49 results on '"DEL PRATO, Stefano"'
Search Results
2. The Relationship Between Dietary Patterns and Glycemic Variability in People with Impaired Glucose Tolerance.
- Author
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Dimova R, Chakarova N, Del Prato S, and Tankova T
- Subjects
- Humans, Adult, Middle Aged, Cross-Sectional Studies, Blood Glucose metabolism, Glucose, Glucose Intolerance, Diabetes Mellitus, Diabetes Mellitus, Type 2
- Abstract
Background: Diurnal glucose fluctuations are increased in prediabetes and might be affected by specific dietary patterns., Objectives: The present study assessed the relationship between glycemic variability (GV) and dietary regimen in people with normal glucose tolerance (NGT) and impaired glucose tolerance (IGT)., Methods: Forty-one NGT (mean age: 45.0 ± 9.0 y, mean BMI: 32.0 ± 7.0 kg/m
2 ) and 53 IGT (mean age: 48.4 ± 11.2 y, mean BMI: 31.3 ± 5.9 kg/m2 ) subjects were enrolled in this cross-sectional study. The FreeStyleLibre Pro sensor was used for 14 d, and several parameters of GV were calculated. The participants were provided with a diet diary to record all meals. ANOVA analysis, Pearson correlation, and stepwise forward regression were performed., Results: Despite no difference in diet patterns between the 2 groups, GV parameters were higher in IGT than in NGT. GV worsened with an increase in overall daily carbohydrate and refined grain consumption and improved with the increase in whole grain intake in IGT. GV parameters were positively related [r = 0.14-0.53; all P < 0.02 for SD, continuous overall net glycemic action 1 (CONGA1), J-index, lability index (LI), glycemic risk assessment diabetes equation, M-value, and mean absolute glucose (MAG)], and low blood glucose index (LBGI) inversely (r = -0.37, P = 0.006) related to the total percentage of carbohydrate, but not to the distribution of carbohydrate between the main meals in the IGT group. A negative relationship existed between total protein consumption and GV indices (r = -0.27 to -0.52; P < 0.05 for SD, CONGA1, J-index, LI, M-value, and MAG). The total EI was related to GV parameters (r = 0.27-0.32; P < 0.05 for CONGA1, J-index, LI, and M-value; and r = -0.30, P = 0.028 for LBGI)., Conclusions: The primary outcome results showed that insulin sensitivity, calories, and carbohydrate content are predictors of GV in individuals with IGT. Overall, the secondary analyses suggested that carbohydrate and daily consumption of refined grains might be associated with higher GV, whereas whole grains and daily protein intake were related to lower GV in people with IGT., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
3. Diabetes registries and high-quality diabetes care.
- Author
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Khunti K, Mathieu C, Torbeyns B, Del Prato S, and Heine R
- Subjects
- Humans, Quality of Health Care, Registries, Diabetes Mellitus, Type 2 epidemiology, Diabetes Mellitus, Type 2 therapy, Diabetes Mellitus epidemiology, Diabetes Mellitus therapy
- Abstract
Competing Interests: KK has acted as a consultant or speaker, or received grants for investigator-initiated studies for AstraZeneca, Novartis, Novo Nordisk, Sanofi, Eli Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie/Menarini Group, Janssen, and Napp Pharmaceuticals. CM serves or has served on the advisory panel for Novo Nordisk, Sanofi, Merck Sharp and Dohme, Eli Lilly, Novartis, AstraZeneca, Boehringer Ingelheim, Roche, Medtronic, ActoBio Therapeutics, Pfizer, Insulet, Imcyse, Vertex, and Zealand Pharma; serves or has served on the speakers bureau for Novo Nordisk, Sanofi, Eli Lilly, Boehringer Ingelheim, Novartis, and Astra Zeneca; and financial compensation for these activities was received by KU Leuven. SDP received grants or contracts from AstraZeneca, Boehringer Ingelheim, Applied Therapeutics, Eli Lilly, Hengrui, MSD, Menarini Pharmaceuticals, Novo Nordisk, Sanofi, and Vertex; received consulting fees from Abbott, Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hengrui, MSD, Menarini Pharmaceuticals, Novo Nordisk, Sanofi, and Vertex; received payment or honoraria from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Merck & Co, Novartis Pharmaceuticals, Novo Nordisk, Sanofi, and Takeda Pharmaceuticals.; and is President of the European Association for the Study of Diabetes (EASD) and Vice-President for the European Diabetes Forum. RH is an employee of Eli Lilly but received no payment for this Comment; and has stock or stock options in Eli Lilly. BT declares no competing interests. KK is supported by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands and the NIHR Leicester Biomedical Research Centre. Members of the EUDF Strategic Forum Data and Registries are listed in the appendix.
- Published
- 2023
- Full Text
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4. The European Diabetes Forum (EUDF): a forum for turning the tide on diabetes in Europe.
- Author
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Mathieu C, Soderberg J, Del Prato S, Felton AM, Cos X, de Beaufort C, Gautier JF, Hauck B, Forbes A, Heine R, Schwarz P, and Torbeyns B
- Subjects
- Humans, Europe, Diabetes Mellitus therapy
- Published
- 2023
- Full Text
- View/download PDF
5. The impact of the COVID-19 pandemic on diabetes services: planning for a global recovery.
- Author
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Khunti K, Aroda VR, Aschner P, Chan JCN, Del Prato S, Hambling CE, Harris S, Lamptey R, McKee M, Tandon N, Valabhji J, and Seidu S
- Subjects
- Humans, Aged, Pandemics, Communicable Disease Control, COVID-19 epidemiology, Disasters, Diabetes Mellitus epidemiology, Diabetes Mellitus therapy
- Abstract
The COVID-19 pandemic has disproportionately affected certain groups, such as older people (ie, >65 years), minority ethnic populations, and people with specific chronic conditions including diabetes, cardiovascular disease, kidney disease, and some respiratory diseases. There is now evidence of not only direct but also indirect adverse effects of COVID-19 in people with diabetes. Recurrent lockdowns and public health measures throughout the pandemic have restricted access to routine diabetes care, limiting new diagnoses, and affecting self-management, routine follow-ups, and access to medications, as well as affecting lifestyle behaviours and emotional wellbeing globally. Pre-pandemic studies have shown that short-term delays in delivery of routine care, even by 12 months, are associated with adverse effects on risk factor control and worse microvascular, macrovascular, and mortality outcomes in people with diabetes. Disruptions within the short-to-medium term due to natural disasters also result in worse diabetes outcomes. However, the true magnitude of the indirect effects of the COVID-19 pandemic on long-term outcomes and mortality in people with diabetes is still unclear. Disasters tend to exacerbate existing health disparities; as we recover ambulatory diabetes services in the aftermath of the pandemic, there is an opportunity to prioritise those with the greatest need, and to target resources and interventions aimed at improving outcomes and reducing inequality., Competing Interests: Declaration of interests KK has acted as a consultant, speaker or received grants for investigator-initiated studies for AstraZeneca, Novartis, Novo Nordisk, Sanofi, Eli Lilly, Merck Sharp & Dohme, Boehringer Ingelheim, Bayer, Berlin-Chemie/Menarini Group, Janssen, and Napp Pharmaceuticals. VRA has served as a consultant for Applied Therapeutics, Fractyl, Novo Nordisk, Pfizer, Sanofi; has a spouse employed at Janssen; and has received research support through their institution for clinical trial investigator, clinical trial leadership roles, or both from Applied Therapeutics, Eli Lilly, Fractyl, Novo Nordisk, and Sanofi. SS reports personal fees from Amgen, AstraZeneca, Napp Pharmaceuticals, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Roche, Sanofi, and Boehringer Ingelheim. Additionally, SS reports grants from AstraZeneca, Sanofi, Servier, and Janssen. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
- Full Text
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6. COVID-19, Hyperglycemia, and New-Onset Diabetes.
- Author
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Khunti K, Del Prato S, Mathieu C, Kahn SE, Gabbay RA, and Buse JB
- Subjects
- Humans, Prospective Studies, SARS-CoV-2, COVID-19, Diabetes Mellitus, Diabetic Ketoacidosis epidemiology, Diabetic Ketoacidosis etiology, Hyperglycemia
- Abstract
Certain chronic comorbidities, including diabetes, are highly prevalent in people with coronavirus disease 2019 (COVID-19) and are associated with an increased risk of severe COVID-19 and mortality. Mild glucose elevations are also common in COVID-19 patients and associated with worse outcomes even in people without diabetes. Several studies have recently reported new-onset diabetes associated with COVID-19. The phenomenon of new-onset diabetes following admission to the hospital has been observed previously with other viral infections and acute illnesses. The precise mechanisms for new-onset diabetes in people with COVID-19 are not known, but it is likely that a number of complex interrelated processes are involved, including previously undiagnosed diabetes, stress hyperglycemia, steroid-induced hyperglycemia, and direct or indirect effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the β-cell. There is an urgent need for research to help guide management pathways for these patients. In view of increased mortality in people with new-onset diabetes, hospital protocols should include efforts to recognize and manage acute hyperglycemia, including diabetic ketoacidosis, in people admitted to the hospital. Whether new-onset diabetes is likely to remain permanent is not known, as the long-term follow-up of these patients is limited. Prospective studies of metabolism in the setting of postacute COVID-19 will be required to understand the etiology, prognosis, and treatment opportunities., (© 2021 by the American Diabetes Association.)
- Published
- 2021
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7. Accuracy of 1-Hour Plasma Glucose During the Oral Glucose Tolerance Test in Diagnosis of Type 2 Diabetes in Adults: A Meta-analysis.
- Author
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Ahuja V, Aronen P, Pramodkumar TA, Looker H, Chetrit A, Bloigu AH, Juutilainen A, Bianchi C, La Sala L, Anjana RM, Pradeepa R, Venkatesan U, Jebarani S, Baskar V, Fiorentino TV, Timpel P, DeFronzo RA, Ceriello A, Del Prato S, Abdul-Ghani M, Keinänen-Kiukaanniemi S, Dankner R, Bennett PH, Knowler WC, Schwarz P, Sesti G, Oka R, Mohan V, Groop L, Tuomilehto J, Ripatti S, Bergman M, and Tuomi T
- Subjects
- Adult, Blood Glucose, Fasting, Glucose Tolerance Test, Glycated Hemoglobin analysis, Humans, Sensitivity and Specificity, Diabetes Mellitus, Diabetes Mellitus, Type 2 diagnosis
- Abstract
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
1c . 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., (© 2021 by the American Diabetes Association.)- Published
- 2021
- Full Text
- View/download PDF
8. Metformin: an inexpensive and effective treatment in people with diabetes and COVID-19?
- Author
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Dardano A and Del Prato S
- Subjects
- Cohort Studies, Humans, Hypoglycemic Agents therapeutic use, Retrospective Studies, Diabetes Mellitus drug therapy, Metformin therapeutic use, COVID-19 Drug Treatment
- Published
- 2021
- Full Text
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9. New-Onset Diabetes in Covid-19.
- Author
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Rubino F, Amiel SA, Zimmet P, Alberti G, Bornstein S, Eckel RH, Mingrone G, Boehm B, Cooper ME, Chai Z, Del Prato S, Ji L, Hopkins D, Herman WH, Khunti K, Mbanya JC, and Renard E
- Subjects
- COVID-19, Global Health, Glucose metabolism, Humans, SARS-CoV-2, Betacoronavirus, Coronavirus Infections complications, Coronavirus Infections metabolism, Diabetes Complications metabolism, Diabetes Mellitus etiology, Pandemics, Pneumonia, Viral complications, Pneumonia, Viral metabolism, Registries
- Published
- 2020
- Full Text
- View/download PDF
10. Diabetes and COVID-19: Risks, Management, and Learnings From Other National Disasters.
- Author
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Hartmann-Boyce J, Morris E, Goyder C, Kinton J, Perring J, Nunan D, Mahtani K, Buse JB, Del Prato S, Ji L, Roussel R, and Khunti K
- Subjects
- COVID-19, Disasters, Emergencies, Humans, Risk Management, SARS-CoV-2, Betacoronavirus, Coronavirus Infections epidemiology, Diabetes Mellitus, Pandemics, Pneumonia, Viral epidemiology
- Abstract
Evidence relating to the impact of COVID-19 in people with diabetes (PWD) is limited but continuing to emerge. PWD appear to be at increased risk of more severe COVID-19 infection, though evidence quantifying the risk is highly uncertain. The extent to which clinical and demographic factors moderate this relationship is unclear, though signals are emerging that link higher BMI and higher HbA
1c to worse outcomes in PWD with COVID-19. As well as posing direct immediate risks to PWD, COVID-19 also risks contributing to worse diabetes outcomes due to disruptions caused by the pandemic, including stress and changes to routine care, diet, and physical activity. Countries have used various strategies to support PWD during this pandemic. There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account. Evidence on the management of long-term conditions during national emergencies suggests various ways to mitigate the risks presented by these events., (© 2020 by the American Diabetes Association.)- Published
- 2020
- Full Text
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11. Heterogeneity of diabetes: heralding the era of precision medicine.
- Author
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Del Prato S
- Subjects
- Follow-Up Studies, Humans, Diabetes Mellitus, Precision Medicine
- Published
- 2019
- Full Text
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12. Gender difference in diabetes related excess risk of cardiovascular events: When does the 'risk window' open?
- Author
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Policardo L, Seghieri G, Francesconi P, Anichini R, Franconi F, and Del Prato S
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- Adult, Aged, Cohort Studies, Female, Heart Failure epidemiology, Humans, Italy epidemiology, Male, Middle Aged, Myocardial Infarction epidemiology, Risk Factors, Sex Factors, Stroke epidemiology, Time Factors, Cardiovascular Diseases epidemiology, Diabetes Mellitus epidemiology, Diabetic Angiopathies epidemiology
- Abstract
Objective: Women with diabetes have a greater excess risk for cardiovascular diseases (CVD) than men. This study was aimed at clarifying whether this effect is lifelong or more evident in some life-periods., Methods: The effect of diabetes and gender on the risk of first ever hospitalization for acute myocardial infarction (AMI), ischemic stroke (IS), congestive heart failure (CHF), lower extremity amputations (LEA) or any of these major cardiovascular events (MACE) have been evaluated by a Cox-hazard model, over years 2008-2012 querying administrative databases of a cohort living in Tuscany, Italy., Results: Comparing subjects with diabetes to those without it the overall age-adjusted excess risk was higher in women than in men for AMI and MACE and higher in men for LEA, with no difference for IS or CHF. In women the excess risk for AMI and MACE started earlier (46yr) and lasted until age of more than 85yr, while 'risk-windows' opened later and had a shorter duration for CHF (56-65yr) and IS (66-75yr)., Conclusion: Diabetic women have a significant diabetes-associated excess of CVD risk, except for LEA, with a 'risk window' opening earlier and lasting longer for AMI and MACE, later and with a shorter duration for IS and CHF., (Copyright © 2017 Elsevier Inc. All rights reserved.)
- Published
- 2017
- Full Text
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13. Hospital incidental diagnosis of diabetes: A population study.
- Author
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Seghieri G, Policardo L, Profili F, Francesconi P, Anichini R, and Del Prato S
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- Adult, Aged, Aged, 80 and over, Diabetes Mellitus diagnosis, Diabetes Mellitus mortality, Female, Hospital Mortality, Humans, Italy epidemiology, Male, Middle Aged, Retrospective Studies, Risk Factors, Diabetes Mellitus epidemiology, Hospitalization statistics & numerical data, Incidental Findings
- Abstract
Aims: To identify incidental previously unrecognized diabetes (IPUD) among hospitalized patients and corresponding mortality risk in comparison with individuals with known diabetes (KDM)., Methods: Out of 214,991 individuals discharged in year 2011 from all hospitals of Tuscany, Italy we retrospectively identified IPUD as individuals with no known diabetes and/or previous antidiabetic medication, receiving at least two prescriptions of glucose-lowering-drugs over the next 6months after discharge. Two-year (2012-2013) adjusted mortality risk was tested by a Cox-regression-analysis, comparing IPUD and KDM patients with at least one hospital admission in 2011., Results: 974 patients with IPUD (375.6×100,000 hospitalized people) have been identified. IPUD risk was associated with aging, male gender and greater burden of co-morbidities, was higher in migrants of non-Italian ancestry and was reduced among patients of family physicians adhering to guidelines resulting in a proactive model of care delivery. In IPUD patients alive at 1st January 2012, (n=865) the adjusted risk of two-year mortality was similar to that of KDM subjects (HR=1.08; 95% CI: 0.92-1.26; p=NS)., Conclusions: IPUD occurs more commonly in older male subjects, migrants of non-Italian ancestry, and among patients of physicians non-adhering to a shared diabetes care model. People with IPUD have similar two-year-mortality risk compared with KDM individuals., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
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14. Effect of diabetes on hospitalization for ischemic stroke and related in-hospital mortality: a study in Tuscany, Italy, over years 2004-2011.
- Author
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Policardo L, Seghieri G, Anichini R, De Bellis A, Franconi F, Francesconi P, Del Prato S, and Mannucci E
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- Adolescent, Adult, Aged, Aged, 80 and over, Female, Follow-Up Studies, Humans, Incidence, Italy epidemiology, Male, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Time Factors, Young Adult, Diabetes Mellitus physiopathology, Hospital Mortality trends, Hospitalization statistics & numerical data, Stroke epidemiology
- Abstract
Background: Incidence of ischemic stroke and associated in-hospital mortality is decreasing in Western populations, while the prevalence of diabetes, a well-known risk factor for ischemic stroke, is progressively rising. This study was aimed at evaluating the effect of diabetes on ischemic stroke hospitalization and in-hospital mortality after ischemic stroke., Methods: Discharges with diagnosis of ischemic stroke were identified in a database containing all hospitalizations of resident population of Tuscany, Italy, over years 2004-2011. Cases with diabetes were identified through specific drug prescriptions, official certifications or previous hospital diagnosis. Rates of annual ischemic stroke incidence and related in-hospital mortality were separately calculated for gender and age class, in subjects with and without diabetes., Results: Sixty-five thousand one hundred sixty-five hospital discharges with ischemic stroke diagnosis were identified. Diabetes was associated with increased risk of stroke odds ratio(95% confidence interval):1.31(1.28-1.34) in men and 1.24(1.21-1.37) in women. Diabetic women, compared with men, had a higher in-hospital mortality risk after ischemic stroke (odds ratio:1.32; 1.06-1.64), whereas in non-diabetic subjects, there was no difference between genders. Incidence of ischemic stroke has declined in non-diabetic subjects, except for women aged ≤70 years; a similar reduction was observed for in-hospital mortality. Among diabetic patients, conversely, annual incidence of ischemic stroke rose by 3% in the elderly people (>70 years), and annual mortality trend remained unchanged., Conclusions: In the last decade, the incidence of ischemic stroke and of related in-hospital mortality declined in persons without diabetes, while increasing among diabetic patients of advanced age. Women with diabetes, compared with men, had a higher in-hospital mortality risk., (Copyright © 2014 John Wiley & Sons, Ltd.)
- Published
- 2015
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15. Introduction to the 4th World Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension (CODHy).
- Author
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Del Prato S and Raz I
- Subjects
- Cardiovascular Diseases epidemiology, Cardiovascular Diseases etiology, Cardiovascular Diseases prevention & control, Consensus, Guideline Adherence, Humans, International Cooperation, Risk Factors, Congresses as Topic, Diabetes Mellitus epidemiology, Diabetes Mellitus etiology, Diabetes Mellitus therapy, Hypertension epidemiology, Hypertension etiology, Hypertension therapy, Obesity epidemiology, Obesity etiology, Obesity therapy
- Published
- 2013
- Full Text
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16. Global call for free academic movement for international dialogue.
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Raz I, Amiel SA, Alberti G, Shehadeh N, Del Prato S, Zimmet P, and Cefalu WT
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- Biomedical Research, Humans, Diabetes Mellitus, International Cooperation
- Published
- 2012
- Full Text
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17. Introduction to the Third World Congress on Controversies to Consensus in Diabetes, Obesity and Hypertension (CODHy): outcome studies versus clinical experience in the treatment of diabetes.
- Author
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Raz I and Del Prato S
- Subjects
- Congresses as Topic, Humans, Diabetes Mellitus, Hypertension, Obesity
- Published
- 2011
- Full Text
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18. How do we define cure of diabetes?
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Buse JB, Caprio S, Cefalu WT, Ceriello A, Del Prato S, Inzucchi SE, McLaughlin S, Phillips GL 2nd, Robertson RP, Rubino F, Kahn R, and Kirkman MS
- Subjects
- Blood Glucose metabolism, Consensus, Diabetes Mellitus genetics, Diabetes Mellitus prevention & control, Diabetes Mellitus, Type 1 prevention & control, Diabetes Mellitus, Type 1 therapy, Diabetes Mellitus, Type 2 prevention & control, Diabetes Mellitus, Type 2 therapy, Genetic Predisposition to Disease epidemiology, Humans, Reference Values, Societies, Medical, United States, Diabetes Mellitus therapy, Health Status, Remission Induction methods
- Published
- 2009
- Full Text
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19. Metabolic syndrome and vascular alterations in normotensive subjects at risk of diabetes mellitus.
- Author
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Ghiadoni L, Penno G, Giannarelli C, Plantinga Y, Bernardini M, Pucci L, Miccoli R, Taddei S, Salvetti A, and Del Prato S
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- Adult, Blood Flow Velocity, Blood Pressure, Brachial Artery diagnostic imaging, Brachial Artery drug effects, Brachial Artery physiopathology, Carotid Artery, Common diagnostic imaging, Carotid Artery, Common physiopathology, Cross-Sectional Studies, Endothelium, Vascular physiopathology, Female, Femoral Artery physiopathology, Humans, Male, Middle Aged, Nitroglycerin pharmacology, Pulse, Radial Artery physiopathology, Regional Blood Flow, Risk Factors, Ultrasonography, Vasodilation, Vasodilator Agents pharmacology, Arteries physiopathology, Diabetes Mellitus etiology, Metabolic Syndrome physiopathology
- Abstract
We evaluated the possible association between early vascular abnormalities and the metabolic syndrome (MS) in 77 normotensive subjects (mean age: 50 years) at risk of developing diabetes for family history of diabetes, obesity, or impaired fasting glucose. Fifty healthy subjects were recruited as controls. MS was defined according to the ATP III criteria. Brachial artery endothelium-dependent and -independent vasodilation were assessed as flow-mediated dilation (FMD) and response to glyceryl trinitrate (GTN, 25 microg sublingual), respectively, by automatic computerized edge detection system. Carotid-femoral pulse wave velocity (PWV) and radial augmentation index (AIx) were assessed by applanation tonometry. PWV was significantly (P<0.01) higher in subjects with MS (n=29, 9.0+/-1.9 m/s) as compared with those without MS (n=48, 7.7+/-1.2 m/s) and controls (7.2+/-1.5 m/s). FMD was significantly (P<0.05) reduced in both subjects with (5.8+/-2.7%) and without MS (6.1+/-3.7%) as compared with controls (6.9+/-2.5%). No significant differences were found for response to GTN and AIx. PWV and FMD were significantly (P<0.05) affected by increasing number of MS components. Among the components of the MS, only blood pressure significantly affected PWV, whereas blood pressure and fasting glucose influenced FMD. Logistic regression analysis showed that MS was associated with increased risk of altered PVW (odd ratio: 7.95, confidence limits: 1.06 to 69.11), whereas only blood pressure component was significantly related with increased risk of impaired FMD (odd ratio: 3.60, confidence limits: 1.01 to 12.78). In conclusion, in normotensive subjects at risk of developing diabetes mellitus, the presence of MS is associated with a selective alteration of central PWV.
- Published
- 2008
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20. ACE/AACE consensus conference on the implementation of outpatient management of diabetes mellitus: consensus conference recommendations.
- Author
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Lebovitz HE, Austin MM, Blonde L, Davidson JA, Del Prato S, Gavin JR 3rd, Handelsman Y, Jellinger PS, Levy P, Riddle MC, Roberts VL, and Siminerio LM
- Subjects
- Adult, Blood Glucose analysis, Diabetes Complications prevention & control, Diabetes Mellitus epidemiology, Diabetes Mellitus prevention & control, Glucose Intolerance therapy, Glycated Hemoglobin analysis, Humans, Information Systems, Insulin Resistance, Internet, Risk Factors, Ambulatory Care, Diabetes Mellitus therapy
- Published
- 2006
- Full Text
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21. Unlocking the opportunity of tight glycaemic control. Far from goal.
- Author
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Del Prato S
- Subjects
- Diabetes Complications prevention & control, Diabetes Mellitus blood, Humans, Hypoglycemic Agents therapeutic use, Insulin therapeutic use, Blood Glucose metabolism, Diabetes Mellitus drug therapy, Hypoglycemic Agents administration & dosage, Insulin administration & dosage
- Abstract
The long-term benefits of providing intensive insulin therapy to control blood glucose levels have been demonstrated in people with type 1 or type 2 diabetes mellitus. However, achieving good glycaemic control in clinical practice continues to be a major challenge with only a small proportion of people with diabetes achieving current treatment goals. Some of the reasons for this include ineffectual diet and weight control initiatives, limited efficacy of therapeutic agents or association with excessive adverse events, delayed initiation of insulin therapy and poor patient acceptance and compliance with a regimen of multiple daily insulin injections. New ways of delivering insulin without the need for subcutaneous injections may overcome many of these limitations and thus help in the early adoption of insulin treatment by patients, assist in achieving and maintaining long-term optimal glycaemic control and improve patients' quality of life.
- Published
- 2005
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22. Expression and activity of CYP2E1 in circulating lymphocytes are not altered in diabetic individuals.
- Author
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Pucci L, Chirulli V, Marini S, Lucchesi D, Penno G, Gervasi PG, Del Prato S, and Longo V
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- Adult, Aged, Cytochrome P-450 Enzyme System genetics, Cytochrome P450 Family 2, Diabetes Mellitus genetics, Female, Humans, Male, Middle Aged, Cytochrome P-450 Enzyme System biosynthesis, Diabetes Mellitus enzymology, Gene Expression Regulation, Enzymologic physiology, Lymphocytes enzymology
- Abstract
Cytochrome P4502E1 (CYP2E1) plays an important role in ROS production thus favouring accelerated membrane lipid peroxidation. This isoform is strongly expressed in the liver but it can be also found in lymphocytes. As such, lymphocyte may provide a non-invasive accessible pool for screening CYP2E1 expression in man. We have, therefore, analysed CYP2E1 expression and activity in lymphocyte microsomes from 12 healthy controls, 11 type 1 and 12 type 2 diabetic subjects by using Western blot and enzymatic activities. Immunoblotting did not show difference among CYP2E1 protein bands in controls, type 1 and type 2 diabetics. To assess CYP2E1 activity we used the 7-ethoxy-4-trifluoromethylcoumarin (7-EFC), as a fluorescent substrate. The rate of deethylation of 7-EFC from controls did not differ from type 1 and type 2 diabetic subjects. The lack of any difference in CYP2E1 activity also was confirmed by the NADPH-dependent microsomal lipid peroxidation CCL4-induced assay showing similar peroxidation rates among controls and diabetic subjects. The results show that CYP2E1 expression/activity in lymphocytes is not enhanced in diabetes.
- Published
- 2005
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23. Effect of alirocumab on individuals with type 2 diabetes, high triglycerides, and low high-density lipoprotein cholesterol
- Author
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Colhoun, Helen M., Leiter, Lawrence A., Müller-Wieland, Dirk, Cariou, Bertrand, Ray, Kausik K., Tinahones, Francisco J., Domenger, Catherine, Letierce, Alexia, Israel, Marc, Samuel, Rita, and Del Prato, Stefano
- Published
- 2020
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24. The IGFBP3/TMEM219 pathway regulates beta cell homeostasis
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DAddio, Francesca, Maestroni, Anna, Assi, Emma, Ben Nasr, Moufida, Amabile, Giovanni, Usuelli, Vera, Loretelli, Cristian, Bertuzzi, Federico, Antonioli, Barbara, Cardarelli, Francesco, El Essawy, Basset, Solini, Anna, Gerling, Ivan C., Bianchi, Cristina, Becchi, Gabriella, Mazzucchelli, Serena, Corradi, Domenico, Fadini, Gian Paolo, Foschi, Diego, Markmann, James F., Orsi, Emanuela, Skrha, Jan, Camboni, Maria Gabriella, Abdi, Reza, Shapiro, A. M. James, Folli, Franco, Ludvigsson, Johnny, Del Prato, Stefano, Zuccotti, Gianvincenzo, Fiorina, Paolo, D'Addio, F., Maestroni, A., Assi, E., Ben Nasr, M., Amabile, G., Usuelli, V., Loretelli, C., Bertuzzi, F., Antonioli, B., Cardarelli, F., El Essawy, B., Solini, A., Gerling, I. C., Bianchi, C., Becchi, G., Mazzucchelli, S., Corradi, D., Fadini, G. P., Foschi, D., Markmann, J. F., Orsi, E., Skrha, J., Camboni, M. G., Abdi, R., James Shapiro, A. M., Folli, F., Ludvigsson, J., Del Prato, S., Zuccotti, G., and Fiorina, P.
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Male ,Cell- och molekylärbiologi ,Inbred C57BL ,cells, cultured ,Transgenic ,Mice ,Mice, Inbred NOD ,Insulin-Secreting Cells ,middle aged ,Homeostasis ,animal ,membrane protein ,Cells, Cultured ,Mice, Knockout ,Cultured ,Reverse Transcriptase Polymerase Chain Reaction ,adult ,gene expression regulation ,Middle Aged ,reverse transcriptase polymerase chain reaction ,diabetes mellitus, type 1 ,female ,diabetes mellitus, type 2 ,Female ,immunoblotting ,signal transduction ,Type 2 ,Type 1 ,Signal Transduction ,Adult ,mice, inbred C57BL ,Cells ,Knockout ,Science ,mice, knockout ,Immunoblotting ,Mice, Transgenic ,Animals ,Diabetes Mellitus, Type 1 ,Diabetes Mellitus, Type 2 ,Humans ,Insulin-Like Growth Factor Binding Protein 3 ,Membrane Proteins ,Mice, Inbred C57BL ,Gene Expression Regulation ,male ,insulin-secreting cell ,Diabetes Mellitus ,human ,mice, inbred NOD ,mice, transgenic ,homeostasi ,Settore FIS/07 - Fisica Applicata(Beni Culturali, Ambientali, Biol.e Medicin) ,Inbred NOD ,insulin-like growth factor binding protein 3 ,Cell and Molecular Biology - Abstract
In this new study the Authors demonstrated that the IGFBP3/TMEM219 pathway is a physiological regulator of pancreatic beta cell homeostasis and it is dysregulated in diabetes. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes. Loss of pancreatic beta cells is a central feature of type 1 (T1D) and type 2 (T2D) diabetes, but a therapeutic strategy to preserve beta cell mass remains to be established. Here we show that the death receptor TMEM219 is expressed on pancreatic beta cells and that signaling through its ligand insulin-like growth factor binding protein 3 (IGFBP3) leads to beta cell loss and dysfunction. Increased peripheral IGFBP3 was observed in established and at-risk T1D/T2D patients and was confirmed in T1D/T2D preclinical models, suggesting that dysfunctional IGFBP3/TMEM219 signaling is associated with abnormalities in beta cells homeostasis. In vitro and in vivo short-term IGFBP3/TMEM219 inhibition and TMEM219 genetic ablation preserved beta cells and prevented/delayed diabetes onset, while long-term IGFBP3/TMEM219 blockade allowed for beta cell expansion. Interestingly, in several patients cohorts restoration of appropriate IGFBP3 levels was associated with improved beta cell function. The IGFBP3/TMEM219 pathway is thus shown to be a physiological regulator of beta cell homeostasis and is also demonstrated to be disrupted in T1D/T2D. IGFBP3/TMEM219 targeting may therefore serve as a therapeutic option in diabetes. Funding Agencies|SID Lombardia Grant; EFSD/JDRF/Lilly Programme on Type 1 Diabetes Research; Italian Ministry of HealthMinistry of Health, Italy [RF-2016-02362512]; Universita di Milano; NIHUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [DK104155]; Juvenile Diabetes Research FoundationJuvenile Diabetes Research Foundation; Enthera S.r.l.
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- 2022
25. 2009 SIPREC Consensus Document — Executive Summary: Cardiovascular Prevention in Subjects with Impaired Fasting Glucose or Impaired Glucose Tolerance
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Volpe, Massimo, Borghi, Claudio, Perin, Paolo Cavallo, Chiariello, Massimo, Manzato, Enzo, Miccoli, Roberto, Modena, Maria G., Riccardi, Gabriele, Sesti, Giorgio, Tiengo, Antonio, Trimarco, Bruno, Vanuzzo, Diego, Verdecchia, Paolo, Zaninelli, Augusto, and Del Prato, Stefano
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- 2010
- Full Text
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26. Cardiovascular Prevention in Subjects with Impaired Fasting Glucose or Impaired Glucose Tolerance
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Volpe, Massimo, Borghi, Claudio, Perin, Paolo Cavallo, Chiariello, Massimo, Manzato, Enzo, Miccoli, Roberto, Modena, Maria Grazia, Riccardi, Gabriele, Sesti, Giorgio, Tiengo, Antonio, Trimarco, Bruno, Vanuzzo, Diego, Verdecchia, Paolo, Zaninelli, Augusto, and Del Prato, Stefano
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- 2010
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27. Panethnic differences in blood pressure in Europe: A systematic review and meta-analysis
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Modesti, Pietro Amedeo, Reboldi, Gianpaolo, Cappuccio, Francesco P, Agyemang, Charles, Remuzzi, Giuseppe, Rapi, Stefano, Perruolo, Eleonora, Parati, Gianfranco, ESH Working Group on CV Risk in Low Resource Settings: Modesti, P. A., Parati, G., Agostoni, P., Agyemang, C., Barros, H., Basu, S., Benetos, A., Cappuccio, F. P., Ceriello, A., DEL PRATO, Stefano, Kalyesubula, R., Kilama, M. O., O'Brien, E., Perlini, S., Picano, E., Reboldi, G., Redon, J., Remuzzi, . G, Stuckler, D., Van Bortel, L. M., Zhao, D., Bamoshmoosh, M., Perruolo, E., Bennet, L., Bruno, ROSA MARIA, Carlsson, A. C., Cifkova, R., Fadnes, L. T., Grech, H., Klocek, M., Kumar, B., Lalic, N., Manolis, A. J., Nørredam, M., Massetti, L., de Courten, M. P., Pereira, M., Pratali, L., Rapi, S., Siegert, A., Szklarska, A., Tendera, M., Twagirumukiza, M., Volodina, A., Watfa, G., Karaye, K. M., Phanzu, B. K., Dzudie, A., N'Guetta, R., Kiiza, M. C., Gudina, E. K., Longo Mbenza, B., Mucumbitsi, J., Anisiuba, B., Ibrahim, T. A., Okechukwu, O. S., Modesti, P, Reboldi, G, Cappuccio, F, Agyemang, C, Remuzzi, G, Rapi, S, Perruolo, E, and Parati, G
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Male ,Epidemiology ,Ethnic group ,Risk-Factor ,lcsh:Medicine ,Social Sciences ,Blood Pressure ,Vascular Medicine ,Cultural Anthropology ,Geographical Locations ,0302 clinical medicine ,Endocrinology ,Mathematical and Statistical Techniques ,Sociology ,Medicine and Health Sciences ,Ethnicity ,Medicine ,Ethnicities ,030212 general & internal medicine ,Adult ,Europe ,Female ,Humans ,Ethnic Groups ,Different Ethnic-Group ,lcsh:Science ,media_common ,Multidisciplinary ,Traditional medicine ,Religion ,Cross-Sectional Data ,Meta-analysis ,Physical Sciences ,Hypertension ,Origin Population ,Statistics (Mathematics) ,Research Article ,Endocrine Disorders ,Research and Analysis Methods ,Ethnic Epidemiology ,03 medical and health sciences ,South Asian Adult ,Diabetes mellitus ,hypertension, diabetes, ethnicity ,Diabetes Mellitus ,media_common.cataloged_instance ,Body-Mass Index ,European union ,Statistical Methods ,business.industry ,Insulin-Resistance ,lcsh:R ,Publication bias ,medicine.disease ,Blood pressure ,Metabolic Disorders ,Anthropology ,People and Places ,Observational study ,lcsh:Q ,Population Groupings ,business ,Coronary-Heart-Disease ,Body mass index ,Publication Bias ,030217 neurology & neurosurgery ,Mathematics ,Demography ,RC ,Africans ,Meta-Analysis ,Cardiovascular Risk - Abstract
Background:\ud \ud People of Sub Saharan Africa (SSA) and South Asians(SA) ethnic minorities living in Europe have higher risk of stroke than native Europeans(EU). Study objective is to provide an assessment of gender specific absolute differences in office systolic(SBP) and diastolic(DBP) blood pressure(BP) levels between SSA, SA, and EU.\ud \ud Methods and Findings:\ud \ud We performed a systematic review and meta-analysis of observational studies conducted in Europe that examined BP in non-selected adult SSA, SA and EU subjects. Medline, PubMed, Embase, Web of Science, and Scopus were searched from their inception through January 31st 2015, for relevant articles. Outcome measures were mean SBP and DBP differences between minorities and EU, using a random effects model and tested for heterogeneity. Twenty-one studies involving 9,070 SSA, 18,421 SA, and 130,380 EU were included. Compared with EU, SSA had higher values of both SBP (3.38 mmHg, 95% CI 1.28 to 5.48 mmHg; and 6.00 mmHg, 95% CI 2.22 to 9.78 in men and women respectively) and DBP (3.29 mmHg, 95% CI 1.80 to 4.78; 5.35 mmHg, 95% CI 3.04 to 7.66). SA had lower SBP than EU(-4.57 mmHg, 95% CI -6.20 to -2.93; -2.97 mmHg, 95% CI -5.45 to -0.49) but similar DBP values. Meta-analysis by subgroup showed that SA originating from countries where Islam is the main religion had lower SBP and DBP values than EU. In multivariate meta-regression analyses, SBP difference between minorities and EU populations, was influenced by panethnicity and diabetes prevalence.\ud \ud Conclusions:\ud \ud 1) The higher BP in SSA is maintained over decades, suggesting limited efficacy of prevention strategies in such group in Europe;2) The lower BP in Muslim populations suggests that yet untapped lifestyle and behavioral habits may reveal advantages towards the development of hypertension;3) The additive effect of diabetes, emphasizes the need of new strategies for the control of hypertension in groups at high prevalence of diabetes.
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- 2016
28. Dietary intake and major food sources of polyphenols in people with type 2 diabetes: The TOSCA.IT Study
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Vitale, M., Masulli, M., Rivellese, A. A., Bonora, E., Cappellini, F., Nicolucci, Andrea, Squatrito, S., Antenucci, D., Barrea, A., Bianchi, C., Bianchini, F., Fontana, L., Fornengo, P., Giorgino, F., Gnasso, A., Mannucci, E., Mazzotti, A., Nappo, R., Palena, A. P., Pata, P., Perriello, G., Potenziani, S., Radin, R., Ricci, L., Romeo, F., Santini, C., Scarponi, M., Serra, Riccardo, Timi, A., Turco, A. A., Vedovato, M., Zavaroni, D., Grioni, S., Riccardi, G., Vaccaro, O., Rivellese, Angela Albarosa, Cocozza, Sara, Auciello, Stefania, Turco, Anna Amelia, Bonora, Enzo, Cigolini, Massimo, Pichiri, Isabella, Brangani, Corinna, Tomasetto, Elena, Perriello, Gabriele, Timi, Alessia, Squatrito, Sebastiano, Sinagra, Tiziana, Longhitano, Sara, Tropea, Vanessa, Ballardini, Giorgio, Babini, Anna Carla, Ripani, Raffaella, Gregori, Giovanna, Dolci, Maria, Bruselli, Laura, Salutini, Isabella, Mori, Mary, Baccetti, Fabio, Lapolla, Annunziata, Sartore, Giovanni, Burlina, Silvia, Chilelli, Nino Cristiano, Buzzetti, Raffaella, Venditti, Chiara, Potenziani, Stella, Carlone, Angela, Galluzzo†, Aldo, Giordano, Carla, Torregrossa, Vittoria, Corsi, Laura, Cuneo, Giacomo, Corsi, Simona, Tizio, Biagio, Clemente, Gennaro, Citro, Giuseppe, Natale, Maria, Salvatore, Vita, Di Cianni, Graziano, Lacaria, Emilia, Russo, Laura, Iannarelli, Rossella, de Gregorio, Antonella, Sciarretta, Filomena, D’Andrea, Settimio, Montani, Valeria, Cannarsa, Emanuela, Dolcetti, Katia, Cordera, Renzo, Bonabello, Laura Affinito, Mazzucchelli, Chiara, Giorda, Carlo Bruno, Romeo, Francesco, Bonetto, Caterina, Antenucci, Daniela, Baldassarre, Maria Pompea Antonia, Iovine, Ciro, Nappo, Rossella, Ciano, Ornella, Dall’Aglio, Elisabetta, Mancastroppa, Giovanni, Grimaldi, Franco, Tonutti, Laura, Boemi, Massimo, D’Angelo, Federica, Leotta, Sergio, Fontana, Lucia, Lauro, Davide, Rinaldi, Maria Elena, Cignarelli, Mauro, la Macchia, Olga, Fariello, Stefania, Tomasi, Franco, Zamboni, Chiara, Dozio, Nicoletta, Trevisan, Roberto, Scaranna, Cristiana, Del Prato, Stefano, Miccoli, Roberto, Bianchi, Cristina, Garofolo, Monia, Pugliese, Giuseppe, Salvi, Laura, Rangel, Graziela, Vitale, Martina, Anichini, Roberto, Tedeschi, Anna, Corsini, Elisa, Cucinotta, Domenico, Di Benedetto, Antonino, Giunta, Loretta, Ruffo, Maria Concetta, Bossi, Antonio Carlo, Carpinter, Rita, Dotta, Francesco, Ceccarelli, Elena, Bartolo, Paolo Di, Caselli, Chiara, Luberto, Alessandra, Santini, Costanza, Mazzotti, Arianna, Calbucci, Giovanni, Consoli, Agostino, Ginestra, Federica, Calabrese, Maria, Zogheri, Alessia, Ricci, Lucia, Giorgino, Francesco, Laviola, Luigi, Ippolito, Claudia, Tarantino, Lucia, Avogaro, Angelo, Vedovato, Monica, Gnasso, Agostino, Carallo, Claudio, Scicchitano, Caterina, Zavaroni, Donatella, Livraga, Stefania, Perin, Paolo Cavallo, Forrnengo, Paolo, Prinzis, Tania, de Cosmo, Salvatore, Palena, Antonio Pio, Bacci, Simonetta, Mannucci, Edoardo, Lamanna, Caterina, Pata, Pietro, Lettina, Gabriele, Aiello, Antimo, Barrea, Angelina, Lalli, Carlo, Scarponi, Maura, Franzetti, Ivano, Radin, Raffaella, Serra, Rosalia, Petrachi, Francesca, Asprino, Vincenzo, Capra, Claudio, Forte, Elisa, Reggiani, Giulio Marchesini, Forlani, Gabriele, Montesi, Luca, Mazzella, Natalia, Piatti, Pier Marco, Monti, Lucilla, Stuccillo, Michela, Auletta, Pasquale, Petraroli, Ettore, Capobianco, Giuseppe, Romano, Geremia, Cutolo, Michele, de Simone, Giosetta, Caiazzo, Gennaro, Nunziata, Peppe, Sorrentino, Susy, Amelia, Umberto, Calatola, Pasqualino, Capuano, Gelsomina, Vitale, M, Masulli, M, Rivellese, AA, Bonora, E, Cappellini, F, Nicolucci, A, Squatrito, S, Antenucci, D, Barrea, A, Bianchi, C, Bianchini, F, Fontana, L, Fornengo,P, Giorgino, F, Gnasso, A, Mannucci, Mazzotti, A, Nappo, R, Palena, AP, Pata, P,Perriello, G, Potenziani, S, Radin, R, Ricci, L, Romeo, F, Santini, C, Scarponi, M, Serra, R, Timi, A, Turco, AA, Vedovato, M, Zavaroni, D, Grioni, S, Riccardi, G, Vaccaro, O, TOSCA.IT Study Group., Giordano, C., Rivellese, Aa, Fornengo, P, Mannucci, E, Mazzotti, A, Nappo, R, Palena, Ap, Pata, P, Perriello, G, Turco, Aa, Tosc, A. IT Study Group., Rivellese, A, Palena, A, Turco, A, Cocozza, S, Auciello, S, Cigolini, M, Pichiri, I, Brangani, C, Tomasetto, E, Sinagra, T, Longhitano, S, Tropea, V, Ballardini, G, Babini, A, Ripani, R, Gregori, G, Dolci, M, Bruselli, L, Salutini, I, Mori, M, Baccetti, F, Lapolla, A, Sartore, G, Burlina, S, Chilelli, N, Buzzetti, R, Venditti, C, Carlone, A, Galluzzo, A, Giordano, C, Torregrossa, V, Corsi, L, Cuneo, G, Corsi, S, Tizio, B, Galluzzo, G, Citro, G, Natale, M, Salvatore, V, Di Cianni, G, Lacaria, E, Russo, L, Iannarelli, R, De Gregorio, A, Sciarretta, F, D'Andrea, S, Montani, V, Cannarsa, E, Dolcetti, K, Cordera, R, Bonabello, L, Mazzucchelli, C, Giorda, C, Bonetto, C, Baldassarre, M, Iovine, C, Ciano, O, Dall'Aglio, E, Mancastroppa, G, Grimaldi, F, Tonutti, L, Boemi, M, D'Angelo, F, Leotta, S, Lauro, D, Rinaldi, M, Cignarelli, M, La Macchia, O, Fariello, S, Tomasi, F, Zamboni, C, Dozio, N, Trevisan, R, Scaranna, C, Del Prato, S, Miccoli, R, Garofolo, M, Pugliese, G, Salvi, L, Rangel, G, Anichini, R, Tedeschi, A, Corsini, E, Cucinotta, D, Di Benedetto, A, Giunta, L, Ruffo, M, Bossi, A, Carpinter, R, Dotta, F, Ceccarelli, E, Bartolo, P, Caselli, C, Luberto, A, Calbucci, G, Consoli, A, Ginestra, F, Calabrese, M, Zogheri, A, Laviola, L, Ippolito, C, Tarantino, L, Avogaro, A, Carallo, C, Scicchitano, C, Livraga, S, Perin, P, Forrnengo, P, Prinzis, T, De Cosmo, S, Bacci, S, Lamanna, C, Lettina, G, Aiello, A, Lalli, C, Franzetti, I, Petrachi, F, Asprino, V, Capra, C, Forte, E, Reggiani, G, Forlani, G, Montesi, L, Mazzella, N, Piatti, P, Monti, L, Stuccillo, M, Auletta, P, Petraroli, E, Capobianco, G, Romano, G, Cutolo, M, De Simone, G, Caiazzo, G, Nunziata, P, Sorrentino, S, Amelia, U, Calatola, P, and Capuano, G
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0301 basic medicine ,Male ,Age, BMI, Diabetes, Diet, Flavonoids, Food groups, Geographical area, Intake, Phenolic acids, Polyphenols, TOSCA.IT study, Aged, Antioxidants, Beverages, Cinnamates, Cohort Studies, Cross-Sectional Studies, Databases, Factual, Diabetes Mellitus, Type 2, Female, Flavonoids, Fruit, Glycosides, Humans, Italy, Male, Middle Aged, Nutritive Value, Phenols, Polyphenols, Diet, Diabetic, Diet, Healthy, Patient Compliance ,Settore MED/09 - Medicina Interna ,Databases, Factual ,Cross-sectional study ,Medicine (miscellaneous) ,Type 2 diabetes ,Diabete ,Antioxidants ,Settore MED/13 - Endocrinologia ,Food group ,Cohort Studies ,0302 clinical medicine ,Diet, Diabetic ,Medicine ,Food science ,Glycosides ,Age ,BMI ,Diabetes ,Diet ,Flavonoids ,Food groups ,Geographical area ,Intake ,Phenolic acids ,Polyphenols ,TOSCA.IT study ,Nutrition and Dietetics ,Phenolic acid ,food and beverages ,Middle Aged ,Polyphenols, Flavonoids, Phenolic acids, Diabetes, Food groups, Diet, Age, BMI, Geographical area, Intake, TOSCA.IT study ,Italy ,Tosca,Age,BMI,Diabetes,Diet,Flavonoids,Food groups,Geographical area,Intake,Phenolic acids,Polyphenols,TOSCA.IT study ,Cohort ,Female ,Diet, Healthy ,Nutritive Value ,Cohort study ,Polyphenol ,030209 endocrinology & metabolism ,Beverages ,03 medical and health sciences ,Phenols ,Diabetes mellitus ,Humans ,Aged ,030109 nutrition & dietetics ,business.industry ,Anthropometry ,medicine.disease ,Tosca ,Cross-Sectional Studies ,Diabetes Mellitus, Type 2 ,Cinnamates ,Fruit ,Flavonoid ,Patient Compliance ,business - Abstract
Purpose: Proper evaluation of polyphenols intake at the population level is a necessary step in order to establish possible associations with health outcomes. Available data are limited, and so far no study has been performed in people with diabetes. The aim of this work was to document the intake of polyphenols and their major food sources in a cohort of people with type 2 diabetes and in socio-demographic subgroups. Methods: We studied 2573 men and women aged 50–75 years. Among others, anthropometry was measured by standard protocol and dietary habits were investigated by food frequency questionnaire (EPIC). The intake of polyphenols was evaluated using US Department of Agriculture and Phenol-Explorer databases. Results: The mean total polyphenol intake was 683.3 ± 5.8 mg/day. Non-alcoholic beverages represented the main food source of dietary polyphenols and provided 35.5% of total polyphenol intake, followed by fruits (23.0%), alcoholic beverages (14.0%), vegetables (12.4%), cereal products and tubers (4.6%), legumes (3.7%) and oils (2.1%); chocolate, cakes and nuts are negligible sources of polyphenols in this cohort. The two most important polyphenol classes contributing to the total intake were flavonoids (47.5%) and phenolic acids (47.4%). Polyphenol intake increased with age and education level and decreased with BMI; furthermore, in the northern regions of Italy, the polyphenol intake was slightly, but significantly higher than in the central or southern regions. Conclusions: The study documents for the first time the intake of polyphenols and their main food sources in people with diabetes using validated and complete databases of the polyphenol content of food. Compared with published data, collected in people without diabetes, these results suggest a lower intake and a different pattern of intake in people with diabetes. © 2016 Springer-Verlag Berlin Heidelberg
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- 2016
29. Insulin degludec, an ultra-longacting basal insulin, versus insulin glargine in basal-bolus treatment with mealtime insulin aspart in type 2 diabetes (BEGIN Basal-Bolus Type 2): a phase 3, randomised, open-label, treat-to-target non-inferiority trial
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Garber, Alan J., King, Allen B., Del Prato, Stefano, Sreenan, Seamus, Mustafa Kemal BALCI, Munoz-Torres, Manuel, Rosenstock, Julio, Endahl, Lars A., Francisco, Ann Marie Ocampo, Hollander, Priscilla, and Trial Inv, Nn -. Begin Bb T. D.
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Insulin degludec ,medicine.medical_specialty ,Insulin glargine ,business.industry ,Insulin ,medicine.medical_treatment ,Type 2 Diabetes Mellitus ,General Medicine ,Type 2 diabetes ,medicine.disease ,Insulin aspart ,Basal (medicine) ,Internal medicine ,Diabetes mellitus ,medicine ,business ,medicine.drug - Abstract
Summary Background Basal insulin therapy does not stop loss of β-cell function, which is the hallmark of type 2 diabetes mellitus, and thus diabetes control inevitably deteriorates. Insulin degludec is a new, ultra-longacting basal insulin. We aimed to assess efficacy and safety of insulin degludec compared with insulin glargine in patients with type 2 diabetes mellitus. Methods In this 52 week, phase 3, open-label, treat-to-target, non-inferiority trial, undertaken at 123 sites in 12 countries, we enrolled adults (aged ≥18 years) with type 2 diabetes mellitus and a glycated haemoglobin (HbA 1c ) of 7·0–10·0% after 3 months or more of any insulin regimen (with or without oral antidiabetic drugs). We randomly allocated eligible participants in a 3:1 ratio to receive once-daily subcutaneous insulin degludec or glargine, stratified by previous insulin regimen, via a central interactive response system. Basal insulin was titrated to a target plasma glucose concentration of 3·9– 1c from baseline to week 52 (non-inferiority limit of 0·4%) by ANOVA in the full analysis set. We assessed rates of hypoglycaemia in all treated patients. This study is registered with ClinicalTrials.gov, number NCT00972283. Findings 744 (99%) of 755 participants randomly allocated degludec and 248 (99%) of 251 allocated glargine were included in the full analysis set (mean age 58·9 years [SD 9·3], diabetes duration 13·5 years [7·3], HbA 1c 8·3% [0·8], and fasting plasma glucose 9·2 mmol/L [3·1]); 618 (82%) and 211 (84%) participants completed the trial. After 1 year, HbA 1c decreased by 1·1% in the degludec group and 1·2% in the glargine group (estimated treatment difference [degludec–glargine] 0·08%, 95% CI −0·05 to 0·21), confirming non-inferiority. Rates of overall confirmed hypoglycaemia (plasma glucose vs 13·6 episodes per patient-year of exposure; estimated rate ratio 0·82, 95% CI 0·69 to 0·99; p=0·0359), as were rates of nocturnal confirmed hypoglycaemia (1·4 vs 1·8 episodes per patient-year of exposure; 0·75, 0·58 to 0·99; p=0·0399). Rates of severe hypoglycaemia seemed similar (0·06 vs 0·05 episodes per patient-year of exposure for degludec and glargine) but were too low for assessment of differences. Rates of other adverse events did not differ between groups. Interpretation A policy of suboptimum diabetes control to reduce the risk of hypoglycaemia and its consequences in advanced type 2 diabetes mellitus might be unwarranted with newer basal insulins such as degludec, which are associated with lower risks of hypoglycaemia than insulin glargine. Funding Novo Nordisk.
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- 2012
30. The effect of the availability of inhaled insulin on glycaemic control in patients with Type2 diabetes failing on oral therapy: the evaluation of Exubera as a therapeutic option on insulin initiation and improvement in glycaemic control in clinical practice (EXPERIENCE) trial
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DEL PRATO, Stefano, Blonde, L, Martinez, L, Göke, B, Woo, V, Millward, A, Gomis, R, Canovatchel, B, Strack, T, Lawrence, D, Freemantle, N, and EXPERIENCE Trial Team
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Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Type 2 diabetes ,law.invention ,Endocrinology ,Randomized controlled trial ,law ,Diabetes mellitus ,Internal medicine ,Administration, Inhalation ,Internal Medicine ,medicine ,Clinical endpoint ,Humans ,Hypoglycemic Agents ,Insulin ,Aged ,Glycated Hemoglobin ,business.industry ,Drug Administration Routes ,Odds ratio ,Middle Aged ,medicine.disease ,Surgery ,Europe ,Clinical trial ,Regimen ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,North America ,Female ,business - Abstract
Aim To examine the impact of inhaled human insulin (Exubera (R), EXU) on patient or physician willingness to adopt insulin after oral glucose-lowering agent failure.Methods During a randomized controlled trial in primary, secondary and tertiary care in Europe and North America, 739 patients using >= 2 oral glucose-lowering agents with glycated haemoglobin (HbA(1c)) >= 8.0% were assigned to two treatment groups: Group 1 (standard care with the option of EXU) or Group 2 (standard care only). Standard care included adjusting oral therapy (optimizing current regimen or adding/omitting agents) and/or initiating subcutaneous (s.c.) insulin. The primary endpoint was difference in HbA(1c) between randomized groups at 26 weeks. Secondary outcomes included differences in the rate of uptake of insulin therapy, proportion achieving satisfactory glycaemic control, treatment satisfaction and safety outcomes.Results At baseline, insulin was initiated by more [odds ratio 6.0; 95% confidence interval (CI) 4.2 to 8.8; P < 0.0001] patients in Group 1 (86.2%; 76.7% EXU plus 9.5% s.c.) than Group 2 (50.7%; s.c. insulin only). At 26 weeks, mean (sd) changes in HbA(1c) from baseline were -2.0% (1.2%) and -1.7% (1.3%) in Groups 1 and 2, respectively, a difference of -0.2% (95% CI: -0.1% to -0.4%; P = 0.004). In Group 1, 45% of patients achieved an HbA(1c)
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- 2008
31. Cytochrome P450 2J2 Polymorphism in Healthy Caucasians and those with Diabetes Mellitus
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Pucci, Laura, Lucchesi, Daniela, Chirulli, Vera, Penno, Giuseppe, Johansson, Inger, Gervasi, Pier Giovanni, Del Prato, Stefano, and Longo, Vincenzo
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medicine.medical_specialty ,Population ,Single-nucleotide polymorphism ,Type 2 diabetes ,Biology ,Cytochrome P-450 CYP2J2 ,White People ,CYP2J2 ,Cytochrome P-450 Enzyme System ,Gene Frequency ,Diabetes mellitus ,Internal medicine ,Genotype ,Diabetes Mellitus ,Genetics ,medicine ,Humans ,Polymorphism ,Allele ,education ,Pharmacology ,Cytochrome P450 2J2 ,education.field_of_study ,Polymorphism, Genetic ,Genetic Carrier Screening ,Genetic Variation ,Type 2 Diabetes Mellitus ,medicine.disease ,Diabetes Mellitus, Type 1 ,Endocrinology ,Diabetes Mellitus, Type 2 ,Oxygenases ,Molecular Medicine - Abstract
Objective: Cytochrome P450 (CYP) 2J2 plays an important role in the biosynthesis of the biologically active cis-epoxyeicosatrienoic acids. An allelic variant named CYP2J2*6, which encodes an enzyme that is almost inactive in the metabolism of arachidonic acid, has recently been described. We investigated the frequency of the CYP2J2*6 variant in a Caucasian population and the relationship between this polymorphism and the development of micro- and macrovascular complications and hypertension in patients with type 1 or type 2 diabetes mellitus. Methods: Genomic DNA was extracted from peripheral blood cells and the fragment containing the A/T single nucleotide polymorphism at position 25 661 in exon 8 of the CYP2J2 gene was amplified. The 532 bp amplified product was subsequently digested with Tsp509I and analyzed on 12% polyacrylamide gel electrophoresis. Results: In the whole population, the frequency of the CYP2J2*6 allele was 0.0064 and the frequency of the CYP2J2*1 allele was 0.9936. Genotype distribution did not show significant differences between controls and patients with type 1 or type 2 diabetes. No homozygotes for CYP2J2*6 allele were found. No association was found between this allele and complications or hypertension in either type of diabetes. Conclusion: The CYP2J2*6 allele is rare in the Caucasian population, and no association is inferred between this allelic variant and diabetic complications.
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- 2003
32. Response to comment on Home et al. Insulin therapy in people with type 2 diabetes: Opportunities and challenges?
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Home, Philip, Riddle, Matthew, Cefalu, William T., Bailey, Clifford J., Bretzel, Reinhard G., DEL PRATO, Stefano, Leroith, Derek, Schernthaner, Guntram, Van Gaal, Luc, and Raz, Itamar
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Blood Glucose ,Diabetes and Metabolism ,Advanced and Specialized Nursing ,Endocrinology ,Diabetes Mellitus, Type 2 ,Humans ,Hypoglycemic Agents ,Insulin ,Internal Medicine ,Endocrinology, Diabetes and Metabolism ,Medicine (all) ,Diabetes Mellitus ,Type 2 - Published
- 2014
33. Diabetes in Pancreatitis, Pancreatectomy and Other Pancreatic Diseases
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Tiengo, A., Kreutzenberg, De, S. V., and DEL PRATO, Stefano
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medicine.medical_specialty ,education.field_of_study ,business.industry ,medicine.medical_treatment ,Insulin ,Population ,Glucagon secretion ,Hypoglycemia ,medicine.disease ,Gastroenterology ,Endocrinology ,Pancreatic cancer ,Internal medicine ,Diabetes mellitus ,Pancreatectomy ,medicine ,Pancreatitis ,education ,business - Abstract
Pancreatogenic diabetes is classified by the American Diabetes Association as a form of type 3 diabetes mellitus (T3cDM) secondary to acquired diseases of the exocrine pancreas. It is a clinically relevant condition, representing 5-10% of all diabetic cases in the Western population. It develops in about 50% of patients with chronic pancreatitis, in 80% of pancreatic cancer cases, in 70% of patients submitted to subtotal pancreatectomy and in over 7% of hemochromatosis cases. Patients typically develop symptoms associated with hyperglycemia, but they have a distinctly increased risk of hypoglycemia and glycemic instability. Hypoglycemic episodes associated with insulin or sulfonylurea therapy are more frequent and tend to be more severe and to last longer. Hypoglycemia is the consequence of impaired counterregulation and glucose recovery due to deficient glucagon secretion, blunted catecholamine response and subsequent impaired activation of hepatic glucose production. In terms of the therapeutic approach, maintenance of plasma glucose levels slightly above the normal range may be necessary to avoid frequent hypoglycemic reactions and to improve the quality of life.
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- 2014
34. Vergleich von Dapagliflozin und Glipizid als Add-on-Therapie bei Typ-2-Diabetikern mit unzureichender Blutzuckerkontrolle unter Metformin: Eine randomisierte, doppelblinde, verumkontrollierte Nichtunterlegenheitsstudie über 52 Wochen
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Nauck, M, DEL PRATO, Stefano, Meier, J. J., Durán García, S., Rohwedder, K., Elze, M., and Parikh, S. J.
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Blood Glucose ,Male ,Glycosylated ,Kaplan-Meier Estimate ,Dose-Response Relationship ,Double-Blind Method ,Drug Therapy ,Glucosides ,Sodium-Glucose Transporter 2 ,Germany ,Balanitis ,Diabetes Mellitus ,Humans ,Hypoglycemic Agents ,Benzhydryl Compounds ,dapagliflozin ,SGLT-2-inhibitors ,type 2 diabetes ,Aged ,Body Weight ,Candidiasis, Vulvovaginal ,Diabetes Mellitus, Type 2 ,Dose-Response Relationship, Drug ,Drug Therapy, Combination ,Female ,Glipizide ,Hemoglobin A, Glycosylated ,Metformin ,Middle Aged ,Urinary Tract Infections ,Medicine (all) ,Candidiasis ,Hemoglobin A ,Combination ,Drug ,Vulvovaginal ,Type 2 - Published
- 2013
35. Metabolic regulation of GLP-1 and PC1/3 in pancreatic α-cell line.
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Sancho, Veronica, Daniele, Giuseppe, Lucchesi, Daniela, Lupi, Roberto, Ciccarone, Annamaria, Penno, Giuseppe, Bianchi, Cristina, Dardano, Angela, Miccoli, Roberto, and Del Prato, Stefano
- Subjects
METABOLIC regulation ,GLUCAGON-like peptide 1 ,GLUCOSE metabolism ,CELL survival ,PATHOLOGICAL physiology - Abstract
Background and aims: An intra-islet incretin system has been recently suggested to operate through modulation of the expression and activity of proconvertase 1/3 and 2 (PC1/3, PC2) in pancreatic alpha-cell accounting for local release of GLP-1. Little is known, whether this alpha-cell activity can be affected by the metabolic alterations occurring in type 2 diabetes, such as hyperglycemia, hyperlipidemia or hyperglucagonemia. Materials and methods: AlphaTC1/6 cells from a mice pancreatic cell line were incubated in the presence of two glucose (G) concentration (5.5 and 16.7 mM) for 16 h with or without free fatty acid, IL6 or glucagon. GLP-1 secretion was measured by ELISA and expression of PC1/3 and PC2 by RT-PCR and western blot; cell viability was determined by MTT method, Reactive Oxygen Species generation (ROS) by H
2 DCFDA fluorescence and apoptosis by Annexin staining and Propidium Iodine (PI) fluorescence. Results: Upon 16.7G incubation, GLP-1 secretion (total and active) was significantly increased in parallel with a significant increment in PC1/3 expression, a slight increase in cell viability and ROS generation and by a decrement in PC2 expression with no change in cell apoptosis. When cells were incubated at 5.5mM glucose with FFA, also an increment in GLP-1 secretion and PC1/3 expression was observed together an increment in ROS generation, a decrement in cell viability, and a modest increment in apoptosis. When incubated with 16.7mM glucose with FFA, the increment in GLP-1 secretion was reduced to basal, accompanied by an increment in apoptosis and ROS generation. This was also observed with IL-6, but in this case, no modification in ROS generation or apoptosis was observed when compared to 16.7mM glucose. The presence of glucagon did not modify any of the parameters studied. Conclusion: These data suggest that under hyperglycemic, hyperlipidemia or inflammatory conditions, alpha cells can increase expression PC1/3 and activate GLP-1 secretion, which may contribute protecting both alpha and beta-cells from glucose and lipotoxicity, while this effect seems to be lost in the presence of both pathophysiological conditions. [ABSTRACT FROM AUTHOR]- Published
- 2017
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36. The TOSCA.IT trial: a study designed to evaluate the effect of pioglitazone versus sulfonylureas on cardiovascular disease in type 2 Diabetes
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Vaccaro, O, Masulli, M, Bonora, E, DEL PRATO, Stefano, Nicolucci, A, Rivellese, Aa, Riccardi, G, and IT Study Group, T. O. S. C. A.
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Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Disease ,Type 2 diabetes ,Hypoglycemia ,cvd ,law.invention ,Therapeutic approach ,Quality of life ,Randomized controlled trial ,law ,cardiovascular disease ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,pioglitazone ,Online Letters: Observations ,sulfonylureas ,Intensive care medicine ,Aged ,Advanced and Specialized Nursing ,business.industry ,type 2 diabetes ,Middle Aged ,medicine.disease ,Surgery ,Sulfonylurea Compounds ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Cardiovascular Diseases ,Quality of Life ,Female ,Thiazolidinediones ,business ,Pioglitazone ,medicine.drug - Abstract
The recently published American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) position statement on the management of hyperglycemia in type 2 diabetes (T2D) (1) underlines the complexity of the therapeutic approach in T2D. This is due to both the increasing number of available drugs and to the paucity of solid data on the superiority of one compound over the others. By and large, antidiabetic drugs reduce blood glucose to a similar extent but have different impacts on cardiovascular (CV) risk factors, durability of efficacy, safety, and possible added values (2–4). A major challenge for clinicians is to select treatments that are capable of achieving and maintaining glucose control for as long as possible while minimizing the risk of chronic complications, including cardiovascular disease (CVD). This goal should be pursued with minimal side effects (mainly hypoglycemia). Although there is agreement on …
- Published
- 2012
37. A call to action--the UN Resolution on diabetes
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DEL PRATO, Stefano
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United Nations ,International Cooperation ,Diabetes Mellitus ,Humans ,Global Health - Published
- 2007
38. Improving glucose management: ten steps to get more patients with type 2 diabetes to glycaemic goal. Recommendations from the Global Partnership for Effective Diabetes Management
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DEL PRATO, Stefano, Felton, Am, Munro, N, Nesto, R, Zimmet, P, Zinman, B, and Global Partnership for Effective Diabetes Management
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medicine.medical_specialty ,business.industry ,MEDLINE ,General Medicine ,Type 2 diabetes ,Holistic health ,medicine.disease ,Surgery ,Glucose management ,Quality of life (healthcare) ,Multidisciplinary approach ,Diabetes management ,Diabetes mellitus ,medicine ,Intensive care medicine ,business - Abstract
Despite increasingly stringent clinical practice guidelines for glycaemic control, the implementation of recommendations has been disappointing, with over 60% of patients not reaching recommended glycaemic goals. As a result, current management of glycaemia falls significantly short of accepted treatment goals. The Global Partnership for Effective Diabetes Management has identified a number of major barriers that can prevent individuals from achieving their glycaemic targets. This article proposes 10 key practical recommendations to aid healthcare providers in overcoming these barriers and to enable a greater proportion of patients to achieve glycaemic goals. These include advice on targeting the underlying pathophysiology of type 2 diabetes, treating early and effectively with combination therapies, adopting a holistic, multidisciplinary approach and improving patient understanding of type 2 diabetes. Implementation of these recommendations should reduce the risk of diabetes-related complications, improve patient quality of life and impact more effectively on the increasing healthcare cost related to diabetes.
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- 2007
39. Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy
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Bakris, George L, Agarwal, Rajiv, Chan, Juliana C., Cooper, Mark E., Gansevoort, Ron T., Haller, Hermann, Remuzzi, Giuseppe, Rossing, Peter, Schmieder, Roland E., Nowack, Christina, Kolkhof, Peter, Joseph, Amer, Pieper, Alexander, Kimmeskamp Kirschbaum, Nina, Ruilope, Luis M., DEL PRATO, Stefano, Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Bakris, G, Agarwal, R, Chan, J, Cooper, Me, Gansevoort, R, Haller, H, Remuzzi, G, Rossing, P, Schmieder, R, Nowack, C, Kolkhof, P, Joseph, A, Pieper, A, Kimmeskamp Kirschbaum, N, Ruilope, L, and Pisani, Antonio.
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Male ,Administration, Oral ,Angiotensin-Converting Enzyme Inhibitors ,Blood Pressure ,law.invention ,chemistry.chemical_compound ,Randomized controlled trial ,law ,Medicine ,Diabetic Nephropathies ,Mineralocorticoid Receptor Antagonists ,Medicine (all) ,Incidence ,General Medicine ,Middle Aged ,Creatinine ,Administration ,Female ,Drug ,medicine.symptom ,Type 2 ,Glomerular Filtration Rate ,Oral ,medicine.medical_specialty ,Finerenone ,Urology ,Renal function ,Placebo ,Drug Administration Schedule ,Dose-Response Relationship ,Angiotensin Receptor Antagonists ,Double-Blind Method ,Internal medicine ,Diabetes mellitus ,Diabetes Mellitus ,Albuminuria ,Humans ,Least-Squares Analysis ,Naphthyridines ,Aged ,Analysis of Variance ,Dose-Response Relationship, Drug ,business.industry ,ta3121 ,medicine.disease ,Endocrinology ,Diabetes Mellitus, Type 2 ,Hyperkalemia ,Potassium ,chemistry ,business ,Kidney disease - Abstract
IMPORTANCE: Steroidal mineralocorticoid receptor antagonists, when added to a renin-angiotensin system blocker, further reduce proteinuria in patients with chronic kidney disease but may be underused because of a high risk of adverse events.OBJECTIVE: To evaluate the safety and efficacy of different oral doses of the nonsteroidal mineralocorticoid receptor antagonist finerenone, given for 90 days to patients with diabetes and high or very high albuminuria who are receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker.DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo-controlled, parallel-group study conducted at 148 sites in 23 countries. Patients were recruited from June 2013 to February 2014 and the study was completed in August 2014. Of 1501 screened patients, 823 were randomized and 821 received study drug.INTERVENTIONS: Participants were randomly assigned to receive oral, once-daily finerenone (1.25 mg/d, n = 96; 2.5 mg/d, n = 92; 5 mg/d, n = 100; 7.5 mg/d, n = 97; 10 mg/d, n = 98; 15 mg/d, n = 125; and 25 mg/d, n = 119) or matching placebo (n = 94) for 90 days.MAIN OUTCOMES AND MEASURES: The primary outcome was the ratio of the urinary albumin-creatinine ratio (UACR) at day 90 vs at baseline. Safety end points were changes from baseline in serum potassium and estimated glomerular filtration rate.RESULTS: The mean age of the participants was 64.2 years; 78% were male. At baseline, 36.7% of patients treated had very high albuminuria (UACR ≥300 mg/g) and 40.0% had an estimated glomerular filtration rate of 60 mL/min/1.73 m2 or lower. Finerenone demonstrated a dose-dependent reduction in UACR. The primary outcome, the placebo-corrected mean ratio of the UACR at day 90 relative to baseline, was reduced in the finerenone 7.5-, 10-, 15-, and 20-mg/d groups (for 7.5 mg/d, 0.79 [90% CI, 0.68-0.91; P = .004]; for 10 mg/d, 0.76 [90% CI, 0.65-0.88; P = .001]; for 15 mg/d, 0.67 [90% CI, 0.58-0.77; PCONCLUSIONS AND RELEVANCE: Among patients with diabetic nephropathy, most receiving an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker, the addition of finerenone compared with placebo resulted in improvement in the urinary albumin-creatinine ratio. Further trials are needed to compare finerenone with other active medications.TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT1874431.
- Published
- 2015
40. Insulin degludec/insulin aspart combination for the treatment of type 1 and type 2 diabetes.
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Dardano, Angela, Bianchi, Cristina, Del Prato, Stefano, and Miccoli, Roberto
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TYPE 2 diabetes treatment ,TREATMENT of diabetes ,TYPE 1 diabetes ,DIABETES complications ,INSULIN therapy ,HYPOGLYCEMIA ,PEOPLE with diabetes ,DISEASE progression - Abstract
Glycemic control remains the major therapeutic objective to prevent or delay the onset and progression of complications related to diabetes mellitus. Insulin therapy represents a cornerstone in the treatment of diabetes and has been used widely for achieving glycemic goals. Nevertheless, a large portion of the population with diabetes does not meet the internationally agreed glycemic targets. Moreover, insulin treatment, especially if intensive, may be associated with emergency room visits and hospitalization due to hypoglycemic events. Therefore, fear of hypoglycemia or hypoglycemic events represents the main barriers to the attainment of glycemic targets. The burden associated with multiple daily injections also remains a significant obstacle to initiating and maintaining insulin therapy. The most attractive insulin treatment approach should meet the patients' preference, rather than demanding patients to change or adapt their lifestyle. Insulin degludec/insulin aspart (IDegAsp) is a new combination, formulated with ultra-long-acting insulin degludec and rapid-acting insulin aspart, with peculiar pharmacological features, clinical efficacy, safety, and tolerability. IDegAsp provides similar, noninferior glycemic control to a standard basal-bolus regimen in patients with type 1 diabetes mellitus, with additional benefits of significantly lower episodes of hypoglycemia (particularly nocturnal) and fewer daily insulin injections. Moreover, although treatment strategy and patients' viewpoint are different in type 1 and type 2 diabetes, trial results suggest that IDegAsp may be an appropriate and reasonable option for initiating insulin therapy in patients with type 2 diabetes inadequately controlled on maximal doses of conventional oral agents. This paper will discuss the role of IDegAsp combination as a novel treatment option in diabetic patients. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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41. Circulating endothelial progenitor cells in women with gestational alterations of glucose tolerance.
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Penno, Giuseppe, Pucci, Laura, Lucchesi, Daniela, Lencioni, Cristina, Iorio, Maria Carla, Vanacore, Renato, Storti, Eugenia, Resi, Veronica, Di Cianni, Graziano, and Del Prato, Stefano
- Abstract
Endothelial progenitor cells (EPCs) play a role in angiogenesis during pregnancy. The aim of this study was to evaluate circulating EPCs in pregnant women with gestational alterations of glucose tolerance. Glucose tolerance, insulin sensitivity and β-cell function were derived from oral glucose tolerance tests in 23 women with normal glucose tolerance (NGT), 18 with gestational impaired glucose tolerance (GIGT) and 24 with gestational diabetes mellitus (GDM). Circulating cells expressing CD34 in combination with CD133, kinase insert domain receptor (KDR) or both were quantified by flow cytometry. Women with GIGT and GDM had lower CD34+KDR+ and CD34+CD133 +KDR+ cells at 27±3.2 weeks’ gestation compared with NGT (ANOVA p<0.02 for both). CD34+KDR+ and CD34+CD133+KDR+ cells were inversely correlated with the area-under-the-glucose-curve (p<0.005, for both) and positively to insulin secretion-sensitivity index (p<0.05, for both). Alterations of glucose tolerance during pregnancy are associated with a decrease in EPCs. Hyperglycaemia might exert a direct effect on depletion of EPCs. [ABSTRACT FROM PUBLISHER]
- Published
- 2011
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42. In situ protein Kinase C activity is increased in cultured fibroblasts from Type 1 diabetic patients with nephropathy
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Iori, E, Marescotti, Mc, Vedovato, M, Ceolotto, G, Baritono, E, Avogaro, A, Tiengo, S, DEL PRATO, Stefano, Trevisan, R. ., Lori, E, Marescotti, M, Vedovato, M, Ceolotto, G, Avogaro, A, Tiengo, A, Del Prato, S, and Trevisan, R
- Subjects
Gene isoform ,Adult ,Blood Glucose ,Male ,medicine.medical_specialty ,Type 1 diabete ,Endocrinology, Diabetes and Metabolism ,Immunoblotting ,Diabetic nephropathy ,Human fibroblast ,Nephropathy ,Diglycerides ,Diabetes mellitus ,Internal medicine ,Internal Medicine ,medicine ,Hyperglycaemia ,Humans ,Diabetic Nephropathies ,Incubation ,Protein kinase C ,Cells, Cultured ,Protein Kinase C ,Diacylglycerol kinase ,Skin ,Type 1 diabetes ,business.industry ,Fibroblasts ,medicine.disease ,Endocrinology ,Diabetes Mellitus, Type 1 ,Female ,Diacylglycerol ,business - Abstract
Aims/hypothesis. To verify whether individual susceptibility to diabetic nephropathy resides in an intrinsic difference in Protein Kinase C (PKC) activity. Methods. We compared the effect of different glucose concentrations on PKC activity, PKC isoform expression and diacylglycerol (DAG) content in cultured fibroblasts from 14 Type I diabetic patients who developed nephropathy with those in cells from 14 patients without nephropathy. We recruited 14 normal subjects as control patients. Forearm skin fibroblasts were cultured in either normal (5 mmol/l) or high (20 mmol/l) glucose concentrations. Results. In normal glucose, in situ PKC activity was higher in Type 1 patients with nephropathy (10.1 +/- 1.4 pmol/min/mg protein; p
43. Exploring the Relationship Between Efpeglenatide Dose and Cardiovascular Outcomes in Type 2 Diabetes: Insights From the AMPLITUDE-O Trial.
- Author
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Gerstein, Hertzel C., Li, Zhuoru, Ramasundarahettige, Chinthanie, Baek, Seungjae, Branch, Kelley R.H., Del Prato, Stefano, Lam, Carolyn S.P., Lopes, Renato D., Pratley, Richard, Rosenstock, Julio, and Sattar, Naveed
- Subjects
- *
TYPE 2 diabetes , *GLUCAGON-like peptide-1 receptor , *MAJOR adverse cardiovascular events , *GLUCAGON-like peptide-1 agonists , *GLOMERULAR filtration rate - Abstract
Background: In the AMPLITUDE-O (Effect of Efpeglenatide on Cardiovascular Outcomes) cardiovascular outcomes trial, adding either 4 mg or 6 mg weekly of the glucagon-like peptide-1 receptor agonist efpeglenatide to usual care reduced major adverse cardiovascular events (MACE) in people with type 2 diabetes at high cardiovascular risk. Whether these benefits are dose related remains uncertain. Methods: Participants were randomly assigned in a 1:1:1 ratio to placebo, 4 mg or 6 mg of efpeglenatide. The effect of 6 mg versus placebo and of 4 mg versus placebo on MACE (a nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular or unknown causes) and on all the secondary composite cardiovascular and kidney outcomes was assessed. A dose-response relationship was assessed using the log-rank test and χ2 statistic for trend. Results: During a median follow-up of 1.8 years, MACE occurred in 125 (9.2%) participants assigned to placebo, 84 (6.2%) participants assigned to 6 mg of efpeglenatide (hazard ratio [HR], 0.65 [95% CI, 0.5–0.86]; P =0.0027), and 105 (7.7%) assigned to 4 mg of efpeglenatide (HR, 0.82 [95% CI, 0.63–1.06]; P =0.14). Participants receiving high-dose efpeglenatide also experienced fewer secondary outcomes, including the composite of MACE, coronary revascularization, or hospitalization for unstable angina (HR, 0.73 for 6 mg, P =0.011; HR, 0.85 for 4 mg, P =0.17), a kidney composite outcome comprising sustained new macroalbuminuria, a ≥40% decline in estimated glomerular filtration rate or renal failure (HR, 0.63 for 6 mg, P <0.0001; HR, 0.73 for 4 mg, P =0.0009), MACE or any death (HR, 0.67 for 6 mg, P =0.0021; HR, 0.81 for 4 mg, P =0.08), a kidney function outcome comprising a sustained ≥40% decline in estimated glomerular filtration rate, renal failure, or death (HR, 0.61 for 6 mg, P =0.0072; HR, 0.97 for 4 mg, P =0.83), and the composite of MACE, any death, heart failure hospitalization, or the kidney function outcome (HR, 0.63 for 6 mg, P =0.0002; HR, 0.81 for 4 mg, P =0.067). A clear dose-response was noted for all primary and secondary outcomes (all P for trend ≤0.018). Conclusions: The graded salutary relationship between efpeglenatide dose and cardiovascular outcomes suggests that titrating efpeglenatide and potentially other glucagon-like peptide-1 receptor agonists to high doses may maximize their cardiovascular and renal benefits. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03496298. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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44. Efpeglenatide and Clinical Outcomes With and Without Concomitant Sodium-Glucose Cotransporter-2 Inhibition Use in Type 2 Diabetes: Exploratory Analysis of the AMPLITUDE-O Trial.
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Lam, Carolyn S.P., Ramasundarahettige, Chinthanie, Branch, Kelley R.H., Sattar, Naveed, Rosenstock, Julio, Pratley, Richard, Del Prato, Stefano, Lopes, Renato D., Niemoeller, Elisabeth, Khurmi, Nardev S., Baek, Seungjae, and Gerstein, Hertzel C.
- Subjects
- *
GLUCAGON-like peptide-1 agonists , *GLUCAGON-like peptide-1 receptor , *TYPE 2 diabetes , *MAJOR adverse cardiovascular events , *LDL cholesterol , *PROPORTIONAL hazards models , *RESEARCH , *RESEARCH methodology , *HYPOGLYCEMIC agents , *EVALUATION research , *COMPARATIVE studies , *PROLINE - Abstract
Background: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists reduce cardiovascular events among patients with type 2 diabetes. However, no cardiovascular outcome trial has evaluated the long-term effects of their combined use. The AMPLITUDE-O trial (Effect of Efpeglenatide on Cardiovascular Outcomes) reported that once-weekly injections of the glucagon-like peptide-1 receptor agonists efpeglenatide (versus placebo) reduced major adverse cardiovascular events (MACEs); MACEs, coronary revascularization, or unstable angina hospitalization (expanded MACEs); a renal composite outcome; and MACEs or death in people with type 2 diabetes and cardiovascular or renal disease. The trial uniquely stratified randomization by baseline or anticipated use of SGLT2 inhibitors and included the highest prevalence at baseline (N=618, 15.2%) of SGLT2 inhibitor use among glucagon-like peptide-1 receptor agonist cardiovascular outcome trials to date. Its results were analyzed to estimate the combined effect of SGLT2 inhibitors and efpeglenatide on clinical outcomes.Methods: Cardiovascular and renal outcomes were analyzed with Cox proportional hazards models adjusted for region, SGLT2 inhibitor randomization strata, and the SGLT2 inhibitor-by-treatment interaction. Continuous variables were analyzed with a mixed-effects models for repeated measures that also included an interaction term.Results: The effect (hazard ratio [95% CI]) of efpeglenatide versus placebo in the absence and presence of baseline SGLT2 inhibitors on MACEs (0.74 [0.58-0.94] and 0.70 [0.37-1.30], respectively), expanded MACEs (0.77 [0.62-0.96] and 0.87 [0.51-1.48]), renal composite (0.70 [0.59-0.83] and 0.52 [0.33-0.83]), and MACEs or death (0.74 [0.59-0.93] and 0.65 [0.36-1.19]) did not differ by baseline SGLT2 inhibitor use (P for all interactions >0.2). The reduction of blood pressure, body weight, low-density lipoprotein cholesterol, and urinary albumin-to-creatinine ratio by efpeglenatide also appeared to be independent of concurrent SGLT2 inhibitor use (all interaction P≥0.08). Last, adverse events did not differ by baseline SGLT2 inhibitor use.Conclusions: The efficacy and safety of efpeglenatide appear to be independent of concurrent SGLT2 inhibitor use. These data support combined SGLT2 inhibitor and glucagon-like peptide-1 receptor agonist therapy in type 2 diabetes. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03496298. [ABSTRACT FROM AUTHOR]- Published
- 2022
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45. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial
- Author
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Adrian F Hernandez, Jennifer B Green, Salim Janmohamed, Ralph B D'Agostino, Christopher B Granger, Nigel P Jones, Lawrence A Leiter, Anne E Rosenberg, Kristina N Sigmon, Matthew C Somerville, Karl M Thorpe, John J V McMurray, Stefano Del Prato, John J.V. McMurray, Ralph B. D'Agostino, Christopher B. Granger, Adrian F. Hernandez, Lawrence A. Leiter, Robert M Califf, Rury Holman, David DeMets, Matthew Riddle, Shaun Goodman, Darren McGuire, Karen Alexander, Adam Devore, Chiara Melloni, Chetan Patel, David Kong, Gerald Bloomfield, Matthew Roe, Pierluigi Tricoci, Rob Harrison, Renato Lopes, Robin Mathews, Rajendra Mehta, William Schuyler Jones, Sreekanth Vemulapalli, Thomas Povsic, Zubin Eapen, Keith Dombrowski, Brad Kolls, Dedrick Jordan, Andrew Ambrosy, Stephen Greene, Aditya Mandawat, Jay Shavadia, Lauren Cooper, Abhinav Sharma, Patricia Guimaraes, Daniel Friedman, Matt Wilson, Patricia Endsley, Tracy Gentry, Jeannie Collier, Kathleen Perez, Kourtnei James, Jennifer Roush, Connie Pope, Christina Howell, Megan Johnson, Matt Bailey, Joanna Cole, Teresa Akers, Beth Vandyne, Betsy Thomas, Jenny Rich, Susan Bartone, Gail Beaulieu, Kim Brown, Tuan Chau, Tamra Christian, Rebecca Coker, Deb Greene, Trevorlyn Haddock, Wendy Jenkins, Ghazala Haque, Marsha Marquess, Jean Pesarchick, Renee Rethaford, Allegra Stone, Firas Al Kawas, Michelle Anderson, Robert Enns, Isaac Sinay, Chantal Mathieu, Victor Yordanov, Irene Hramiak, Martin Haluzik, Søren Galatius, Bruno Guerci, Michael Nauck, Ilias Migdalis, Choon Beng Kathryn Tan, Gyozo Kocsis, Andrea Giaccari, Moon Kyu Lee, Ernesto German Cardona Muñoz, Jan Cornel, Kare Birkeland, Miguel Pinto, Louie Tirador, Martyna Olesinska-Mader, Marina Shestakova, Larry Distiller, Jose Lopez-Sendon, Bjorn Eliasson, Chern-En Chiang, Suphot Srimahachota, Boris Mankovsky, M Angelyn Bethel, Kathleen Dungan, Mikhail Kosiborod, Andres Alvarisqueta, Jorge Baldovino, Diego Besada, Pedro Calella, Maria Cecilia Cantero, Patricia Castaño, Alejandro Chertkoff, Jesus Cuadrado, Luis De Loredo, Andrea Dominguez, Maria Vanesa Español, Hernan Finkelstein, Gustavo Frechtel, Jose Fretes, Natalia Garrido Santos, Joaquin Gonzalez, Marcos Litvak, Juan Loureyro, Laura Maffei, Natacha Maldonado, Diego Mohr Gasparini, Silvia Orio, Federico Perez Manghi, Nelson Rodriguez Papini, Jorgelina Sala, Pablo Schygiel, Georgina Sposetti, Maria Ulla, Fernando Verra, Silvina Zabalua, Cesar Zaidman, Laurent Crenier, Corinne Debroye, Francis Duyck, André Scheen, Luc Van Gaal, Chris Vercammen, Velichka Damyanova, Stefan Dimitrov, Snezhina Kovacheva, Lachezar Lozanov, Viktor Margaritov, Rositsa Mihaylova-Shumkova, Antoaneta Nikolaeva, Zhasmina Stoyanova, Ronald Akhras, Yves Beaudry, Jacques Bedard, Joseph Berlingieri, Raja Chehayeb, Stephen Cheung, James Conway, Jean Cusson, Anthony Della Siega, Richard Dumas, Peter Dzongowski, Murdo Ferguson, Daniel Gaudet, Francois Grondin, Anil Gupta, Milan Gupta, Frank Halperin, Pierre-Alain Houle, Michael Jones, Simon Kouz, Christopher Kovacs, Daniel Landry, Eva Lonn, William O'Mahony, Sean Peterson, Dennis Reich, Alan Rosenbloom, Francois St-Maurice, Barna Tugwell, Saul Vizel, Vincent Woo, Tomas Brychta, Vladimir Cech, Eva Dvorakova, Tomas Edelsberger, Katarina Halciakova, Jarmila Krizova, Jiri Lastuvka, Martin Piperek, Vera Prymkova, Lea Raclavska, Elena Silhova, Robin Urbanek, Jan Vrkoc, Ulla Andersen, Jens Brønnum-Schou, Jens Hove, Jan Skov Jensen, Lars Kober, Ole Peter Kristiansen, Per Lund, Thomas Melchior, Ole Nyvad, Morten Schou, Alain Boye, Didier Cadinot, Didier Gouet, Patrick Henry, Laurence Kessler, Jean-Daniel Lalau, Catherine Petit, Jean-Francois Thuan, Christel Voinot, Julien Vouillarmet, Christoph Axthelm, Dirk Berger, Tasso Bieler, Andreas Birkenfeld, Jochen Bott, Klaus Busch, Karel Caca, Julia Chevts, Torsten Donaubauer, Rudolf Erlinger, Klaus Funke, Josef Grosskopf, Andreas Hagenow, Monika Hamann, Manfred Hartard, Peter Heymer, Wolfgang Huppertz, Gabriele Illies, Stephan Jacob, Thomas Jung, Gerd Kahrmann, Petra Kast, Monika Kellerer, Hans-Peter Kempe, Andrei Khariouzov, Gerhard Klausmann, Christiane Klein, Uwe Kleinecke-Pohl, Klaus Kleinertz, Thorsten Koch, Christine Kosch, Babette Lorra, Joerg Luedemann, Matthias Luttermann, Stephan Maxeiner, Karsten Milek, Andrea Moelle, Gerhard Neumann, Ruth Nischik, Edith Oehrig-Pohl, Georg Plassmann, Lars Pohlmeier, Felix Proepper, Stefan Regner, Werner Rieker, Ludger Rose, Holger Samer, Joachim Sauter, Frank Schaper, Clemens Schiffer, Juergen Schmidt, Bernd-M. Scholz, Joerg Schulze, Alexander Segner, Jochen Seufert, Helena Sigal, Joerg Steindorf, Juergen Stockhausen, Petra Stuebler, Heidrun Taeschner, Dietrich Tews, Diethelm Tschoepe, Karl Wilhelm, Helga Zeller-Stefan, Iakovos Avramidis, Stavros Bousboulas, Magdalini Bristianou, Georgios Dimitriadis, Moses Elisaf, Kalliopi Kotsa, Andreas Melidonis, Asimina Mitrakou, Emmanouil Pagkalos, Nikolaos Papanas, Angelos Pappas, Christos Sampanis, Nikolaos Tentolouris, Apostolos Tsapas, Glykeria Tzatzagou, Risa Ozaki, Csaba Hajdú, Eleonóra Harcsa, Laszlo Konyves, János Mucsi, Zsolt Pauker, Gizella Petró, Zsolt Plés, Katalin Revesz, Vangel Sándor, Viktor Vass, Angelo Avogaro, Massimo Boemi, Riccardo Bonadonna, Agostino Consoli, Salvatore De Cosmo, Paolo Di Bartolo, Francesco Dotta, Simona Frontoni, Marianna Galetta, Alessandra Gambineri, Carmine Gazzaruso, Francesco Giorgino, Davide Lauro, Emanuela Orsi, Giuseppe Paolisso, Gabriele Perriello, Piermarco Piatti, Antonio Pontiroli, Paola Ponzani, Angela Albarosa Rivellese, Giorgio Sesti, Giancarlo Tonolo, Roberto Trevisan, Chul Woo Ahn, Sei-Hyun Baik, Bong-Soo Cha, Choon-Hee Chung, Hak Chul Jang, Chong-Jin Kim, Hye Soon Kim, In Joo Kim, Eun Young Lee, Hyoung Woo Lee, Kwan-Woo Lee, Keon-Woong Moon, June Namgung, Kyong Soo Park, Soon Jib Yoo, Jaemyung Yu, Edmundo-Alfredo Bayram Llamas, Jose-Luis Cervantes-Escárcega, Luis Fernando Flota-Cervera, José Gerardo González-González, Sara Pascoe-Gonzalez, Emilia Susana Pelayo-Orozco, Santiago-Paulino Ramirez-Diaz, Arturo Saldana-Mendoza, Carlos Sánchez Jerjes-Díaz, Jose Juan Torres-Colores, Maricela Vidrio-Velázquez, Juan Villagordoa-Mesa, Hugo Peter Beijerbacht, Reginald G.E.J. Groutars, Boudewijn A Hoek, Pieter A.M. Hoogslag, Adriaan Kooy, Johannes A. Kragten, Aloysius G. Lieverse, Hendrik P. Swart, Eric P. Viergever, Jørn Ahlqvist, John Cooper, Hanne Gulseth, Gaute Guttormsen, Cecilie Wium, Hugo Arbañil, Jorge Calderon, Luis Camacho, Augusto Dextre Espinoza, Elizabeth Garrido, Alejandro Luna, Helard Manrique, Frederick Massucco Revoredo, Rolando Vargas Gonzales, Luis Zapata Rincon, Carlos Zubiate, Geraldine Ebo, Ellen Morales-Palomares, Malgorzata Arciszewska, Marek Banach, Renata Bijata-Bronisz, Tadeusz Derezinski, Waldemar Gadzinski, Jacek Gajek, Katarzyna Klodawska, Ewa Krzyzagorska, Andrzej Madej, Pawel Miekus, Jaroslaw Opiela, Piotr Romanczuk, Anna Siegel, Ewa Skokowska, Andrzej Stankiewicz, Teresa Stasinska, Iwona Trznadel-Morawska, Robert Witek, Sergey Aksentyev, Irina Bondar, Irina Demidova, Alexander Dreval, Olga Ershova, Gagik Galstyan, Alla Garganeeva, Nadezhda Izmozherova, Victoria Karetnikova, Marina Kharakhulakh, Aleksandr Khokhlov, Zhanna Kobalava, Olga Koshelskaya, Elena Kosmacheva, Vladimir Kostin, Natalia Koziolova, Anatoly Kuzin, Victor Lesnov, Tatyana Lysenko, Valentin Markov, Alexander Mayorov, Sergey Moiseev, Svetlana Myasoedova, Nina Petunina, Andrey Rebrov, Ludmila Ruyatkina, Julia Samoylova, Olga Sazonova, Natalia Shilkina, Nadezhda Sokolova, Olga Vasilevskaya, Nelli Verbovaya, Elena Vishneva, Sergey Vorobyev, Natalya Vorokhobina, Olga Zanozina, Elena Zhdanova, Tatyana Zykova, Lesley Burgess, Kathleen Coetzee, Saleem Dawood, Landman Lombard, Ellen Makotoko, Rajendran Moodley, Wessels Oosthuysen, Mohamed Sarvan, Carlos Calvo Gómez, Isidoro Cano Rodríguez, Almudena Castro Conde, Angel Cequier Fillat, Guillem Cuatrecasas Cambra, Fernando de Álvaro Moreno, Luis De Teresa Parreño, Javier Delgado Lista, José Ramón Domínguez Escribano, Santiago Durán García, Javier Elvira González, José María Fernández Rodríguez, Alberto Goday Arno, Ricardo Gomez Huelgas, José Ramón González Juanatey, Antonio Hernandez Mijares, Víctor Alfonso Jiménez Díaz, Esteban Jodar Gimeno, Tomás Lucas Morante, Monica Marazuela, Nieves Martell Claros, Didac Mauricio Puente, Elena Mena Ribas, Juan Francisco Merino Torres, Pedro Mezquita Raya, Andreu Nubiola Calonge, Xavier Ordoñez Sánchez, Jose Maria Pascual Izuel, Verónica Perea Castilla, Antonio Pérez Pérez, Isabel Perez Soto, Miguel Quesada Charneco, Angustias Quesada Simón, Josep Redón Mas, Antonia Rego Iraeta, Maria Rodriguez Alvarez, Irene Rodríguez Rodríguez, José Sabán Ruiz, Alfonso Soto González, Francisco Tinahones Madueno, Carlos Trescoli Serrano, Angels Ulied Armiñana, Erasmus Bachus, Katarina Berndtsson Blom, Ken Eliasson, Pekka Koskinen, Hans Larnefeldt, Cornelia Lif-Tiberg, Carina Linderfalk, Gustav Lund, Pia Lundman, Linda Moris, Åke Olsson, Staffan Salmonsson, Johan Sanmartin Berglund, Folke Sjöberg, Stefan Söderberg, Ingemar Torstensson, Jung-Fu Chen, Kai Jen Tien, Shih-Ting Tseng, Shih-Te Tu, Chih-Yuan Wang, Ji-Hung Wang, Arintaya Phrommintikul, Sukit Yamwong, Woravut Jintapakorn, Pisit Hutayanon, Nakarin Sansanayudh, Larysa Bazhan, Ivan Fushtey, Mariya Grachova, Vitaliy Katerenchuk, Vadym Korpachev, Nonna Kravchun, Oleksandr Larin, Galyna Mykhalchyshyn, Halyna Myshanych, Olga Oleksyk, Valeriia Orlenko, Nataliia Pashkovska, Nataliia Pertseva, Olena Petrosyan, Ivan Smirnov, Maryna Vlasenko, Tetiana Zlova, Myint Aye, Arun Baksi, Mathangi Balasubramani, Ronnie Beboso, Mark Blagden, Charles Bundy, Tobias Cookson, Allan Copland, Alistair Emslie-Smith, Fiona Green, Anthony Gunstone, Basil Issa, Ewart Jackson-Voyzey, Andrew Johnson, Malcolm Maclean, John McKnight, Solomon Muzulu, Ian O'Connell, Babatunde Oyesile, Catherine Patterson, Ewan Pearson, Sam Philip, Paul Smith, Usha Sukumaran, Jalal Abbas, Gaurav Aggarwala, Faiq Akhter, James Andersen, Moise Anglade, Georges Argoud, Mehrdad Ariani, Reswan Ashdji, Ladan Bakhtari, Subhash Banerjee, Andrew Bartlett, Howard Baum, Harold Bays, Richard Beasley, Renata Belfort de Aguiar, Sabrina Benjamin, Ravi Bhagwat, Anuj Bhargava, Bruce Bode, Christina Bratcher, Toby Briskin, Andrew Brockmyre, Raymond Broughton, Judith Brown, Madhusudan Budhraja, Kevin Cannon, Jewell Carr, Harold Cathcart, Arvind Cavale, Louis Chaykin, Deanna Cheung, Richard Childress, Allan Cohen, Jonathan Condit, Erin Cooksey, George Mitchell Cornett, Ira Dauber, William Davila, Luis De Armas, Julius Dean, Robert Detweiler, Ernesto Diaz, Michael Di Giovanna, Isaac Dor, Waymon Drummond, Donald Eagerton, John Earl, Charles Eaton, Howard Ellison, Neil Farris, Thomas Fiel, Anthony Firek, Brian First, Les Forgosh, William French, Winston Gandy, Ronald Garcia, Santosh Gill, Murray Gordon, Michael Guice, Siva Gummadi, Jonathan Hackenyos, Kristen Hairston, Lenita Hanson, Lindsay Harrison, Israel Hartman, John Heitner, Srini Hejeebu, Paul Hermany, Carlos Hernandez-Cassis, Horacio Hidalgo, Alexander Higgins, Hassan Ibrahim, Shahram Jacobs, David Johnson, Parag Joshi, Steven Kaster, Daniel Kellum, Christopher Kim, Ellen Kim, William Kirby, Albert Knouse, Steven Kulback, Mariananda Kumar, Tulsidas Kuruvanka, Ajay Labroo, William Lasswell, John Lentz, Thomas Lenzmeier, David Lewis, Zhaoping Li, Michael Lillestol, Raymond Little, Richard Lorraine, Cecilia McKeown-Biagas, Robert McNeill, Anand Mehta, Alan Miller, Joseph Moran, Emily Morawski, Venkatesh Nadar, Thomas O'Connor, Alberto Odio, Reginald Parker, Rajesh Patel, Lawrence Phillips, George Raad, Aref Rahman, Marina Raikhel, Ajit Raisinghani, Raj Rajan, Neda Rasouli, Frank Rauzi, Kathryn Rohr, Hal Roseman, Sergio Rovner, Fadi Saba, Richard Sachson, Alex Schabauer, Ricky Schneider, Timothy Schuchard, John Sensenbrenner, Yshay Shlesinger, Narendra Singh, Kanagaratnam Sivalingam, Larry Stonesifer, Daniel Storey, David Suh, Mohammed Tahir, Anjanette Tan, Marilyn Tan, Alain Taylon, Maitreya Thakkar, Devjit Tripathy, Gabriel Uwaifo, Amarnath Vedere, Chandra Venugopal, Anthony Vo, Michelle Welch, James Welker, Alexander White, John Willis, Alan Wynne, Shahram Yazdani, Anne Rosenberg, Lauren Price, Kristina Sigmon, Yuliya Lokhngina, Weibing Xing, Robert Overton, Murray Stewart, Janet Stead, Alistair Lindsay, Vickas Patel, Jorge Ross, Joseph Soffer, Shruti Daga, Margaret Sowell, Prashant Patel, Louisa Garvey, Jessica Ackert, Sybil Abraham, Mary Beth Sabol, Desma Altobelli, JuYoung Ha, Mangesh Kulkarni, Matthew Somerville, Drusilla Noronha, Ed Casson, Eddie Zang, Chamandeep Sandhu, Rakesh Kumar, David Chen, Lin Taft, Rajivkumar Patel, June Ye, Jennifer Shannon, Tim Wilson, Charleen Babi, Diane Miller, Karl Thorpe, Rachael Russell, Georgina Bull, Belinda Hereghty, Eva Fernandez-Salazar, Troy Longley, Jill Donaldson, Marie Jarosz, Karen Murphy, Patricia Adams, Peter Smith, Rachel James, Jackie Richards, Sangeeta Sedani, Denise Althouse, David Watson, Jamie Lorimer, Steven Lauder, Ron Schultheis, Terese Womer, Ella Wraight, Wenyan Li, Emma Price-Olsen, Anthony Watson, Aoife Kelly, Patricia McLaughlin, John Fleming, Jessica Schubert, Debra Schleiden, Tara Harris, Rahul Prakash, Jody Breneman, Sameer Deshpande, Aarti Saswadkar, Aditi Kumari, Aditi Shitut, Amruta Raorane, Anisha Karmalkar, Ankita Mhambrey, Archana Bhosale, Ashok Vaphare, Ashwini P Patil, Chaitali Khandelwal, Fayaz Shaik, Madhumitha Nadar, Mounika Karka, Neha Kadgaonkar, Nikita Gupta, Nutan Aher, Omkar Potnis, Pallavi Naicker, Rakesh Shinde, Richa Sharma, Rupali Godse, Sheetal Solanki, Shruti Sahu, Snehal Dumbre, Somesh Kumar, Suradnya Patil, Trisha Mandal, Hernandez, Adrian F, Green, Jennifer B, Janmohamed, Salim, D'Agostino, Ralph B, Granger, Christopher B, Jones, Nigel P, Leiter, Lawrence A, Rosenberg, Anne E, Sigmon, Kristina N, Somerville, Matthew C, Thorpe, Karl M, Mcmurray, John J V, Del Prato, Stefano, Mcmurray, John J. V., D'Agostino, Ralph B., Granger, Christopher B., Hernandez, Adrian F., Leiter, Lawrence A., Califf, Robert M, Holman, Rury, Demets, David, Riddle, Matthew, Goodman, Shaun, Mcguire, Darren, Alexander, Karen, Devore, Adam, Melloni, Chiara, Patel, Chetan, Kong, David, Bloomfield, Gerald, Roe, Matthew, Tricoci, Pierluigi, Harrison, Rob, Lopes, Renato, Mathews, Robin, Mehta, Rajendra, Schuyler Jones, William, Vemulapalli, Sreekanth, Povsic, Thoma, Eapen, Zubin, Dombrowski, Keith, Kolls, Brad, Jordan, Dedrick, Ambrosy, Andrew, Greene, Stephen, Mandawat, Aditya, Shavadia, Jay, Cooper, Lauren, Sharma, Abhinav, Guimaraes, Patricia, Friedman, Daniel, Wilson, Matt, Endsley, Patricia, Gentry, Tracy, Collier, Jeannie, Perez, Kathleen, James, Kourtnei, Roush, Jennifer, Pope, Connie, Howell, Christina, Johnson, Megan, Bailey, Matt, Cole, Joanna, Akers, Teresa, Vandyne, Beth, Thomas, Betsy, Rich, Jenny, Bartone, Susan, Beaulieu, Gail, Brown, Kim, Chau, Tuan, Christian, Tamra, Coker, Rebecca, Greene, Deb, Haddock, Trevorlyn, Jenkins, Wendy, Haque, Ghazala, Marquess, Marsha, Pesarchick, Jean, Rethaford, Renee, Stone, Allegra, Al Kawas, Fira, Anderson, Michelle, Enns, Robert, Sinay, Isaac, Mathieu, Chantal, Yordanov, Victor, Hramiak, Irene, Haluzik, Martin, Galatius, Søren, Guerci, Bruno, Nauck, Michael, Migdalis, Ilia, Tan, Choon Beng Kathryn, Kocsis, Gyozo, Giaccari, Andrea, Lee, Moon Kyu, Muñoz, Ernesto German Cardona, Cornel, Jan, Birkeland, Kare, Pinto, Miguel, Tirador, Louie, Olesinska-Mader, Martyna, Shestakova, Marina, Distiller, Larry, Lopez-Sendon, Jose, Eliasson, Bjorn, Chiang, Chern-En, Srimahachota, Suphot, Mankovsky, Bori, Bethel, M Angelyn, Dungan, Kathleen, Kosiborod, Mikhail, Alvarisqueta, Andre, Baldovino, Jorge, Besada, Diego, Calella, Pedro, Cantero, Maria Cecilia, Castaño, Patricia, Chertkoff, Alejandro, Cuadrado, Jesu, De Loredo, Lui, Dominguez, Andrea, Español, Maria Vanesa, Finkelstein, Hernan, Frechtel, Gustavo, Fretes, Jose, Garrido Santos, Natalia, Gonzalez, Joaquin, Litvak, Marco, Loureyro, Juan, Maffei, Laura, Maldonado, Natacha, Mohr Gasparini, Diego, Orio, Silvia, Perez Manghi, Federico, Rodriguez Papini, Nelson, Sala, Jorgelina, Schygiel, Pablo, Sposetti, Georgina, Ulla, Maria, Verra, Fernando, Zabalua, Silvina, Zaidman, Cesar, Crenier, Laurent, Debroye, Corinne, Duyck, Franci, Scheen, André, Van Gaal, Luc, Vercammen, Chri, Damyanova, Velichka, Dimitrov, Stefan, Kovacheva, Snezhina, Lozanov, Lachezar, Margaritov, Viktor, Mihaylova-Shumkova, Rositsa, Nikolaeva, Antoaneta, Stoyanova, Zhasmina, Akhras, Ronald, Beaudry, Yve, Bedard, Jacque, Berlingieri, Joseph, Chehayeb, Raja, Cheung, Stephen, Conway, Jame, Cusson, Jean, Della Siega, Anthony, Dumas, Richard, Dzongowski, Peter, Ferguson, Murdo, Gaudet, Daniel, Grondin, Francoi, Gupta, Anil, Gupta, Milan, Halperin, Frank, Houle, Pierre-Alain, Jones, Michael, Kouz, Simon, Kovacs, Christopher, Landry, Daniel, Lonn, Eva, O'Mahony, William, Peterson, Sean, Reich, Denni, Rosenbloom, Alan, St-Maurice, Francoi, Tugwell, Barna, Vizel, Saul, Woo, Vincent, Brychta, Toma, Cech, Vladimir, Dvorakova, Eva, Edelsberger, Toma, Halciakova, Katarina, Krizova, Jarmila, Lastuvka, Jiri, Piperek, Martin, Prymkova, Vera, Raclavska, Lea, Silhova, Elena, Urbanek, Robin, Vrkoc, Jan, Andersen, Ulla, Brønnum-Schou, Jen, Hove, Jen, Jensen, Jan Skov, Kober, Lar, Kristiansen, Ole Peter, Lund, Per, Melchior, Thoma, Nyvad, Ole, Schou, Morten, Boye, Alain, Cadinot, Didier, Gouet, Didier, Henry, Patrick, Kessler, Laurence, Lalau, Jean-Daniel, Petit, Catherine, Thuan, Jean-Francoi, Voinot, Christel, Vouillarmet, Julien, Axthelm, Christoph, Berger, Dirk, Bieler, Tasso, Birkenfeld, Andrea, Bott, Jochen, Busch, Klau, Caca, Karel, Chevts, Julia, Donaubauer, Torsten, Erlinger, Rudolf, Funke, Klau, Grosskopf, Josef, Hagenow, Andrea, Hamann, Monika, Hartard, Manfred, Heymer, Peter, Huppertz, Wolfgang, Illies, Gabriele, Jacob, Stephan, Jung, Thoma, Kahrmann, Gerd, Kast, Petra, Kellerer, Monika, Kempe, Hans-Peter, Khariouzov, Andrei, Klausmann, Gerhard, Klein, Christiane, Kleinecke-Pohl, Uwe, Kleinertz, Klau, Koch, Thorsten, Kosch, Christine, Lorra, Babette, Luedemann, Joerg, Luttermann, Matthia, Maxeiner, Stephan, Milek, Karsten, Moelle, Andrea, Neumann, Gerhard, Nischik, Ruth, Oehrig-Pohl, Edith, Plassmann, Georg, Pohlmeier, Lar, Proepper, Felix, Regner, Stefan, Rieker, Werner, Rose, Ludger, Samer, Holger, Sauter, Joachim, Schaper, Frank, Schiffer, Clemen, Schmidt, Juergen, Scholz, Bernd-M., Schulze, Joerg, Segner, Alexander, Seufert, Jochen, Sigal, Helena, Steindorf, Joerg, Stockhausen, Juergen, Stuebler, Petra, Taeschner, Heidrun, Tews, Dietrich, Tschoepe, Diethelm, Wilhelm, Karl, Zeller-Stefan, Helga, Avramidis, Iakovo, Bousboulas, Stavro, Bristianou, Magdalini, Dimitriadis, Georgio, Elisaf, Mose, Kotsa, Kalliopi, Melidonis, Andrea, Mitrakou, Asimina, Pagkalos, Emmanouil, Papanas, Nikolao, Pappas, Angelo, Sampanis, Christo, Tentolouris, Nikolao, Tsapas, Apostolo, Tzatzagou, Glykeria, Ozaki, Risa, Hajdú, Csaba, Harcsa, Eleonóra, Konyves, Laszlo, Mucsi, Jáno, Pauker, Zsolt, Petró, Gizella, Plés, Zsolt, Revesz, Katalin, Sándor, Vangel, Vass, Viktor, Avogaro, Angelo, Boemi, Massimo, Bonadonna, Riccardo, Consoli, Agostino, De Cosmo, Salvatore, Di Bartolo, Paolo, Dotta, Francesco, Frontoni, Simona, Galetta, Marianna, Gambineri, Alessandra, Gazzaruso, Carmine, Giorgino, Francesco, Lauro, Davide, Orsi, Emanuela, Paolisso, Giuseppe, Perriello, Gabriele, Piatti, Piermarco, Pontiroli, Antonio, Ponzani, Paola, Rivellese, Angela Albarosa, Sesti, Giorgio, Tonolo, Giancarlo, Trevisan, Roberto, Ahn, Chul Woo, Baik, Sei-Hyun, Cha, Bong-Soo, Chung, Choon-Hee, Jang, Hak Chul, Kim, Chong-Jin, Kim, Hye Soon, Kim, In Joo, Lee, Eun Young, Lee, Hyoung Woo, Lee, Kwan-Woo, Moon, Keon-Woong, Namgung, June, Park, Kyong Soo, Yoo, Soon Jib, Yu, Jaemyung, Llamas, Edmundo-Alfredo Bayram, Cervantes-Escárcega, Jose-Lui, Flota-Cervera, Luis Fernando, González-González, José Gerardo, Pascoe-Gonzalez, Sara, Pelayo-Orozco, Emilia Susana, Ramirez-Diaz, Santiago-Paulino, Saldana-Mendoza, Arturo, Jerjes-Díaz, Carlos Sánchez, Torres-Colores, Jose Juan, Vidrio-Velázquez, Maricela, Villagordoa-Mesa, Juan, Beijerbacht, Hugo Peter, Groutars, Reginald G. E. J., Hoek, Boudewijn A, Hoogslag, Pieter A. M., Kooy, Adriaan, Kragten, Johannes A., Lieverse, Aloysius G., Swart, Hendrik P., Viergever, Eric P., Ahlqvist, Jørn, Cooper, John, Gulseth, Hanne, Guttormsen, Gaute, Wium, Cecilie, Arbañil, Hugo, Calderon, Jorge, Camacho, Lui, Espinoza, Augusto Dextre, Garrido, Elizabeth, Luna, Alejandro, Manrique, Helard, Revoredo, Frederick Massucco, Gonzales, Rolando Varga, Rincon, Luis Zapata, Zubiate, Carlo, Ebo, Geraldine, Morales-Palomares, Ellen, Arciszewska, Malgorzata, Banach, Marek, Bijata-Bronisz, Renata, Derezinski, Tadeusz, Gadzinski, Waldemar, Gajek, Jacek, Klodawska, Katarzyna, Krzyzagorska, Ewa, Madej, Andrzej, Miekus, Pawel, Opiela, Jaroslaw, Romanczuk, Piotr, Siegel, Anna, Skokowska, Ewa, Stankiewicz, Andrzej, Stasinska, Teresa, Trznadel-Morawska, Iwona, Witek, Robert, Aksentyev, Sergey, Bondar, Irina, Demidova, Irina, Dreval, Alexander, Ershova, Olga, Galstyan, Gagik, Garganeeva, Alla, Izmozherova, Nadezhda, Karetnikova, Victoria, Kharakhulakh, Marina, Khokhlov, Aleksandr, Kobalava, Zhanna, Koshelskaya, Olga, Kosmacheva, Elena, Kostin, Vladimir, Koziolova, Natalia, Kuzin, Anatoly, Lesnov, Victor, Lysenko, Tatyana, Markov, Valentin, Mayorov, Alexander, Moiseev, Sergey, Myasoedova, Svetlana, Petunina, Nina, Rebrov, Andrey, Ruyatkina, Ludmila, Samoylova, Julia, Sazonova, Olga, Shilkina, Natalia, Sokolova, Nadezhda, Vasilevskaya, Olga, Verbovaya, Nelli, Vishneva, Elena, Vorobyev, Sergey, Vorokhobina, Natalya, Zanozina, Olga, Zhdanova, Elena, Zykova, Tatyana, Burgess, Lesley, Coetzee, Kathleen, Dawood, Saleem, Lombard, Landman, Makotoko, Ellen, Moodley, Rajendran, Oosthuysen, Wessel, Sarvan, Mohamed, Calvo Gómez, Carlo, Cano Rodríguez, Isidoro, Castro Conde, Almudena, Cequier Fillat, Angel, Cuatrecasas Cambra, Guillem, de Álvaro Moreno, Fernando, De Teresa Parreño, Lui, Delgado Lista, Javier, Domínguez Escribano, José Ramón, Durán García, Santiago, Elvira González, Javier, Fernández Rodríguez, José María, Goday Arno, Alberto, Gomez Huelgas, Ricardo, González 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Avogaro, A, Boemi, M, Bonadonna, R, Consoli, A, De Cosmo, S, Di Bartolo, P, Dotta, F, Frontoni, S, Galetta, M, Gambineri, A, Gazzaruso, C, Giorgino, F, Lauro, D, Orsi, E, Paolisso, G, Perriello, G, Piatti, P, Pontiroli, A, Ponzani, P, Rivellese, A, Sesti, G, Tonolo, G, Trevisan, R, Ahn, C, Baik, S, Cha, B, Chung, C, Jang, H, Kim, C, Kim, H, Kim, I, Lee, E, Lee, H, Lee, K, Moon, K, Namgung, J, Park, K, Yoo, S, Yu, J, Llamas, E, Cervantes-Escarcega, J, Flota-Cervera, L, Gonzalez-Gonzalez, J, Pascoe-Gonzalez, S, Pelayo-Orozco, E, Ramirez-Diaz, S, Saldana-Mendoza, A, Jerjes-Diaz, C, Torres-Colores, J, Vidrio-Velazquez, M, Villagordoa-Mesa, J, Beijerbacht, H, Groutars, R, Hoek, B, Hoogslag, P, Kooy, A, Kragten, J, Lieverse, A, Swart, H, Viergever, E, Ahlqvist, J, Cooper, J, Gulseth, H, Guttormsen, G, Wium, C, Arbanil, H, Calderon, J, Camacho, L, Espinoza, A, Garrido, E, Luna, A, Manrique, H, Revoredo, F, Gonzales, R, Rincon, L, Zubiate, C, Ebo, G, Morales-Palomares, E, Arciszewska, M, 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Escribano, J, Duran Garcia, S, Elvira Gonzalez, J, Fernandez Rodriguez, J, Goday Arno, A, Gomez Huelgas, R, Gonzalez Juanatey, J, Hernandez Mijares, A, Jimenez Diaz, V, Jodar Gimeno, E, Lucas Morante, T, Marazuela, M, Martell Claros, N, Mauricio Puente, D, Mena Ribas, E, Merino Torres, J, Mezquita Raya, P, Nubiola Calonge, A, Ordonez Sanchez, X, Pascual Izuel, J, Perea Castilla, V, Perez Perez, A, Perez Soto, I, Quesada Charneco, M, Quesada Simon, A, Redon Mas, J, Rego Iraeta, A, Rodriguez Alvarez, M, Rodriguez Rodriguez, I, Saban Ruiz, J, Soto Gonzalez, A, Tinahones Madueno, F, Trescoli Serrano, C, Ulied Arminana, A, Bachus, E, Berndtsson Blom, K, Eliasson, K, Koskinen, P, Larnefeldt, H, Lif-Tiberg, C, Linderfalk, C, Lund, G, Lundman, P, Moris, L, Olsson, A, Salmonsson, S, Sanmartin Berglund, J, Sjoberg, F, Soderberg, S, Torstensson, I, Chen, J, Tien, K, Tseng, S, Tu, S, Wang, C, Wang, J, Phrommintikul, A, Yamwong, S, Jintapakorn, W, Hutayanon, P, Sansanayudh, N, Bazhan, L, Fushtey, I, Grachova, M, Katerenchuk, V, Korpachev, V, Kravchun, N, Larin, O, Mykhalchyshyn, G, Myshanych, H, Oleksyk, O, Orlenko, V, Pashkovska, N, Pertseva, N, Petrosyan, O, Smirnov, I, Vlasenko, M, Zlova, T, Aye, M, Baksi, A, Balasubramani, M, Beboso, R, Blagden, M, Bundy, C, Cookson, T, Copland, A, Emslie-Smith, A, Green, F, Gunstone, A, Issa, B, Jackson-Voyzey, E, Johnson, A, Maclean, M, Mcknight, J, Muzulu, S, O'Connell, I, Oyesile, B, Patterson, C, Pearson, E, Philip, S, Smith, P, Sukumaran, U, Abbas, J, Aggarwala, G, Akhter, F, Andersen, J, Anglade, M, Argoud, G, Ariani, M, Ashdji, R, Bakhtari, L, Banerjee, S, Bartlett, A, Baum, H, Bays, H, Beasley, R, Belfort de Aguiar, R, Benjamin, S, Bhagwat, R, Bhargava, A, Bode, B, Bratcher, C, Briskin, T, Brockmyre, A, Broughton, R, Brown, J, Budhraja, M, Cannon, K, Carr, J, Cathcart, H, Cavale, A, Chaykin, L, Cheung, D, Childress, R, Cohen, A, Condit, J, Cooksey, E, Cornett, G, Dauber, I, Davila, W, De Armas, L, Dean, J, Detweiler, R, Diaz, E, Di Giovanna, M, Dor, I, Drummond, W, Eagerton, D, Earl, J, Eaton, C, Ellison, H, Farris, N, Fiel, T, Firek, A, First, B, Forgosh, L, French, W, Gandy, W, Garcia, R, Gill, S, Gordon, M, Guice, M, Gummadi, S, Hackenyos, J, Hairston, K, Hanson, L, Harrison, L, Hartman, I, Heitner, J, Hejeebu, S, Hermany, P, Hernandez-Cassis, C, Hidalgo, H, Higgins, A, Ibrahim, H, Jacobs, S, Johnson, D, Joshi, P, Kaster, S, Kellum, D, Kim, E, Kirby, W, Knouse, A, Kulback, S, Kumar, M, Kuruvanka, T, Labroo, A, Lasswell, W, Lentz, J, Lenzmeier, T, Lewis, D, Li, Z, Lillestol, M, Little, R, Lorraine, R, McKeown-Biagas, C, Mcneill, R, Mehta, A, Miller, A, Moran, J, Morawski, E, Nadar, V, O'Connor, T, Odio, A, Parker, R, Patel, R, Phillips, L, Raad, G, Rahman, A, Raikhel, M, Raisinghani, A, Rajan, R, Rasouli, N, Rauzi, F, Rohr, K, Roseman, H, Rovner, S, Saba, F, Sachson, R, Schabauer, A, Schneider, R, Schuchard, T, Sensenbrenner, J, Shlesinger, Y, Singh, N, Sivalingam, K, Stonesifer, L, Storey, D, Suh, D, Tahir, M, Tan, A, Tan, M, Taylon, A, Thakkar, M, Tripathy, D, Uwaifo, G, Vedere, A, Venugopal, C, Vo, A, Welch, M, Welker, J, White, A, Willis, J, Wynne, A, Yazdani, S, Price, L, Lokhngina, Y, Xing, W, Overton, R, Stewart, M, Stead, J, Lindsay, A, Patel, V, Ross, J, Soffer, J, Daga, S, Sowell, M, Patel, P, Garvey, L, Ackert, J, Abraham, S, Sabol, M, Altobelli, D, Ha, J, Kulkarni, M, Noronha, D, Casson, E, Zang, E, Sandhu, C, Kumar, R, Chen, D, Taft, L, Ye, J, Shannon, J, Wilson, T, Babi, C, Miller, D, Russell, R, Bull, G, Hereghty, B, Fernandez-Salazar, E, Longley, T, Donaldson, J, Jarosz, M, Murphy, K, Adams, P, James, R, Richards, J, Sedani, S, Althouse, D, Watson, D, Lorimer, J, Lauder, S, Schultheis, R, Womer, T, Wraight, E, Li, W, Price-Olsen, E, Watson, A, Kelly, A, Mclaughlin, P, Fleming, J, Schubert, J, Schleiden, D, Harris, T, Prakash, R, Breneman, J, Deshpande, S, Saswadkar, A, Kumari, A, Shitut, A, Raorane, A, Karmalkar, A, Mhambrey, A, Bhosale, A, Vaphare, A, Patil, A, Khandelwal, C, Shaik, F, Nadar, M, Karka, M, Kadgaonkar, N, Gupta, N, Aher, N, Potnis, O, Naicker, P, Shinde, R, Sharma, R, Godse, R, Solanki, S, Sahu, S, Dumbre, S, Kumar, S, Patil, S, and Mandal, T
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Male ,Placebo-controlled study ,Myocardial Infarction ,alanine aminotransferase, albiglutide, bilirubin, placebo, antidiabetic agent, glucagon like peptide 1, rGLP-1 protein ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,law.invention ,0302 clinical medicine ,Randomized controlled trial ,law ,Glucagon-Like Peptide 1 ,Cardiovascular Disease ,Medicine(all) ,education.field_of_study ,Subcutaneous ,Medicine (all) ,albigutide ,Hazard ratio ,General Medicine ,Middle Aged ,Albiglutide ,Stroke ,Treatment Outcome ,Tolerability ,Cardiovascular Diseases ,Female ,type 2 diabetes ,Type 2 ,Human ,Adult ,medicine.medical_specialty ,Injections, Subcutaneous ,Population ,030209 endocrinology & metabolism ,Placebo ,Injections, Subcutaneou ,Drug Administration Schedule ,Injections ,03 medical and health sciences ,Double-Blind Method ,Internal medicine ,Diabetes Mellitus ,medicine ,Humans ,Hypoglycemic Agents ,education ,Aged ,Diabetes Mellitus, Type 2 ,Hypoglycemic Agent ,business.industry ,Semaglutide ,Settore MED/13 - ENDOCRINOLOGIA ,Harmony ,business - Abstract
Background: \ud Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke.\ud \ud Methods: \ud We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515.\ud \ud Findings: \ud Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p
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- 2018
46. Diabetes and acute bacterial skin and skin structure infections.
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Falcone, Marco, Meier, Juris J, Marini, Maria Giulia, Caccialanza, Riccardo, Aguado, José María, Del Prato, Stefano, Menichetti, Francesco, Giulia Marini, Maria, and María Aguado, José
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SKIN infections , *HYPERGLYCEMIA , *DIABETES complications , *TYPE 2 diabetes , *SOFT tissue infections , *LENGTH of stay in hospitals , *MULTIDRUG resistance - Abstract
Acute bacterial skin and skin structures infections (ABSSSIs) are associated with high morbidity, costs and mortality in patients with diabetes mellitus. Their appropriate management should include several figures and a well-organized approach. This review aims to highlight the interplay between diabetes and ABSSSIs and bring out the unmet clinical needs in this area. Pathogenetic mechanisms underlying the increased risk of ABSSSIs in diabetes mellitus are multifactorial: high glucose levels play a crucial pathogenetic role in the tissue damage and delayed clinical cure. Moreover, the presence of diabetes complications (neuropathy, vasculopathy) further complicates the management of ABSSSIs in patients with diabetes. Multidrug resistance organisms should be considered in this population based on patient risk factors and local epidemiology and etiological diagnosis should be obtained whenever possible. Moreover, drug-drug interactions and drug-related adverse events (such as nephrotoxicity) should be considered in the choice of antibiotic therapy. Reducing unnecessary hospitalizations and prolonged length of hospital stay is of primary importance now, more than ever. To achieve these objectives, a better knowledge of the interplay between acute and chronic hyperglycemia, multidrug resistant etiology, and short and long-term outcome is needed. Of importance, a multidisciplinary approach is crucial to achieve full recovery of these patients. [ABSTRACT FROM AUTHOR]
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- 2021
- Full Text
- View/download PDF
47. Effects on the incidence of cardiovascular events of the addition of pioglitazone versus sulfonylureas in patients with type 2 diabetes inadequately controlled with metformin (TOSCA.IT): a randomised, multicentre trial
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Vaccaro, O, Masulli, M, Nicolucci, A, Bonora, E, Del Prato, S, Maggioni, Ap, Rivellese, Aa, Squatrito, S, Giorda, Cb, Sesti, G, Mocarelli, P, Lucisano, G, Sacco, M, Signorini, S, Cappellini, F, Perriello, G, Babini, Ac, Lapolla, A, Gregori, G, Giordano, C, Corsi, L, Buzzetti, R, Clemente, G, Di Cianni, G, Iannarelli, R, Cordera, R, La Macchia, O, Zamboni, C, Scaranna, C, Boemi, M, Iovine, C, Lauro, D, Leotta, S, Dall'Aglio, E, Cannarsa, E, Tonutti, L, Pugliese, G, Bossi, Ac, Anichini, R, Dotta, F, Di Benedetto, A, Citro, G, Antenucci, D, Ricci, L, Giorgino, F, Santini, C, Gnasso, A, De Cosmo, S, Zavaroni, D, Vedovato, M, Consoli, A, Calabrese, M, di Bartolo, P, Fornengo, P, Riccardi, G, IT) study group, Thiazolidinediones Or Sulfonylureas Cardiovascular Accidents Intervention Trial (TOSCA., Collaborators: Vaccaro O, Italian Diabetes Society., D'Angelo, F, Giansanti, R, Tanase, L, Lanari, L, Testa, I, Pancani, F, Ranchelli, A, Vagheggi, P, Scatona, A, Fontana, L, Laviola, L, Tarantino, L, Ippolito, C, Gigantelli, V, Manicone, M, Conte, E, Trevisan, R, Rota, R, Corsi, A, Dodesini, Ar, Reggiani, Gm, Montesi, L, Mazzella, N, Forlani, G, Caselli, C, Di Luzio, R, Mazzotti, A, Aiello, A, Barrea, A, Musto, A, D'Amico, F, Sinagra, T, Longhitano, S, Trowpea, V, Sparti, M, Italia, S, Lisi, E, Grasso, G, Pezzino, V, Insalaco, F, Carallo, C, Scicchitano, C, De Franceschi MS, Calbucci, G, Ripani, R, Cuneo, G, Corsi, S, Romeo, F, Lesina, A, Comoglio, M, Bonetto, C, Robusto, A, Nada, E, Asprino, V, Cetraro, R, Impieri, M, Lucchese, G, Donnarumma, G, Tizio, B, Lenza, L, Paraggio, P, Tomasi, F, Dozio, N, Scalambra, E, Mannucci, E, Lamanna, C, Cignarelli, M, Macchia, O, Fariello, S, Sorrentino, Mr, Franzetti, I, Radin, R, Annunziata, F, Bonabello, La, Durante, A, Dolcino, M, Gallo, F, Mazzucchelli, C, Aleo, A, Melga, P, Briatore, L, Maggi, D, Storace, D, Cecoli, F, D'Ugo, E, Pupillo, M, Baldassarre, Mpa, Salvati, F, Minnucci, A, De Luca, A, Zugaro, A, Santarelli, L, Bosco, A, Petrella, V, La Verghetta GG, De Gregorio, A, D'Andrea, S, Giuliani, Ae, Polidoro, Wl, Sperandio, A, Sciarretta, F, Pezzella, A, Carlone, A, Potenziani, S, Venditti, C, Foffi, C, Carbone, S, Cipolloni, L, Moretti, C, Leto, G, Serra, R, Petrachi, F, Romano, I, Lacaria, E, Russo, L, Goretti, C, Sannino, C, Dolci, M, Bruselli, L, Mori, Ml, Baccetti, F, Del Freo, M, Cucinotta, D, Giunta, L, Ruffo, Mc, Cannizzaro, D, Pintaudi, B, Perrone, G, Pata, P, Ragonese, F, Lettina, G, Mancuso, T, Coppolino, A, Piatti, Pm, Monti, L, Stuccillo, M, Lucotti, P, Setola, M, Crippa, Gv, Loi, C, Oldani, M, Bottalico, Ml, Pellegata, B, Bonomo, M, Menicatti, Lsm, Resi, V, Bertuzzi, F, Disoteo, Eo, Pizzi, G, Annuzzi, G, Capaldo, B, Nappo, R, Auciello, Sm, Turco, Aa, Costagliola, L, Corte, Gd, Vallefuoco, P, Nappi, F, Vitale, M, Cocozza, S, Ciano, O, Massimino, E, Garofalo, N, Avogaro, A, Guarneri, G, Fedele, D, Sartore, G, Chilelli, Nc, Burlina, S, Bonsembiante, B, Galluzzo, A, Torregrossa, V, Mancastroppa, G, Arsenio, L, Cioni, F, Caronna, S, Papi, M, Babini, M, Santeusanio, F, Calagreti, G, Timi, A, Tantucci, A, Marino, C, Ginestra, F, Di Biagio, R, Taraborelli, M, Miccoli, R, Bianchi, C, Garofolo, M, Politi, Ks, Penno, G, Livraga, S, Calzoni, F, Mancastroppa, Glf, Corsini, E, Tedeschi, A, Gaglianò, Ms, Ippolito, G, Salutini, E, Cervellino, F, Natale, M, Salvatore, V, Zampino, A, Sinisi, R, Arcangeli, A, Zogheri, A, Guizzotti, S, Longo, R, Di Bartolo, P, Pellicano, F, Scolozzi, P, Termine, S, Luberto, A, Ballardini, G, Trojani, C, Mazzuca, P, Bruglia, M, Ciamei, M, Genghini, S, Zannoni, C, Rangel, G, Salvi, L, Zappaterreno, A, Cordone, S, Simonelli, P, Meggiorini, M, Frasheri, A, Di Pippo, C, Maglio, C, Mazzitelli, G, Rinaldi, Me, Galli, A, Romano, M, D'Angelo, P, Suraci, C, Bacci, S, Palena, Ap, Genovese, S, Mancino, M, Rondinelli, M, Capone, F, Calabretto, E, Bulgheroni, M, Bucciarelli, L, Ceccarelli, E, Fondelli, C, Santacroce, C, Guarino, E, Nigi, L, Lalli, C, Di Vizia, G, Scarponi, M, Montani, V, Di Bernardino, P, Romagni, P, Dolcetti, K, Forte, E, Tamburo, L, Perin, Pc, Prinzis, T, Gruden, G, Bruno, G, Zucco, C, Perotta, M, Marena, S, Monsignore, S, Panero, F, Ponzi, F, Carpinteri, R, Casagrande, Ml, Coletti, Mf, Balini, A, Filopanti, M, Madaschi, S, Pulcina, A, Grimaldi, F, Venturini, G, Agus, S, Pagnutti, S, Guidotti, F, Cavarape, A, Cigolini, M, Pichiri, I, Brangani, C, Fainelli, G, Tomasetto, E, Zoppini, G, Galletti, A, Perrone, D, Capra, C, Bianchini, F, Ceseri, M, Di Nardo, B, Sasso, E, Bartolomei, B, Suliman, I, Fabbri, G, Romano, G, Maturo, N, Nunziata, G, Capobianco, G, De Simone, G, Villa, V, Rota, G, Pentangelo, C, Carbonara, O, Caiazzo, G, Cutolo, M, Sorrentino, T, Mastrilli, V, Amelia, U, Masi, S, Corigliano, G, Gaeta, I, Armentano, V, Calatola, P, Capuano, G, Angiulli, B, Auletta, P, Petraroli, E, Iodice, Ce, Agrusta, M., Vaccaro, Olga, Masulli, Maria, Nicolucci, Antonio, Bonora, Enzo, Del Prato, Stefano, Maggioni, Aldo P, Rivellese, Angela A, Squatrito, Sebastiano, Giorda, Carlo B, Sesti, Giorgio, Mocarelli, Paolo, Lucisano, Giuseppe, Sacco, Michele, Signorini, Stefano, Cappellini, Fabrizio, Perriello, Gabriele, Babini, Anna Carla, Lapolla, Annunziata, Gregori, Giovanna, Giordano, Carla, Corsi, Laura, Buzzetti, Raffaella, Clemente, Gennaro, Di Cianni, Graziano, Iannarelli, Rossella, Cordera, Renzo, La Macchia, Olga, Zamboni, Chiara, Scaranna, Cristiana, Boemi, Massimo, Iovine, Ciro, Lauro, Davide, Leotta, Sergio, Dall'Aglio, Elisabetta, Cannarsa, Emanuela, Tonutti, Laura, Pugliese, Giuseppe, Bossi, Antonio C, Anichini, Roberto, Dotta, Francesco, Di Benedetto, Antonino, Citro, Giuseppe, Antenucci, Daniela, Ricci, Lucia, Giorgino, Francesco, Santini, Costanza, Gnasso, Agostino, De Cosmo, Salvatore, Zavaroni, Donatella, Vedovato, Monica, Consoli, Agostino, Calabrese, Maria, Di Bartolo, Paolo, Fornengo, Paolo, Riccardi, Gabriele, Maggioni, Aldo Pietro, D'Angelo, Federica, Giansanti, Roberto, Tanase, Laura, Lanari, Luigi, Testa, Ivano, Pancani, Francesca, Ranchelli, Anna, Vagheggi, Paolo, Scatona, Alessia, Fontana, Lucia, Laviola, Luigi, Tarantino, Lucia, Ippolito, Claudia, Gigantelli, Vittoria, Manicone, Mariangela, Conte, Eleonora, Trevisan, Roberto, Rota, Rossella, Corsi, Anna, Dodesini, Alessandro R., Reggiani, Giulio Marchesini, Montesi, Luca, Mazzella, Natalia, Forlani, Gabriele, Caselli, Chiara, Di Luzio, Raffaella, Mazzotti, Arianna, Aiello, Antimo, Barrea, Angelina, Musto, Antonio, D'Amico, Fiorentina, Sinagra, Tiziana, Longhitano, Sara, Trowpea, Vanessa, Sparti, Maria, Italia, Salvatore, Lisi, Enrico, Grasso, Giuseppe, Pezzino, Vincenzo, Insalaco, Federica, Carallo, Claudio, Scicchitano, Caterina, De Franceschi, Maria Serena, Calbucci, Giovanni, Ripani, Raffaella, Cuneo, Giacomo, Corsi, Simona, Giorda, Carlo B., Romeo, Francesco, Lesina, Annalisa, Comoglio, Marco, Bonetto, Caterina, Robusto, Anna, Nada, Elisa, Asprino, Vincenzo, Cetraro, Rosa, Impieri, Michelina, Lucchese, Giuseppe, Donnarumma, Giovanna, Tizio, Biagio, Lenza, Lazzaro, Paraggio, Pia, Tomasi, Franco, Dozio, Nicoletta, Scalambra, Egle, Mannucci, Edoardo, Lamanna, Caterina, Cignarelli, Mauro, Macchia, Olga La, Fariello, Stefania, Sorrentino, Maria Rosaria, Franzetti, Ivano, Radin, Raffaella, Annunziata, Francesca, Bonabello, Laura Affinito, Durante, Arianna, Dolcino, Mara, Gallo, Fiorenza, Mazzucchelli, Chiara, Aleo, Anna, Melga, Pierluigi, Briatore, Lucia, Maggi, Davide, Storace, Daniela, Cecoli, Francesca, D'Ugo, Ercole, Pupillo, Mario, Baldassarre, Maria Pompea Antonia, Salvati, Filippo, Minnucci, Anita, De Luca, Angelo, Zugaro, Antonella, Santarelli, Livia, Bosco, Angela, Petrella, Vittorio, La Verghetta, Grazia Giovanna, De Gregorio, Antonella, D'Andrea, Settimio, Giuliani, Anna Elisa, Polidoro, W. Lorella, Sperandio, Alessandra, Sciarretta, Filomena, Pezzella, Alfonso, Carlone, Angela, Potenziani, Stella, Venditti, Chiara, Foffi, Chiara, Carbone, Salvatore, Cipolloni, Laura, Moretti, Chiara, Leto, Gaetano, Serra, Rosalia, Petrachi, Francesca, Romano, Isabella, Lacaria, Emilia, Russo, Laura, Goretti, Chiara, Sannino, Claudia, Dolci, Maria, Bruselli, Laura, Mori, Mary L., Baccetti, Fabio, Del Freo, Maria, Cucinotta, Domenico, Giunta, Loretta, Ruffo, Maria Concetta, Cannizzaro, Desiree, Pintaudi, Basilio, Perrone, Giovanni, Pata, Pietro, Ragonese, Francesco, Lettina, Gabriele, Mancuso, Teresa, Coppolino, Aldo, Piatti, Pier Marco, Monti, Lucilla, Stuccillo, Michela, Lucotti, Pietro, Setola, Manuela, Crippa, Giulia Valentina, Loi, Cinzia, Oldani, Matteo, Bottalico, Maria Luisa, Pellegata, Beatrice, Bonomo, Matteo, Menicatti, Laura Silvia Maria, Resi, Veronica, Bertuzzi, Federico, Disoteo, Eugenia Olga, Pizzi, Gianluigi, Rivellese, Angela Albarosa, Annuzzi, Giovanni, Capaldo, Brunella, Nappo, Rossella, Auciello, Stefania Michela, Turco, Anna Amelia, Costagliola, Lucia, Corte, Giuseppina Della, Vallefuoco, Pasquale, Nappi, Francesca, Vitale, Marilena, Cocozza, Sara, Ciano, Ornella, Massimino, Elena, Garofalo, Nadia, Avogaro, Angelo, Guarneri, Gabriella, Fedele, Domenico, Sartor, Giovanni, Chilelli, Nino Cristiano, Burlina, Silvia, Bonsembiante, Barbara, Galluzzo, Aldo, Torregrossa, Vittoria, Mancastroppa, Giovanni, Arsenio, Leone, Cioni, Federico, Caronna, Silvana, Papi, Matteo, Babini, Massimiliano, Santeusanio, Fausto, Calagreti, Gioia, Timi, Alessia, Tantucci, Alice, Marino, Cecilia, Ginestra, Federica, Di Biagio, Rosamaria, Taraborelli, Merilda, Miccoli, Roberto, Bianchi, Cristina, Garofolo, Monia, Politi, Konstantina Savina, Penno, Giuseppe, Livraga, Stefania, Calzoni, Fabio, Mancastroppa, Giovanni Luigi Francesco, Corsini, Elisa, Tedeschi, Anna, Gaglianã², Maria Sole, Ippolito, Giulio, Salutini, Elisabetta, Cervellino, Francesco, Natale, Maria, Salvatore, Vita, Zampino, Armando, Sinisi, Rosa, Arcangeli, Adolfo, Zogheri, Alessia, Guizzotti, Sandra, Longo, Rossella, Pellicano, Francesca, Scolozzi, Patrizia, Termine, Simona, Luberto, Alessandra, Ballardini, Giorgio, Trojani, Cristina, Mazzuca, Paolo, Bruglia, Matteo, Ciamei, Monica, Genghini, Silvia, Zannoni, Chiara, Vitale, Martina, Rangel, Graziela, Salvi, Laura, Zappaterreno, Alessandra, Cordone, Samantha, Simonelli, Paola, Meggiorini, Marilla, Frasheri, Aurora, Di Pippo, Clelia, Maglio, Cristina, Mazzitelli, Giulia, Rinaldi, Maria Elena, Galli, Angelica, Romano, Maria, D'Angelo, Paola, Suraci, Concetta, Bacci, Simonetta, Palena, Antonio Pio, Genovese, Stefano, Mancino, Monica, Rondinelli, Maurizio, Capone, Filippo, Calabretto, Elisabetta, Bulgheroni, Monica, Bucciarelli, Loredana, Ceccarelli, Elena, Fondelli, Cecilia, Santacroce, Clorinda, Guarino, Elisa, Nigi, Laura, Lalli, Carlo, Di Vizia, Giovanni, Scarponi, Maura, Montani, Valeria, Di Bernardino, Paolo, Romagni, Paola, Dolcetti, Katia, Forte, Elisa, Tamburo, Lucilla, Perin, Paolo Cavallo, Prinzis, Tania, Gruden, Gabriella, Bruno, Graziella, Zucco, Chiara, Perotta, Massimo, Marena, Saverio, Monsignore, Simona, Panero, Francesco, Ponzi, Fulvia, Bossi, Antonio Carlo, Carpinteri, Rita, Casagrande, Maria Linda, Coletti, Maria Francesca, Balini, Annalisa, Filopanti, Marcello, Madaschi, Sara, Pulcina, Anna, Grimaldi, Franco, Venturini, Giorgio, Agus, Sandra, Pagnutti, Stefania, Guidotti, Francesca, Cavarape, Alessandro, Cigolini, Massimo, Pichiri, Isabella, Brangani, Corinna, Fainelli, Giulia, Tomasetto, Elena, Zoppini, Giacomo, Galletti, Anna, Perrone, Dominica, Capra, Claudio, Bianchini, Francesca, Ceseri, Martina, Di Nardo, Barbara, Sasso, Elisa, Bartolomei, Barbara, Suliman, Irina, Fabbri, Gianna, Romano, Geremia, Maturo, Nicola, Nunziata, Giuseppe, Capobianco, Giuseppe, De Simone, Giuseppina, Villa, Valeria, Rota, Giuseppe, Pentangelo, Carmine, Carbonara, Ornella, Caiazzo, Gennaro, Cutolo, Michele, Sorrentino, Tommasina, Mastrilli, Valeria, Amelia, Umberto, Masi, Stefano, Corigliano, Gerardo, Gaeta, Iole, Armentano, Vincenzo, Calatola, Pasqualino, Capuano, Gelsomina, Angiulli, Bruno, Auletta, Pasquale, Petraroli, Ettore, Iodice, Cinzia E., Agrusta, Mariano, Vaccaro, O, Masulli, M, Nicolucci, A, Bonora, E, Del Prato, S, Maggioni, A, Rivellese, A, Squatrito, S, Giorda, C, Sesti, G, Mocarelli, P, Lucisano, G, Sacco, M, Signorini, S, Cappellini, F, Perriello, G, Babini, A, Lapolla, A, Gregori, G, Giordano, C, Corsi, L, Buzzetti, R, Clemente, G, Di Cianni, G, Iannarelli, R, Cordera, R, La Macchia, O, Zamboni, C, Scaranna, C, Boemi, M, Iovine, C, Lauro, D, Leotta, S, Dall'Aglio, E, Cannarsa, E, Tonutti, L, Pugliese, G, Bossi, A, Anichini, R, Dotta, F, Di Benedetto, A, Citro, G, Antenucci, D, Ricci, L, Giorgino, F, Santini, C, Gnasso, A, De Cosmo, S, Zavaroni, D, Vedovato, M, Consoli, A, Calabrese, M, di Bartolo, P, Fornengo, P, Riccardi, G, D'Angelo, F, Giansanti, R, Tanase, L, Lanari, L, Testa, I, Pancani, F, Ranchelli, A, Vagheggi, P, Scatona, A, Fontana, L, Laviola, L, Tarantino, L, Ippolito, C, Gigantelli, V, Manicone, M, Conte, E, Trevisan, R, Rota, R, Dodesini, A, Reggiani, G, Montesi, L, Mazzella, N, Forlani, G, Caselli, C, Di Luzio, R, Mazzotti, A, Aiello, A, Barrea, A, Musto, A, D'Amico, F, Sinagra, T, Longhitano, S, Trowpea, V, Sparti, M, Italia, S, Lisi, E, Grasso, G, Pezzino, V, Insalaco, F, Carallo, C, Scicchitano, C, De Franceschi, M, Calbucci, G, Ripani, R, Cuneo, G, Corsi, S, Romeo, F, Lesina, A, Comoglio, M, Bonetto, C, Robusto, A, Nada, E, Asprino, V, Cetraro, R, Impieri, M, Lucchese, G, Donnarumma, G, Tizio, B, Lenza, L, Paraggio, P, Tomasi, F, Dozio, N, Scalambra, E, Mannucci, E, Lamanna, C, Cignarelli, M, Macchia, O, Fariello, S, Sorrentino, M, Franzetti, I, Radin, R, Annunziata, F, Bonabello, L, Durante, A, Dolcino, M, Gallo, F, Mazzucchelli, C, Aleo, A, Melga, P, Briatore, L, Maggi, D, Storace, D, Cecoli, F, D'Ugo, E, Pupillo, M, Baldassarre, M, Salvati, F, Minnucci, A, De Luca, A, Zugaro, A, Santarelli, L, Bosco, A, Petrella, V, La Verghetta, G, D'Andrea, S, Giuliani, A, Polidoro, W, Sperandio, A, Sciarretta, F, Pezzella, A, Carlone, A, Potenziani, S, Venditti, C, Foffi, C, Carbone, S, Cipolloni, L, Moretti, C, Leto, G, Serra, R, Petrachi, F, Romano, I, Lacaria, E, Russo, L, Goretti, C, Sannino, C, Dolci, M, Bruselli, L, Mori, M, Baccetti, F, Del Freo, M, Cucinotta, D, Giunta, L, Ruffo, M, Cannizzaro, D, Pintaudi, B, Perrone, G, Pata, P, Ragonese, F, Lettina, G, Mancuso, T, Coppolino, A, Piatti, P, Monti, L, Stuccillo, M, Lucotti, P, Setola, M, Crippa, G, Loi, C, Oldani, M, Bottalico, M, Pellegata, B, Bonomo, M, Menicatti, L, Resi, V, Bertuzzi, F, Disoteo, E, Pizzi, G, Annuzzi, G, Capaldo, B, Nappo, R, Auciello, S, Turco, A, Costagliola, L, Corte, G, Vallefuoco, P, Nappi, F, Vitale, M, Cocozza, S, Ciano, O, Massimino, E, Garofalo, N, Avogaro, A, Guarneri, G, Fedele, D, Sartore, G, Chilelli, N, Burlina, S, Bonsembiante, B, Galluzzo, A, Torregrossa, V, Mancastroppa, G, Arsenio, L, Cioni, F, Caronna, S, Papi, M, Santeusanio, F, Calagreti, G, Timi, A, Tantucci, A, Marino, C, Ginestra, F, Di Biagio, R, Taraborelli, M, Miccoli, R, Bianchi, C, Garofolo, M, Politi, K, Penno, G, Livraga, S, Calzoni, F, Corsini, E, Tedeschi, A, Gagliano, M, Ippolito, G, Salutini, E, Cervellino, F, Natale, M, Salvatore, V, Zampino, A, Sinisi, R, Arcangeli, A, Zogheri, A, Guizzotti, S, Longo, R, Pellicano, F, Scolozzi, P, Termine, S, Luberto, A, Ballardini, G, Trojani, C, Mazzuca, P, Bruglia, M, Ciamei, M, Genghini, S, Zannoni, C, Rangel, G, Salvi, L, Zappaterreno, A, Cordone, S, Simonelli, P, Meggiorini, M, Frasheri, A, Di Pippo, C, Maglio, C, Mazzitelli, G, Rinaldi, M, Galli, A, Romano, M, D'Angelo, P, Suraci, C, Bacci, S, Palena, A, Genovese, S, Mancino, M, Rondinelli, M, Capone, F, Calabretto, E, Bulgheroni, M, Bucciarelli, L, Ceccarelli, E, Fondelli, C, Santacroce, C, Guarino, E, Nigi, L, Lalli, C, Di Vizia, G, Scarponi, M, Montani, V, Di Bernardino, P, Romagni, P, Dolcetti, K, Forte, E, Tamburo, L, Perin, P, Prinzis, T, Gruden, G, Bruno, G, Zucco, C, Perotta, M, Marena, S, Monsignore, S, Panero, F, Ponzi, F, Carpinteri, R, Casagrande, M, Coletti, M, Balini, A, Filopanti, M, Madaschi, S, Pulcina, A, Grimaldi, F, Venturini, G, Agus, S, Pagnutti, S, Guidotti, F, Cavarape, A, Cigolini, M, Pichiri, I, Brangani, C, Fainelli, G, Tomasetto, E, Zoppini, G, Galletti, A, Perrone, D, Capra, C, Bianchini, F, Ceseri, M, Di Nardo, B, Sasso, E, Bartolomei, B, Suliman, I, Fabbri, G, Romano, G, Maturo, N, Nunziata, G, Capobianco, G, De Simone, G, Villa, V, Rota, G, Pentangelo, C, Carbonara, O, Caiazzo, G, Cutolo, M, Sorrentino, T, Mastrilli, V, Amelia, U, Masi, S, Corigliano, G, Gaeta, I, Armentano, V, Calatola, P, Capuano, G, Angiulli, B, Auletta, P, Petraroli, E, Iodice, C, Agrusta, M, di Bartolo, Paolo, Polidoro, w Lorella, Sartore, Giovanni, and Gaglianò, Maria Sole
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Male ,Diabetes and Metabolism, ipoglycemic drugs, cardiovascualr event ,Settore MED/09 - Medicina Interna ,endocrine system diseases ,IMPACT ,pioglitazone versus sulfonylureas ,Endocrinology, Diabetes and Metabolism ,GLIMEPIRIDE ,Diabetes, cardiovascular events, metformin, pioglitazone, sulphonylureas ,Type 2 diabetes ,030204 cardiovascular system & hematology ,Internal Medicine ,Endocrinology ,law.invention ,Settore MED/13 - Endocrinologia ,Glibenclamide ,0302 clinical medicine ,Randomized controlled trial ,law ,GLYCEMIC CONTROL ,Gliclazide ,Internal medicine ,diabetes and metabolism ,RISK ,education.field_of_study ,diabetes ,Incidence ,endocrinology, diabetes and metabolism ,endocrinology ,Middle Aged ,INSULIN ,Metformin ,Treatment Outcome ,Editorial ,sulphonylureas ,Cardiovascular Diseases ,Combination ,Drug Therapy, Combination ,Female ,Type 2 ,medicine.drug ,medicine.medical_specialty ,Population ,030209 endocrinology & metabolism ,Aged ,Diabetes Mellitus, Type 2 ,Humans ,Hypoglycemic Agents ,Pioglitazone ,Sulfonylurea Compounds ,Thiazolidinediones ,Cardiovascular events ,03 medical and health sciences ,GLUCOSE-LOWERING DRUGS ,Drug Therapy ,Diabetes Mellitus ,medicine ,sulfonylureas ,education ,TOSCA.IT ,business.industry ,MORTALITY ,nutritional and metabolic diseases ,Insulin resistance ,medicine.disease ,Surgery ,Glimepiride ,business ,FOLLOW-UP - Abstract
Background The best treatment option for patients with type 2 diabetes in whom treatment with metformin alone fails to achieve adequate glycaemic control is debated. We aimed to compare the long-term effects of pioglitazone versus sulfonylureas, given in addition to metformin, on cardiovascular events in patients with type 2 diabetes. Methods TOSCA.IT was a multicentre, randomised, pragmatic clinical trial, in which patients aged 50â75 years with type 2 diabetes inadequately controlled with metformin monotherapy (2â3 g per day) were recruited from 57 diabetes clinics in Italy. Patients were randomly assigned (1:1), by permuted blocks randomisation (block size 10), stratified by site and previous cardiovascular events, to add-on pioglitazone (15â45 mg) or a sulfonylurea (5â15 mg glibenclamide, 2â6 mg glimepiride, or 30â120 mg gliclazide, in accordance with local practice). The trial was unblinded, but event adjudicators were unaware of treatment assignment. The primary outcome, assessed with a Cox proportional-hazards model, was a composite of first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, or urgent coronary revascularisation, assessed in the modified intention-to-treat population (all randomly assigned participants with baseline data available and without any protocol violations in relation to inclusion or exclusion criteria). This study is registered with ClinicalTrials.gov, number NCT00700856. Findings Between Sept 18, 2008, and Jan 15, 2014, 3028 patients were randomly assigned and included in the analyses. 1535 were assigned to pioglitazone and 1493 to sulfonylureas (glibenclamide 24 [2%], glimepiride 723 [48%], gliclazide 745 [50%]). At baseline, 335 (11%) participants had a previous cardiovascular event. The study was stopped early on the basis of a futility analysis after a median follow-up of 57·3 months. The primary outcome occurred in 105 patients (1·5 per 100 person-years) who were given pioglitazone and 108 (1·5 per 100 person-years) who were given sulfonylureas (hazard ratio 0·96, 95% CI 0·74â1·26, p=0·79). Fewer patients had hypoglycaemias in the pioglitazone group than in the sulfonylureas group (148 [10%] vs 508 [34%], p
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- 2017
48. 2009 SIPREC consensus document executive summary: Cardiovascular prevention in subjects with impaired fasting glucose or impaired glucose tolerance
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Maria Grazia Modena, Bruno Trimarco, Diego Vanuzzo, Paolo Cavallo Perin, Paolo Verdecchia, Claudio Borghi, Stefano Del Prato, Massimo Chiariello, Enzo Manzato, Roberto Miccoli, Gabriele Riccardi, Augusto Zaninelli, Massimo Volpe, Giorgio Sesti, Antonio Tiengo, Volpe, Massimo, Borghi, Claudio, Cavallo Perin, Paolo, Chiariello, Massimo, Manzato, Enzo, Miccoli, Roberto, Modena, Maria G., Riccardi, Gabriele, Sesti, Giorgio, Tiengo, Antonio, Trimarco, Bruno, Vanuzzo, Diego, Verdecchia, Paolo, Zaninelli, Augusto, and Del Prato, Stefano
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medicine.medical_specialty ,hypertension ,Population ,metabolic syndrome ,Impaired glucose tolerance ,Diabetes mellitus ,insulin resistance ,Epidemiology ,medicine ,Internal Medicine ,Intensive care medicine ,education ,Socioeconomic status ,education.field_of_study ,Executive summary ,business.industry ,diabetes mellitu ,cardiovascular prevention ,medicine.disease ,Impaired fasting glucose ,impaired glucose tolerance ,abnormal glucose regulation ,diabetes mellitus ,Medical emergency ,Metabolic syndrome ,business ,Cardiology and Cardiovascular Medicine - Abstract
Cardiovascular diseases still represent the leading cause of mortality and hospitalization, worldwide. As a consequence of the marked demographic changes observed in the general population, the improved survival rate after an acute cardiovascular event and the progressive rise of costs (mostly due to technological and pharmacological innovations), the estimated burden of cardiovascular diseases will be soon become insurmountable for national healthcare systems. In this view, an integrated approach aimed at improving strategies for cardiovascular disease prevention and, thus, limiting the negative outcomes, would probably be successful. Such an approach may not only achieve long-term benefits, but even significant advantages in the short to medium term, mostly in asymptomatic high-risk individuals. Indeed, this latter population of asymptomatic high-risk individuals would mostly benefit from extensive application and improvement of strategies for cardiovascular disease prevention with a favourable cost-benefit ratio. The Italian Society for Cardiovascular Disease Prevention — Societa Italiana per la Prevenzione Cardiovascolare (SIPREC) — has recognized this strategic aim, focusing a significant part of its institutional actions on the effort for providing educational supports and consensus documents, which represent an overview of the scientific knowledge and personal clinical expertise by national and international key opinion leaders. Expert committees periodically generate ‘state-of-the-art’ documents on specific scientific topics with relevant socioeconomic implications and large clinical impact. The present article is dedicated to healthcare professionals, is based on the available evidence, and provides information on diagnostic algorithms and therapeutic options on abnormal glucose regulation (or dysglycaemia). The relationship between abnormalities in glucose metabolism and cardiovascular complications represents an important and relatively early target for cardiovascular disease prevention. SIPREC identified, even in this clinical setting, a group of scientific experts in order to form a multidisciplinary ‘task force’. This group has been asked to explain in a short, simple and effective fashion the epidemiological impact and the pathophysiological nature of the problem, its clinical features, potential diagnostic algorithms and therapeutic options, and its influence on the clinical practice of both specialist physicians and general practitioners. This work provides the background for discussing novel future strategies for cardiovascular prevention. It is also aimed at highlighting the importance of an emerging marker of cardiovascular risk, which is often not recognized and underestimated.
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- 2010
49. Cardiovascular prevention in subjects with impaired fasting glucose or impaired glucose tolerance
- Author
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Volpe, M, Borghi, C, Cavallo Perin, P, Chiariello, M, Manzato, E, Miccoli, R, Modena, Riccardi, G, Sesti, G, Tiengo, A, Trimarco, B, Vanuzzo, D, Verdecchia, P, Zaninelli, A, Del Prato, S, Volpe M, Borghi C, Cavallo Perin P, Chiariello M, manzato E, Miccoli R, Modena MG, Riccardi G, Sesti G, Tiengo A, Trimarco B, vannuzzo D, Verdecchia P, Zaninelli A, Del Prato S., Volpe, Massimo, Borghi, Claudio, Cavallo Perin, Paolo, Chiariello, Massimo, Manzato, Enzo, Miccoli, Roberto, Modena, Maria Grazia, Riccardi, Gabriele, Sesti, Giorgio, Tiengo, Antonio, Trimarco, Bruno, Vanuzzo, Diego, Verdecchia, Paolo, Zaninelli, Augusto, and Del Prato, Stefano
- Subjects
medicine.medical_specialty ,hypertension ,Population ,metabolic syndrome ,Impaired glucose tolerance ,impaired glucose tolerance insulin resistance abnormal glucose regulation metabolic syndrome diabetes mellitus hypertension cardiovascular prevention ,insulin resistance ,Epidemiology ,medicine ,Internal Medicine ,Clinical significance ,abnormal glucose regulation ,cardiovascular prevention ,diabetes mellitus ,impaired glucose tolerance ,Intensive care medicine ,education ,Socioeconomic status ,education.field_of_study ,business.industry ,diabetes mellitu ,Type 2 Diabetes Mellitus ,medicine.disease ,Impaired fasting glucose ,Medical emergency ,Metabolic syndrome ,business ,Cardiology and Cardiovascular Medicine - Abstract
Cardiovascular diseases still represent the leading cause of mortality and hospitalization, particularly in Western countries. As a consequence of the marked changes observed on the demographic characteristics of the general population, the improved survival rate after an acute cardiovascular event, and the progressive rise of costs (mostly due to technological and pharmacological innovations), the estimated burden of cardiovascular diseases will soon become insurmountable for national healthcare systems. In this view, an integrated approach aimed at improving strategies for cardiovascular disease prevention and, thus, limiting the negative outcomes, would probably be successful. Such an approach may not only achieve long-term benefits, but even significant advantages in the short to medium term, mostly in asymptomatic high-risk individuals. Indeed, this latter population of asymptomatic high-risk individuals would mostly benefit from extensive application and improvement of strategies for cardiovascular disease prevention with a favourable cost-benefit ratio. The Italian Society for Cardiovascular Disease Prevention — Società Italiana per la Prevenzione Cardiovascolare (SIPREC) — has recognized this strategic aim, focusing a vast majority of its institutional action on the effort for providing educational supports and consensus documents, which represent an overview of the scientific knowledge and personal clinical expertise by national and international key opinion leaders. Expert committees periodically generate ‘state-of-the-art’ documents on specific scientific topics with relevant socioeconomic implications and large clinical impact. The present article is dedicated to healthcare professionals, and is based on the available evidence, and provides useful information on diagnostic algorithms and therapeutic options. In 2006, the SIPREC Scientific Committee promoted a consensus document on the metabolic syndrome,[1] which is still widely used, frequently cited and updated, from which originated a broad educational programme throughout the Italian territory. This programme has certainly contributed to improving knowledge of a widespread clinical condition, such as the metabolic syndrome, which SIPREC interpreted not only as a theoretical pathophysiological concept or a nosographic entity, but rather as a real clinical tool for identifying and ‘intercepting’ those asymptomatic individuals at risk of cardiovascular events, before the estimated level of risk becomes high. This new article may be viewed in the same strategic line. The relationship between abnormalities in blood glucose metabolism (or dysglycaemia) and cardiovascular complications represents another important and relatively early target for cardiovascular disease prevention. SIPREC Scientific Committee identified even in this clinical setting an excellent group of scientific experts, in order to collect a multidisciplinary ‘task force’. This group has been asked to explain in a short, simple and effective fashion the epidemiological impact and the pathophysiological nature of the problem, its clinical features, potential diagnostic algorithms and therapeutic options, and its influence on the clinical practice of both specialist physicians and general practitioners. The work of this Task Force, which is reported in this article, is primarily a baseline for discussing novel future strategies for cardiovascular prevention. Also, this article is aimed at highlighting the importance of an emerging marker of cardiovascular risk, which is little recognized and often undervalued. Dysglycaemia, in turn, has a clinical significance, which is at least, in part, comparable with that of type 2 diabetes mellitus, both in terms of epidemiological prevalence and of long-term cardiovascular prognosis.
- Published
- 2010
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