Giuseppe Paolisso

Second University of Naples, Caserta, Campania, Italy

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Publications (410)1914.82 Total impact

  • Diabetes 05/2015; 64(5):e6. DOI:10.2337/db14-1676 · 8.47 Impact Factor
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    ABSTRACT: Severe hypoglycemia is associated with cognitive decline and dementia in older persons with type 2 diabetes. The role of antidiabetic treatments on severe hypoglycemia is unknown in dementia. The aims were to determine the prevalence of severe hypoglycemic events and investigate associations among severe hypoglycemic and specific antidiabetic treatments (classes of oral agents and types of insulin analogs) in a large sample of nursing home patients with diabetes according to dementia status. Cross-sectional observational study. A total of 150 nursing homes across Italy. A total of 2258 patients with type 2 diabetes (dementia = 1138, no dementia = 1120). Diagnosis of dementia before nursing home admission. Data were collected regarding functional status, glycemic control, antidiabetic treatments, comorbidities, and biochemical and clinical measurements. Logistic regression models with severe hypoglycemia as the dependent variable were used to test associations with antidiabetic agents. Patients had a mean age (SD) of 82 (8) years, body mass index (BMI) of 25.4 (4.8), fasting plasma glucose (FPG) of 7.5 (3.0) mmol/L, postprandial glucose (PPG) of 10.3 (3.6) mmol/L, HbA1c of 7.1% (54 mmol/L), and impairments in activities of daily living (ADLs) of 3.7 (2.1). Severe hypoglycemia was more prevalent in patients with dementia (18%) compared with patients without dementia (8%). Patients with dementia were older, showed greater ADL impairments, greater number of comorbidities, lower FPG, and higher PPG compared with those without dementia. Adjusted logistic regression models in patients with dementia showed that rapid- and long-acting insulin analogs were associated with reduced odds ratio (OR) (OR 0.333; 95% confidence interval [CI] 0.184-0.602; OR 0.248, 95% CI 0.070-0.882, respectively), whereas sulphonylureas and combined metformin + sulphonylurea were associated with increased ORs (OR 8.805, 95% CI 4.260-18.201; OR 6.639; 95% CI 3.273-14.710, respectively) of experiencing severe hypoglycemia. No correlations were found in patients without dementia. In older nursing home patients with type 2 diabetes, severe hypoglycemia was significantly higher in dementia. Our findings suggest that sulphonylureas should be used with caution, whereas rapid- and long-acting insulin analogs seem safer. Copyright © 2015 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.
    Journal of the American Medical Directors Association 02/2015; 16(4). DOI:10.1016/j.jamda.2014.12.014 · 4.78 Impact Factor
  • Virginia Boccardi, Giuseppe Paolisso
    Diet and Exercise in Cognitive Function and Neurological Diseases, 02/2015;
  • Virginia Boccardi, Giuseppe Paolisso
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    ABSTRACT: There is a rapidly growing number of persons reaching extreme age limits. Indeed, the fastest growth is found in those over the age of 80 years or octogenarians. Along with this continuous rise, there is a significant increase in type 2 diabetes in this population. Unfortunately, individuals living past 80 years of age are often accompanied by numerous comorbidities and geriatric conditions, all which render anti-diabetic treatment options challenging. Indeed the principles of managing type 2 diabetes is similar to younger patients. Special considerations in this delicate group are essential due to the increased prevalence of comorbidities and relative inability to tolerate adverse effects of medication and severe hypoglycemia. It is important to recall that octogenarians have shown to have a greater prevalence for cognitive impairment, physical disability, renal and hepatic dysfunction, and syndromes, such as frailty compared to younger elders. The frailty syndrome is considered one of the most important limitations when treating octogenarians with type 2 diabetes in polypharmacy. Due to the lack of evidence for specific targets of glucose and glycated hemoglobin (A1C) levels in the elderly, available treatment guidelines are based on data extrapolation from younger adults and expert opinion citing reliable evidence. Overall, the most important conclusion emerging from these groups is to accomplish a moderate glycemic control (A1C levels between 7 -8%) in complex elderly patients. However, the risk of hypoglycemia from some treatments may present the greatest significant barrier to optimal glycemic control for the very old. The present review discusses the highlights from the latest guidelines for treating older persons and underlines the need for specific considerations when treating the very old in order to maintain a balance between treating comorbidities and maintaining quality of life.
    Current Pharmaceutical Design 01/2015; 21(13). DOI:10.2174/1381612821666150130120747 · 3.29 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate the impact of metabolic syndrome (MS) on outcome of catheter ablation (CA) for treatment of frequent premature ventricular contraction beats (PVCs) originating from right ventricular outflow tract (RVOT), left ventricular outflow tract (LVOT) or coronary cusps (CUSPs), in patients with normal ventricular systolic function and absence of cardiac structural disease. In this multicentre prospective study we evaluated 90 patients with frequent PVCs originating from RVOT (n = 68), LVOT (n = 19) or CUSPs (n = 3), treated with CA. According to baseline diagnosis they were divided in patients with MS (n = 24) or without MS (n = 66). The study endpoint was a composite of recurrence of acute or delayed outflow tract ventricular arrhythmia: acute spontaneous or inducible outflow tract ventricular arrhythmia recurrence or recurrence of outflow tract PVCs in holter monitoring at follow up. Patients with MS compared to patients without MS showed a higher acute post-procedural recurrence of outflow tract PVCs (n = 8, 66.6%, vs. n = 6, 9.0%, p = 0.005). At a mean follow up of 35 (17-43) months survival free of recurrence of outflow tract PVCs was lower in patients with baseline MS compared to patients without MS diagnosis (log-rank test, p < 0.001). In cox regression analysis, only MS was independently associated with study endpoint (HR = 9.655 , 95% CI 3.000-31.0.68 , p < 0.001). MS is associated with a higher recurrence rate of outflow tract PVCs after CA in patients without structural heart disease.
    BMC Cardiovascular Disorders 12/2014; 14(1):176. DOI:10.1186/1471-2261-14-176 · 1.50 Impact Factor
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    ABSTRACT: The role of sirtuin-6 (SIRT6) in atherosclerotic progression of diabetic patients is unknown. We evaluated SIRT6 expression and the effect of incretin-based therapies in carotid plaques of asymptomatic diabetic and non-diabetic patients. Plaques were obtained from 52 type 2 diabetic and 30 non-diabetic patients undergoing carotid endarterectomy. Twenty-two diabetic patients were treated with the drugs that work on the incretin system, glucagon-like-peptide-1 (GLP-1) receptor agonists and dipeptidyl-peptidase-4 (DPP-4)-inhibitors, for 26±8 months before endarterectomy. Compared to non-diabetic plaques, diabetic plaques had more inflammation and oxidative stress, along with a lesser SIRT6 expression and collagen content. Compared with no-GLP-1 therapies-treated plaques, GLP-1 therapies-treated plaques presented greater SIRT6 expression and collagen content, less inflammation and oxidative stress, indicating a more stable plaque phenotype. These results were supported by in vitro observations on endothelial progenitor cells (EPCs) and endothelial cells (EC). Indeed, both EPCs and EC treated with high-glucose (25mM) in the presence of GLP-1 (100 nM liraglutide) presented a greater SIRT6 and lower nuclear factor-kappa B (NF-ĸB) expression compared to cells treated only with high-glucose. These findings establish the involvement of SIRT6 in the inflammatory pathway(s) of diabetic atherosclerotic lesions and suggest its possible positive modulation by incretin, whose effect is associated with morphological and compositional characteristics of a potential stable plaque phenotype.
    Diabetes 10/2014; DOI:10.2337/db14-1149 · 8.47 Impact Factor
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    ABSTRACT: AimsTo investigate the validity and reliability of the Audit of Diabetes-Dependent Quality of Life instrument in older Italians with diabetes and to test the association of diabetes-related quality of life with glycaemic control over time.MethodsA total of 558 outpatients with Type 2 diabetes from the Diabetic Unit of the Italian National Research Centre on Aging Hospital in Ancona were enrolled to complete questionnaires (Audit of Diabetes-Dependent Quality of Life-19 and the Short-Form-12), and to undergo clinical and biochemical testing at baseline and at 12 months of follow-up. The overall impact of diabetes using the average weighted impact score from the Audit of Diabetes-Dependent Quality of Life questionnaire was calculated. Participants were categorized according to this score as having either less or more negative diabetes-related quality of life.ResultsParticipants had a mean ± sd age of 67.7 ± 9.2 years and 51.8% were male. Factor analysis and Cronbach's coefficient of internal consistency (Cronbach's α=0.931) confirmed that the 19 domain-specific Audit of Diabetes-Dependent Quality of Life items could be combined into a single scale in this Italian population. The impact score correlated with the physical (r=0.275; P<0.001) and mental components (r=0.291; P<0.001) of the Short-Form-12 questionnaire. Significant differences were found according to diabetic complications in specific Audit of Diabetes-Dependent Quality of Life items and impact scores. Insulin use had a greater association with a more negative quality of life compared with other antidiabetic agents. A multivariate linear regression model with restricted linear spline application showed that the relationship between HbA1c and impact score was not linear and that the change in the impact score was associated with improved glycaemic control in those with a less negative diabetes-related quality of life at 12 months.Conclusions The Audit of Diabetes-Dependent Quality of Life-19 is a valid tool for measuring the impact of diabetes on quality of life in older Italians. Perception of diabetes-related quality of life is associated with glycaemic control over time.This article is protected by copyright. All rights reserved.
    Diabetic Medicine 10/2014; 32(2). DOI:10.1111/dme.12605 · 3.06 Impact Factor
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    ABSTRACT: Background and Aims This study aimed to investigate the relationship between asymptomatic episodes of atrial fibrillation (AF) and abnormalities of the autonomic nervous system in type 2 diabetic patients who did not have evidence of atrial fibrillation at baseline. Methods and Results In a multicentric cross-sectional controlled study, 1992 patients with type 2 diabetes were screened. All underwent ambulatory ECG recording for 48-hour at 3, 6, 9, and 12 months. Heart rate variability (HRV) was used as indicator of autonomic activity. 176 diabetics with silent atrial fibrillation episodes (SAFE group) and 288 without silent atrial fibrillation (non-SAFE group) were enrolled. These selected diabetics were matched on clinical and anthropometric data to 120 control subjects without diabetes of the control group. HRV analysis evidenced that LF/HF ratio was significantly higher in the SAFE group than in the non-SAFE group (P < 0.05) in the whole period of HM analysis. AF absolute burdens were positively correlated with LF/HF ratio (r = 0.31, P < 0.001). Multiple regression analysis showed that LF/HF ratio was an independent determinant of AF episodes. Conclusions This study originally showed a strong relationship between autonomic dysfunction and silent atrial fibrillation in type 2 diabetes.
    Journal of Diabetes and its Complications 09/2014; 29(1). DOI:10.1016/j.jdiacomp.2014.09.002 · 1.93 Impact Factor
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    ABSTRACT: Pseudomonas aeruginosa (PA) is a gram-negative bacillus capable of producing infections, which usually occur in hospital environment. Cutaneous manifestations represent a wide spectrum of pathologic entities, ranging from minor skin lesions to necrotizing skin infection and to potentially life-threatening PA septicemia. The pathogenesis of PA infections must be understood in the context of its role as an opportunistic pathogen. In particular, it rarely causes disease in healthy patients because of its low virulence. This species primarily cause disease in patients with local anatomical changes or in the immunocompromised host. In fact, it is rarely able to start an infection in healthy subjects, unless there is a local or general impairment of defense mechanisms. We described an otherwise healthy 75-year-old woman who developed a necrotizing PA skin infection after a routinely mosquito bite skin lesion.
    The American journal of emergency medicine 09/2014; 32(9). DOI:10.1016/j.ajem.2014.02.028 · 1.15 Impact Factor
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    ABSTRACT: The risk-to-benefit ratio for the use of low dose of aspirin in primary cardiovascular (CV) prevention in patients with diabetes mellitus remains to be clarified. We assessed the effect of aspirin on risk of CV events in type 2 diabetic patients with nephropathy, in order to verify the usefulness of Guidelines in clinical practice. We carried out a prospective multicentric study in 564 patients with type 2 diabetic nephropathy free of CV disease attending outpatient diabetes clinics . A total of 242 patients received antiplatelet treatment with aspirin 100 mg/day (group A), and 322 were not treated with antiplatelet drugs (group B). Primary end point was the occurrence of total major adverse cardio-vascular events (MACE). Secondary end points were the relative occurrence of fatal MACE. The average follow-up was 8 years. Total MACE occurred in 49 patients from group A and in 52 patients from group B. Fatal MACE occurred in 22 patients from group A and in 20 from group B; nonfatal MACE occurred in 27 patients from group A and in 32 patients from group B. Kaplan-Meier analysis did not show a statistically significant difference of cumulative MACE between the two groups. A not statistically significant difference in the incidence of both fatal (p = 0.225) and nonfatal CV events (p = 0.573) between the two groups was observed. These results were confirmed after adjustment for confounders (HR for MACE 1.11, 95 % CI 0.91-1.35). These findings suggest that low dose of aspirin is ineffective in primary prevention for patients with nephropathy.
    Acta Diabetologica 08/2014; 52(2). DOI:10.1007/s00592-014-0623-x · 3.68 Impact Factor
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    ABSTRACT: Although metabolic syndrome (MS) is a typical condition of middle-aged/older person, the association between MS and mortality risk has not been confirmed in people over 65 years. We hypothesized that while in the elderly MS phenotype might lose its value in predicting mortality risk, the two core factors of MS, i.e. insulin resistance (IR) and low grade systemic inflammation (LGSI) would not.
    Atherosclerosis 06/2014; 235(2):538-545. DOI:10.1016/j.atherosclerosis.2014.05.959 · 3.97 Impact Factor
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    ABSTRACT: Heart failure (HF) disease progression is related to numerous adaptive processes including cardiac fibrosis, hypertrophy and apoptosis by activation of the 'fetal' gene program and downregulation of mRNA signatures, suggesting the importance of molecular mechanisms that suppress mRNA steady-state levels. miRNAs (miRs) are small, noncoding RNAs that bind mRNAs at their 3'-UTRs, leading to mRNA degradation or inhibition of protein translation. Several miRs are unregulated in response to cellular stress and can modify cellular functions such as proliferation, differentiation and programmed death; these miRs are also regulated in cardiac disease. Cardiac resynchronization therapy improves cardiac performance and myocardial mechanical efficiency. . In this updated critical appraisal we report on the main miRs that play a key role in response to cardiac resynchronization therapy (i.e., responder vs nonresponder HF patients), focusing on the miR-mediated modulation of cardiac angiogenesis, apoptosis, fibrosis and membrane ionic currents.
    Pharmacogenomics 06/2014; DOI:10.2217/pgs.14.76 · 3.43 Impact Factor
  • Virginia Boccardi, Giuseppe Paolisso
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    ABSTRACT: Statins are well-established drugs for primary and secondary prevention of cardiovascular diseases. Many statin cholesterol-lowering independent actions, known as 'pleiotropic effects', have been identified in different cell types, including modulation of inflammation, oxidative stress, apoptosis, cell proliferation, immune response and platelet aggregation. Recent evidence suggested an additional pleiotropic effect of statins on cellular senescence mediated by their interaction with telomere maintenance system. In this special report, we will present the most important findings regarding the association between statins therapy and telomere dynamic.
    Clinical Lipidology 06/2014; 9(3):311-315. DOI:10.2217/clp.14.21 · 0.86 Impact Factor
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    Virginia Boccardi, Giuseppe Paolisso
    New England Journal of Medicine 04/2014; · 54.42 Impact Factor
  • Virginia Boccardi, Giuseppe Paolisso
    New England Journal of Medicine 04/2014; 370(16):1565. DOI:10.1056/NEJMc1401241#SA3 · 54.42 Impact Factor
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    ABSTRACT: Previous studies identified comorbidities as predictors of older driver performance and driving pattern, while the direct impact of comorbidities on road crash risk in elderly drivers is still unknown. The present study is a cross-sectional aimed at investigating the association between levels of comorbidity and crash involvement in adult and elderly drivers. 327 drivers were stratified according to age range in two groups: elderly drivers (age ≥70 years old, referred as older) and adult drivers (age <70 years old, referred as younger). Driving information was obtained through a driving questionnaire. Distance traveled was categorized into low, medium and high on the basis of kilometers driven in a year. CIRS-illness severity (IS) and CIRS-comorbidity indices (CI) in all populations were calculated. Older drivers had a significantly higher crash involvements rate (p = .045) compared with the younger group based on the number of licensed drivers. Dividing comorbidity indices into tertiles among all licensed subjects, the number of current drivers significantly decreased (p<.0001) with increasing level of comorbidity. The number of current drivers among older subjects significantly decreased with increasing comorbidity level (p = .026) while no difference among younger group was found (p = .462). Among younger drivers with increasing comorbidity level, the number of road accidents significantly increased (p = .048) and the logistic regression analysis showed that comorbidity level significantly associated with crash involvement independent of gender and driving exposure. Older subjects with high level of comorbidity are able to self-regulate driving while comorbidity burden represents a significant risk factor for crash involvements among younger drivers.
    PLoS ONE 04/2014; 9(4):e94564. DOI:10.1371/journal.pone.0094564 · 3.53 Impact Factor
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    ABSTRACT: The vasculature of each organ expresses distinct molecular signatures critically influenced by the pathological status. The heterogeneous profile of the vascular beds has been successfully unveiled by the in vivo phage display, a high-throughput tool for mapping normal, diseased, and tumor vasculature. Specific challenges of this growing field are targeted therapies against cancer and cardiovascular diseases, as well as novel bioimaging diagnostic tools. Tumor vasculature-homing peptides have been extensively evaluated in several preclinical and clinical studies both as targeted-therapy and diagnosis. To date, results from several Phase I and II trials have been reported and many other trials are currently ongoing or recruiting patients. In this review, advances in the identification of novel peptide ligands and their corresponding receptors on tumor endothelium through the in vivo phage display technology are discussed. Emphasis is given to recent findings in the clinical setting of vascular-homing peptides selected by in vivo phage display for the treatment of advanced malignancies and their altered vascular bed.
    Biochimica et Biophysica Acta 04/2014; 1846(1). DOI:10.1016/j.bbcan.2014.03.004 · 4.66 Impact Factor
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    ABSTRACT: Older adults with type 2 diabetes have an increased risk for mild and severe cognitive impairment probably as consequence of chronic hyperglycemia or fasting plasma glucose levels. Variability in glucose level and recurrent hypoglycemic episodes are also associated with cognitive impairment. Dipeptidyl peptidase-4 inhibitor (DPP-4I) therapy affects glycemic variability. The purpose of this study was to evaluate the effect of DPP-4I therapy on changes in cognitive function in older patients with type 2 diabetes complicated by mild cognitive impairment. This retrospective longitudinal study used data from a database of 240 older patients with type 2 diabetes, "drug naive," affected by mild cognitive impairment, subsequently treated for 2 years with antidiabetic drugs (DPP-4I group: DPP-4I + metformin, n = 120; SU group: sulfonylurea + metformin, n = 120) and reassessed in our ambulatory by comprehensive clinical, cognitive, instrumental examinations, and continuous subcutaneous glucose monitoring. At baseline, larger mean amplitude of glycemic excursion values correlated with poorer Mini-Mental State Examination and composite cognitive function scores. We found that higher body mass index, higher 2-hour postprandial glucose, and greater mean amplitude of glycemic excursion values measured at baseline were significant independent predictors of cognitive worsening. In addition, reduction in mean amplitude of glycemic excursions and the use of DPP-4I therapy predicted improvement in cognitive functions. In older patients with type 2 diabetes affected by mild cognitive impairment, DPP-4I administration improves glucose control and protects against worsening in cognitive functioning.
    The Journals of Gerontology Series A Biological Sciences and Medical Sciences 03/2014; DOI:10.1093/gerona/glu032 · 4.98 Impact Factor
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    ABSTRACT: The aim of this study was to determine the long-term effects of a moderate protein diet (MPD) on renal function, low-grade inflammation, and oxidative stress in older adults with type 2 diabetes, which to date are unclear.
    Nutrition 03/2014; DOI:10.1016/j.nut.2014.03.007 · 3.05 Impact Factor

Publication Stats

14k Citations
1,914.82 Total Impact Points


  • 1982–2015
    • Second University of Naples
      • • Faculty of Medicine and Surgery
      • • Dipartimento di Psicologia
      • • Dipartimento di Biochimica, Biofisica e Patologia Generale
      Caserta, Campania, Italy
  • 1983–2014
    • Naples Eastern University
      Napoli, Campania, Italy
  • 1981–2012
    • University of Naples Federico II
      • Department of Molecular Medicine and Medical Biotechnology
      Napoli, Campania, Italy
  • 2006
    • University of Catania
      Catania, Sicily, Italy
    • University of Ferrara
      • Department of Clinical and Experimental Medicine
      Ferrare, Emilia-Romagna, Italy
  • 2003
    • University of Bologna
      Bolonia, Emilia-Romagna, Italy
  • 1995–1996
    • National Institutes of Health
      • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
      Maryland, United States
    • Interactive Institute
      Tukholma, Stockholm, Sweden
    • Albert Einstein College of Medicine
      New York, New York, United States
  • 1989–1996
    • Centre Hospitalier Universitaire de Liège
      Luik, Walloon Region, Belgium
  • 1987–1995
    • University of Liège
      • Diabetes, Nutrition and Metabolic Disorders Unit
      Liège, WAL, Belgium
  • 1990
    • Università degli Studi di Napoli L'Orientale
      Napoli, Campania, Italy
  • 1985
    • Catholic University of Louvain
      • School of Medicine
      Walloon Region, Belgium