Dario Giugliano

Second University of Naples, Caserta, Campania, Italy

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Publications (501)3166.15 Total impact

  • Katherine Esposito · Annalisa Capuano · Dario Giugliano ·
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    ABSTRACT: Introduction: Type 2 diabetes is a chronic and progressive disease, and ultimately, most patients will require insulin therapy for the optimization of their glycemic control. Areas covered: We review the recent literature investigating the efficacy and safety of the insulin analogue lispro in type 2 diabetes. Relevant publications were identified by means of a PubMed literature search in the period January 1990 to May 2012. We included randomized controlled trials (RCTs), which included at least one arm evaluating insulin lispro in type 2 diabetes. Expert opinion: Insulin is the most effective therapy for reducing hyperglycemia: when the desired decrease of HbA1c is ≥ 1.5%, it is unlikely than any other antidiabetes drug may work as better as insulin. The pharmacodynamic and pharmacokinetic profiles of lispro analogues offer discrete advantage over human insulin. The preliminary results of comparative RCTs versus insulin glargine or insulin detemir indicate that insulin lispro protamine suspension (ILPS) has a similar effect on glucose control and the risk of hypoglycemia while using lower doses when injected once a day. Lispro/ILPS premixed formulations can be injected immediately before a meal because they are absorbed more rapidly than premixed human insulin, thus allowing more flexibility with insulin therapy.
    Expert opinion on biological therapy 10/2012; 12(11). DOI:10.1517/14712598.2012.728584 · 3.74 Impact Factor
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    ABSTRACT: Currently there is debate on whether hypoglycemia is an independent risk factor for atherosclerosis, but little attention has been paid to the effects of recovery from hypoglycemia. In normal control individuals and in people with type 1 diabetes, recovery from a 2-h induced hypoglycemia was obtained by reaching normoglycemia or hyperglycemia for another 2 h and then maintaining normal glycemia for the following 6 h. Hyperglycemia after hypoglycemia was also repeated with the concomitant infusion of vitamin C. Recovery with normoglycemia is accompanied by a significant improvement in endothelial dysfunction, oxidative stress, and inflammation, which are affected by hypoglycemia; however, a period of hyperglycemia after hypoglycemia worsens all of these parameters, an effect that persists even after the additional 6 h of normoglycemia. This effect is partially counterbalanced when hyperglycemia after hypoglycemia is accompanied by the simultaneous infusion of vitamin C, suggesting that when hyperglycemia follows hypoglycemia, an ischemia-reperfusion-like effect is produced. This study shows that the way in which recovery from hypoglycemia takes place in people with type 1 diabetes could play an important role in favoring the appearance of endothelial dysfunction, oxidative stress, and inflammation, widely recognized cardiovascular risk factors.
    Diabetes 08/2012; 61(11):2993-7. DOI:10.2337/db12-0224 · 8.10 Impact Factor
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    Dario Giugliano · Katherine Esposito ·
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    ABSTRACT: The three currently marketed long-acting insulin analogs, glargine, detemir and insulin lispro protamine suspension (ILPS), represent the most significant advances in basal insulin supplementation since the 1940s and 1950s and the introduction of the intermediate-acting NPH (neutral protamine Hagedorn) insulin. As injection of NPH insulin lacks chronic maintenance of a steady-state low-level basal insulin during fasting periods, which can also expose patients to unpredictable nocturnal hypoglycemia, long-acting insulin analogs have been developed to overcome this important limitation of NPH insulin. ILPS is a protamine-based, intermediate-acting insulin formulation of the short-acting analog insulin lispro: its pharmacokinetic and pharmacodynamic characteristics are quite similar to the other basal insulin analogs glargine and detemir. In recent head-to-head randomized controlled trials of insulin-naïve patients with type 2 diabetes, ILPS achieved similar glycemic control compared with glargine or detemir. ILPS administered once daily is an effective and safe way to maintain a steady-state low-level basal insulin during night time, not dissimilar from that currently obtained with a one-day glargine or detemir administration.
    Therapeutic advances in endocrinology and metabolism 06/2012; 3(3):99-108. DOI:10.1177/2042018812442949
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    Katherine Esposito · Dario Giugliano ·

    Diabetes care 06/2012; 35(6):e51; author reply e52. DOI:10.2337/dc12-0247 · 8.42 Impact Factor
  • Marco Gallo · Katherine Esposito · Dario Giugliano ·

    Diabetes research and clinical practice 05/2012; 97(2):175-7. DOI:10.1016/j.diabres.2012.04.007 · 2.54 Impact Factor
  • Katherine Esposito · Dario Giugliano ·

    Evidence-based nursing 03/2012; 15(3):71-2. DOI:10.1136/ebnurs-2011-100490
  • Katherine Esposito · Dario Giugliano ·

    Archives of internal medicine 02/2012; 172(3):295-6; author reply 296. DOI:10.1001/archinternmed.2011.785 · 17.33 Impact Factor
  • Katherine Esposito · Paolo Chiodini · Antonio Ceriello · Dario Giugliano ·
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    ABSTRACT: We assessed the efficacy of noninsulin antidiabetic medications used in current clinical practice (metformin, sulfonylureas, α-glucosidase inhibitors, thiazolidinediones, glinides, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 agonists) to reach the HbA1c target <7% in people with type 2 diabetes. MEDLINE, EMBASE, and the Cochrane CENTRAL were searched from inception through April 2011 for randomized controlled trials (RCTs) involving noninsulin antidiabetic drugs. RCTs had to report the effect of any diabetes medication on the HbA1c levels, to include at least 30 subjects in every arm of the study, and to last at least 12 weeks. Data were summarized across studies using random-effects meta-regression. We found 137 RCTs with 205 arms and 39,845 patients. The proportion of patients who achieved the HbA1c goal ranged from 25.9% (95% CI 18.5-34.9) with α-glucosidase inhibitors to 48.6% (95% CI, 53.6) with GLP-1 analogs. Baseline HbA1c was the major determinant of the proportion of patients at HbA1c goal. The meta-regression model with mean baseline HbA1c value, concomitant drug use, and class of drugs as covariates explained almost 67% of the between-study variability. A nomogram was developed to estimate the proportion of patients at target for each noninsulin drug class: for a baseline HbA1c level of 7.5%, all noninsulin drugs, except α-glucosidase inhibitors, achieved the HbA1c goal <7% in more than 50% of patients. Starting or intensifying pharmacological therapy at baseline HbA1c 8% or less was associated with more than 50% of patients at HbA1c goal for most noninsulin drugs.
    Acta Diabetologica 01/2012; 51(2). DOI:10.1007/s00592-012-0370-9 · 2.40 Impact Factor
  • Katherine Esposito · Dario Giugliano ·
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    ABSTRACT: INTRODUCTION: Although traditionally used as a final treatment option, early use of insulin is a therapeutic option after metformin failure in type 2 diabetes. Injection of native insulin lacks the rapid onset of action after food ingestion and the chronic maintenance of a steady-state low-level basal insulin in fasting periods. These limitations have fuelled the development of insulin analogues, which mainly fall into two different categories: short-acting and long-acting analogues. AREAS COVERED: We review the recent literature investigating the efficacy and safety of insulin analogues in human diabetes, with emphasis on type 2 diabetes, as about 30% of these patients are being treated with insulin. We also examine novel developments in this area, including the new long-acting basal analogues whose longer duration of action might reduce dosing frequency to three times a week. EXPERT OPINION: Insulin analogues show some advantage compared with native insulin. However, improvements in reducing their pharmacological variability would be expected to lower the risk of hypoglycemia and hyperglycemia, as well as to simplify and perhaps also encourage optimal insulin titration in real-life clinical practice. Extending the duration of insulin effect would also allow for greater flexibility and potentially reduce the frequency of blood glucose monitoring.
    Expert opinion on biological therapy 01/2012; 12(2):209-21. DOI:10.1517/14712598.2012.648181 · 3.74 Impact Factor
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    Cardiology Research and Practice 12/2011; 2011:386892. DOI:10.4061/2011/386892
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    Katia Esposito · Maria Rosaria Improta · Dario Giugliano ·
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    ABSTRACT: The progressive muscular damage in patients affected by Glycogenosis type II can be slowed down through lifestyle changes based on a specific dietotherapy and daily physical ex-ercise. Dietary treatment provides for a diet made up of pro-teins (25-30%), carbohydrates (30-35%), fat (35-40%), that is a high-protein diet for the most part. Patients suffering such the-saurismosis need a higher amount of proteins since the increase in amino acids, which function as substrate for the synthesis of proteins, could make up for the proteolysis of muscular tissue. Proteins coming from meat, fish, egg, and dairy products are to be preferred; such food, moreover, is rich in alanine, an amino acid playing a key role in glycide metabolism and, consequently, in the employment of glucose as a source of energy. So much so that a further oral supplement is recommended, in a dose of 0,4g/kg divided 3-4 times per day. Lipids are recommended in the form of unsaturated fats (omega-3, which are mainly con-tained in bluefish) and saturated fats (omega-6, which are main-ly contained in olive oil, dried fruit and cereals), reducing to a minimum saturated ones due to their aterogenic effect. The assumption of carbohydrates must not only be reduced to 30-35%, but also distributed in the space of a day. The "a little and often" rational consists in avoiding the build-up of glycogen on the one hand, and hypoglycaemia on the other. Among complex carbohydrates wholemeal ones such as cereals, legumes, and wholemeal pasta are to be preferred, in small helpings; whereas, among simple ones, dried or skinned (if fresh) fruit; such recom-mendation aims at increasing the input of fibres in order to coun-ter constipation, which is often found in those patients. Muscular pain, in fact, can also concern the gastrointestinal system, with consequent dysphagia, gastroesophageal reflux, gastroparesis and a reduction in appetite. Such conditions are treated with die-tary and pharmacological measures to avoid malnutrition. In the team in charge of treatment, the presence of a physiotherapist is essential to carry out exercises in coordination and contraction of facial muscles, postural training and rehabilitation to tasting. Anthropometric data and bodily composition represent param-Testing); c. pain with several scales such as VAS (Visual Ana-logic Scale), Pediatric Pain Objective scale, and BPI (Brief Pain Inventory) (3) global functioning with the Six Minute Walk (4) and the Gross Motor Function Measure (GMFM) (5) disability with the Pediatric Evaluation of Disability Index (PEDI), (6) the Pompe PEDI,(7) the Functional Independent Measure (FIM), (8) the WeeFIM, (9) the Barthel Index (10) and the ADL (11)/ IADL(12); quality of life with the Rotterdam Handicap Scale (RHS) (13) and the Short Form 12 (SF-12)(14). In particular, in patients with Pompe disease we have to deal with a deep, progressive and symmetrical muscle weakness, proximal more than distal, involving the lower extremities more frequently than the upper ones, that will determine contractures and deformi-ties. Moreover there are often neck and trunk muscle weakness involving respiratory muscles (diaphragm, intercostals, abdomi-nal and accessory muscles) and this might lead to respiratory failure. Facial and oralmotor weakness is responsible not only of problems of mastication and phonation, but can also give the typical myopathic facies. In terms of functional limitations, my-opathic patients experience deficit of walking ability resulting in the need of orthoses or wheelchair, loss of personal autonomy in the activities of daily living, relational-communicative, mental and emotional disabilities. The rehabilitation management of Pompe disease should be comprehensive and preventive, based on an understanding of the pathogenesis of disease progression and on individual assessment. The key of management lies in considering the interaction between the presence, progression and potential remediation of weakness and fatigue. It should op-timize and preserve motor and physiological function, prevent or minimize secondary complications, promote and maintain the maximum level of functional independence and participation, and improve the quality of life; maximize the benefits of therapy recombinant and other therapies when they become available. The rehabilitative approach is nowadays mandatory for comprehensive management of patients affected by metabolic myopathies.
    Acta myologica: myopathies and cardiomyopathies: official journal of the Mediterranean Society of Myology / edited by the Gaetano Conte Academy for the study of striated muscle diseases 11/2011; 30(3).
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    D R Meldrum · J C Gambone · MA Morris · K Esposito · D Giugliano · L J Ignarro ·
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    ABSTRACT: Oxidative stress and inflammation, which disrupt nitric oxide (NO) production directly or by causing resistance to insulin, are central determinants of vascular diseases including ED. Decreased vascular NO has been linked to abdominal obesity, smoking and high intakes of fat and sugar, which all cause oxidative stress. Men with ED have decreased vascular NO and circulating and cellular antioxidants. Oxidative stress and inflammatory markers are increased in men with ED, and all increase with age. Exercise increases vascular NO, and more frequent erections are correlated with decreased ED, both in part due to stimulation of endothelial NO production by shear stress. Exercise and weight loss increase insulin sensitivity and endothelial NO production. Potent antioxidants or high doses of weaker antioxidants increase vascular NO and improve vascular and erectile function. Antioxidants may be particularly important in men with ED who smoke, are obese or have diabetes. Omega-3 fatty acids reduce inflammatory markers, decrease cardiac death and increase endothelial NO production, and are therefore critical for men with ED who are under age 60 years, and/or have diabetes, hypertension or coronary artery disease, who are at increased risk of serious or even fatal cardiac events. Phosphodiesterase inhibitors have recently been shown to improve antioxidant status and NO production and allow more frequent and sustained penile exercise. Some angiotensin II receptor blockers decrease oxidative stress and improve vascular and erectile function and are therefore preferred choices for lowering blood pressure in men with ED. Lifestyle modifications, including physical and penile-specific exercise, weight loss, omega-3 and folic acid supplements, reduced intakes of fat and sugar, and improved antioxidant status through diet and/or supplements should be integrated into any comprehensive approach to maximizing erectile function, resulting in greater overall success and patient satisfaction, as well as improved vascular health and longevity.
    International journal of impotence research 11/2011; 24(2):61-8. DOI:10.1038/ijir.2011.51 · 1.76 Impact Factor
  • Dario Giugliano · Antonio Ceriello · Katherine Esposito ·

    Diabetes research and clinical practice 10/2011; 96(3):414-5. DOI:10.1016/j.diabres.2011.09.007 · 2.54 Impact Factor
  • K Esposito · P Chiodini · G Bellastella · M I Maiorino · D Giugliano ·
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    ABSTRACT: We assessed the efficacy of eight classes of diabetes medications used in current clinical practice [metformin, sulphonylureas, α-glucosidase inhibitors, thiazolidinediones, glinides, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 (GLP-1) analogues and insulin analogues] to reach the HbA1c target <7% in type 2 diabetes. MEDLINE, EMBASE and the Cochrane CENTRAL were searched from inception through April 2011 for randomized controlled trials (RCTs) involving antidiabetic drugs. RCTs had to report the effect of any diabetes medication on the HbA1c levels, to include at least 30 subjects in every arm of the study, and to report the effect of therapy after a minimum of 12 weeks. Data were summarized across studies using random-effects meta-regression. A total of 218 RCTs (339 arms and 77 950 patients) met the inclusion criteria. The proportion of patients who achieved the HbA1c goal ranged from 25.9% (95% CI 18.5-34.9) with α-glucosidase inhibitors to 63.2% (54.1-71.5) with the long-acting GLP-1 analogue. There was a progressive decrease of the proportion of patients at target for each 0.5% increase in baseline HbA1c, ranging from 57.8% for HbA1c ≤7.5% to 20.8% for HbA1c ≥10% (p for trend <0.0001), with some difference between insulin and non-insulin drugs: for insulin, the proportion of patients at goal reached a plateau for basal HbA1c value >9.0% with no further decrease, whereas for non-insulin drugs the relationship was continuous without any evidence of plateau. CONCLUSIONs: There is a considerable variability with regard to attainment of HbA1c goal of <7% among the different classes of diabetes medications; baseline HbA1c is an important determinant of observed efficacy.
    Diabetes Obesity and Metabolism 09/2011; 14(3):228-33. DOI:10.1111/j.1463-1326.2011.01512.x · 6.36 Impact Factor
  • V Koivisto · S Cleall · AE Pontiroli · D Giugliano ·
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    ABSTRACT: To compare the efficacy and safety of insulin lispro protamine suspension (ILPS) versus insulin glargine once daily in a basal-bolus regimen in type 2 diabetes mellitus (T2DM) patients. Three hundred eighty-three insulin-treated patients were randomized to either ILPS plus lispro or glargine plus lispro in this open-label 24-week European study. Insulin doses were titrated to predefined blood glucose (BG) targets. Non-inferiority of ILPS versus glargine was assessed by comparing the upper limit of the 95% confidence interval (CI) for the change of HbA1c from baseline to week 24 (adjusted for country and baseline HbA1c) with the non-inferiority margin of 0.4%. Secondary endpoints included HbA1c categories, BG profiles, insulin doses, hypoglycaemic episodes, adverse events and vital signs. Non-inferiority of ILPS versus glargine in the change of HbA1c from baseline was shown: least-square mean between-treatment difference (95% CI) was 0.1% (-0.11; 0.31). Mean changes at week 24 were -1.05% (ILPS) and -1.20% (glargine). HbA1c <7.0% was achieved by 21.7 versus 29.4% of patients. Mean basal/mealtime insulin doses at week 24 were 29.6/36.2 IU/day (ILPS) versus 32.8/42.2 IU/day (glargine); the difference was not statistically significant for total dose (p = 0.7). In both groups, 56.1/25.7% versus 63.6/19.3% of patients experienced any/nocturnal hypoglycaemia (p = 0.2 for both). No relevant differences were noted in any other variables. A basal-bolus regimen with ILPS once daily resulted in non-inferior glycaemic control compared to a similar regimen with glargine, without statistically significant or clinically relevant differences in hypoglycaemia. ILPS-based regimens can be considered an alternative to basal-bolus regimens with glargine for T2DM patients.
    Diabetes Obesity and Metabolism 08/2011; 13(12):1149-57. DOI:10.1111/j.1463-1326.2011.01484.x · 6.36 Impact Factor
  • Katherine Esposito · Dario Giugliano ·
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    ABSTRACT: Sexual problems are diffuse in both genders. Although epidemiologic evidence seems to support a role for lifestyle factors in erectile dysfunction, limited data are available suggesting the treatment of underlying risk factors may improve erectile dysfunction. The results are sparse regarding associations between lifestyle factors and female sexual dysfunction, and conclusions regarding influence of healthy behaviors on female sexual dysfunction cannot be made before more studies have been performed. Beyond the specific effects on sexual dysfunctions in men and women, adoption of these measures promotes a healthier life and increased well-being, which may help reduce the burden of sexual dysfunction.
    Urologic Clinics of North America 08/2011; 38(3):293-301. DOI:10.1016/j.ucl.2011.04.006 · 1.20 Impact Factor
  • Dario Giugliano · Katherine Esposito ·

    JAMA The Journal of the American Medical Association 07/2011; 306(4):383. DOI:10.1001/jama.2011.1045 · 35.29 Impact Factor
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    K Esposito · D Giugliano ·
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    ABSTRACT: Our understanding of the relationships between obesity, metabolic syndrome, and erectile dysfunction (ED) has advanced significantly over the past decades. Increase in visceral adiposity and related risk factors are associated with a proinflammatory state that results in decreased nitric oxide (NO) availability and activity that is responsible, at least in part, for endothelial injury and dysfunction as well as for ED. The reduced testosterone levels associated with obesity and metabolic syndrome may contribute to ED.Clinical Pharmacology & Therapeutics (2011) 90 1, 169-173. doi:10.1038/clpt.2011.91
    Clinical Pharmacology &#38 Therapeutics 07/2011; 90(1):169-73. DOI:10.1038/clpt.2011.91 · 7.90 Impact Factor
  • K Esposito · C Mosca · C Brancario · P Chiodini · A Ceriello · D Giugliano ·
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    ABSTRACT: Glucagon-like peptide-1 (GLP-1) receptor agonists are available for the treatment of type 2 diabetes. We assessed the efficacy of exenatide and liraglutide to reach the HbA(1c) target of <7% in people with type 2 diabetes. We conducted an electronic search for randomized controlled trials (RCTs) involving GLP-1 agonists through September 2010. RCTs were included if they lasted at least 12 weeks, included 30 patients or more, and reported the proportion of patients reaching the HbA(1c) target of <7%. A total of 25 RCTs reporting 28 comparisons met the selection criteria, which included 9771 study participants evaluated for the primary endpoint, 5083 treated with a GLP-1 agonist and 4688 treated with placebo or a comparator drug. GLP-1 agonists showed a statistically significant reduction in HbA(1c) compared to placebo and the proportion of participants achieving the HbA(1c) goal <7% was 46% for exenatide, 47% for liraglutide, and 63% for exenatide LAR (long-acting release). Moreover, the reduction of the HbA(1c) level and the rate of HbA(1c) goal attainment were higher for both exenatide LAR and liraglutide, as compared to comparator drugs. Higher rates of hypoglycemia with exenatide b.i.d. and liraglutide compared to placebo were associated with the concomitant use of a sulfonylurea. Exenatide b.i.d. and liraglutide were associated with weight loss compared to placebo or other antidiabetic drugs. Baseline HbA(1c) was the best predictor for achievement of A1c target (overall weighted R(2) value = 0.513, p < 0.001). A greater proportion of patients with type 2 diabetes can achieve the HbA(1c) goal <7% with GLP-1 agonists compared to placebo or other antidiabetic drugs; in absolute terms, exenatide LAR was best for the attainment of the HbA(1c) goal.
    Current Medical Research and Opinion 06/2011; 27(8):1519-28. DOI:10.1185/03007995.2011.590127 · 2.65 Impact Factor
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    ABSTRACT: Insulin analogues are increasingly used in patients with type 2 diabetes. We performed a systematic review of randomized controlled trials (RCTs) to assess the role of insulin analogues to reach different hemoglobin A1c (HbA1c) targets (from 6.5% to 8%) in type 2 diabetic patients. RCTs involving insulin regimens (basal, prandial, biphasic, and basal-bolus) with insulin analogues in type 2 diabetes were identified through electronic searches (MEDLINE, EMBASE, CINAHL, and The Cochrane Library) through August 2010. We included any study arm of RCTs if they were at least 12 weeks in duration, and reported HbA1c as an outcome and the proportion of diabetic patients reaching the HbA1c target of <7%. The proportion of patients with HbA1c <6.5%, <7.0%, <7.5%, and <8.0% was estimated using mean and standard deviation of HbA1c at the end of treatment. We identified 53 RCTs, with 92 arms, and 32,689 patients. The proportion of patients at target was highest with the basal-bolus regimen, and ranged from 27.8% (95% CI, 22.2-34%) for the HbA1c target <6.5% to 88% (CI 83-92%) for the HbA1c target <8%. Biphasic insulin regimen ranked second at any HbA1c target, while prandial and basal regimens alternated across different HbA1c targets. At any HbA1c target, basal-bolus insulin regimens with insulin analogues obtained the best results, which may be useful for detailing the best treatment effect in individual patients.
    Journal of diabetes and its complications 05/2011; 25(4):275-81. DOI:10.1016/j.jdiacomp.2011.03.005 · 3.01 Impact Factor

Publication Stats

19k Citations
3,166.15 Total Impact Points


  • 1978-2015
    • Second University of Naples
      • • Faculty of Medicine and Surgery
      • • Dipartimento di Psicologia
      • • Dipartimento di Biochimica, Biofisica e Patologia Generale
      Caserta, Campania, Italy
  • 1991-2014
    • Naples Eastern University
      Napoli, Campania, Italy
  • 1986-2004
    • Università degli Studi di Napoli L'Orientale
      Napoli, Campania, Italy
  • 1976-2004
    • University of Naples Federico II
      • Department of Molecular Medicine and Medical Biotechnology
      Napoli, Campania, Italy
  • 1995
    • Interactive Institute
      Tukholma, Stockholm, Sweden
  • 1990-1992
    • University of Udine
      • Department of Medical and Biological Sciences
      Udine, Friuli Venezia Giulia, Italy
    • Bologna Center
      Bolonia, Emilia-Romagna, Italy
  • 1980-1987
    • University of Liège
      • Diabetes, Nutrition and Metabolic Disorders Unit
      Luik, Wallonia, Belgium
  • 1980-1981
    • Istituto Medicina Sport Torino
      Torino, Piedmont, Italy