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101. ANGPTL4 gene E40K variation protects against obesity‐associated dyslipidemia in participants with obesity.

Author

Bailetti, D., Bertoccini, L., Mancina, R. M., Barchetta, I., Capoccia, D., Cossu, E., Pujia, A., Lenzi, A., Leonetti, F., Cavallo, M. G., Romeo, S., and Baroni, M. G.

Subjects
DYSLIPIDEMIA, OBESITY complications, HUMAN genetic variation
Abstract

Summary: Objective ANGPTL4 inhibits lipoprotein lipase in adipose tissue, regulating plasma triglycerides levels. In persons with obesity plasma ANGPTL4 levels have been positively correlated with body fat mass, TG levels and low HDL. A loss‐of‐function E40K mutation in ANGPTL4 prevents LPL inhibition, resulting in lower TGs and higher HDLc in the general population. Since obesity determines metabolic alterations and consequently is a major risk factor for cardiovascular disease, the aim was to explore if obesity‐related metabolic abnormalities are modified by the ANGPTL4‐E40K mutation. Methods: ANGPTL4‐E40K was screened in 1206 Italian participants, of which 863 (71.5%) with obesity. All subjects without diabetes underwent OGTT with calculation of indices of insulin‐sensitivity. Results: Participants with obesity carrying the E40K variant had significantly lower TG (p = 0.001) and higher HDLc levels (p = 0.024). Also in the whole population low TGs and high HDLc were confirmed in E40K carriers. In the obese subpopulation it was observed that almost all E40K carriers were within the lowest quartile of TGs (p = 1.1 × 10−9). E40K had no substantial effect of on glucose metabolism. Finally, none of the obese E40K carriers had T2D, and together with the favourable lipid profile, they resemble a metabolically healthy obese (MHO) phenotype, compared to 38% of E40E wild‐type obese that had diabetes and/or dyslipidaemia (p = 0.0106). Conclusions: In participants with obesity the ANGPTL4‐E40K variant protects against dyslipidemia. The phenotype of obese E40K carriers is that of a patient with obesity without metabolic alterations, similar to the phenotype described as metabolic healthy obesity. [ABSTRACT FROM AUTHOR]

Published
2019
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103. Mapping ligand binding pockets in chloride ClC-1 channels through an integrated in silico and experimental approach using anthracene-9-carboxylic acid and niflumic acid.

Author

Altamura, C., Mangiatordi, G. F., Nicolotti, O., Sahbani, D., Farinato, A., Leonetti, F., Carratù, M. R., Conte, D., Desaphy, J‐F, Imbrici, P., and Desaphy, J-F

Subjects
CHLORIDE channels, PROTEINS, MYOTONIA congenita, MYOTONIA atrophica, ION channels, ALGORITHMS, BINDING sites, COMPARATIVE studies, COMPUTER simulation, EPITHELIAL cells, HYDROCARBONS, LIGANDS (Biochemistry), RESEARCH methodology, MEDICAL cooperation, MEMBRANE proteins, GENETIC mutation, PYRIDINE, RESEARCH, EVALUATION research, CHEMICAL inhibitors
Abstract

Background and Purpose: Although chloride channels are involved in several physiological processes and acquired diseases, the availability of compounds selectively targeting CLC proteins is limited. ClC-1 channels are responsible for sarcolemma repolarization after an action potential in skeletal muscle and have been associated with myotonia congenita and myotonic dystrophy as well as with other muscular physiopathological conditions. To date only a few ClC-1 blockers have been discovered, such as anthracene-9-carboxylic acid (9-AC) and niflumic acid (NFA), whereas no activator exists. The absence of a ClC-1 structure and the limited information regarding the binding pockets in CLC channels hamper the identification of improved modulators.Experimental Approach: Here we provide an in-depth characterization of drug binding pockets in ClC-1 through an integrated in silico and experimental approach. We first searched putative cavities in a homology model of ClC-1 built upon an eukaryotic CLC crystal structure, and then validated in silico data by measuring the blocking ability of 9-AC and NFA on mutant ClC-1 channels expressed in HEK 293 cells.Key Results: We identified four putative binding cavities in ClC-1. 9-AC appears to interact with residues K231, R421 and F484 within the channel pore. We also identified one preferential binding cavity for NFA and propose R421 and F484 as critical residues.Conclusions and Implications: This study represents the first effort to delineate the binding sites of ClC-1. This information is fundamental to discover compounds useful in the treatment of ClC-1-associated dysfunctions and might represent a starting point for specifically targeting other CLC proteins. [ABSTRACT FROM AUTHOR]

Published
2018
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104. Continuosus subcutaneos glucose minitoring in diabetic patients: a multicenter analysis

Author

Maran A, Crepaldi C, Tiengo A, Grassi G, Vitali E, Pagano G, Bistoni S, Calabrese G, Santeusanio F, Leonetti F, Ribaudo M, Di Mario U, Previti M, Cucinotta D, Giorgino F, Bellomo A, Giorgino R, Poscia A, Varalli M., ANNUZZI, GIOVANNI, GENOVESE, SALVATORE, RICCARDI, GABRIELE, Maran, A, Crepaldi, C, Tiengo, A, Grassi, G, Vitali, E, Pagano, G, Bistoni, S, Calabrese, G, Santeusanio, F, Leonetti, F, Ribaudo, M, Di Mario, U, Annuzzi, Giovanni, Genovese, Salvatore, Riccardi, Gabriele, Previti, M, Cucinotta, D, Giorgino, F, Bellomo, A, Giorgino, R, Poscia, A, and Varalli, M.

Published
2002

105. The thirsty and sleepy young athlete

Author

Di Natale, V, Barile, M, Umbro, Ilaria, Tinti, Francesca, Leonetti, F, and Mitterhofer, Anna Paola

Subjects
non presenti
Published
2013

106. Butterfly support for off diagonal coefficients and boundedness of solutions to quasilinear elliptic systems

Author

Leonardi Salvatore, Leonetti Francesco, Rocha Eugenio, and Staicu Vasile

Subjects
quasilinear, elliptic, system, weak, solution, regularity, primary: 35j47, secondary: 35b65, 49n60, Analysis, QA299.6-433
Abstract

We consider quasilinear elliptic systems in divergence form. In general, we cannot expect that weak solutions are locally bounded because of De Giorgi’s counterexample. Here we assume that off-diagonal coefficients have a “butterfly support”: this allows us to prove local boundedness of weak solutions.

Published
2021
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109. Pathogenetic mechanisms and cardiovascular risk: Differences between HbA1cand oral glucose tolerance test for the diagnosis of glucose tolerance

Author

Bianchi, C, Miccoli, Roberto, Bonadonna, Rc, Giorgino, F, Frontoni, S, Faloia, E, Marchesini, G, Dolci, Ma, Cavalot, F, Cavallo, Gm, Leonetti, F, DEL PRATO, Stefano, Genfiev, Investigators, C. Bianchi, R. Miccoli, R.C. Bonadonna, F. Giorgino, S. Frontoni, E. Faloia, G. Marchesini Reggiani, M.A. Dolci, F. Cavalot, G.M. Cavallo, F. Leonetti, S. Del Prato, and the GENFIEV Investigators

Subjects
cardiovascular risk, TYPE 2 DIABETES, insulin secretion, GENFIEV Study, HbA(1c), glucose tolerance, endocrine system diseases, nutritional and metabolic diseases, Oral glucose tolerance test, INSULIN RESISTANCE
Abstract

OBJECTIVE To ascertain to which extent the use of HbA1c and oral glucose tolerance test (OGTT) for diagnosis of glucose tolerance could identify individuals with different pathogenetic mechanisms and cardiovascular risk profile. RESEARCH DESIGN AND METHODS A total of 844 subjects (44%men; age 49.5 +- 11 years; BMI 29 +- 5 kg/m2) participated in this study. Parameters of b-cell functionwere derived from deconvolution of the plasma C-peptide concentration after a 75-g OGTT and insulin sensitivity assessed by homeostasismodel assessment of insulin resistance (IR). Cardiovascular risk profile was based on determination of plasma lipids and measurements of body weight, waist circumference, and blood pressure. Glucose regulation categories byOGTT and HbA1c were comparedwith respect to insulin action, insulin secretion, and cardiovascular risk profile. RESULTS OGTT results showed 42% of the subjects had prediabetes and 15% had type 2 diabetes mellitus (T2DM), whereas the corresponding figures based on HbA1c were 38 and 11%, with a respective concordance rate of 54 and 44%. Subjects meeting both diagnostic criteria for prediabetes presented greater IR and impairment of insulin secretion and had aworse cardiovascular risk profile than those with normal glucose tolerance at both diagnostic methods. In a logistic regression analyses adjusted for age, sex, and BMI, prediabetic subjects, and even more T2DM subjects by OGTT, had greater chance to have IR and impaired insulin secretion. CONCLUSIONS HbA1c identifies a smaller proportion of prediabetic individuals and even a smaller proportion of T2DM individuals than OGTT, with no difference in IR, insulin secretion, and cardiovascular risk profile. Subjects fulfilling both diagnostic methods for prediabetes or T2DM are characterized by a worse metabolic profile.

Published
2012

111. Continuous Subcutaneous Insulin Infusion (CSII) in Inpatient Setting: Unmet Needs and the Proposal of a CSII Unit

Author

Morviducci, L, Di Flaviani, A, Lauria, A, Pitocco, D, Pozzilli, P, Suraci, C, Frontoni, S, CSII Study Group Of Lazio Region, Collaborators: Cappa, Italy, M, Patera, I, Manfrini, S, Bracaglia, D, Ciampittiello, G, Cicconetti, E, Ventura, C, Bloise, D, Tatti, P, Leotta, S, Visalli, N, Caputo, S, Ghirlanda, G, Giaccari, A, Cavallo, G, Leonetti, F, Lauro, D, MANCA BITTI, Ml, Marini, Ma, Spallone, V, Napoli, A, Pugliese, G, Nardone, M, Tubili, C, Giuliano, M, Fava, D, Piergiovanni, F, Forte, E, Tuccinardi, F, Chiaramonte, F, Buzzetti, R, and Leto, G

Subjects
Insulin pump, medicine.medical_specialty, Settore MED/09 - Medicina Interna, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Settore MED/50 - Scienze Tecniche Mediche Applicate, Unmet needs, Endocrinology, Diabetes mellitus, GLYCEMIA, medicine, Intensive care medicine, Glycemic, Inpatient care, business.industry, Insulin, Diabetes, Diabetes, Glucose Homeostasis, Continuos Subcutaneous Insulin Infusion, Settore MED/13 - ENDOCRINOLOGIA, Inpatient setting, medicine.disease, Continuos Subcutaneous Insulin Infusion, Subcutaneous insulin, INSULIN INFUSION, Medical Laboratory Technology, Glucose Homeostasis, business
Abstract

Continuous subcutaneous insulin infusion (CSII) represents an increasingly popular method of treating diabetes. Patients with diabetes are often hospitalized, and current data indicate that inpatient hyperglycemia results in poorer outcomes. When patients on insulin pump therapy require hospitalization, practitioners caring for them face the issue of how to manage the inpatient care of these patients. We believe that patients using insulin pumps can safely have their therapy transitioned when hospitalized. Moreover, CSII during hospitalization should be regarded not only as a fundamental tool in patients already on insulin pump therapy, but also as an effective method to obtain euglycemia, in critically ill patients. However, a standard policy on CSII use during hospitalization is still lacking, and literature data are inconclusive about the benefits of insulin pump on glycemic homeostasis, in hospitalized patients. We suggest that a CSII unit should be activated inside the hospital, in order to increase compliance with required procedures and to properly address the unmet needs of CSII in inpatient setting.

Published
2011

112. The “Sapienza University Mortality and Morbidity Event Rate (SUMMER) study in diabetes”: Study protocol

Author

Barchetta, I., primary, Capoccia, D., additional, Baroni, M.G., additional, Buzzetti, R., additional, Cavallo, M.G., additional, De Cosmo, S., additional, Leonetti, F., additional, Leotta, S., additional, Morano, S., additional, Morviducci, L., additional, Prudente, S., additional, Pugliese, G., additional, Trischitta, V., additional, Bertoccini, L., additional, Copetti, M., additional, Pibiri, C., additional, D'Angelo, P., additional, Fallarino, M., additional, Bailetti, D., additional, Alessi, E., additional, and Basile, G., additional

Published
2016
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115. Localization and surgical treatment of pancreatic insulinomas

Author

Caronna, Roberto, Cardi, Maurizio, Leonetti, F, Polettini, E, Casciani, E, Schiratti, M, Prezioso, G, Romeo, G, Benedetti, Michele, Mangioni, Simona, Fanello, Gianfranco, Fusco, G, Marengo, Michele, Keinan, F, and Chirletti, Piero

Published
2007

124. Continuous subcutaneous glucose monitoring in diabetic patients: a multicenter analysis

Author

Maran, Alberto, Crepaldi, C, Tiengo, Antonio, Grassi, G, Vitali, E, Pagano, G, Bistoni, S, Calabrese, G, Santeusanio, F, Leonetti, F, Ribaudo, M, DI MARIO, U, Annuzzi, G, Genovese, S, Riccardi, G, Previti, M, Cucinotta, D, Giorgino, F, Bellomo, A, Giorgino, R, Poscia, A, and Varalli, M.

Subjects
Adult, Male, Diabetes Mellitus, Type 1, Glucose, Diabetes Mellitus, Type 2, Microdialysis, Humans, Reproducibility of Results, Female, Middle Aged, Monitoring, Physiologic, Skin
Abstract

To evaluate the accuracy of a new subcutaneous glucose sensor (Glucoday; A. Menarini Diagnostics) compared with venous blood glucose measurement in type 1 and type 2 diabetic patients.A multicenter study was performed in 70 diabetic patients. A microdialysis fiber was inserted subcutaneously into the periumbelical region and perfused with a buffer solution. Glucose concentrations in the dialysate were then measured every 3 min by the glucose sensor over a 24-h period, during which nine venous blood samples were also collected throughout the day.Both the insertion of the fiber and the wearing of the device were well tolerated by the patients. Subcutaneous glucose levels were well correlated with venous glucose measurements (r = 0.9, P0.001) over a wide range (40-400 mg/dl) for up to 24 h, with a single-point calibration. An analysis of 381 data pairs showed a linear relationship between the GlucoDay and serial venous blood glucose levels, and 97% of the data fell in the A and B regions of the error grid analysis. Percentage bias between the GlucoDay and the blood venous levels was -2.0% in the hypoglycemic range (70 mg/dl), 6.9% in the euglycemic range (70-180 mg/dl), and 11.2% in the hyperglycemic range (180 mg/dl).The GlucoDay system demonstrated high reliability and reported values that closely agreed with venous blood glucose measurements. The system was well tolerated and thus constitutes a relatively easy method to monitor glucose excursions in diabetic patients.

Published
2002

125. Relationship between plasma free fatty acids and uncoupling protein-3 gene expression in skeletal muscle of obese subjects: in vitro evidence of a causal link

Author

Sbraccia, P, D'Adamo, M, Leonetti, F, Buongiorno, A, Silecchia, G, Basso, Ms, Tamburrano, G, Lauro, D, Federici, M, Di Daniele, N, and Lauro, R

Subjects
Blood Glucose, Leptin, Male, obesity, Cytoplasmic and Nuclear, correlation analysis, Messenger, Gene Expression, fatty acid blood level, Ion Channels, Settore MED/13 - Endocrinologia, Receptors, Insulin, glucose, Settore MED/49 - Scienze Tecniche Dietetiche Applicate, clinical article, Cultured, messenger RNA, Reverse Transcriptase Polymerase Chain Reaction, adult, Fatty Acids, Statistics, article, fatty acid, insulin, leptin, peroxisome proliferator activated receptor gamma, uncoupling protein 2, uncoupling protein 3, anthropometric parameters, body build, body composition, body mass, controlled study, female, gene expression, glucose clamp technique, hormone action, human, human cell, impedance, insulin sensitivity, male, metabolic parameters, metabolism, muscle cell, nucleotide sequence, priority journal, reverse transcription polymerase chain reaction, skeletal muscle, Adult, Carrier Proteins, Case-Control Studies, Cells, Cultured, Fatty Acids, Nonesterified, Female, Glucose Clamp Technique, Humans, Linear Models, Membrane Transport Proteins, Mitochondrial Proteins, Muscle, Skeletal, Obesity, Proteins, Receptors, Cytoplasmic and Nuclear, RNA, Messenger, Statistics, Nonparametric, Transcription Factors, Skeletal, Muscle, Cells, Nonparametric, Nonesterified, RNA
Published
2002

126. This title is unavailable for guests, please login to see more information.

Author

Bianchi, C, Miccoli, R, Trombetta, M, Giorgino, F, Frontoni, S, Faloia, E, Marchesini, G, Dolci, Ma, Cavalot, F, Cavallo, G, Leonetti, F, Bonadonna, Rc, Del Prato, S, Giaccari, Andrea, Giaccari, Andrea (ORCID:0000-0002-7462-7792), Bianchi, C, Miccoli, R, Trombetta, M, Giorgino, F, Frontoni, S, Faloia, E, Marchesini, G, Dolci, Ma, Cavalot, F, Cavallo, G, Leonetti, F, Bonadonna, Rc, Del Prato, S, Giaccari, Andrea, and Giaccari, Andrea (ORCID:0000-0002-7462-7792)

Abstract

In subjects with normal glucose tolerance (NGT) 1-hour postload plasma glucose (1-h oral glucose tolerance test [OGTT]) of >155 mg/dL predicts type 2 diabetes (T2DM) and is associated with subclinical atherosclerosis.

Published
2013

129. Prediction of QTc length as function of BMI: a clinical tool to establish arrhythmias risk in obesity

Author

Curione, M, Tego, A, Capoccia, D, Varrenti, M, Baiocco, E, Salvatore, S, Maglio, C, Leonetti, F, Curione, M, Tego, A, Capoccia, D, Varrenti, M, Baiocco, E, Salvatore, S, Maglio, C, and Leonetti, F

Abstract

Among the electrocardiographic alterations used for stratifying the cardiovascular risk of life threatening arrhythmias (LFA) and sudden death (SD) there is the increment of the corrected QT(QTc). This increment is usually observable in obese patients (OP). Therefore, a study has been planned to investigate the possibility to predict QTc values in OP simply by detecting the best fitting regression method that represents the relationship between QTc and Body Mass Index (BMI). The study has been carried on 144 individuals classified as a function of their BMI in normoponderal subjects (NPS, No. 24; F/M=15/9; BMI=21.8± 1.7 kg/m(2)), Class I OP (No. 24; F/M=17/7; BMI=32.5± 1.1 kg/m(2)); Class II OP (No. 24; F/M=17/7; BMI=37.7± 1.5 kg/m(2)). Class IIIa (No. 24, F/M=15/9; BMI=44.4± 27 kg/m(2)), Class IIIb (No. 24; F/M=14/10; BMI 54.3± 2.7 kg/m(2)); Class IIIc (No. 24; F/M=14/10; BMI=63.3± 4.5 kg/m(2)). Both linear and non-linear fitting modes have been tested. While the BMI progressively increases in classified OP, the QTc shows an intergroup difference that is not only not constant but also declining in Class IIIc obesity. The optimal regressive model was found to be the following fourth order degree polynomial: QTc=317,15+(7,47xBMI)+(-0,28*BMI(2))+(0,005xBMI(3))+ (-0,00003xBMI(4)). By entering the BMI of a given OP into the above-cited formula, the QTc can be easily predicted and compared to that of NPS. Importantly, to have the possibility for a pre-electrocardiographic estimation of QTc allows all the medical and paramedical personnel, involved in the multidisciplinary treatment of obesity, to immediately establish the cardiovascular risk in the OP under observation

Published
2011

130. Metabolic syndrome in subjects at high risk for type 2 diabetes: the genetic, physiopathology and evolution of type 2 diabetes (GENFIEV) study

Author

Bianchi, Caterina Bianca Neve Aurora, Miccoli, R, Bonadonna, Rc, Giorgino, F, Frontoni, S, Faloia, E, Marchesini, G, Dolci, Maria, Alviggi, L, Gnasso, A, Consoli, Agostino, Cavalot, F, Cavallo, Mg, Leonetti, F, Giaccari, Andrea, Del Prato, S., Giaccari, Andrea (ORCID:0000-0002-7462-7792), Bianchi, Caterina Bianca Neve Aurora, Miccoli, R, Bonadonna, Rc, Giorgino, F, Frontoni, S, Faloia, E, Marchesini, G, Dolci, Maria, Alviggi, L, Gnasso, A, Consoli, Agostino, Cavalot, F, Cavallo, Mg, Leonetti, F, Giaccari, Andrea, Del Prato, S., and Giaccari, Andrea (ORCID:0000-0002-7462-7792)

Abstract

We evaluated the relationship between insulin resistance (IR) and insulin secretion with the metabolic syndrome (MS) in 885 subjects (377 men/508 women, age 49±11 years, BMI 29±5.2kgm(-2)) at risk of diabetes enrolled in the genetics, pathophysiology and evolution of type 2 diabetes (GENFIEV) study.

Published
2011

150. On the Hölder continuity for a class of vectorial problems

Author

Cupini Giovanni, Focardi Matteo, Leonetti Francesco, and Mascolo Elvira

Subjects
holder, continuity, regularity, vectorial, minimizer, variational, integral, primary: 49n60, secondary: 35j50, Analysis, QA299.6-433
Abstract

In this paper we prove local Hölder continuity of vectorial local minimizers of special classes of integral functionals with rank-one and polyconvex integrands. The energy densities satisfy suitable structure assumptions and may have neither radial nor quasi-diagonal structure. The regularity of minimizers is obtained by proving that each component stays in a suitable De Giorgi class and, from this, we conclude about the Hölder continuity. In the final section, we provide some non-trivial applications of our results.

Published
2019
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