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1. Antihistamines improve cardiovascular manifestations and other symptoms of long-COVID attributed to mast cell activation

Author

Fabrizio Salvucci, Roberto Codella, Adriana Coppola, Irene Zacchei, Gabriella Grassi, Maria Luisa Anti, Nicolita Nitisoara, Livio Luzi, and Carmine Gazzaruso

Subjects
long-COVID, histamine receptors, mast cell activation, antihistamines, treatment, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

IntroductionLong-COVID is a broadly defined condition and there are no effective therapies. Cardiovascular manifestations of long-COVID include high heart rate, postural tachycardia, and palpitations. Previous studies have suggested that mast cell activation (MCA) may play a role in the pathophysiology of long-COVID, including in the mechanisms of its cardiovascular manifestations. The present study aimed to evaluate the effectiveness of a treatment with blockers of histamine receptors in patients with long-COVID who did not respond to other therapies.MethodsIn all, 14 patients (F/M = 9/5; 49.5 ± 11.5 years) and 13 controls (F/M = 8/5; 47.3 ± 8.0 years) with long-COVID symptoms attributed to MCA were evaluated. Patients were treated with fexofenadine (180 mg/day) and famotidine (40 mg/day). Fatigue, brain fog, abdominal disorders, and increased heart rate were evaluated in treated and untreated patients at baseline and 20 days later.ResultsLong-COVID symptoms disappeared completely in 29% of treated patients. There was a significant improvement in each of the considered symptoms (improved or disappeared) in all treated patients, and the improvement grade was significantly greater in treated patients compared to controls. No significant differences in the outcomes were observed in the controls.ConclusionsOur data confirm that histamine receptors blockade may be an effective target to successfully treat long-COVID. Our finding supports the underlying role of MCA in the pathophysiology of long-COVID.

Published
2023
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2. Dapagliflozin acutely improves kidney function in type 2 diabetes mellitus. The PRECARE study

Author

Elisa Lazzaroni, Maria Elena Lunati, Laura Montefusco, Ida Pastore, Enrica Chebat, Vincenzo Cimino, Paola Silvia Morpurgo, Milena Muratori, Laura Plebani, Andrea Bolla, Antonio Rossi, Luciana Vallone, Alessandra Gandolfi, Camilla Tinari, Francesca D’Addio, Moufida Ben Nasr, Cristian Loretelli, Cristiana Scaranna, Rosalia Bellante, Roberto Manfrini, Fabrizio Muratori, Ivano Franzetti, Emanuela Orsi, Carmine Gazzaruso, Renata Ghelardi, Paolo Desenzani, Stefano Genovese, Angela Girelli, Franco Folli, Cesare Berra, and Paolo Fiorina

Subjects
Dapagliflozin, Hb1Ac, Albuminuria, Cardio-vascular risk, Therapeutics. Pharmacology, RM1-950
Abstract

Dapagliflozin has been demonstrated to improve glycemic control, blood pressure, and body weight in type 2 diabetes mellitus (T2D); indeed, it can also reduce the risk of progression to renal failure, of hospitalization for heart failure and of cardiovascular death. We aim to investigate the acute effect of Dapagliflozin on kidney function in the common clinical practice in T2D. This is a study including 1402 patients with T2D recruited from 11 centers in Lombardia, Italy, who were evaluated at baseline and after 6 months of treatment with Dapagliflozin 10 mg per day. The primary outcome of the study was the change in HbA1c, while the secondary outcomes were modification of weight, BMI, systolic and diastolic pressure, creatinine, eGFR and albuminuria status. After 24 weeks of treatment with Dapagliflozin, a reduction in Hb1Ac was observed (−0.6 ± 1.8%) as well as in BMI (−1.5 ± 5.2 kg/m2). Statistically significant changes were also found for systolic and diastolic blood pressure, cholesterol and triglycerides. Interestingly, a statistically significant acute improvement of kidney function was evident. Our analyses confirm the beneficial effects of dapagliflozin after 6 months of therapy, with improvements of glycemic and lipid profiles, blood pressure, BMI. Finally, an acute positive effect on albuminuria and KIDGO classes was observed during a 6 months treatment with dapagliflozin in patients with T2D.

Published
2022
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3. Effects of a Portfolio-Mediterranean Diet and a Mediterranean Diet with or without a Sterol-Enriched Yogurt in Individuals with Hypercholesterolemia

Author

Yvelise Ferro, Elisa Mazza, Mariantonietta Salvati, Emma Santariga, Salvatore Giampà, Rocco Spagnuolo, Patrizia Doldo, Roberta Pujia, Adriana Coppola, Carmine Gazzaruso, Arturo Pujia, and Tiziana Montalcini

Subjects
cholesterol, ldl, diet, mediterranean, yogurt, anticholesteremic agents, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Background A growing number of functional foods have been proposed to reduce cholesterol levels and the Portfolio Diet, which includes a combination of plant sterols, fibres, nuts, and soy protein, reduces low density lipoprotein cholesterol (LDL-C) from 20% to 30% in individuals with hyperlipidaemia. In this pilot study, the aim was to investigate whether a Mediterranean Diet incorporating a new and simple combination of cholesterol-lowering foods, excluding soy and nuts (namely the Portfolio-Mediterranean Diet), would reduce LDL-C levels, in the short-term, better than a Mediterranean Diet plus a sterol-enriched yogurt or a Mediterranean Diet alone. Methods We retrospectively evaluated 24 individuals on a Portfolio-Mediterranean Diet and 48 matched individuals on a Mediterranean Diet with or without a sterol-enriched yogurt (24 each groups) as controls. Results At follow-up (after 48±12 days), we observed an LDL reduction of 21±4, 23±4, and 44±4 mg/dL in the Mediterranean Diet alone, Mediterranean Diet plus yogurt and Portfolio-Mediterranean Diet respectively (P

Published
2020
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4. The Effects of COVID-19 on the Eating Habits of Children and Adolescents in Italy: A Pilot Survey Study

Author

Roberta Pujia, Yvelise Ferro, Samantha Maurotti, Janin Khoory, Carmine Gazzaruso, Arturo Pujia, Tiziana Montalcini, and Elisa Mazza

Subjects
COVID-19, eating habits, body weight gain, children, adolescents, obesity, Nutrition. Foods and food supply, TX341-641
Abstract

Nutrition during childhood and adolescence is very important for growth and can have long-term health implications. The COVID-19 lockdown caused significant changes in everyday life, including in children and adolescents. This study evaluated the effects of the first COVID-19 lockdown on eating habits and body weight in children and adolescents. An online cross-sectional survey was carried out among the parents of children (5–9 years) and adolescents (10–14 years) living in Italy. The online self-administered questionnaire included demographic and anthropometric data (reported weight and height) weight and dietary habit changes during the COVID-19 lockdown in Italy (March to June 2020). A total of 439 participants were included. We found a change in eating habits with an increase in consumption of sweet packaged snacks (34%) and processed meat (25%), as well as bread, pizza and bakery products (47%). We also found an increase in vegetable, fresh fruit and legume intake (19%), and a reduction in sweet beverage and candy intake. A total of 59.7% of the participants reported body weight gain, with adolescents gaining more than children (67% vs. 55%, p = 0.010, respectively). In children, body weight gain was associated with a change in body height and increased consumption of dairy products and sweet packaged snacks, while in adolescents it was associated with an increased intake of comfort foods and processed meat. Our data highlighted the need to carefully monitor eating behaviors to avoid the establishment of unhealthy eating habits and prevent obesity in children and adolescents during periods of self-isolation.

Published
2021
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5. Evaluation of circulating sRAGE in osteoporosis according to BMI, adipokines and fracture risk: a pilot observational study

Author

Emanuela Galliera, Monica Gioia Marazzi, Carmine Gazzaruso, Pietro Gallotti, Adriana Coppola, Tiziana Montalcini, Arturo Pujia, and Massimiliano M. Corsi Romanelli

Subjects
Circulating RAGE, Glycation end products, Osteoporosis, Fracture risk, Immunologic diseases. Allergy, RC581-607, Geriatrics, RC952-954.6
Abstract

Abstract Background Osteoporosis is a systemic metabolic disease based on age-dependent imbalance between the rates of bone formation and bone resorption. Recent studies on the pathogenesis of this disease identified that bone remodelling impairment, at the base of osteoporotic bone fragility, could be related to protein glycation, in association to oxidative stress. The glycation reactions lead to the generation of glycation end products (AGEs) which, in turn, accumulates into bone, where they binds to the receptor for AGE (RAGE). The aim of this study is to investigate the potential role of circulating sRAGE in osteoporosis, in particular evaluating the correlation of sRAGE with the fracture risk, in association with bone mineral density, the fracture risk marker FGF23, and lipid metabolism. Results Circulating level of soluble RAGE correlate with osteopenia and osteoporosis level. Serum sRAGE resulted clearly associated on the one hand to bone fragility and, on the other hand, with BMI and leptin. sRAGE is particularly informative because serum sRAGE is able to provide, as a single marker, information about both the aspects of osteoporotic disease, represented by bone fragility and lipid metabolism. Conclusions The measure serum level of sRAGE could have a potential diagnostic role in the monitoring of osteoporosis progression, in particular in the evaluation of fracture risk, starting from the prevention and screening stage, to the osteopenic level to osteoporosis.

Published
2017
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6. Lipid Oxidation Assessed by Indirect Calorimetry Predicts Metabolic Syndrome and Type 2 Diabetes

Author

Arturo Pujia, Elisa Mazza, Yvelise Ferro, Carmine Gazzaruso, Adriana Coppola, Patrizia Doldo, Rosa Daniela Grembiale, Roberta Pujia, Stefano Romeo, and Tiziana Montalcini

Subjects
lipid oxidation, metabolic syndrome, diabetes, respiratory quotient, calorimetry, Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

Purpose: Diabetes has been linked to an impaired ability to oxidize fatty acids. Fat oxidation can be assessed clinically by a respiratory quotient measurement during fasting. We hypothesized that a respiratory quotient might predict metabolic syndrome and type 2 diabetes onset.Methods: In this longitudinal study we used an existing database of 233 individuals who had complete nutritional and biochemical data at baseline and after 12-month follow-up. All participants underwent an indirect calorimetry to measure the respiratory quotient. We excluded participants with diabetes, metabolic syndrome, chronic diseases, and those who had changed food habits in the previous 3 months. Only 88 subjects met the inclusion criteria.Results: Two individuals developed type 2 diabetes and 10 metabolic syndrome after 1 year. Participants in the high respiratory quotient group (>0.91) had a higher incidence of metabolic syndrome/diabetes than those in the low quotient group (25 vs. 8% p = 0.04). In this group, mean basal respiratory quotient was 0.97 ± 0.04. In the high respiratory quotient group, Kaplan-Meier curves showed a greater probability of having metabolic syndrome/diabetes than those in the low respiratoryquotient group (log Rank χ2-test = 8.44; p = 0.004). A multivariable Cox proportional hazards model demonstrated that energy expenditure and weight increase did not predict metabolic syndrome/diabetes [HR (95% CI) = 1 (0.996–1.005), p = 0.86 and 3.9 (0.407–38.061), p = 0.23, respectively).Conclusions: A greater probability of metabolic syndrome/diabetes was found in individuals with a basal respiratory quotient of >0.91 than in those with a respiratoryquotient of ≤ 0.91 after 1 year. In the short-term anthropometric measurements and their variation overtime were not correlated with metabolic syndrome/diabetes.

Published
2019
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7. Nutrients Utilization in Obese Individuals with and without Hypertriglyceridemia

Author

Tiziana Montalcini, Theodora Lamprinoudi, Attilio Morrone, Elisa Mazza, Carmine Gazzaruso, Stefano Romeo, and Arturo Pujia

Subjects
triglyceride, fatty acid, obesity, fatty acid oxidation, lipids, nutrients, indirect calorimetry, carboidrates, respiratory quotient, Nutrition. Foods and food supply, TX341-641
Abstract

Background: Low fat utilization is linked to weight gain and to the presence of certain atherosclerosis markers. It is not clear whether the presence of hyperlipidemia can further affect nutrients utilization. The main objective of this study was to investigate the fasting fuel utilization of obese subjects suffering from hypertriglyceridemia, and to compare it with that of individuals that are solely obese. Method: We recruited 20 obese individuals with hypertriglyceridemia and 20 matched individuals not affected by hypertriglyceridemia. The fuel utilization (respiratory quotient) was measured by respiratory gas exchange, by Indirect Calorimetry. Results: There was a significant difference in fuel utilization and HDL-cholesterol between cases and controls (respiratory quotient 0.89 ± 0.07 vs. 0.84 ± 0.06; p = 0.020 respectively). The univariate and multivariate linear regression analysis confirmed that hypertrygliceridemia was positively correlated to the respiratory quotient (p = 0.035). Conclusion: obese subjects with hypertriglyceridemia had a higher respiratory quotient in comparison to unaffected subjects. This could suggest a limitation in the beta-oxidation mechanisms; this could actually imply that fatty acids may be redirected from oxidation to reesterification into triglycerides. The study could suggest the presence of different mechanisms unrelated to obesity and also a potential new therapeutic target for hypertriglyceridemia management.

Published
2014
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8. Soluble RAGE Plasma Levels in Patients with Coronary Artery Disease and Peripheral Artery Disease

Author

Colomba Falcone, Sara Bozzini, Luigina Guasti, Angela D’Angelo, Anna Clizia Capettini, Edoardo Maria Paganini, Rossana Falcone, Roberto Moia, Carmine Gazzaruso, and Gabriele Pelissero

Subjects
Technology, Medicine, Science
Abstract

The objective of the present study was define in a relatively large patient population with coronary artery disease (CAD) whether the concomitant presence of peripheral artery disease (PAD), which is known to convey additional cardiovascular risk, was associated with different circulating levels of sRAGE with respect to CAD alone and control subjects. Clinical and laboratory parameters including the ankle brachial index (ABI) and sRAGE (enzyme-linked immunosorbent assay kit) were investigated in 544 patients with angiographically documented CAD and 328 control subjects. 213/554 CAD patients (39%) showed an ABI

Published
2013
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9. Individuals with Metabolically Healthy Overweight/Obesity Have Higher Fat Utilization than Metabolically Unhealthy Individuals

Author

Arturo Pujia, Carmine Gazzaruso, Yvelise Ferro, Elisa Mazza, Samantha Maurotti, Cristina Russo, Veronica Lazzaro, Stefano Romeo, and Tiziana Montalcini

Subjects
obesity, nutrition assessment, fat utilization, Metabolic Syndrome, metabolically unhealthy Obesity, diabetes, Nutrition. Foods and food supply, TX341-641
Abstract

The mechanisms underlying the change in phenotype from metabolically healthy to metabolically unhealthy obesity are still unclear. The aim of this study is to investigate whether a difference in fasting fat utilization exists between overweight/obese individuals with a favorable cardiovascular risk profile and those with Metabolic Syndrome and Type 2 diabetes. Furthermore, we sought to explore whether there is an association between fasting fat utilization and insulin resistance. In this cross-sectional study, 172 overweight/obese individuals underwent a nutritional assessment. Those with fasting glucose ≥126 mg/dL or antidiabetic treatment were considered to be diabetics. If at least three of the NCEP criteria were present, they had Metabolic Syndrome, while those with less criteria were considered to be healthy overweight/obese. An indirect calorimetry was performed to estimate Respiratory Quotient, an index of nutrient utilization. A lower Respiratory Quotient (i.e., higher fat utilization) was found in healthy overweight/obese individuals than in those with Metabolic Syndrome and Type 2 diabetes (0.85 ± 0.05; 0.87 ± 0.06; 0.88 ± 0.05 respectively, p = 0.04). The univariate and multivariable analysis showed a positive association between the Respiratory Quotient and HOMA-IR (slope in statistic (B) = 0.004; β = 0.42; p = 0.005; 95% Confidence interval = 0.001–0.006). In this study, we find, for the first time, that the fasting Respiratory Quotient is significantly lower (fat utilization is higher) in individuals who are metabolically healthy overweight/obese than in those with metabolically unhealthy obesity. In addition, we demonstrated the association between fat utilization and HOMA-IR, an insulin resistance index.

Published
2016
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10. Association of erectile dysfunction with diabetic foot and its outcomes in type 2 diabetic men

Author

Adriana Coppola, Pietro Gallotti, Tiziana Montalcini, Ileana Terruzzi, Arturo Pujia, Livio Luzi, and Carmine Gazzaruso

Subjects
Endocrinology, Diabetes and Metabolism, General Medicine
Abstract

Erectile dysfunction (ED) and diabetic foot (DF) are common complications in patients with diabetes. However, the relationship between ED and DF has been little studied. In particular, no study has evaluated whether ED is associated with the outcomes of DF. The aim of this retrospective cohort study was to investigate whether ED is a predictor of the outcomes of DF in a large population of men with DF.Three hundred and twenty-six consecutive men with type 2 diabetes and a recent and single DF ulcer were recruited and followed up for 41.7 ± 22.7 months.Among men with DF, 56.1% had ED (ED group) and 43.9% did not (NO ED group). Wound healing rate was significantly higher in the NO ED than in the ED group (90.2 versus 73.3%; p = 0.0001). Minor amputation rate (13.7 versus 4.8%; p = 0.007) and mortality (25.7 versus 0.7%; p 0.001) were significantly greater in the ED than in the NO ED group. Among 263 patients with healed ulcers, recurrence rate was significantly higher in the ED than in the NO ED group (51.5 versus 26.3%; p 0.001). Multivariate analysis showed that the absence of ED was associated with wound healing (OR: 0.459; 95% CI: 0.213-0.993; p = 0.048), while the presence of ED predicted mortality (OR: 22.644; 95% CI: 2.976-34.271; p = 0.002) and DF recurrence (OR: 3.498; 95% CI: 1.882-6.499; p 0.001).Our data show that among men with DF the prevalence of ED is very high. Moreover, ED may be a strong predictor of wound healing, mortality, and ulcer recurrence.

Published
2022

11. Impact of microvascular complications on the outcomes of diabetic foot in type 2 diabetic patients with documented peripheral artery disease

Author

Carmine Gazzaruso, Tiziana Montalcini, Pietro Gallotti, Anna Ferrulli, Cesare Massa Saluzzo, Arturo Pujia, Livio Luzi, and Adriana Coppola

Subjects
Endocrinology, Microvascular complications, Peripheral artery disease, Endocrinology, Diabetes and Metabolism, Retinopathy, Type 2 diabetes, Vascular diabetic foot, Settore MED/13 - Endocrinologia
Abstract

Microvascular disease (MVD) is associated with amputation linked to peripheral artery disease (PAD) in the general population. No study evaluated the impact of diabetic microvascular complications on the outcomes of vascular diabetic foot ulcers (DFU). The aim of the study was to investigate whether retinopathy, nephropathy, and polyneuropathy can predict the outcomes of DFU in type 2 diabetic patients with PAD.Three hundred and thirty-one consecutive patients with vascular DFU were enrolled and followed up for 44.1 ± 23.9 months.The prevalence of retinopathy was significantly higher in subjects with ulcer persistence (45.2%; p 0.01), minor amputation (48.9%; p 0.001), and major amputation (57.9%; p 0.001) than in healed patients (23.3%), and in non-survivors than in survivors (64.9 versus 20.5%; p 0.001). The prevalence of nephropathy was significantly greater in subjects with ulcer persistence (83.9%; p 0.01), minor amputation (86.7%; p 0.001), and major amputation (94.7%; p 0.001) than in those with healed DFU (64.4%), and in non-survivors than in survivors (88.3 versus 65.7%; p 0.001). The prevalence of polyneuropathy was significantly higher in non-survivors than in survivors (76.6 versus 61.0%; p = 0.012). Multivariate analysis showed that absence of retinopathy (OR: 0.451; 95% CI: 0.250-0.815; p 0.001) and nephropathy (OR: 0.450; 95% CI: 0.212-0.951; p = 0.036) were independently associated with healing. Moreover, retinopathy was a predictor both of minor amputation (OR: 2.291; 95% CI: 1.061-4.949; p = 0.034) and mortality (OR: 5.274; 95% CI: 2.524-11.020; p 0.001). Polyneuropathy never entered the regression model.Diabetic microvascular complications, in particular retinopathy, may predict the outcomes of vascular DFU. Longitudinal studies should confirm this finding.

Published
2022

13. Lupus anticoagulant and mortality in patients hospitalized for COVID-19

Author

Luigi Bevilacqua, Giuseppe Mariani, Teodoro Altavilla, Carolina Ravetto, Laura Malinverni, Pietro Gallotti, Maria Cerrone, Elena Tondelli, Adriana Coppola, Vittorio Sala, and Carmine Gazzaruso

Subjects
Male, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, 030204 cardiovascular system & hematology, Risk Assessment, Article, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, death, Internal medicine, Intensive care, medicine, Humans, Hospital Mortality, Obesity, 030212 general & internal medicine, thrombosis, Aged, Retrospective Studies, Aged, 80 and over, Mechanical ventilation, Lupus anticoagulant, Hematology, biology, business.industry, COVID-19, Middle Aged, medicine.disease, Respiration, Artificial, Troponin, Thrombosis, Hospitalization, Oxygen, lupus anticoagulant, Lupus Coagulation Inhibitor, biology.protein, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers
Abstract

Coronavirus disease 2019 (COVID-19) is characterized by a procoagulant state that can lead to fatal thromboembolic events. Several studies have documented a high prevalence of lupus anticoagulant that may at least partially explain the procoagulant profile of COVID-19. However, the association between lupus anticoagulant and thrombotic complications in COVID-19 is controversial and no study has specifically evaluated the impact of lupus anticoagulant on mortality. The aim of our study was to investigate the association between lupus anticoagulant and mortality in a large group of 192 consecutive patients hospitalized for COVID-19. Lupus anticoagulant was found in 95 patients (49.5%). No difference in the percentage of patients with lupus anticoagulant was observed between 130 survivors and 62 non-survivors (47.7 versus 53,2%; p = 0.4745). When the combined outcome of death or need for mechanical ventilation in survivors was taken into account, the difference in the prevalence of patients with lupus anticoagulant between the patients with the combined outcome (n = 76) and survivors who did not require mechanical ventilation (n = 116) was not significant (52.6% versus 47.4%; p = 0.4806). In multivariate analysis predictors of mortality or need for mechanical ventilation in survivors were obesity, low oxygen saturation and elevated troponin levels measured on admission. In conclusion, our study did not show any association of lupus anticoagulant with mortality and with need for mechanical ventilation in survivors. The role of obesity, low SaO2 and elevated troponin levels as predictors of a worse prognosis in patients hospitalized for COVID-19 was confirmed.

Published
2020

14. Predictors of healing, ulcer recurrence and persistence, amputation and mortality in type 2 diabetic patients with diabetic foot: a 10-year retrospective cohort study

Author

Andrea Giustina, Arturo Pujia, Adriana Coppola, Tiziana Montalcini, Carmine Gazzaruso, and Pietro Gallotti

Subjects
medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, 030209 endocrinology & metabolism, Type 2 diabetes, Revascularization, Amputation, Surgical, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, medicine, Humans, Retrospective Studies, Wound Healing, business.industry, Incidence (epidemiology), Retrospective cohort study, medicine.disease, Diabetic foot, Diabetic Foot, Diabetic foot ulcer, Diabetes Mellitus, Type 2, Amputation, 030220 oncology & carcinogenesis, business
Abstract

Predictors of outcome of diabetic foot ulcer (DFU) are important to improve the management of patients. Aim of the study was to find these predictors in type 2 diabetic patients with DFU. We recruited 583 patients. They were followed-up by a multidisciplinary team. A holistic and conservative approach was used and all risk factors and co-morbidities were aggressively treated. During the follow-up period, 79.6% of patients healed in a mean time of 7.6 ± 3.8 months, 6.9% showed DFU persistence, 9.9% had minor amputations, and 3.6% experienced major amputation. Seventeen percent of the patients died. Among patients who healed, 37.1% of them showed DFU recurrence. Impairment of renal function was associated to DFU persistence, amputation, and mortality. Previous cardiovascular disease predicted DFU persistence, DFU recurrence, and mortality. Lower BMI predicted DFU persistence and mortality. Osteomyelitis was a predictor of amputation and death. Markers of peripheral artery disease (PAD) predicted minor amputation and DFU recurrence. Our study shows a relatively low incidence of complications of DFU. Some predictors of outcome of DFU were confirmed and new predictors, like BMI and markers of PAD, were found. Our new findings suggest future strategies for nutrition support and revascularization. In addition, a holistic and conservative approach may improve the prognosis.

Published
2020

15. Effects of a Portfolio-Mediterranean Diet and a Mediterranean Diet with or without a Sterol-Enriched Yogurt in Individuals with Hypercholesterolemia

Author

Emma Santariga, Patrizia Doldo, Tiziana Montalcini, Mariantonietta Salvati, Rocco Spagnuolo, Roberta Pujia, Elisa Mazza, Arturo Pujia, Carmine Gazzaruso, Yvelise Ferro, Salvatore Giampà, and Adriana Coppola

Subjects
Mediterranean climate, Male, Mediterranean diet, Endocrinology, Diabetes and Metabolism, Hypercholesterolemia, Low density lipoprotein cholesterol, mediterranean, 030209 endocrinology & metabolism, Biology, Diet, Mediterranean, lcsh:Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, chemistry.chemical_compound, yogurt, 0302 clinical medicine, Endocrinology, Humans, Food science, Soy protein, Retrospective Studies, lcsh:RC648-665, Cholesterol, food and beverages, cholesterol, Middle Aged, Green tea, Prognosis, Sterol, ldl, Sterols, chemistry, 030220 oncology & carcinogenesis, Case-Control Studies, anticholesteremic agents, Female, Original Article, lipids (amino acids, peptides, and proteins), diet, Plant sterols, Follow-Up Studies
Abstract

Background A growing number of functional foods have been proposed to reduce cholesterol levels and the Portfolio Diet, which includes a combination of plant sterols, fibres, nuts, and soy protein, reduces low density lipoprotein cholesterol (LDL-C) from 20% to 30% in individuals with hyperlipidaemia. In this pilot study, the aim was to investigate whether a Mediterranean Diet incorporating a new and simple combination of cholesterol-lowering foods, excluding soy and nuts (namely the Portfolio-Mediterranean Diet), would reduce LDL-C levels, in the short-term, better than a Mediterranean Diet plus a sterol-enriched yogurt or a Mediterranean Diet alone. Methods We retrospectively evaluated 24 individuals on a Portfolio-Mediterranean Diet and 48 matched individuals on a Mediterranean Diet with or without a sterol-enriched yogurt (24 each groups) as controls. Results At follow-up (after 48±12 days), we observed an LDL reduction of 21±4, 23±4, and 44±4 mg/dL in the Mediterranean Diet alone, Mediterranean Diet plus yogurt and Portfolio-Mediterranean Diet respectively (Pl0.001). Conclusion A Portfolio-Mediterranean Diet, incorporating a new combination of functional foods such as oats or barley, plant sterols, chitosan, and green tea but not soy and nuts, may reduce LDL of 25% in the short term in individuals with hypercholesterolemia.

Published
2020

16. The Effects of COVID-19 on the Eating Habits of Children and Adolescents in Italy: A Pilot Survey Study

Author

Elisa Mazza, Samantha Maurotti, Carmine Gazzaruso, Arturo Pujia, Roberta Pujia, Yvelise Ferro, Janin Khoory, and Tiziana Montalcini

Subjects
Male, obesity, Pediatric Obesity, Body height, Weight Gain, Body Mass Index, 0302 clinical medicine, Surveys and Questionnaires, Vegetables, Dietary habit, TX341-641, Processed meat, 030212 general & internal medicine, adolescents, Child, Health implications, Nutrition and Dietetics, digestive, oral, and skin physiology, food and beverages, Italy, Child, Preschool, Female, Coronavirus disease 2019 (COVID-19), Adolescent, body weight gain, Pilot survey, Nutritional Status, 030209 endocrinology & metabolism, Article, 03 medical and health sciences, children, Environmental health, medicine, Humans, Eating habits, Nutrition. Foods and food supply, business.industry, SARS-CoV-2, Body Weight, COVID-19, eating habits, Feeding Behavior, medicine.disease, Obesity, Cross-Sectional Studies, Fruit, Communicable Disease Control, Snacks, business, Food Science
Abstract

Nutrition during childhood and adolescence is very important for growth and can have long-term health implications. The COVID-19 lockdown caused significant changes in everyday life, including in children and adolescents. This study evaluated the effects of the first COVID-19 lockdown on eating habits and body weight in children and adolescents. An online cross-sectional survey was carried out among the parents of children (5–9 years) and adolescents (10–14 years) living in Italy. The online self-administered questionnaire included demographic and anthropometric data (reported weight and height) weight and dietary habit changes during the COVID-19 lockdown in Italy (March to June 2020). A total of 439 participants were included. We found a change in eating habits with an increase in consumption of sweet packaged snacks (34%) and processed meat (25%), as well as bread, pizza and bakery products (47%). We also found an increase in vegetable, fresh fruit and legume intake (19%), and a reduction in sweet beverage and candy intake. A total of 59.7% of the participants reported body weight gain, with adolescents gaining more than children (67% vs. 55%, p = 0.010, respectively). In children, body weight gain was associated with a change in body height and increased consumption of dairy products and sweet packaged snacks, while in adolescents it was associated with an increased intake of comfort foods and processed meat. Our data highlighted the need to carefully monitor eating behaviors to avoid the establishment of unhealthy eating habits and prevent obesity in children and adolescents during periods of self-isolation.

Published
2021

17. Bending Resistance at Hip and Fractures Risk in Postmenopausal Women Independent of Bone Mineral Density

Author

Elisa Mazza, Arturo Pujia, Tiziana Montalcini, Roberta Pujia, Nadia Geirola, Carmine Gazzaruso, Stefano Romeo, Samantha Maurotti, and Yvelise Ferro

Subjects
Fracture risk, Male, Endocrinology, Diabetes and Metabolism, Osteoporosis, Hip structure, Dentistry, Absorptiometry, Photon, Bone Density, medicine, Humans, Radiology, Nuclear Medicine and imaging, Orthopedics and Sports Medicine, Osteoporosis, Postmenopausal, Bone mineral, Postmenopausal women, business.industry, Femur Neck, Hip Fractures, Odds ratio, medicine.disease, Postmenopause, Cross-Sectional Studies, Axial load, Female, business, Bone mass
Abstract

Several studies suggest that aging loss of bone mass is not necessarily associated with reduced mechanical proprieties as bending resistance. Since postmenopausal women with fracture and without osteoporosis might have an impairment in the bending mechanisms at hip, our aim was to assess if women with and without fractures differ in the femoral parameters of resistance to bending, independent of the bone loss. In this cross-sectional study we enrolled 192 postmenopausal women who underwent X-ray absorptiometry scan to measure bone mineral density as well as cross-sectional geometry parameters at the hip (Hip structure analysis). Among women with osteoporosis, a higher odds ratio for fracture was found in the first tertile of NN-Dmax, a parameter linked to the resistance to bending forces in a cross-section (tertile I, OR = 6.7, p = 0.03; CI 1.19–38.01; reference tertile III). We also found a significantly higher risk for major fracture in the first tertile of NN-Dmax (tertile I, OR = 6.0, p = 0.02; CI 1.26−28.4; reference tertile III). Among women without osteoporosis, a significantly higher odds ratio for fracture was found in the first tertile of IT-CSA, a parameter of resistance to axial load (tertile I, OR = 7.2, p = 0.002; CI 2.04–25.9; reference tertile III). We also found a significantly higher risk for major fracture in the first tertile of IT-CSA (OR = 18.4, p = 0.001; CI 1.52−221.8; tertile III reference). We demonstrate that some hip structural parameters are independently associated to the fracture risk in postmenopausal women.

Published
2021

18. Association between clitoral tissue perfusion and female sexual dysfunction in healthy women of reproductive age: a pilot study

Author

Carmine Gazzaruso, Tiziana Montalcini, Adriana Coppola, Dimitrios Choussos, Pietro Gallotti, and Arturo Pujia

Subjects
Adult, medicine.medical_specialty, Sexual Behavior, Urology, media_common.quotation_subject, Female sexual dysfunction, 030232 urology & nephrology, Pilot Projects, Human sexuality, Clitoris, Personal Satisfaction, Orgasm, Arousal, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, medicine, Humans, Sexual Dysfunctions, Psychological, Heterosexuality, Reproductive health, media_common, Mucous Membrane, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics, medicine.disease, Oxygen tension, Sexual Dysfunction, Physiological, medicine.anatomical_structure, Vagina, Female, business, Blood Gas Monitoring, Transcutaneous
Abstract

The impact of abnormalities in the vascular bed of the external genitalia and vagina on female sexuality is not well defined because of some methodological difficulties in correctly assessing vascular changes of genitalia in women. Transmucosal oxygen tension (TmPO2) represents a precise measure of oxygen partial pressure at the clitoris surface and is expression of clitoral tissue perfusion. Aim of the study was to correlate TmPO2 with female sexual dysfunction (FSD) in healthy women in order to evaluate the impact of clitoral vascularization on female sexual health. Twenty-seven healthy, heterosexual, and sexually active women of reproductive age (mean age: 31.18 ± 4.71) were enrolled in the study. TmPO2 was assessed in every woman. In addition, all the women filled out the Female sexual function index (FSFI). After adjustment for some covariates (age, BMI, and smoking), TmPO2 significantly correlated with FSFI total score (r = 0.4261; p = 0.0379) and with arousal (r = 0.3239; p = 0.0390), lubrication (r = 0.4345; p = 0.0339), orgasm (r = 0.4092; p = 0.0471), and satisfaction (r = 0.4456; p = 0.0291) scores. In addition, TmPO2 was significantly lower in the FSD than in the NO FSD group (28.4 ± 14.5 versus 48.1 ± 25.1 mmHg; p = 0.0416). This study first shows that in healthy women of reproductive age clitoral tissue perfusion, as assessed by TmPO2, correlates very well with FSD and in particular with arousal, lubrication, orgasm, and satisfaction. Further studies should confirm our data and test TmPO2 as potential predictor for cardiovascular disease and metabolic conditions in women.

Published
2019

19. Impact of convalescent and nonimmune plasma on mortality of patients with COVID-19: a potential role for antithrombin

Author

Adriana Coppola, Pietro Gallotti, Cinzia Valenti, and Carmine Gazzaruso

Subjects
Microbiology (medical), 2019-20 coronavirus outbreak, obesity, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Antithrombins, Disease Outbreaks, Plasma, death, Medicine, Humans, Letter to the Editor, thrombosis, COVID-19 Serotherapy, business.industry, SARS-CoV-2, Antithrombin, Immunization, Passive, COVID-19, General Medicine, Virology, Coronavirus, antithrombin, Infectious Diseases, business, medicine.drug
Published
2021
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20. Multi-access Services for the Management of Diabetes Mellitus: The M2DM Project.

Author

Riccardo Bellazzi, Giuliana Bensa, Eulalia Brugués, Ewart R. Carson, Claudio Cobelli, Derek G. Cramp, Giuseppe d'Annunzio, Pasquale De Cata, Alberto de Leiva, Tibor Deutsch, Pietro Fratino, Carmine Gazzaruso, Angel Garcia, Tamás Gergely, Enrique J. Gómez, Fiona E. Harvey, Pietro Ferrari, Christiane Harras Friederich, M. Elena Hernando, Maged N. Kamel Boulos, Cristiana Larizza, Hans Ludekke, Monika Luebker, Alberto Maran, Gianluca Nucci, Fernando Ortiz Garcia, Cristina Pennati, Abdul V. Roudsari, Mercedes Rigla, Karsten Schutte, and Mario Stefanelli

Published
2002

22. Bone microarchitecture abnormalities in type 1 diabetes and in latent autoimmune diabetes in adults. A potential role for C-peptide

Author

Tiziana Montalcini, Adriana Coppola, and Carmine Gazzaruso

Subjects
Adult, Type 1 diabetes, C-Peptide, C-peptide, business.industry, Glutamate Decarboxylase, Endocrinology, Diabetes and Metabolism, MEDLINE, medicine.disease, Bioinformatics, chemistry.chemical_compound, Endocrinology, Diabetes Mellitus, Type 1, chemistry, Diabetes Mellitus, Type 2, Diabetes mellitus, Autoimmune diabetes, medicine, Humans, business, Latent Autoimmune Diabetes in Adults, Autoantibodies
Published
2020

23. Impact of anti-rheumatic drugs and steroids on clinical course and prognosis of COVID-19

Author

Pietro Garini, Nicoletta Carlo Stella, Elena Freddi, Giuseppe Mariani, Anna Tamburlini, Adriana Coppola, Pietro Gallotti, Carmine Gazzaruso, and Carolina Ravetto

Subjects
Male, medicine.medical_specialty, Coronavirus disease 2019 (COVID-19), Pneumonia, Viral, MEDLINE, Comorbidity, Letters of Biomedical and Clinical Research, Betacoronavirus, Rheumatology, Rheumatic Diseases, Internal medicine, medicine, Humans, Pandemics, Aged, Aged, 80 and over, biology, SARS-CoV-2, business.industry, Anti rheumatic drugs, Clinical course, COVID-19, General Medicine, Middle Aged, medicine.disease, biology.organism_classification, Pneumonia, Italy, Antirheumatic Agents, Female, Steroids, Coronavirus Infections, business
Published
2020
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24. Effects of C-Peptide Replacement Therapy on Bone Microarchitecture Parameters in Streptozotocin-Diabetic Rats

Author

Elisa Mazza, Francesca Bosco, Cristina Russo, Domenico Britti, Saverio Nucera, Sandro Giannini, Arturo Pujia, Vincenzo Musolino, Miriam Scicchitano, Roberta Pujia, Samantha Maurotti, Michela Deiana, Carmine Gazzaruso, Micaela Gliozzi, Stefano Romeo, Luca Dalle Carbonare, Vincenzo Mollace, Maria Teresa Valenti, Tiziana Montalcini, Monica Ragusa, and Valeria Maria Morittu

Subjects
0301 basic medicine, Male, medicine.medical_specialty, Bone density, Endocrinology, Diabetes and Metabolism, Osteoporosis, Urology, Type 1 diabetes mellitus, 030209 endocrinology & metabolism, c-peptide, Streptozocin, Diabetes Mellitus, Experimental, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Bone Density, Internal medicine, Diabetes mellitus, Diabetic rat model, medicine, Animals, Orthopedics and Sports Medicine, Tibia, Rats, Wistar, Normal control, Pathological, Bone microarchitectural parameters, C-peptide, business.industry, medicine.disease, Streptozotocin, Rats, Trabecular bone, chemistry, 030101 anatomy & morphology, business, Diabetic control, medicine.drug
Abstract

Pathological pathways involved in the development of diabetic complications are still unclear. Several studies suggested a pathogenic role of C-peptide deficiency in vascular and neuropathic complications. However, to date, the role of C-peptide on diabetes-related bone loss has not been investigated. The objective of this study was to test the effects of a 6-week regimen of rat C-peptide infusion on bone by combining micro-CT imaging with histological testing.Twenty-three, four-month-old male Wistar rats were randomly divided into three groups: Normal control group; Sham diabetic control group; Diabetic plus C-peptide group. Diabetes was induced by injection of streptozotocin. Rat C-peptide was delivered via subcutaneously osmopumps. We assessed several trabecular microarchitectural parameters and cellular and matrix proteins in bone tissue sections.At the end of the study, both the normal control and diabetic plus C-peptide groups had a higher tibia weight than the diabetic control group (p= 0.05 andp= 0.02, respectively). C-peptide levels significantly and positively correlated with the trabecular thickness (r= 0.45, p=0.08) and negatively with structure model index (r= −0.40, p=0.09). Furthermore, it positively correlated with one of the histological assessments (i.e. PLIN1 score; p=0.02). Micro-CT evaluation showed significant inter-group differences in trabecular thickness (p=0.02), trabecular space (p= 0.05) and cross-sectional thickness (p=0.05). Diabetic plus C-peptide group showed a higher trabecular thickness (pFor the first time we demonstrated that the diabetic rats receiving rat C-peptide had higher quality of trabecular bone, than diabetic rats not receiving it. C-peptide could have a role in the prevention of diabetes-related bone loss.

Published
2020

25. Comment on Khunti et al. COVID-19, Hyperglycemia, and New-Onset Diabetes. Diabetes Care 2021;44:2645–2655

Author

Carmine Gazzaruso, Adriana Coppola, Pietro Gallotti, Ileana Terruzzi, Tiziana Montalcini, and Livio Luzi

Subjects
Advanced and Specialized Nursing, Perspectives in Care, Diabetes Mellitus, Type 2, SARS-CoV-2, Hyperglycemia, Endocrinology, Diabetes and Metabolism, Internal Medicine, COVID-19, Humans
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.

Published
2022

26. Transmucosal oxygen tension of the clitoris: a new parameter for future investigations of the sexual, metabolic, and cardiovascular health of women

Author

Tiziana Montalcini, Carmine Gazzaruso, Arturo Pujia, Adriana Coppola, Livio Luzi, Pietro Gallotti, Andrea Giustina, Coppola, A., Montalcini, T., Gallotti, P., Luzi, L., Pujia, A., Giustina, A., and Gazzaruso, C.

Subjects
Adult, medicine.medical_specialty, Tissue perfusion, Health Status, Sexual Behavior, Endocrinology, Diabetes and Metabolism, Cardiovascular health, Cardiovascular risk factors, 030209 endocrinology & metabolism, Clitoris, Cardiovascular Physiological Phenomena, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Reference Values, Internal medicine, Diabetes mellitus, Skin surface, medicine, Humans, Oximetry, Oxygen tension, Female sexuality, Mucous Membrane, business.industry, Reproducibility of Results, Cardiovascular risk, medicine.disease, Metabolism, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cardiology, Vagina, Women's Health, Female, business, Blood Gas Monitoring, Transcutaneous, Perfusion
Abstract

Background: Several studies suggested that abnormalities in tissue perfusion of external genitalia and vagina can lead to female sexual dysfunctions (FSDs) and can be associated to metabolic and cardiovascular risk factors. However, there are some technical difficulties in assessing these abnormalities. The measurement of oxygen partial pressure is a noninvasive method to measure oxygen partial pressure (pO 2 ) at the skin surface to assess tissue perfusion. The aim of this study was to evaluate whether transmucosal oxygen tension (TmPO 2 ) can be measured at the mucosal surface of clitoris and whether the measurements are reliable. Methods: TmPO 2 was measured in six young healthy women by using a device to measure transcutaneous pO 2 on the skin and by choosing a small sensor, usually used for newborns. The identical procedure for the detection of pO 2 at the skin surface was used. Results: The mean value of TmPO 2 was 42.3 mmHg (range: 24.1–53.4 mmHg). All the trend curves of the TmPO 2 showed the same behavior: after a stabilization time, there was a stable pO 2 (plateau phase) that corresponds to the TmPO 2 of the clitoris. These curves had a similar trend to those recorded at the skin surface. Conclusions: TmPO 2 can be easily measured at the mucosal surface of clitoris. Large epidemiological studies in healthy and unhealthy women and in women with FSD are needed to establish both the normal range of TmPO 2 and the meaning that different values of TmPO 2 can have on sexual and general health of the women.

Published
2018

27. Microbiota and metabolic diseases

Author

Andrea Giustina, Nicoletta Marchesi, Cristina Marelli, Livio Luzi, Stefano Govoni, Carmine Gazzaruso, Alessia Pascale, and Adriana Coppola

Subjects
0301 basic medicine, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Inflammation, Biology, digestive system, 03 medical and health sciences, fluids and secretions, 0302 clinical medicine, Endocrinology, Insulin resistance, Metabolic Diseases, Diabetes mellitus, medicine, Humans, Microbiome, Gastrointestinal tract, Microbiota, Gastrointestinal Microbiome, medicine.disease, Obesity, stomatognathic diseases, 030104 developmental biology, Immunology, Insulin Resistance, medicine.symptom, Metabolic syndrome
Abstract

The microbiota is a complex ecosystem of microorganisms consisting of bacteria, viruses, protozoa, and fungi, living in different districts of the human body, such as the gastro-enteric tube, skin, mouth, respiratory system, and the vagina. Over 70% of the microbiota lives in the gastrointestinal tract in a mutually beneficial relationship with its host. The microbiota plays a major role in many metabolic functions, including modulation of glucose and lipid homeostasis, regulation of satiety, production of energy and vitamins. It exerts a role in the regulation of several biochemical and physiological mechanisms through the production of metabolites and substances. In addition, the microbiota has important anti-carcinogenetic and anti-inflammatory actions. There is growing evidence that any modification in the microbiota composition can lead to several diseases, including metabolic diseases, such as obesity and diabetes, and cardiovascular diseases. This is because alterations in the microbiota composition can cause insulin resistance, inflammation, vascular, and metabolic disorders. The causes of the microbiota alterations and the mechanisms by which microbiota modifications can act on the development of metabolic and cardiovascular diseases have been reported. Current and future preventive and therapeutic strategies to prevent these diseases by an adequate modulation of the microbiota have been also discussed.

Published
2018

28. Evaluation of circulating sRAGE in osteoporosis according to BMI, adipokines and fracture risk: a pilot observational study

Author

Carmine Gazzaruso, Emanuela Galliera, Arturo Pujia, Tiziana Montalcini, Pietro Gallotti, M. Marazzi, Massimiliano Marco Corsi Romanelli, and Adriana Coppola

Subjects
0301 basic medicine, lcsh:Immunologic diseases. Allergy, Aging, medicine.medical_specialty, Fracture risk, Immunology, Osteoporosis, Adipokine, 030209 endocrinology & metabolism, lcsh:Geriatrics, Bone resorption, Bone remodeling, 03 medical and health sciences, 0302 clinical medicine, Glycation end products, Glycation, Internal medicine, Medicine, Bone mineral, business.industry, Leptin, Research, medicine.disease, Osteopenia, lcsh:RC952-954.6, 030104 developmental biology, Endocrinology, business, lcsh:RC581-607, Circulating RAGE
Abstract

Background Osteoporosis is a systemic metabolic disease based on age-dependent imbalance between the rates of bone formation and bone resorption. Recent studies on the pathogenesis of this disease identified that bone remodelling impairment, at the base of osteoporotic bone fragility, could be related to protein glycation, in association to oxidative stress. The glycation reactions lead to the generation of glycation end products (AGEs) which, in turn, accumulates into bone, where they binds to the receptor for AGE (RAGE). The aim of this study is to investigate the potential role of circulating sRAGE in osteoporosis, in particular evaluating the correlation of sRAGE with the fracture risk, in association with bone mineral density, the fracture risk marker FGF23, and lipid metabolism. Results Circulating level of soluble RAGE correlate with osteopenia and osteoporosis level. Serum sRAGE resulted clearly associated on the one hand to bone fragility and, on the other hand, with BMI and leptin. sRAGE is particularly informative because serum sRAGE is able to provide, as a single marker, information about both the aspects of osteoporotic disease, represented by bone fragility and lipid metabolism. Conclusions The measure serum level of sRAGE could have a potential diagnostic role in the monitoring of osteoporosis progression, in particular in the evaluation of fracture risk, starting from the prevention and screening stage, to the osteopenic level to osteoporosis.

Published
2017

29. Association between low C-peptide and fragility fractures in postmenopausal women without diabetes

Author

Carmine Gazzaruso, Sandro Giannini, Massimiliano Marco Corsi Romanelli, Adriana Coppola, Mariangela Fodaro, V. Zambianchi, Pietro Gallotti, M. Marazzi, Arturo Pujia, Diego Russo, Cristina Russo, Tiziana Montalcini, Yvelise Ferro, Stefano Romeo, and Emanuela Galliera

Subjects
0301 basic medicine, medicine.medical_specialty, Inverse Association, Bone density, Endocrinology, Diabetes and Metabolism, Osteoporosis, 030209 endocrinology & metabolism, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Lumbar, Bone Density, Risk Factors, Diabetes mellitus, Internal medicine, Diabetes Mellitus, Prevalence, medicine, Humans, Osteoporosis, Postmenopausal, Aged, Bone mineral, C-Peptide, business.industry, Diabetes, Middle Aged, Prognosis, medicine.disease, Postmenopausal women, Postmenopause, Cross-Sectional Studies, 030104 developmental biology, Italy, Cohort, Fractures, Female, business, Biomarkers, Osteoporotic Fractures, Follow-Up Studies
Abstract

C-peptide has been shown to exert several, previously unknown, biological effects. A recent cross-sectional study demonstrated an association between low C-peptide serum levels and low lumbar bone density of postmenopausal women not affected by diabetes. To date, very little research attention has been directed toward the association between C-peptide and osteoporotic fractures. To contribute toward filling this gap, we investigated the association between C-peptide and fractures in postmenopausal women. A cohort of 133 non-diabetic postmenopausal women with and without a history of fractures was evaluated in this cross-sectional investigation. Standardized interviews were performed to gather information on the patients’ fracture history. All of the participants underwent a bone mineral density assessment by DXA, radiographs, and a serum C-peptide measurement. Thirty-four women presented fractures. Bivariate analysis revealed an inverse correlation between C-peptide and fractures (r = −0.27, p = 0.002). A significant difference in mean C-peptide levels was also found between women with vs. without fractures (p = 0.01, adjusted for age, BMI and glucose). Logistic regression analysis showed that C-peptide levels, femoral and vertebral BMD were all negatively associated with fracture status (B = −1.097, ES = 0.401, p = 0.006, 95% CI 0.15–0.73; B = −15.6, SE = 4.17, p

Published
2017

30. Anti-diabetic agents and heart health: how to use new diabetes medications in a global strategy for the prevention of cardiovascular complications in type 2 diabetes

Author

Carmine Gazzaruso, Adriana Coppola, Tiziana Montalcini, and Colomba Falcone

Subjects
Male, medicine.medical_specialty, MEDLINE, Angiotensin-Converting Enzyme Inhibitors, Blood Pressure, Type 2 diabetes, Disease, 030204 cardiovascular system & hematology, 03 medical and health sciences, Angiotensin Receptor Antagonists, 0302 clinical medicine, Double-Blind Method, Internal medicine, Diabetes mellitus, medicine, Secondary Prevention, Humans, Hypoglycemic Agents, 030212 general & internal medicine, Risk factor, Aged, Proportional Hazards Models, Heart health, Aspirin, business.industry, Sitagliptin Phosphate, Smoking, Type 2 Diabetes Mellitus, General Medicine, Cholesterol, LDL, Middle Aged, medicine.disease, Editorial, Logistic Models, Treatment Outcome, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Female, business, Follow-Up Studies
Abstract

Intensive risk factor modification significantly improves outcomes for patients with diabetes mellitus and cardiovascular disease. However, the degree to which secondary prevention treatment goals are achieved in international clinical practice is unknown.Attainment of 5 secondary prevention parameters-aspirin use, lipid control (low-density lipoprotein cholesterol70 mg/dL or statin therapy), blood pressure control (140 mm Hg systolic,90 mm Hg diastolic), angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use, and nonsmoking status-was evaluated among 13 616 patients from 38 countries with diabetes mellitus and known cardiovascular disease at entry into TECOS (Trial Evaluating Cardiovascular Outcomes With Sitagliptin). Logistic regression was used to evaluate the association between individual and regional factors and secondary prevention achievement at baseline. Cox proportional hazards regression analysis was used to determine the association between baseline secondary prevention achievement and cardiovascular death, myocardial infarction, or stroke.Overall, 29.9% of patients with diabetes mellitus and cardiovascular disease achieved all 5 secondary prevention parameters at baseline, although 71.8% achieved at least 4 parameters. North America had the highest proportion (41.2%), whereas Western Europe, Eastern Europe, and Latin America had proportions of ≈25%. Individually, blood pressure control (57.9%) had the lowest overall attainment, whereas nonsmoking status had the highest (89%). Over a median 3.0 years of follow-up, a higher baseline secondary prevention score was associated with improved outcomes in a step-wise graded relationship (adjusted hazard ratio, 0.60; 95% confidence interval, 0.47-0.77 for those patients achieving all 5 measures versus those achieving ≤2).In an international trial population, significant opportunities exist to improve the quality of cardiovascular secondary prevention care among patients with diabetes mellitus and cardiovascular disease, which in turn could lead to reduced risk of downstream cardiovascular events.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00790205.

Published
2018

31. Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Author

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 Juanatey, José Ramón, Hernandez Mijares, Antonio, Jiménez Díaz, Víctor Alfonso, Jodar Gimeno, Esteban, Lucas Morante, Tomá, Marazuela, Monica, Martell Claros, Nieve, Mauricio Puente, Didac, Mena Ribas, Elena, Merino Torres, Juan Francisco, Mezquita Raya, Pedro, Nubiola Calonge, Andreu, Ordoñez Sánchez, Xavier, Pascual Izuel, Jose Maria, Perea Castilla, Verónica, Pérez Pérez, Antonio, Perez Soto, Isabel, Quesada Charneco, Miguel, Quesada Simón, Angustia, Redón Mas, Josep, Rego Iraeta, Antonia, Rodriguez Alvarez, Maria, Rodríguez Rodríguez, Irene, Sabán Ruiz, José, Soto González, Alfonso, Tinahones Madueno, Francisco, Trescoli Serrano, Carlo, Ulied Armiñana, Angel, Bachus, Erasmu, Berndtsson Blom, Katarina, Eliasson, Ken, Koskinen, Pekka, Larnefeldt, Han, Lif-Tiberg, Cornelia, Linderfalk, Carina, Lund, Gustav, Lundman, Pia, Moris, Linda, Olsson, Åke, Salmonsson, Staffan, Sanmartin Berglund, Johan, Sjöberg, Folke, Söderberg, Stefan, Torstensson, Ingemar, Chen, Jung-Fu, Tien, Kai Jen, Tseng, Shih-Ting, Tu, Shih-Te, Wang, Chih-Yuan, Wang, Ji-Hung, Phrommintikul, Arintaya, Yamwong, Sukit, Jintapakorn, Woravut, Hutayanon, Pisit, Sansanayudh, Nakarin, Bazhan, Larysa, Fushtey, Ivan, Grachova, Mariya, Katerenchuk, Vitaliy, Korpachev, Vadym, Kravchun, Nonna, Larin, Oleksandr, Mykhalchyshyn, Galyna, Myshanych, Halyna, Oleksyk, Olga, Orlenko, Valeriia, Pashkovska, Nataliia, Pertseva, Nataliia, Petrosyan, Olena, Smirnov, Ivan, Vlasenko, Maryna, Zlova, Tetiana, Aye, Myint, Baksi, Arun, Balasubramani, Mathangi, Beboso, Ronnie, Blagden, Mark, Bundy, Charle, Cookson, Tobia, Copland, Allan, Emslie-Smith, Alistair, Green, Fiona, Gunstone, Anthony, Issa, Basil, Jackson-Voyzey, Ewart, Johnson, Andrew, Maclean, Malcolm, Mcknight, John, Muzulu, Solomon, O'Connell, Ian, Oyesile, Babatunde, Patterson, Catherine, Pearson, Ewan, Philip, Sam, Smith, Paul, Sukumaran, Usha, Abbas, Jalal, Aggarwala, Gaurav, Akhter, Faiq, Andersen, Jame, Anglade, Moise, Argoud, George, Ariani, Mehrdad, Ashdji, Reswan, Bakhtari, Ladan, Banerjee, Subhash, Bartlett, Andrew, Baum, Howard, Bays, Harold, Beasley, Richard, Belfort de Aguiar, Renata, Benjamin, Sabrina, Bhagwat, Ravi, Bhargava, Anuj, Bode, Bruce, Bratcher, Christina, Briskin, Toby, Brockmyre, Andrew, Broughton, Raymond, Brown, Judith, Budhraja, Madhusudan, Cannon, Kevin, Carr, Jewell, Cathcart, Harold, Cavale, Arvind, Chaykin, Loui, Cheung, Deanna, Childress, Richard, Cohen, Allan, Condit, Jonathan, Cooksey, Erin, Cornett, George Mitchell, Dauber, Ira, Davila, William, De Armas, Lui, Dean, Juliu, Detweiler, Robert, Diaz, Ernesto, Di Giovanna, Michael, Dor, Isaac, Drummond, Waymon, Eagerton, Donald, Earl, John, Eaton, Charle, Ellison, Howard, Farris, Neil, Fiel, Thoma, Firek, Anthony, First, Brian, Forgosh, Le, French, William, Gandy, Winston, Garcia, Ronald, Gill, Santosh, Gordon, Murray, Guice, Michael, Gummadi, Siva, Hackenyos, Jonathan, Hairston, Kristen, Hanson, Lenita, Harrison, Lindsay, Hartman, Israel, Heitner, John, Hejeebu, Srini, Hermany, Paul, Hernandez-Cassis, Carlo, Hidalgo, Horacio, Higgins, Alexander, Ibrahim, Hassan, Jacobs, Shahram, Johnson, David, Joshi, Parag, Kaster, Steven, Kellum, Daniel, Kim, Christopher, Kim, Ellen, Kirby, William, Knouse, Albert, Kulback, Steven, Kumar, Mariananda, Kuruvanka, Tulsida, Labroo, Ajay, Lasswell, William, Lentz, John, Lenzmeier, Thoma, Lewis, David, Li, Zhaoping, Lillestol, Michael, Little, Raymond, Lorraine, Richard, McKeown-Biagas, Cecilia, Mcneill, Robert, Mehta, Anand, Miller, Alan, Moran, Joseph, Morawski, Emily, Nadar, Venkatesh, O'Connor, Thoma, Odio, Alberto, Parker, Reginald, Patel, Rajesh, Phillips, Lawrence, Raad, George, Rahman, Aref, Raikhel, Marina, Raisinghani, Ajit, Rajan, Raj, Rasouli, Neda, Rauzi, Frank, Rohr, Kathryn, Roseman, Hal, Rovner, Sergio, Saba, Fadi, Sachson, Richard, Schabauer, Alex, Schneider, Ricky, Schuchard, Timothy, Sensenbrenner, John, Shlesinger, Yshay, Singh, Narendra, Sivalingam, Kanagaratnam, Stonesifer, Larry, Storey, Daniel, Suh, David, Tahir, Mohammed, Tan, Anjanette, Tan, Marilyn, Taylon, Alain, Thakkar, Maitreya, Tripathy, Devjit, Uwaifo, Gabriel, Vedere, Amarnath, Venugopal, Chandra, Vo, Anthony, Welch, Michelle, Welker, Jame, White, Alexander, Willis, John, Wynne, Alan, Yazdani, Shahram, Rosenberg, Anne, Price, Lauren, Sigmon, Kristina, Lokhngina, Yuliya, Xing, Weibing, Overton, Robert, Stewart, Murray, Stead, Janet, Lindsay, Alistair, Patel, Vicka, Ross, Jorge, Soffer, Joseph, Daga, Shruti, Sowell, Margaret, Patel, Prashant, Garvey, Louisa, Ackert, Jessica, Abraham, Sybil, Sabol, Mary Beth, Altobelli, Desma, Ha, Juyoung, Kulkarni, Mangesh, Somerville, Matthew, Noronha, Drusilla, Casson, Ed, Zang, Eddie, Sandhu, Chamandeep, Kumar, Rakesh, Chen, David, Taft, Lin, Patel, Rajivkumar, Ye, June, Shannon, Jennifer, Wilson, Tim, Babi, Charleen, Miller, Diane, Thorpe, Karl, Russell, Rachael, Bull, Georgina, Hereghty, Belinda, Fernandez-Salazar, Eva, Longley, Troy, Donaldson, Jill, Jarosz, Marie, Murphy, Karen, Adams, Patricia, Smith, Peter, James, Rachel, Richards, Jackie, Sedani, Sangeeta, Althouse, Denise, Watson, David, Lorimer, Jamie, Lauder, Steven, Schultheis, Ron, Womer, Terese, Wraight, Ella, Li, Wenyan, Price-Olsen, Emma, Watson, Anthony, Kelly, Aoife, Mclaughlin, Patricia, Fleming, John, Schubert, Jessica, Schleiden, Debra, Harris, Tara, Prakash, Rahul, Breneman, Jody, Deshpande, Sameer, Saswadkar, Aarti, Kumari, Aditi, Shitut, Aditi, Raorane, Amruta, Karmalkar, Anisha, Mhambrey, Ankita, Bhosale, Archana, Vaphare, Ashok, Patil, Ashwini P, Khandelwal, Chaitali, Shaik, Fayaz, Nadar, Madhumitha, Karka, Mounika, Kadgaonkar, Neha, Gupta, Nikita, Aher, Nutan, Potnis, Omkar, Naicker, Pallavi, Shinde, Rakesh, Sharma, Richa, Godse, Rupali, Solanki, Sheetal, Sahu, Shruti, Dumbre, Snehal, Kumar, Somesh, Patil, Suradnya, Mandal, Trisha, McMurray, John J V, McMurray, John J.V., DeMets, David, McGuire, Darren, Groutars, Reginald G.E.J., Hoogslag, Pieter A.M., McKnight, John, McNeill, Robert, Ha, JuYoung, McLaughlin, Patricia, Hernandez, A. F., Green, J. B., Janmohamed, S., D'Agostino, R. B., Granger, C. B., Jones, N. P., Leiter, L. A., Rosenberg, A. E., Sigmon, K. N., Somerville, M. C., Thorpe, K. M., Mcmurray, J. J. V., Del Prato, S., Califf, R. M., Holman, R., Demets, D., Riddle, M., Goodman, S., Mcguire, D., Alexander, K., Devore, A., Melloni, C., Patel, C., Kong, D., Bloomfield, G., Roe, M., Tricoci, P., Harrison, R., Lopes, R., Mathews, R., Mehta, R., Schuyler Jones, W., Vemulapalli, S., Povsic, T., Eapen, Z., Dombrowski, K., Kolls, B., Jordan, D., Ambrosy, A., Greene, S., Mandawat, A., Shavadia, J., Cooper, L., Sharma, A., Guimaraes, P., Friedman, D., Wilson, M., Endsley, P., Gentry, T., Collier, J., Perez, K., James, K., Roush, J., Pope, C., Howell, C., Johnson, M., Bailey, M., Cole, J., Akers, T., Vandyne, B., Thomas, B., Rich, J., Bartone, S., Beaulieu, G., Brown, K., Chau, T., Christian, T., Coker, R., Greene, D., Haddock, T., Jenkins, W., Haque, G., Marquess, M., Pesarchick, J., Rethaford, R., Stone, A., Al Kawas, F., Anderson, M., Enns, R., Sinay, I., Mathieu, C., Yordanov, V., Hramiak, I., Haluzik, M., Galatius, S., Guerci, B., Nauck, M., Migdalis, I., Tan, C. B. K., Kocsis, G., Giaccari, A., Lee, M. K., Munoz, E. G. C., Cornel, J., Birkeland, K., Pinto, M., Tirador, L., Olesinska-Mader, M., Shestakova, M., Distiller, L., Lopez-Sendon, J., Eliasson, B., Chiang, C. -E., Srimahachota, S., Mankovsky, B., Bethel, M. A., Dungan, K., Kosiborod, M., Alvarisqueta, A., Baldovino, J., Besada, D., Calella, P., Cantero, M. C., Castano, P., Chertkoff, A., Cuadrado, J., De Loredo, L., Dominguez, A., Espanol, M. V., Finkelstein, H., Frechtel, G., Fretes, J., Garrido Santos, N., Gonzalez, J., Litvak, M., Loureyro, J., Maffei, L., Maldonado, N., Mohr Gasparini, D., Orio, S., Perez Manghi, F., Rodriguez Papini, N., Sala, J., Schygiel, P., Sposetti, G., Ulla, M., Verra, F., Zabalua, S., Zaidman, C., Crenier, L., Debroye, C., Duyck, F., Scheen, A., Van Gaal, L., Vercammen, C., Damyanova, V., Dimitrov, S., Kovacheva, S., Lozanov, L., Margaritov, V., Mihaylova-Shumkova, R., Nikolaeva, A., Stoyanova, Z., Akhras, R., Beaudry, Y., Bedard, J., Berlingieri, J., Chehayeb, R., Cheung, S., Conway, J., Cusson, J., Della Siega, A., Dumas, R., Dzongowski, P., Ferguson, M., Gaudet, D., Grondin, F., Gupta, A., Gupta, M., Halperin, F., Houle, P. -A., Jones, M., Kouz, S., Kovacs, C., Landry, D., Lonn, E., O'Mahony, W., Peterson, S., Reich, D., Rosenbloom, A., St-Maurice, F., Tugwell, B., Vizel, S., Woo, V., Brychta, T., Cech, V., Dvorakova, E., Edelsberger, T., Halciakova, K., Krizova, J., Lastuvka, J., Piperek, M., Prymkova, V., Raclavska, L., Silhova, E., Urbanek, R., Vrkoc, J., Andersen, U., Bronnum-Schou, J., Hove, J., Jensen, J. S., Kober, L., Kristiansen, O. P., Lund, P., Melchior, T., Nyvad, O., Schou, M., Boye, A., Cadinot, D., Gouet, D., Henry, P., Kessler, L., Lalau, J. -D., Petit, C., Thuan, J. -F., Voinot, C., Vouillarmet, J., Axthelm, C., Berger, D., Bieler, T., Birkenfeld, A., Bott, J., Busch, K., Caca, K., Chevts, J., Donaubauer, T., Erlinger, R., Funke, K., Grosskopf, J., Hagenow, A., Hamann, M., Hartard, M., Heymer, P., Huppertz, W., Illies, G., Jacob, S., Jung, T., Kahrmann, G., Kast, P., Kellerer, M., Kempe, H. -P., Khariouzov, A., Klausmann, G., Klein, C., Kleinecke-Pohl, U., Kleinertz, K., Koch, T., Kosch, C., Lorra, B., Luedemann, J., Luttermann, M., Maxeiner, S., Milek, K., Moelle, A., Neumann, G., Nischik, R., Oehrig-Pohl, E., Plassmann, G., Pohlmeier, L., Proepper, F., Regner, S., Rieker, W., Rose, L., Samer, H., Sauter, J., Schaper, F., Schiffer, C., Schmidt, J., Scholz, B. -M., Schulze, J., Segner, A., Seufert, J., Sigal, H., Steindorf, J., Stockhausen, J., Stuebler, P., Taeschner, H., Tews, D., Tschoepe, D., Wilhelm, K., Zeller-Stefan, H., Avramidis, I., Bousboulas, S., Bristianou, M., Dimitriadis, G., Elisaf, M., Kotsa, K., Melidonis, A., Mitrakou, A., Pagkalos, E., Papanas, N., Pappas, A., Sampanis, C., Tentolouris, N., Tsapas, A., Tzatzagou, G., Ozaki, R., Hajdu, C., Harcsa, E., Konyves, L., Mucsi, J., Pauker, Z., Petro, G., Ples, Z., Revesz, K., Sandor, V., Vass, V., 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. A., Sesti, G., Tonolo, G., Trevisan, R., Ahn, C. W., Baik, S. -H., Cha, B. -S., Chung, C. -H., Jang, H. C., Kim, C. -J., Kim, H. S., Kim, I. J., Lee, E. Y., Lee, H. W., Lee, K. -W., Moon, K. -W., Namgung, J., Park, K. S., Yoo, S. J., Yu, J., Llamas, E. -A. B., Cervantes-Escarcega, J. -L., Flota-Cervera, L. F., Gonzalez-Gonzalez, J. G., Pascoe-Gonzalez, S., Pelayo-Orozco, E. S., Ramirez-Diaz, S. -P., Saldana-Mendoza, A., Jerjes-Diaz, C. S., Torres-Colores, J. J., Vidrio-Velazquez, M., Villagordoa-Mesa, J., Beijerbacht, H. P., Groutars, R. G. E. J., Hoek, B. A., Hoogslag, P. A. M., Kooy, A., Kragten, J. A., Lieverse, A. G., Swart, H. P., Viergever, E. P., Ahlqvist, J., Cooper, J., Gulseth, H., Guttormsen, G., Wium, C., Arbanil, H., Calderon, J., Camacho, L., Espinoza, A. D., Garrido, E., Luna, A., Manrique, H., Revoredo, F. M., Gonzales, R. V., Rincon, L. Z., Zubiate, C., Ebo, G., Morales-Palomares, E., Arciszewska, M., Banach, M., Bijata-Bronisz, R., Derezinski, T., Gadzinski, W., Gajek, J., Klodawska, K., Krzyzagorska, E., Madej, A., Miekus, P., Opiela, J., Romanczuk, P., Siegel, A., Skokowska, E., Stankiewicz, A., Stasinska, T., Trznadel-Morawska, I., Witek, R., Aksentyev, S., Bondar, I., Demidova, I., Dreval, A., Ershova, O., Galstyan, G., Garganeeva, A., Izmozherova, N., Karetnikova, V., Kharakhulakh, M., Khokhlov, A., Kobalava, Z., Koshelskaya, O., Kosmacheva, E., Kostin, V., Koziolova, N., Kuzin, A., Lesnov, V., Lysenko, T., Markov, V., Mayorov, A., Moiseev, S., Myasoedova, S., Petunina, N., Rebrov, A., Ruyatkina, L., Samoylova, J., Sazonova, O., Shilkina, N., Sokolova, N., Vasilevskaya, O., Verbovaya, N., Vishneva, E., Vorobyev, S., Vorokhobina, N., Zanozina, O., Zhdanova, E., Zykova, T., Burgess, L., Coetzee, K., Dawood, S., Lombard, L., Makotoko, E., Moodley, R., Oosthuysen, W., Sarvan, M., Calvo Gomez, C., Cano Rodriguez, I., Castro Conde, A., Cequier Fillat, A., Cuatrecasas Cambra, G., de Alvaro Moreno, F., De Teresa Parreno, L., Delgado Lista, J., Dominguez Escribano, J. R., Duran Garcia, S., Elvira Gonzalez, J., Fernandez Rodriguez, J. M., Goday Arno, A., Gomez Huelgas, R., Gonzalez Juanatey, J. R., Hernandez Mijares, A., Jimenez Diaz, V. A., Jodar Gimeno, E., Lucas Morante, T., Marazuela, M., Martell Claros, N., Mauricio Puente, D., Mena Ribas, E., Merino Torres, J. F., Mezquita Raya, P., Nubiola Calonge, A., Ordonez Sanchez, X., Pascual Izuel, J. M., 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. -F., Tien, K. J., Tseng, S. -T., Tu, S. -T., Wang, C. -Y., Wang, J. -H., 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. M., 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, C., 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. B., 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. P., 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., Mandal, T., Skin function and permeability, Dermatology, Hernandez, A, Green, J, Janmohamed, S, D'Agostino, R, Granger, C, Jones, N, Leiter, L, Rosenberg, A, Sigmon, K, Somerville, M, Thorpe, K, Mcmurray, J, Del Prato, S, Califf, R, Holman, R, Demets, D, Riddle, M, Goodman, S, Mcguire, D, Alexander, K, Devore, A, Melloni, C, Patel, C, Kong, D, Bloomfield, G, Roe, M, Tricoci, P, Harrison, R, Lopes, R, Mathews, R, Mehta, R, Schuyler Jones, W, Vemulapalli, S, Povsic, T, Eapen, Z, Dombrowski, K, Kolls, B, Jordan, D, Ambrosy, A, Greene, S, Mandawat, A, Shavadia, J, Cooper, L, Sharma, A, Guimaraes, P, Friedman, D, Wilson, M, Endsley, P, Gentry, T, Collier, J, Perez, K, James, K, Roush, J, Pope, C, Howell, C, Johnson, M, Bailey, M, Cole, J, Akers, T, Vandyne, B, Thomas, B, Rich, J, Bartone, S, Beaulieu, G, Brown, K, Chau, T, Christian, T, Coker, R, Greene, D, Haddock, T, Jenkins, W, Haque, G, Marquess, M, Pesarchick, J, Rethaford, R, Stone, A, Al Kawas, F, Anderson, M, Enns, R, Sinay, I, Mathieu, C, Yordanov, V, Hramiak, I, Haluzik, M, Galatius, S, Guerci, B, Nauck, M, Migdalis, I, Tan, C, Kocsis, G, Giaccari, A, Lee, M, Munoz, E, Cornel, J, Birkeland, K, Pinto, M, Tirador, L, Olesinska-Mader, M, Shestakova, M, Distiller, L, Lopez-Sendon, J, Eliasson, B, Chiang, C, Srimahachota, S, Mankovsky, B, Bethel, M, Dungan, K, Kosiborod, M, Alvarisqueta, A, Baldovino, J, Besada, D, Calella, P, Cantero, M, Castano, P, Chertkoff, A, Cuadrado, J, De Loredo, L, Dominguez, A, Espanol, M, Finkelstein, H, Frechtel, G, Fretes, J, Garrido Santos, N, Gonzalez, J, Litvak, M, Loureyro, J, Maffei, L, Maldonado, N, Mohr Gasparini, D, Orio, S, Perez Manghi, F, Rodriguez Papini, N, Sala, J, Schygiel, P, Sposetti, G, Ulla, M, Verra, F, Zabalua, S, Zaidman, C, Crenier, L, Debroye, C, Duyck, 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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, Banach, M, Bijata-Bronisz, R, Derezinski, T, Gadzinski, W, Gajek, J, Klodawska, K, Krzyzagorska, E, Madej, A, Miekus, P, Opiela, J, Romanczuk, P, Siegel, A, Skokowska, E, Stankiewicz, A, Stasinska, T, Trznadel-Morawska, I, Witek, R, Aksentyev, S, Bondar, I, Demidova, I, Dreval, A, Ershova, O, Galstyan, G, Garganeeva, A, Izmozherova, N, Karetnikova, V, Kharakhulakh, M, Khokhlov, A, Kobalava, Z, Koshelskaya, O, Kosmacheva, E, Kostin, V, Koziolova, N, Kuzin, A, Lesnov, V, Lysenko, T, Markov, V, Mayorov, A, Moiseev, S, Myasoedova, S, Petunina, N, Rebrov, A, Ruyatkina, L, Samoylova, J, Sazonova, O, Shilkina, N, Sokolova, N, Vasilevskaya, O, Verbovaya, N, Vishneva, E, Vorobyev, S, Vorokhobina, N, Zanozina, O, Zhdanova, E, Zykova, T, Burgess, L, Coetzee, K, Dawood, S, Lombard, L, Makotoko, E, Moodley, R, Oosthuysen, W, Sarvan, M, Calvo Gomez, C, Cano Rodriguez, I, Castro Conde, A, Cequier Fillat, A, Cuatrecasas Cambra, G, de Alvaro Moreno, F, De Teresa Parreno, L, Delgado Lista, J, Dominguez 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

Subjects
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

Published
2018

32. Relationship between high sodium and low PUFA intake and carotid atherosclerosis in elderly women

Author

Patrizia Doldo, Elisa Mazza, Tiziana Montalcini, Arturo Pujia, Yvelise Ferro, Theodora Lamprinoudi, and Carmine Gazzaruso

Subjects
Carotid atherosclerosis, Carotid Artery Diseases, Aging, medicine.medical_specialty, Endothelium, Sodium, Linoleic acid, Population, High sodium, chemistry.chemical_element, 030204 cardiovascular system & hematology, Biochemistry, Asymptomatic, Carotid Intima-Media Thickness, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Risk Factors, Internal medicine, Genetics, medicine, Humans, 030212 general & internal medicine, education, Molecular Biology, Aged, chemistry.chemical_classification, education.field_of_study, Ultrasonography, Doppler, Duplex, business.industry, Sodium, Dietary, Cell Biology, Diet Records, Plaque, Atherosclerotic, Diet, medicine.anatomical_structure, Carotid Arteries, chemistry, Multivariate Analysis, Fatty Acids, Unsaturated, Linear Models, Female, medicine.symptom, business, Polyunsaturated fatty acid
Abstract

Several biologically active molecules including nutrients can affect the vascular endothelium which becomes dysfunctional and, as a consequence, predisposes to atherosclerosis. However, the impact of the intake of sodium and polyunsaturated fatty acids on carotid atherosclerosis in a population of elderly women has scarcely been studied. Our aim was to investigate the association between carotid intima-media thickness and atherosclerotic plaque and nutrient intake in asymptomatic elderly women. Carotid atherosclerosis was determined by duplex ultrasound in 108 elderly women. Dietary intake was assessed by a combination of a 24-hour recall and a 7-day food record. A physical examination and laboratory tests were performed. We found an association between the C-IMT and polyunsaturated fatty acid (negative, B = −0.014; p = 0.03; CI −0.027/−0.001) and sodium (positive, r = 0.16; P = 0.09) intake. When linoleic acid was added to the multivariable regression analysis instead of polyunsaturated fatty acids, C-IMT was associated with linoleic acid (B = −0.017; p = 0.02; CI −0.032/−0.003). In normotensive women we found a positive association between the C-IMT and sodium intake. The atherosclerotic plaque prevalence increased with the increase in sodium intake (66% vs 90% Tertile I vs Tertile III; p = 0.02). Iin conclusion, A low salt diet to a level of about 1.5 g/d and a polyunsaturated fatty acid intake of >9 g/d were found to be associate with a low atherosclerotic plaque prevalence in an elderly female population. Sodium and polyunsaturated fatty acids-mediated functional changes of the carotid endothelium may be implicated in atherosclerosis development.

Published
2017

33. Role of structured individual patient education in the prevention of vascular complications in newly diagnosed type 2 diabetes: the INdividual Therapeutic Education in Newly Diagnosed type 2 diabetes (INTEND) randomized controlled trial

Author

Andrea Giustina, Livio Luzi, Carmine Gazzaruso, Tiziana Montalcini, Adriana Coppola, Coppola, Adriana, Luzi, Livio, Montalcini, Tiziana, Giustina, Andrea, and Gazzaruso, Carmine

Subjects
Blood Glucose, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Macrovascular complication, Type 2 diabetes, Disease, Diabete, law.invention, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Quality of life, Randomized controlled trial, Patient Education as Topic, law, Internal medicine, Diabetes mellitus, Self-management, Medicine, Humans, 030212 general & internal medicine, Stroke, business.industry, Patient education, medicine.disease, Surgery, Self Care, Sexual dysfunction, Diabetes Mellitus, Type 2, Quality of Life, medicine.symptom, business, Diabetic Angiopathies
Abstract

Objective: Recent studies showed that a structured patient therapeutic education (PTE) may decrease both mortality and the development of diabetes complications. Nevertheless, no data are available in the literature on the impact of individual PTE on the complications in newly diagnosed type 2 diabetic patients. Aim of the present randomized controlled trial is to evaluate the impact of individual PTE on the occurrence of macrovascular complications in newly diagnosed type 2 diabetic patients when compared to usual care (UC) and group PTE. Design and methods: Six hundred newly diagnosed type 2 diabetic patients will be enrolled. The patients will be randomly assigned to one of these three groups: individual PTE, group PTE and UC. A comprehensive and complete PTE will be delivered to all the patients: PTE will include eleven themes. Primary composite endpoint of the study is occurrence of vascular complications, including cardiovascular death, non fatal coronary disease, non fatal stroke, peripheral artery disease. Secondary endpoints are: foot ulcers, amputations, sexual dysfunction, quality of life, microvascular complications, bone health, intensification of diabetes and hypertension therapy. Results and Conclusions: The present trial can give precious information on the features for the most effective PTE.

Published
2017

34. Cardiovascular characteristics of chronic fatigue syndrome

Author

Carmine Gazzaruso, Andrea Albergati, Gabriele Pelissero, Colomba Falcone, Enrica Capelli, Lorenzo Lorusso, and Sara Bozzini

Subjects
musculoskeletal diseases, medicine.medical_specialty, Nausea, Population, Orthostatic intolerance, 030204 cardiovascular system & hematology, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Vertigo, Epidemiology, Chronic fatigue syndrome, medicine, 030212 general & internal medicine, General Pharmacology, Toxicology and Pharmaceutics, education, education.field_of_study, biology, business.industry, General Neuroscience, virus diseases, General Medicine, Articles, medicine.disease, biology.organism_classification, Blood pressure, Age of onset, medicine.symptom, business
Abstract

Patients with chronic fatigue syndrome (CFS) commonly exhibit orthostatic intolerance. Abnormal sympathetic predominance in the autonomic cardiovascular response to gravitational stimuli was previously described in numerous studies. The aim of the current study was to describe cardiological and clinical characteristics of Italian patients with CFS. All of the patients were of Caucasian ethnicity and had been referred to our center, the Cardiology Department of the University Hospital of Pavia (Pavia, Italy) with suspected CFS. A total of 44 patients with suspected CFS were included in the present study and the diagnosis was confirmed in 19 patients according to recent clinical guidelines. The characteristics at baseline of the population confirm findings from various previous reports regarding the prevalence in females with a female to male ratio of 4:1, the age of onset of the pathology and the presence of previous infection by the Epstein-Barr virus, cytomegalovirus and other human herpesviruses. Despite the current data indicating that the majority of the cardiological parameters investigated are not significantly different in patients with and without CFS, a significant association between the disease and low levels of blood pressure was identified. Other pilot studies revealed a higher prevalence of hypotension and orthostatic intolerance in patients with CFS. Furthermore, many of the CFS symptoms, including fatigue, vertigo, decreased concentration, tremors and nausea, may be explained by hypotension.

Published
2017

35. An update on the potential role of C-peptide in diabetes and osteoporosis

Author

Arturo Pujia, Carmine Gazzaruso, and Tiziana Montalcini

Subjects
0301 basic medicine, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Osteoporosis, Renal function, 030209 endocrinology & metabolism, Bioinformatics, Bone and Bones, Diabetes Complications, 03 medical and health sciences, chemistry.chemical_compound, Fractures, Bone, 0302 clinical medicine, Endocrinology, Internal medicine, Diabetes mellitus, medicine, Diabetes Mellitus, Humans, Type 1 diabetes, C-Peptide, C-peptide, business.industry, Insulin, medicine.disease, Pathophysiology, 030104 developmental biology, chemistry, business, Complication
Abstract

C-peptide secretion is deficient or absent in type 1 diabetes mellitus. It is well accepted that insulin replacement therapy cannot prevent the development of long-term diabetes-related complications, which can often be disabling or even life-threatening. Several cross-sectional investigations have suggested that residual C-peptide production in patients with type 1 diabetes mellitus would help prevent a number of complications. In animal models of diabetes and in patients with type 1 diabetes mellitus, C-peptide replacement improves renal function, skin and skeletal muscle blood flow, nerve conduction, glucose utilization, and other diabetes-related complications. Recent investigations suggest a new beneficial effect of C-peptide, which to date has never been studied. It is known that osteoporosis is the most prevalent short-term complication in type 1 diabetes mellitus. This review will highlight new insights into the pathophysiology and future therapeutic modalities for osteoporosis in individuals with diabetes.This review provides a concise summary of old and new insights into the role of C-peptide in diabetes-related complications.The data suggest that C-peptide is a bioactive peptide, acting independently of insulin, which binds to a G-protein-coupled membrane binding site in different cell types. By triggering CaTaken together these studies encourage further investigations to elucidate the role of C-peptide in preventing bone loss in type 1 diabetes mellitus and in those individuals with C-peptide deficiency and osteoporosis.

Published
2017

36. Nutrients Utilization in Obese Individuals with and without Hypertriglyceridemia

Author

Elisa Mazza, Carmine Gazzaruso, Tiziana Montalcini, Arturo Pujia, Theodora Lamprinoudi, Stefano Romeo, and Attilio Morrone

Subjects
Male, obesity, Blood Pressure, Body Mass Index, chemistry.chemical_compound, Hyperlipidemia, Insulin, Micronutrients, fatty acid oxidation, Hypertriglyceridemia, indirect calorimetry, Nutrition and Dietetics, Fasting, Middle Aged, lipids (amino acids, peptides, and proteins), Female, medicine.symptom, lcsh:Nutrition. Foods and food supply, Adult, medicine.medical_specialty, lcsh:TX341-641, Biology, Article, lipids, nutrients, Internal medicine, medicine, Humans, triglyceride, Life Style, carboidrates, Triglycerides, Triglyceride, respiratory quotient, Cholesterol, HDL, Case-control study, nutritional and metabolic diseases, Calorimetry, Indirect, medicine.disease, Obesity, Respiratory quotient, Endocrinology, chemistry, Case-Control Studies, Multivariate Analysis, Linear Models, fatty acid, Energy Intake, Weight gain, Body mass index, Food Science
Abstract

Background: Low fat utilization is linked to weight gain and to the presence of certain atherosclerosis markers. It is not clear whether the presence of hyperlipidemia can further affect nutrients utilization. The main objective of this study was to investigate the fasting fuel utilization of obese subjects suffering from hypertriglyceridemia, and to compare it with that of individuals that are solely obese. Method: We recruited 20 obese individuals with hypertriglyceridemia and 20 matched individuals not affected by hypertriglyceridemia. The fuel utilization (respiratory quotient) was measured by respiratory gas exchange, by Indirect Calorimetry. Results: There was a significant difference in fuel utilization and HDL-cholesterol between cases and controls (respiratory quotient 0.89 ± 0.07 vs. 0.84 ± 0.06, p = 0.020 respectively). The univariate and multivariate linear regression analysis confirmed that hypertrygliceridemia was positively correlated to the respiratory quotient (p = 0.035). Conclusion: obese subjects with hypertriglyceridemia had a higher respiratory quotient in comparison to unaffected subjects. This could suggest a limitation in the beta-oxidation mechanisms, this could actually imply that fatty acids may be redirected from oxidation to reesterification into triglycerides. The study could suggest the presence of different mechanisms unrelated to obesity and also a potential new therapeutic target for hypertriglyceridemia management.

Published
2014

37. Cardiovascular Risk in Adult Patients With Growth Hormone (GH) Deficiency and Following Substitution With GH—An Update

Author

Ioannis Karamouzis, Raffaele Giubbini, Carmine Gazzaruso, Andrea Giustina, and M. Gola

Subjects
Adult, medicine.medical_specialty, Hormone Replacement Therapy, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Clinical Biochemistry, Adipokine, Context (language use), Carbohydrate metabolism, Biochemistry, Hypopituitarism, Proinflammatory cytokine, Endocrinology, Risk Factors, Internal medicine, medicine, Humans, biology, Human Growth Hormone, business.industry, Biochemistry (medical), C-reactive protein, Hormone replacement therapy (menopause), Somatropin, Glucose, Cytokine, Cardiovascular Diseases, biology.protein, Insulin Resistance, business
Abstract

GH deficiency (GHD) of the adult is a clinical condition characterized by the presence of several traditional and emerging cardiovascular risk factors that can significantly increase cardiovascular morbidity and mortality. It is still an open issue whether GH replacement is able not only to improve cardiovascular risk factors but also to decrease cardiovascular morbidity and mortality.The major source of data acquisition included PubMed research strategies. Original articles, systematic reviews and meta-analyses, and included relevant citations were screened.In untreated GHD, cardiovascular risk is increased due to abnormal lipid profile (increased total and low-density lipoprotein cholesterol, increased triglycerides, and reduced high-density lipoprotein cholesterol) and impaired glucose metabolism. Emerging cardiovascular risk factors/markers such as proinflammatory cytokines, C-reactive protein, and adipokines are also increased in GHD patients. Increased cardiovascular morbidity and mortality have also been reported in GHD. GH treatment has been shown to improve both traditional and emerging cardiovascular risk factors and markers. However, evidence on the effects of GH replacement on cardiovascular events and mortality is limited.The GHD population may be considered at high cardiovascular risk, and GH substitution may be expected to bring an added value to patients with hypopituitarism in terms of cardiovascular protection. However, there is too limited evidence (rarely coming from randomized and controlled studies) to recommend GH treatment based on the cardiovascular status of the patients.

Published
2014

38. Integrated cardiovascular/respiratory control in type 1 diabetes evidences functional imbalance: Possible role of hypoxia

Author

Pietro Fratino, Cesare Porta, Carmine Gazzaruso, Andrea Rinaldi, R. Paltro, Pasquale Decata, L. Bianchi, P. Protti, Luciano Bernardi, Department of Medical and Clinical Genetics, and Medicum

Subjects
Adult, Male, Diabetic neuropathy, AUTONOMIC NEUROPATHY, Chemoreflex, 030209 endocrinology & metabolism, 030204 cardiovascular system & hematology, Baroreflex, 03 medical and health sciences, MELLITUS, Electrocardiography, 0302 clinical medicine, Diabetes mellitus, OBSTRUCTIVE SLEEP-APNEA, medicine, Heart rate variability, Autonomic nervous system, Humans, OXIDATIVE STRESS, Hypoxia, business.industry, VENTILATORY RESPONSES, Blood Pressure Determination, ASSOCIATION, Hypoxia (medical), SPONTANEOUS BAROREFLEX SENSITIVITY, medicine.disease, OXYGEN-SATURATION, CHRONIC HEART-FAILURE, Chemoreceptor Cells, 3. Good health, LUNG-FUNCTION, Type 1 diabetes, Diabetes Mellitus, Type 1, Anesthesia, 3121 General medicine, internal medicine and other clinical medicine, Reflex, Respiratory Mechanics, Female, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Hypercapnia, circulatory and respiratory physiology
Abstract

Background: Cardiovascular (baroreflex) and respiratory (chemoreflex) control mechanisms were studied separately in diabetes, but their reciprocal interaction (well known for diseases like heart failure) had never been comprehensively assessed. We hypothesized that prevalent autonomic neuropathy would depress both reflexes, whereas prevalent autonomic imbalance through sympathetic activation would depress the baroreflex but enhance the chemoreflexes. Methods: In 46 type-1 diabetic subjects (7.0 +/- 0.9 year duration) and 103 age-matched controls we measured the baroreflex (average of 7 methods), and the chemoreflexes, (hypercapnic: ventilation/carbon dioxide slope during hyperoxic progressive hypercapnia; hypoxic: ventilation/oxygen saturation slope during normocapnic progressive hypoxia). Autonomic dysfunction was evaluated by cardiovascular reflex tests. Results: Resting oxygen saturation and baroreflex sensitivity were reduced in the diabetic group, whereas the hypercapnic chemoreflex was significantly increased in the entire diabetic group. Despite lower oxygen saturation the hypoxic chemoreflex showed a trend toward a depression in the diabetic group. Conclusion: Cardio-respiratory control imbalance is a common finding in early type 1 diabetes. A reduced sensitivity to hypoxia seems a primary factor leading to reflex sympathetic activation (enhanced hypercapnic chemoreflex and baroreflex depression), hence suggesting a functional origin of cardio-respiratory control imbalance in initial diabetes. (C) 2017 Elsevier B.V. All rights reserved.

Published
2016

39. Concomitant carotid plaque development and brachial artery diameter enlargement: A retrospective, recall-based study in postmenopausal women

Author

Carmine Gazzaruso, G. Gorgone, Tiziana Montalcini, and Arturo Pujia

Subjects
Carotid Artery Diseases, medicine.medical_specialty, Brachial Artery, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), White People, Heart Rate, Risk Factors, Internal medicine, medicine.artery, Heart rate, Humans, Medicine, cardiovascular diseases, Brachial artery, Aged, Retrospective Studies, Ultrasonography, Subclinical infection, Nutrition and Dietetics, Recall, business.industry, Incidence, Incidence (epidemiology), Hypertrophy, Middle Aged, Plaque, Atherosclerotic, Postmenopause, body regions, Carotid Arteries, Logistic Models, Blood pressure, Intima-media thickness, Concomitant, cardiovascular system, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Follow-Up Studies
Abstract

Background and aim To verify if the carotid plaque development is concomitant to brachial artery diameter enlargement, in healthy postmenopausal women. Methods and results This is a retrospective, recall study. We enrolled 40 postmenopausal women, selected from a database for the period 2000–2008, not affected by subclinical carotid atherosclerosis and without risk factors for cardiovascular disease. At the recall visit, carotid and brachial duplex scan was again obtained. The incidence of plaque was 30% after a mean follow-up period of 60 months. There were no differences in baseline characteristics between subjects developing carotid atherosclerosis and subjects who did not, except for the brachial diameter change, follow-up and heart rate. The logistic-regression analysis confirmed that only brachial diameter change resulted to be correlated with the development of carotid atherosclerosis. Conclusion Brachial artery diameter increase is concomitant to carotid plaque development. Vascular enlargement could not be a focal change but a systemic process associated with atherosclerotic plaque development. Brachial diameter could be a tool with a predictive significance.

Published
2013

40. Transcutaneous Oxygen Tension as a Potential Predictor of Cardiovascular Events in Type 2 Diabetes

Author

Gabriele Pelissero, Pietro Gallotti, Elisabetta Baffero, Adriana Coppola, Colomba Falcone, Arturo Pujia, Carmine Gazzaruso, Chiara Luppi, Tiziana Montalcini, Sebastiano Bruno Solerte, and Andrea Giustina

Subjects
Advanced and Specialized Nursing, medicine.medical_specialty, Longitudinal study, Receiver operating characteristic, Proportional hazards model, business.industry, Endocrinology, Diabetes and Metabolism, Hazard ratio, Type 2 diabetes, medicine.disease, Surgery, medicine.anatomical_structure, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Cardiology, cardiovascular diseases, Ankle, business, Mace
Abstract

OBJECTIVE Transcutaneous oxygen tension (TcPO2) measures tissue perfusion and is important in the management of peripheral artery disease (PAD). Ankle brachial index (ABI) is used for the diagnosis of PAD and represents a predictor of major adverse cardiovascular events (MACE), even if in diabetes its diagnostic and predictive value seems to be reduced. No study has evaluated TcPO2 as a predictor of cardiovascular events. Aim of this longitudinal study was to assess whether TcPO2 is better than ABI at predicting MACE in type 2 diabetic patients. RESEARCH DESIGN AND METHODS Among 361 consecutive patients with apparently uncomplicated diabetes, 67 MACE occurred during a follow-up period of 45.8 ± 23.2 months. RESULTS The percentage of both subjects with low ABI (≤0.9) and subjects with low TcPO2 (≤46 mmHg as measured by a receiver operating characteristic curve) was significantly ( 0.0001) were associated with a higher rate of MACEs. Cox regression analysis showed that low TcPO2 (hazard ratio 1.78 [95% CI 1.44–2.23]; P < 0.001) was a significant predictor of MACE, while ABI did not enter the model. CONCLUSIONS This longitudinal study showed that TcPO2 may be a potential predictor of MACE among patients with uncomplicated type 2 diabetes and that its predictive value seems to be greater than that of ABI.

Published
2013

41. Proinsulin C-peptide modulates the expression of ERK1/2, type I collagen and RANKL in human osteoblast-like cells (Saos-2)

Author

Emanuela Galliera, Massimiliano Marco Corsi Romanelli, Yvelise Ferro, Valentina Zambianchi, Tiziana Montalcini, Francesca Fumo, Stefano Romeo, Pietro Gallotti, M. Marazzi, Cristina Russo, Arturo Pujia, Veronica Lazzaro, Samantha Maurotti, Piero Pingitore, Adriana Coppola, Sandro Giannini, Carmine Gazzaruso, and Mariangela Fodaro

Subjects
0301 basic medicine, medicine.medical_specialty, MAP Kinase Signaling System, 030209 endocrinology & metabolism, Biochemistry, Collagen Type I, Bone remodeling, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, Insulin, Osteoporosis, Proinsulin C-peptide, RANKL, Type I collagen, Molecular Biology, Endocrinology, 0302 clinical medicine, Internal medicine, medicine, Humans, Receptor, Proinsulin, Osteoblasts, biology, C-Peptide, Chemistry, C-peptide, RANK Ligand, NF-kappa B, Osteoblast, 030104 developmental biology, medicine.anatomical_structure, biology.protein, Bone Remodeling, Intracellular, Signal Transduction
Abstract

A lower bone mass accompanied by a higher bone fragility with increased risk of fracture are observed in individuals with type 1 diabetes mellitus. Low C-peptide levels are associated with low lumbar mineral density in postmenopausal woman. In this work, we investigated the role of C-peptide on the osteoblast cell biology in vitro. We examined intracellular pathways and we found that C peptide activates ERK1/2 in human osteoblast-like cells (Saos-2). We also observed that proinsulin C-peptide prevents a reduction of type I collagen expression and decreases, in combination with insulin, receptor activator of nuclear factor-κB (RANKL) levels. In this work we show for the first time that Cpeptide activates a specific intracellular pathway in osteoblasts and it modulates the expression of protein involved in bone remodeling. Our results suggest that both C-peptide may have a role in bone metabolism. Further studies are needing to fully clarify its role.

Published
2016

42. Structured therapeutic education in diabetes: is it time to re-write the chapter on the prevention of diabetic complications?

Author

Carmine Gazzaruso, Mariangela Fodaro, and Adriana Coppola

Subjects
medicine.medical_specialty, business.industry, Endocrinology, Diabetes and Metabolism, MEDLINE, 030209 endocrinology & metabolism, Therapeutic education, medicine.disease, Diabetes Complications, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetes mellitus, medicine, Diabetes Mellitus, Humans, 030212 general & internal medicine, Intensive care medicine, business
Published
2016

43. THE ROLE OF PATIENT EDUCATION IN THE PREVENTION AND MANAGEMENT OF TYPE 2 DIABETES: AN OVERVIEW

Author

Andrea Giustina, Adriana Coppola, Carmine Gazzaruso, Loredana Sasso, Annamaria Bagnasco, Coppola, A, Sasso, L, Bagnasco, A, Giustina, Andrea, and Gazzaruso, C.

Subjects
medicine.medical_specialty, Emerging technologies, Contact time, Endocrinology, Diabetes and Metabolism, media_common.quotation_subject, 030209 endocrinology & metabolism, Disease, Type 2 diabetes, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Nursing, Patient Education as Topic, Self-management, Medicine, Humans, 030212 general & internal medicine, Empowerment, Life Style, media_common, business.industry, Diabetes, Type 2 Diabetes Mellitus, Patient education, medicine.disease, Lifestyle, Self Care, Diabetes and Metabolism, Diabetes Mellitus, Type 2, Physical therapy, business
Abstract

The management of type 2 diabetes mellitus includes ability and empowerment of the patient to change lifestyle, maintain an adequate diet and physical activity, manage the disease, and follow a specific program of periodic medical checks and education sessions. In addition, the patient should be able to correctly identify and adequately solve problems related to the disease and actively collaborate with the healthcare system. To obtain these goals, therapeutic patient education (TPE) is now considered a crucial element not only in the treatment but also in the prevention of type 2 diabetes. Several trials showed that TPE is able to improve clinical, lifestyle, and psycho-social outcomes. Nevertheless, studies have not clarified the ideal characteristics of a comprehensive patient education program in clinical practice. Other work is needed to answer open questions regarding the type of PTE (individual or group education), themes, frequency and number of education sessions, contact time between educator and patient, background of educators, use of new technologies, and barriers to self-management. The present review discusses these points on the basis of the most recent data of the literature.

Published
2016

44. Metabolic fuel utilization and subclinical atherosclerosis in overweight/obese subjects

Author

Valeria Migliaccio, Tiziana Montalcini, Arturo Pujia, Alberto Castagna, Stefania Rotundo, Yvelise Ferro, and Carmine Gazzaruso

Subjects
Adult, Carotid Artery Diseases, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Overweight, Carotid Intima-Media Thickness, Endocrinology, Internal medicine, Diabetes mellitus, medicine, Humans, Obesity, Subclinical infection, business.industry, Middle Aged, medicine.disease, Respiratory quotient, Asymptomatic Diseases, Basal metabolic rate, Lipogenesis, Cardiology, Female, Basal Metabolism, medicine.symptom, Energy Metabolism, business, Body mass index
Abstract

The utilization of different macronutrients is relevant for the risk of obesity, diabetes, or the appearing of vascular complications. The Respiratory Quotient (RQ) is a parameter measuring the fuel utilizations; in fact, it can indicate the fat stores utilization or lipogenesis activation. Aim of this study was to investigate the link between the RQ and the subclinical carotid atherosclerosis presence in overweight/obese subjects. 132 subjects with body mass index at least 25, at conventional diet, underwent an Indirect Calorimetry for the measurement of the Resting Metabolic Rate as well as the RQ and an evaluation of carotid arteries with ultrasound. Biochemical analyses were also performed. The mean age was 48 ± 12 years. There was a positive relation between carotid intima-media thickness and RQ (p = 0.010), with the high value in the subgroup with high RQ (p = 0.045 vs. group with low RQ). The RQ, an index of fuel utilization, is positively associated to subclinical carotid atherosclerosis in overweight/obese individuals.

Published
2012

45. Osteoporosis in chronic inflammatory disease: the role of malnutrition

Author

Tiziana Montalcini, Yvelise Ferro, Arturo Pujia, Valeria Migliaccio, Carmine Gazzaruso, and Stefano Romeo

Subjects
Male, Aging, medicine.medical_specialty, Cachexia, Bone disease, Endocrinology, Diabetes and Metabolism, Osteoporosis, Anorexia, Hormonal Change, Bone and Bones, Endocrinology, Diabetes mellitus, medicine, Humans, Intensive care medicine, Osteoporosis, Postmenopausal, business.industry, Malnutrition, medicine.disease, Metabolic Bone Disorder, Chronic Disease, Physical therapy, Cytokines, Female, medicine.symptom, business, Osteoporotic Fractures
Abstract

Osteoporosis is a metabolic bone disorder affecting million of people worldwide. Increased understanding of bone disease has led to a greater recognition of factors affecting bones, and consequently many secondary causes of osteoporosis were demonstrated. In this study, we aim to explore possible causes of bone loss and fractures in subjects affected by chronic inflammatory disease and to suggest new targets for intervention. In fact several studies, evaluated to perform this study, suggest that the patients with chronic inflammatory disease could be at high risk for fractures due to bone loss as consequence of malnutrition, caused by inflammation and hormonal change. Consequently, some actions could derive from the considerations of these mechanisms: a change in actual approach of chronic patients, that may include the investigation on the possible presence of osteoporosis, as well as further research on this topic to find a better therapy to prevent osteoporosis considering all the mechanisms described.

Published
2012

46. Brachial artery diameter measurement: A tool to simplify non-invasive vascular assessment

Author

Domenico Bosco, Gaetano Gorgone, Tiziana Montalcini, Arturo Pujia, Carmine Gazzaruso, and Stefano Romeo

Subjects
medicine.medical_specialty, Diameter measurement, Brachial Artery, Endothelium, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Coronary Disease, Disease, Risk Factors, Internal medicine, medicine.artery, medicine, Animals, Humans, Brachial artery, Nutrition and Dietetics, business.industry, Data synthesis, Non invasive, Atherosclerosis, Vessel diameter, medicine.anatomical_structure, Models, Animal, Assessment methods, cardiovascular system, Cardiology, Endothelium, Vascular, Cardiology and Cardiovascular Medicine, business
Abstract

Aim The mechanisms of vascular remodeling have attracted great interest since it is a phenomenon related to cardiovascular diseases. We would like to examine studies that contributed to clarify the remodeling mechanisms, to explore the different faces of atherosclerosis process. Data synthesis A number of invasive and non-invasive vascular assessment methods were developed, to detect the early sign of atherosclerosis. It became clear that the invasive tests were not applicable to large-scale studies. Consequently, a non-invasive test was developed. Studies showed that the endothelial function evaluation is a predictor of future cardiac events in individuals at cardiovascular risk and in those with established disease. However, analyzing several works, an interesting concept emerged, i.e., the inverse relation between endothelium-dependent dilation and vessel size, since large vessel tend not to dilate significantly. This notion emphasized the role of basal diameter on vascular response. In particular, as brachial artery diameter is the measure on which FMD is based, it could add more information in clinical evaluation, simplifying the assessment. Several studies showed that morphological change of brachial artery is a better indicator of the extent of coronary disease rather than FMD. Other studies showed that brachial diameter has predictive significance in the stratification of cardiovascular risk. Conclusion Brachial diameter is a useful and simple tool. It should be incorporated into the overall assessment of cardiovascular risk but further studies are warranted to determine the final place of brachial diameter assessment in routine clinical setting.

Published
2012

47. Erectile dysfunction can improve the effectiveness of the current guidelines for the screening for asymptomatic coronary artery disease in diabetes

Author

Fabrizio Salvucci, Arturo Pujia, Andrea Giustina, Gabriele Pelissero, Pietro Gallotti, Tiziana Montalcini, Sebastiano Bruno Solerte, Adriana Garzaniti, Cinzia Valenti, Carmine Gazzaruso, Colomba Falcone, Adriana Coppola, Gazzaruso, C, Coppola, A, Montalcini, T, Valenti, C, Garzaniti, A, Pelissero, G, Salvucci, F, Gallotti, P, Pujia, A, Falcone, C, Solerte, Sb, and Giustina, Andrea

Subjects
Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Coronary Artery Disease, Type 2 diabetes, Coronary Angiography, Severity of Illness Index, Asymptomatic, Coronary artery disease, Endocrinology, Erectile Dysfunction, Risk Factors, Surveys and Questionnaires, Internal medicine, Diabetes mellitus, Severity of illness, Prevalence, medicine, Humans, Mass Screening, cardiovascular diseases, Mass screening, business.industry, Coronary Stenosis, Middle Aged, medicine.disease, Surgery, Early Diagnosis, Erectile dysfunction, Diabetes Mellitus, Type 2, Italy, Multivariate Analysis, Practice Guidelines as Topic, medicine.symptom, business, Biomarkers, Diabetic Angiopathies, Dyslipidemia
Abstract

About 40% of diabetic patients with asymptomatic coronary artery disease (CAD) are missed on the basis of the current screening guidelines. Erectile Dysfunction (ED) is a powerful marker of asymptomatic CAD. Aim of the study is to evaluate whether ED can improve the effectiveness of the current guidelines for the screening of CAD in diabetes. From among 299 consecutive men with newly diagnosed type 2 diabetes without any apparent vascular complication, 293 (mean age 56.6 ± 5.9 years) were enrolled. Among them, 219 did not have myocardial ischemia (NO CAD group) and 74 men had a coronary stenosis angiographically proven (CAD group). Five risk factors (RFs) of the current screening guidelines (hypertension, dyslipidemia, family history for CAD, smoking e micro/macroalbuminuria) and ED were assessed. ED was significantly more prevalent in the CAD than in the NO CAD group (37.8 versus 15.1%; P

Published
2011

48. Erectile Dysfunction and Coronary Artery Disease in Patients with Diabetes

Author

Adriana Coppola, Carmine Gazzaruso, Andrea Giustina, Gazzaruso, C, Coppola, A, and Giustina, Andrea

Subjects
Adult, Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Coronary Disease, Coronary disease, Diabetes Complications, Coronary artery disease, Endocrinology, Erectile Dysfunction, Diabetes mellitus, Internal medicine, medicine, Humans, In patient, cardiovascular diseases, Endothelial dysfunction, Aged, business.industry, Middle Aged, medicine.disease, Pathophysiology, Surgery, Erectile dysfunction, Cardiology, Endothelium, Vascular, business
Abstract

The review deals with recent findings regarding the association between erectile dysfunction (ED) and coronary artery disease (CAD) in patients with diabetes. Indeed recent longitudinal studies have shown that ED is able to predict future cardiovascular events not only in nondiabetic but also in diabetic patients. In addition, in diabetic patients ED seems to be strongly associated with the presence of silent CAD. The mechanism by which ED is linked to CAD seems to be the presence of endothelial dysfunction. This pathophysiological mechanism has been extensively analysed. The possible clinical usefulness of ED to identify diabetic patients with silent CAD or at particularly high cardiovascular risk has been discussed in the review. At last, the review reports current guidelines and recent data available in the literature on the treatment of ED in patients with and without CAD and on the prevention of CAD in patients with ED.

Published
2011

49. Carotid distension and distensibility impairment in individuals affected by familial combined hyperlipidemia

Author

Gaetano Gorgone, Tiziana Montalcini, Carmine Gazzaruso, and Arturo Pujia

Subjects
Adult, Blood Glucose, Carotid Artery Diseases, Male, medicine.medical_specialty, Hyperlipidemia, Familial Combined, Blood Pressure, Distension, Risk Assessment, Risk Factors, Elastic Modulus, Internal medicine, medicine.artery, Hyperlipidemia, medicine, Humans, Insulin, Common carotid artery, Triglycerides, Apolipoproteins B, Ultrasonography, Doppler, Duplex, Chi-Square Distribution, Vascular disease, business.industry, Cholesterol, HDL, Confounding, Middle Aged, medicine.disease, Compliance (physiology), Carotid Arteries, Cholesterol, medicine.anatomical_structure, Italy, Case-Control Studies, Circulatory system, Cardiology, Regression Analysis, Female, Cardiology and Cardiovascular Medicine, business, Biomarkers, Compliance, Artery
Abstract

Objective To investigate whether individuals affected by familial combined hyperlipidemia, a common lipid disorder increasing the cardiovascular risk, had different carotid ultrasound parameters compared to control subjects without this family disorders. Methods 127 cases and 127 controls matched for age and gender were enrolled. Serum glucose, total cholesterol, high-density lipoprotein-cholesterol, triglycerides, ApoB, insulinemia were measured by standard laboratory techniques. All the subjects underwent B-mode ultrasonography to measure the end-diastolic and end-systolic diameter of the common carotid artery and, successively, to calculate distensibility, compliance, Young's elastic modulus and distension. Results Carotid diameter and Young's elastic modulus were significantly greater among FCH subjects than among controls, and carotid distensibility, compliance, distension and score distension were significantly lower than control, also after analysis of covariance in order to adjust all the carotid indexes for confounding variables. A multiple regression analysis confirmed that familial combined hyperlipidemia status was correlated to carotid indexes. In a model including the lipid parameters, triglycerides was the only lipid variable correlated with distensibility but not with distension. Conclusion This hyperlipidemia, particularly hypertrigliceridemia, could be the direct responsibility of carotid modification leading to the impairment of the distension/distensibility that, in turn, makes the patients prone to atherosclerosis.

Published
2010

50. Large extracoronary artery diameter in obese postmenopausal women

Author

Tiziana Montalcini, Antonietta Fava, Carmine Gazzaruso, Alberto Castagna, Arturo Pujia, and Gaetano Gorgone

Subjects
Carotid Artery Diseases, medicine.medical_specialty, Waist, Brachial Artery, Carotid Artery, Common, Body Mass Index, Risk Factors, medicine.artery, Internal medicine, medicine, Humans, Obesity, Common carotid artery, Brachial artery, Ultrasonography, business.industry, Confounding, Obstetrics and Gynecology, Organ Size, Middle Aged, medicine.disease, Postmenopause, Menopause, Cross-Sectional Studies, Blood pressure, medicine.anatomical_structure, Italy, Multivariate Analysis, cardiovascular system, Cardiology, Female, business, Body mass index, Artery
Abstract

OBJECTIVE The aim of this study was to investigate the association between extracoronary artery diameter (brachial and carotid arteries) and obesity. METHODS This was a cross-sectional study conducted among women referred to the Menopause Clinic of the University of Catanzaro. The study included 102 obese and 102 nonobese (controls) postmenopausal women. Medical histories were reviewed, and participants underwent clinical and biochemical evaluations to assess risk factors for cardiovascular disease. Common carotid artery and brachial artery diameters and atherosclerotic lesions were evaluated by ultrasonography. Associations between brachial artery and common carotid artery diameters with age, body mass index, waist circumference, and cardiovascular risk factors were analyzed by stepwise multivariate analysis. RESULTS Brachial and common carotid artery diameters were significantly greater in obese women than in nonobese women. After adjustment for confounding variables, brachial artery diameter but not common carotid artery diameter correlated with obesity (beta = 0.229, P = 0.002) and with waist circumference (beta = 0.013, P < 0.001) independently of systolic blood pressure and other risk factors. CONCLUSIONS Extracoronary artery diameter measurement, if confirmed by other studies, may be considered a useful tool to assess vascular remodeling in obese postmenopausal women.

Published
2010

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