G Paolisso

Second University of Naples, Caserta, Campania, Italy

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Publications (403)1857.41 Total impact

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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; · 7.90 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; · 3.24 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;
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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;
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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. · 3.71 Impact Factor
  • Virginia Boccardi, Giuseppe Paolisso
    Clinical Lipidology 06/2014; 9(3):311-315. · 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. · 54.42 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; · 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; · 4.31 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 (Burbank, Los Angeles County, Calif.). 03/2014;
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    ABSTRACT: It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p=1.00) or cell type (p=0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required.
    Experimental gerontology 03/2014; 51:15-27. · 3.34 Impact Factor
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    ABSTRACT: Diabetes mellitus is a risk factor for cardiovascular and cerebrovascular events independently of other factors such as age, sex, BMI and blood pressure. Diabetes plays an important role in the pathogenesis of atrial fibrillation because it causes alterations to the autonomic nervous system. It may also be associated with an increased prevalence of asymptomatic episodes of atrial fibrillation, which cause cerebrovascular disease more often than chronic atrial fibrillation. The presence of silent cerebral ischemia doubles the risk of stroke in the general population independently of other cardiovascular risk factors; therefore, early detection of these episodes is important to determine preventive measures against the first cerebrovascular disease.
    Expert Review of Cardiovascular Therapy 01/2014;
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    ABSTRACT: Objectives The long-term effects of moderate protein diet (MPD) on renal function, grade inflammation and oxidative stress in elderly type 2 diabetic are unclear. Methods Seventy-four elderly type 2 diabetic patients with chronic kidney disease (stage G3b-G4) were enrolled in the study. During the four-week baseline period (T0), all patients were asked to follow, a normal protein diet regimen, providing 1.1 g/kg per day. Successively, all patients were asked to follow, moderate MPD, for 36 months, providing 0.7 g/kg per day, for only six days a week. Patients who refused to follow MPD treatment were included in the control (NPD group). During the 36 months of the study, creatinine clearance (CrCl), blood urea nitrogen (BUN), proteinuria, blood pressure (BP), HbA1c, free fat mass (FFM), grade inflammation (IL-6 and CRP) were all evaluated monthly and oxidative stress (urinary 8-Epi- PGF 2alpha) was evaluated every 3 months. Results During T0, mean CrCl, proteinuria, BUN, BP, HbA1c, FFM, grade inflammation and oxidative stress were similar in NPD and MPD groups. After 36 months, a significantly reduction on decline of renal function, was observed in the MPD group in comparison to NPD (2.4±0.2 vs 5.7±0.5 ml/min/y, respectively; p<0.05 vs NPD). Similarly, a significantly reduction in proteinuria, serum IL-6, serum CRP and urinary 8-Epi-PGF 2alpha excretion, was observed in the MPD group (p<0.05 vs NPD). Conclusion In elderly type 2 diabetic patients, long-term effects of MPD regimen are associated with a significant decline of renal function, proteinuria, grade inflammation and oxidative stress without change in FFM.
    Nutrition. 01/2014;
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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 01/2014; · 3.86 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 01/2014; 9(4):e94564. · 3.53 Impact Factor
  • The American journal of emergency medicine 01/2014; · 1.54 Impact Factor
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    ABSTRACT: The time of diagnosis is crucial for type 2 diabetes mellitus (T2DM) in terms of disease severity and chronic complications, as initial glycated haemoglobin (HbA1c) predicts 5-year cardiovascular mortality. The Italian health-care system relies on about 650 diabetes care units (DCU) interfacing with a large number of general practitioners (GPs). It may thus reach the goal of preventing complications easier than others by adopting a more comprehensive multifactorial approach. To assess whether the interval between diagnosis and referral to the DCU might influence the course of the disease in terms of HbA1c, associated cardiovascular risk factors, drug utilisation, and chronic complications in the elderly, the electronic records of 313 elderly T2DM patients (74.6 ± 4.9 years) followed by their GPs until referral to our DCU were retrospectively analysed for the above-mentioned parameters and divided into an early referral (ER) group (diagnosed within 12 months, n = 111) and a late referral (LR) group (diagnosed >12 months before, n = 202). A further set of 200 patients routinely taken care by our DCU, matched with the LR group for age, gender, and disease duration, was classified as "long-standing follow-up" (LSF) and compared to the others to rule out any confounding effects of long-standing disease per se on the clinical outcomes investigated in our study. About 35 % of T2DM patients referred to our DCU within 12 months of diagnosis; the rest did so some 5 years after diagnosis. LR patients displayed worse HbA1c levels (10.8 vs. 7.7 %, p < 0.01), used more drugs, and had more than twice as high complication rates as their ER counterparts. Almost all risk factors and complications were lower in the LSF (0.001 < p < 0.05) and ER groups than in the LR group. In both the ER and the LSF groups, we observed a lower burden of diabetes than in the LR group. This rules out the possibility that disease duration might play a major role per se in the burden of the disease in the elderly as opposed to the thoughtful patient care attitude exhibited by the DCU. A better and more efficient organisation has to be developed, including a strong interaction among GPs, diabetes specialists, and elderly people with T2DM allowing the latter to take charge of their own disease management through a sustained empowerment policy.
    Acta Diabetologica 12/2013; · 4.63 Impact Factor
  • The American journal of emergency medicine 12/2013; · 1.54 Impact Factor
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    ABSTRACT: Alterations in glucose metabolism in individuals with diabetes have been considered for many years, as they appear at first glance, i.e., simply as hyperglycemia, and its surrogate marker, glycated hemoglobin (HbA1c), used both to estimate the risk of developing diabetic complications and to define the targets and measure the efficacy of diabetes treatments. However, over time diabetes-related glycemic alterations have been considered in more complex terms, by attempting to identify the role of fasting glycemia, postprandial glycemia and hypoglycemia in the overall assessment of the disease. This set of evaluations has led to the concept of glucose variability. Although intuitively easy to understand, it cannot be equally simply translated into terms of definition, measuring, prognostic and therapeutic impact. The literature available on glucose variability is extensive yet confused, with the only common element being the need to find out more on the subject. The purpose of this manuscript is not only to review the most recent evidence on glucose variability, but also to help the reader to better understand the available measurement options, and how the various definitions can differently be related with the development of diabetic complications. Finally, we provide how new and old drugs can impact on glucose variability.
    Diabetes research and clinical practice 09/2013; · 2.74 Impact Factor

Publication Stats

10k Citations
1,857.41 Total Impact Points


  • 1983–2014
    • Second University of Naples
      • • Faculty of Medicine and Surgery
      • • Dipartimento di Biochimica, Biofisica e Patologia Generale
      Caserta, Campania, Italy
  • 2012
    • Catholic University of the Sacred Heart
      • Institute of Internal and Geriatric Medicine
      Roma, Latium, Italy
  • 2008–2010
    • Università degli studi di Parma
      • Department of Clinical and Experimental Medicine
      Parma, Emilia-Romagna, Italy
    • University of Exeter
      • Peninsula College of Medicine and Dentistry
      Exeter, ENG, United Kingdom
  • 2007–2010
    • National Institute on Aging
      • Clinical Research Branch (CRB)
      Baltimore, Maryland, United States
    • University of Padova
      • Department of Medicine DIMED
      Padova, Veneto, Italy
    • Universita degli studi di Ferrara
      • Department of Morphology, Surgery and Experimental Medicine
      Ferrara, Emilia-Romagna, Italy
  • 2009
    • INRCA Istituto Nazionale di Ricovero e Cura per Anziani
      • Gerontological Research Department
      Ancona, The Marches, Italy
  • 1981–2008
    • University of Naples Federico II
      • • Department of Molecular Medicine and Medical Biotechnology
      • • Department of Translational Medical Sciences
      Napoli, Campania, Italy
  • 2001–2007
    • University of Bologna
      • Department of Experimental, Diagnostic and Specialty Medicine DIMES
      Bologna, Emilia-Romagna, Italy
  • 2006
    • University of Catania
      Catania, Sicily, Italy
  • 1999–2006
    • Università degli studi di Palermo
      • • Dipartimento di Discipline Chirurgiche, Oncologiche e Stomatologiche (Di.Chir.On.S.)
      • • Department of internal medicine and medical specialties (DIMIS)
      Palermo, Sicily, Italy
  • 2005
    • Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele Pisana
      Roma, Latium, Italy
  • 1983–2005
    • Naples Eastern University
      Napoli, Campania, Italy
  • 1995–1998
    • National Institutes of Health
      • National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
      Bethesda, MD, 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