney disease, and previous cardiovascular events. Endothelium-dependent vasodilation was investigated by intra-arterial infusion of acetylcholine, and laboratory determinations were obtained by standard procedures. During the follow-up [median 114 months (range 26-206)], there were 208 new cases of heart failure (3.1 events/100 patient-years). Dividing the study population in progressors and non-progressors, we observed that progressors were older, showed a higher prevalence of being female, and had a higher baseline heart rate, glucose, insulin, Homeostatic Model Assessment (HOMA), creatinine, and high-sensitivity C-reactive protein (hs-CRP) mean values, while estimated glomerular filtration rate and maximal acetylcholine-stimulated forearm blood flow were lower. In the multiple Cox regression analysis, female gender [hazard ratio (HR) = 1.454, 95% CI = 1.067-1.981], fasting glucose (HR = 1.186, 95% CI = 1.038-1.357), hs-CRP (HR = 1.162, 95% CI = 1.072-1.259), HOMA (HR = 1.124, 95% CI = 1.037-1.219), acetylcholine-stimulated forearm blood flow (HR = 0.779, 95% CI = 0.695-0.874), and estimated glomerular filtration rate (HR = 0.767, 95% CI = 0.693-0.849) maintained an independent association with the outcome. Successively, testing the interaction between forearm blood flow and hs-CRP, we observed that patients who have hs-CRP values above the median and forearm blood flow under the median show a higher risk of developing heart failure (HR = 7.699, 95% CI = 4.407-13.451).

Conclusions: The present data demonstrate that an impaired endothelium-dependent vasodilation and hs-CRP predict development of incident heart failure in hypertensives.
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http://dx.doi.org/10.1002/ehf2.13088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7835547PMC
February 2021

Psychological Distress in Patients with Autoimmune Arthritis during the COVID-19 Induced Lockdown in Italy.

Microorganisms 2020 Nov 18;8(11). Epub 2020 Nov 18.

Department of Clinical and Molecular Medicine, Sant'Andrea University Hospital, Sapienza University of Rome, 00185 Rome, Italy.

Lockdowns imposed by governments worldwide as a way to limit the spread of severe atypical respiratory syndrome-coronavirus-2 (SARS-CoV2) have had heavy psychological and economic consequences. Arthritis patients are a vulnerable population at an increased risk of peritraumatic stress. This could be due to several reasons, including the fear of shortage of medicine and difficulty receiving periodical medical checks. In the present case-control study, psychological distress in patients with autoimmune arthritis during the coronavirus disease 2019 (COVID-19) pandemic were investigated. An electronic survey was conducted to gather information on the perceived change in the emotional state, general health (GH), fatigue, joint pain, and disease activity during the lockdown, in 100 patients with autoimmune arthritis and 100 controls. Mental health status was measured using the Depression, Anxiety and Stress Scale (DASS-21). The COVID-19 Peritraumatic Distress Index (CPDI) was used to assess the frequency of peritraumatic stress disorders related to COVID-19. Patients reported a significant worsening of perceived GH (36% vs. 7%; < 0.001), a significantly higher mean CPDI score ( < 0.001) than controls. Using multivariate analysis, arthritis patients had significantly higher CPDI scores (+3.67 points; = 0.019), independent of depression, anxiety, and stress symptoms, comorbidities, and sociodemographic and lifestyle characteristics. Logistic regression analysis showed that the risk of reporting worsened GH was 9-fold higher in patients than controls ( < 0.001). Patients with autoimmune arthritis are at higher risk of psychological distress related to COVID-19 pandemic; thus targeted intervention should be designed to strengthen coping capacity in this vulnerable population.
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http://dx.doi.org/10.3390/microorganisms8111818DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698862PMC
November 2020

Pioglitazone corrects dysregulation of skeletal muscle mitochondrial proteins involved in ATP synthesis in type 2 diabetes.

Metabolism 2021 01 31;114:154416. Epub 2020 Oct 31.

Division of Diabetes, Department of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, TX, United States of America; Endocrinology and Metabolism, Department of Health Science, University of Milan, Diabetologia e Malattie Metaboliche, Aziende Socio Sanitarie Territoriali Santi Paolo e Carlo, Milan, Italy. Electronic address:

Context: In this study, we aimed to identify the determinants of mitochondrial dysfunction in skeletal muscle (SKLM) of subjects with type 2 diabetes (T2DM), and to evaluate the effect of pioglitazone (PIO) on SKLM mitochondrial proteome.

Methods: Two different groups of adults were studied. Group I consisted of 8 individuals with normal glucose tolerance (NGT) and 8 with T2DM, subjected to SKLM mitochondrial proteome analysis by 2D-gel electrophoresis followed by mass spectrometry-based protein identification. Group II included 24 individuals with NGT and 24 with T2DM, whose SKLM biopsies were subjected to immunoblot analysis. Of the 24 subjects with T2DM, 20 were randomized to receive placebo or PIO (15 mg daily) for 6 months. After 6 months of treatment, SKLM biopsy was repeated.

Results: Mitochondrial proteomic analysis on Group I revealed that several mitochondrial proteins involved in oxidative metabolism were differentially expressed between T2DM and NGT groups, with a downregulation of ATP synthase alpha chain (ATP5A), electron transfer flavoprotein alpha-subunit (ETFA), cytochrome c oxidase subunit VIb isoform 1 (CX6B1), pyruvate dehydrogenase protein X component (ODPX), dihydrolipoamide dehydrogenase (DLDH), dihydrolipoamide-S-succinyltransferase (DLST), and mitofilin, and an up-regulation of hydroxyacyl-CoA-dehydrogenase (HCDH), 3,2-trans-enoyl-CoA-isomerase (D3D2) and delta3,5-delta2,4-dienoyl-CoA-isomerase (ECH1) in T2DM as compared to NGT subjects. By immunoblot analysis on SKLM lysates obtained from Group II we confirmed that, in comparison to NGT subjects, those with T2DM exhibited lower protein levels of ATP5A (-30%, P = 0.006), ETFA (-50%, P = 0.02), CX6B1 (-30%, P = 0.03), key factors for ATP biosynthesis, and of the structural protein mitofilin (-30%, P = 0.01). T2DM was associated with a reduced abundance of the enzymes involved in the Krebs cycle DLST and ODPX (-20%, P ≤ 0.05) and increased levels of HCDH and ECH1, enzymes implicated in the fatty acid catabolism (+30%, P ≤ 0.05). In subjects with type 2 diabetes treated with PIO for 6 months we found a restored SKLM protein abundance of ATP5A, ETFA, CX6B1, and mitofilin. Moreover, protein levels of HCDH and ECH1 were reduced by -10% and - 15% respectively (P ≤ 0.05 for both) after PIO treatment.

Conclusion: Type 2 diabetes is associated with reduced levels of mitochondrial proteins involved in oxidative phosphorylation and an increased abundance of enzymes implicated in fatty acid catabolism in SKLM. PIO treatment is able to improve SKLM mitochondrial proteomic profile in subjects with T2DM.
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http://dx.doi.org/10.1016/j.metabol.2020.154416DOI Listing
January 2021

Coinfection of Tuberculosis Pneumonia and COVID-19 in a Patient Vaccinated with Bacille Calmette-Guérin (BCG): Case Report.

SN Compr Clin Med 2020 Oct 17:1-4. Epub 2020 Oct 17.

Faculty of Medicine and Psychology, Department of Clinical and Molecular Medicine, Internal Medicine Unit, Sant'Andrea University Hospital, Sapienza University, Rome, Italy.

COVID-19 is a respiratory tract infection caused by the new coronavirus SARS-COV2 that can be complicated by acute distress respiratory syndrome and multiorgan failure. In light of the high rate of mortality associated with COVID-19, pharmacological and non-pharmacological strategies to prevent the infection are currently being tested. Among non-pharmacological preventive measures, vaccines represent one of the main resources for public health. It has been suggested that Bacille Calmette-Guérin (BCG) vaccine may protect individuals against infection from COVID-19 virus, and two clinical trials addressing this question are underway. Here, we report the case of a 32-year-old woman, vaccinated with BCG when she was 1 year old, who was diagnosed with apical tuberculous pneumonia of the right lung along with COVID 19 pneumonia.
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http://dx.doi.org/10.1007/s42399-020-00601-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568690PMC
October 2020

HDL (High-Density Lipoprotein) and ApoA-1 (Apolipoprotein A-1) Potentially Modulate Pancreatic α-Cell Glucagon Secretion.

Arterioscler Thromb Vasc Biol 2020 12 22;40(12):2941-2952. Epub 2020 Oct 22.

Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Italy (G.S.).

Objective: Subjects with low levels of HDL (high-density lipoprotein) and ApoA-1 (apolipoprotein A-1) have increased risk to develop type 2 diabetes. HDL levels are an independent predictor of β-cell function and positively modulate it. Type 2 diabetes is characterized by defects in both β and α-cell function, but the effect of HDL and ApoA1 on α-cell function is unknown. Approach and Results: We observed a significant negative correlation (=-0.422, <0.0001) between HDL levels and fasting glucagon in a cohort of 132 Italian subjects. In a multivariable regression analysis including potential confounders such as age, sex, BMI, triglycerides, total cholesterol, fasting and 2-hour postload glucose, and fasting insulin, the association between HDL and fasting glucagon remained statistically significant (β=-0.318, =0.006). CD1 mice treated with HDL or ApoA-1 for 3 consecutive days showed a 32% (<0.001) and 23% (<0.05) reduction, respectively, in glucagon levels following insulin-induced hypoglycemia, compared with controls. Treatment of pancreatic αTC1 clone 6 cells with HDL or ApoA-1 for 24 hours resulted in a significant reduction of glucagon expression (<0.04) and secretion (<0.01) after an hypoglycemic stimulus and increased Akt (RAC-alpha serine/threonine-protein kinase) and FoxO1 (forkhead/winged helix box gene, group O-1) phosphorylation. Pretreatment with Akt inhibitor VIII, PI3K (phosphatidylinositol 3-kinase) inhibitor LY294002, and HDL receptor SCARB-1 (scavenger receptor class B type 1) inhibitor BLT-1 (block lipid transport-1) restored αTC1 cell response to low glucose levels.

Conclusions: These results support the notion that HDL and ApoA-1 modulate glucagon expression and secretion by binding their cognate receptor SCARB-1, and activating the PI3K/Akt/FoxO1 signaling cascade in an in vitro α-cell model. Overall, these results raise the hypothesis that HDL and ApoA-1 may have a role in modulating glucagon secretion.
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http://dx.doi.org/10.1161/ATVBAHA.120.314640DOI Listing
December 2020

Liraglutide Increases Serum Levels of MicroRNA-27b, -130a and -210 in Patients with Type 2 Diabetes Mellitus: A Novel Epigenetic Effect.

Metabolites 2020 Sep 30;10(10). Epub 2020 Sep 30.

Department of Health Promotion Sciences Maternal and Infantile Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy.

Liraglutide has shown favourable effects on several cardiometabolic risk factors, beyond glucose control. MicroRNAs (miRNAs) regulate gene expression, resulting in post-transcriptional modifications of cell response and function. Specific miRNAs, including miRNA-27b, miRNA-130a, and miRNA-210, play a role in cardiometabolic disease. We aimed to determine the effect of liraglutide on the serum levels of miRNA-27b, miRNA-130a and miRNA-210. Twenty-five subjects with type-2 diabetes mellitus (T2DM), naïve to incretin-based therapy, were treated with liraglutide (1.2 mg/day as an add-on to metformin) for 4 months. miRNAs were quantified using real-time polymerase chain reaction. After liraglutide treatment, we found significant reductions in fasting glucose (from 9.8 ± 5.3 to 6.7 ± 1.6 mmol/L, = 0.0042), glycosylated haemoglobin (HbA1c) (from 8.1 ± 0.8 to 6.6 ± 1.0%, = 0.0008), total cholesterol (from 5.0 ± 1.0 to 4.0 ± 0.7 mmol/L, = 0.0011), triglycerides (from 1.9 ± 1.0 to 1.5 ± 0.8 mmol/L, = 0.0104) and low-density lipoprotein cholesterol (from 2.9 ± 1.2 to 2.2 ± 0.6 mmol/L, = 0.0125), while the serum levels of miRNA-27b, miRNA-130a and miRNA-210a were significantly increased (median (interquartile range, IQR) changes: 1.73 (7.12) ( = 0.0401), 1.91 (3.64) ( = 0.0401) and 2.09 (11.0) ( = 0.0486), respectively). Since the changes in miRNAs were independent of changes in all the metabolic parameters investigated, liraglutide seems to exert a direct epigenetic effect in T2DM patients, regulating microRNAs involved in the maintenance of endothelial cell homeostasis. These changes might be implicated in liraglutide's benefits and may represent useful targets for cardiometabolic management.
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http://dx.doi.org/10.3390/metabo10100391DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599907PMC
September 2020

Relative Risk of Cardiovascular Disease Is Higher in Women With Type 2 Diabetes, but Not in Those With Prediabetes, as Compared With Men.

Diabetes Care 2020 12 30;43(12):3070-3078. Epub 2020 Sep 30.

Department of Clinical and Molecular Medicine, University of Rome-Sapienza, Rome, Italy.

Objective: Most but not all studies suggest that women with type 2 diabetes have higher relative risk (RR) for cardiovascular disease (CVD) than men. More uncertainty exists on whether the RR for CVD is higher in women with prediabetes compared with men with prediabetes.

Research Design And Methods: In a cross-sectional study, in 3,540 adults with normal glucose tolerance (NGT), prediabetes, and diabetes, we compared the RR for prevalent nonfatal CVD between men and women. In a longitudinal study including 1,658 adults with NGT, prediabetes, and diabetes, we compared the RR for incidences of major adverse outcomes, including all-cause death, coronary heart disease, and cerebrovascular disease events, after 5.6 years of follow-up.

Results: Women with prediabetes and diabetes exhibited greater relative differences in BMI, waist circumference, blood pressure, total cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, fasting glucose, hs-CRP, and white blood cell count than men with prediabetes and diabetes when compared with their NGT counterparts. We found a higher RR for prevalent CVD in women with diabetes (RR 9.29; 95% CI 4.73-18.25; < 0.0001) than in men (RR 4.56; 95% CI 3.07-6.77; < 0.0001), but no difference in RR for CVD was observed comparing women and men with prediabetes. In the longitudinal study, we found that women with diabetes, but not those with prediabetes, have higher RR (RR 5.25; 95% CI 3.22-8.56; < 0.0001) of incident major adverse outcomes than their male counterparts (RR 2.72; 95% CI 1.81-4.08; < 0.0001).

Conclusions: This study suggests that women with diabetes, but not those with prediabetes, have higher RR for prevalent and incident major adverse outcomes than men.
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http://dx.doi.org/10.2337/dc20-1401DOI Listing
December 2020
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