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1. Sodium Glucose Cotransporter-2 Inhibitors in Non-Diabetic Kidney Disease: Evidence in Experimental Models

Author: Castoldi, G, Carletti, R, Barzaghi, F, Meani, M, Zatti, G, Perseghin, G, Di Gioia, C, Zerbini, G, Castoldi G., Carletti R., Barzaghi F., Meani M., Zatti G., Perseghin G., Di Gioia C. R. T., Zerbini G., Castoldi, G, Carletti, R, Barzaghi, F, Meani, M, Zatti, G, Perseghin, G, Di Gioia, C, Zerbini, G, Castoldi G., Carletti R., Barzaghi F., Meani M., Zatti G., Perseghin G., Di Gioia C. R. T., and Zerbini G.
Abstract: Sodium glucose cotransporter 2 (SGLT2) inhibitors are a class of glucose-lowering agents widely used for the treatment of type 2 diabetes mellitus. A number of clinical trials in type 2 diabetic patients with different degrees of renal impairment have clearly demonstrated that SGLT2 inhibitors reduce the progression rate of diabetic kidney disease. Furthermore, recent studies have shown that SGLT2 inhibitors also exert a protective effect in the case of non-diabetic kidney disease. Consequently, it has been hypothesized that the nephroprotective activity of these drugs could exceed the canonical impact on glycemic control and that the resulting beneficial effects could be the consequence of their pleiotropic properties (proven reduction of inflammation, fibrosis, oxidative stress and sympathetic nervous activity) both at systemic and tissue levels, suggesting that the efficacy of these drugs could also be extended to non-diabetic nephropathies. This review focuses on the nephroprotective effects of SGLT2 inhibitors in different experimental models of non-diabetic kidney disease. The different glucose-independent mechanisms potentially implemented by SGLT2 inhibitors to ultimately protect the non-diabetic kidney are described in detail, and conflicting results, when present, are discussed.
Published: 2024

2. COVID-19 related psychological burden and potential benefits of vaccination - Data from a repeated cross-sectional survey in healthcare workers

Author: Reicherts, P., Zerbini, G., Halms, T., Strasser, M., Papazova, I., Hasan, A., and Kunz, M.
Published: 2022
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3. Communication skills of medical students: Evaluation of a new communication curriculum at the University of Augsburg

Author: Zerbini, G, Reicherts, P, Reicherts, M, Roob, N, Schneider, P, Dankert, A, Greiner, SK, Kadmon, M, Lechner, V, Roos, M, Schimmel, M, Strube, W, Temizel, S, Uhrmacher, L, Kunz, M, Zerbini, G, Reicherts, P, Reicherts, M, Roob, N, Schneider, P, Dankert, A, Greiner, SK, Kadmon, M, Lechner, V, Roos, M, Schimmel, M, Strube, W, Temizel, S, Uhrmacher, L, and Kunz, M
Abstract: Objectives: Teaching communication skills plays a pivotal role in medical curricula. The aim of this article is to describe and evaluate a new communication curriculum developed at the Faculty of Medicine, University of Augsburg (KomCuA), which was conceptualized by an interdisciplinary team based on recommended quality standards (i.e., helical, integrated, longitudinal).Methods: A total of 150 medical students enrolled in the 1st, 3rd, and >=5th semester participated in the study. They completed an online survey (numerical rating scales and validated questionnaires) evaluating their current communication skills, how these developed across the curriculum in terms of quality and self-confidence, and how helpful they considered practicing in small group tutorials with simulated patients. The students' attitudes towards communication and empathy in the context of medical care were additionally assessed. The students' responses were compared across semesters using one-way univariate analysis of variance (ANOVA).Results: Overall, students reported improved communications skills due to attending the KomCuA and further considered practicing with simulated patients as being very helpful (large effect sizes). Compared to 1st semester students, 3rd and >=5th semester students reported better communication skills (medium to large effect sizes). Additionally, >=5th semester students showed stronger agreement towards the relevance of empathy in the context of medical care (medium effect size) compared to both 1st and 3rd semester students. Conclusion: The KomCuA has shown to be an effective communication curriculum to support medical students in the development of their communication skills and positive attitudes towards empathy. Additional studies assessing students' communication skills and empathic attitudes longitudinally are warranted to confirm the present results and to gain further knowledge on how these essential skills and attitudes develop across medical curricula., Zielsetzungen: Die Vermittlung kommunikativer Kompetenzen spielt in der medizinischen Ausbildung eine zentrale Rolle. Ziel dieses Artikels ist es, ein neues Kommunikationscurriculum an der Medizinischen Fakultät der Universität Augsburg (KomCuA) zu beschreiben und zu evaluieren, welches von einem interdisziplinären Team basierend auf empfohlenen Qualitätsstandards (d.h. helikal, integriert, longitudinal) konzipiert wurde.Methoden: An der Online-Studie nahmen insgesamt 150 Medizinstudierende aus den Semestern 1., 3. und >=5. teil. Mithilfe numerischer Bewertungsskalen und validierter Fragebögen wurden Aspekte wie Kommunikationskompetenz, Veränderungen in Qualität und Sicherheit der eigenen Kommunikation und Nutzen der Übungen mit Schauspielpatient*innen erfasst. Zusätzlich wurden die Einstellungen der Studierenden zu Kommunikation und Empathie im Kontext der medizinischen Versorgung bewertet. Die Antworten der Studierenden wurden mithilfe von Varianzanalysen (ANOVA) über die Semester hinweg verglichen.Ergebnisse: Insgesamt gaben die Studierenden an, dass sich ihre Kommunikationskompetenz durch die Teilnahme am KomCuA verbessert habe, und bewerteten das Üben mit Schauspielpatient*innen als sehr hilfreich (große Effektstärken). Im Vergleich zu den Studierenden des 1. Semesters berichteten die Studierenden des 3. und >=5. Semesters über bessere Kommunikationskompetenzen (mittlere bis große Effektstärken). Die Relevanz von Empathie im Kontext der medizinischen Versorgung (mittlere Effektstärke) wurde von den Studierenden des >=5. Semesters höher eingestuft als von Studierenden des 1. und 3 Semesters. Schlussfolgerung: Das KomCuA hat sich als wirksames Kommunikationscurriculum erwiesen, das sowohl die Entwicklung von Kommunikationskompetenzen bei Medizinstudierenden befördert als auch zu einer positiven Einstellung zur Rolle von Empathie beiträgt. Weitere Studien, in denen Kommunikationskompetenzen und empathischen Einstellungen der Studierenden im Längsschnitt untersucht
Published: 2024

4. Cardioprotective Effects of Sodium Glucose Cotransporter 2 Inhibition in Angiotensin II-Dependent Hypertension Are Mediated by the Local Reduction of Sympathetic Activity and Inflammation

Author: Castoldi, G, Carletti, R, Ippolito, S, Colzani, M, Pelucchi, S, Zerbini, G, Perseghin, G, Zatti, G, di Gioia, C, Castoldi G., Carletti R., Ippolito S., Colzani M., Pelucchi S., Zerbini G., Perseghin G., Zatti G., di Gioia C. R. T., Castoldi, G, Carletti, R, Ippolito, S, Colzani, M, Pelucchi, S, Zerbini, G, Perseghin, G, Zatti, G, di Gioia, C, Castoldi G., Carletti R., Ippolito S., Colzani M., Pelucchi S., Zerbini G., Perseghin G., Zatti G., and di Gioia C. R. T.
Abstract: The cardioprotective effects of sodium glucose cotrasponter 2 (SGLT2) inhibitors seem to be independent from the effects on glycemic control, through little-known mechanisms. In this study, we investigate whether the cardioprotective effects of empagliflozin, a SGLT2 inhibitor, may be associated with myocardial sympathetic activity and inflammatory cell infiltration in an experimental model of angiotensin II-dependent hypertension. Angiotensin II (Ang II), Ang II plus Empagliflozin, physiological saline, or physiological saline plus empagliflozin were administered to Sprague Dawley rats for two weeks. Blood pressure was measured by plethysmographic method. Myocardial hypertrophy and fibrosis were analysed by histomorphometry, and inflammatory cell infiltration and tyrosine hydroxylase expression, implemented as a marker of sympathetic activity, were evaluated by immunohistochemistry. Ang II increased blood pressure, myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase expression, as compared to the control group. Empagliflozin administration prevented the development of myocardial hypertrophy, fibrosis, inflammatory infiltrates and tyrosine hydroxylase overexpression in Ang II-treated rats, without affecting blood glucose and the Ang II-dependent increase in blood pressure. These data demonstrate that the cardioprotective effects of SGLT2 inhibition in Ang II-dependent hypertension may result from the myocardial reduction of sympathetic activity and inflammation and are independent of the modulation of blood pressure and blood glucose levels.
Published: 2023

5. Gold, silver or bronze: circadian variation strongly affects performance in Olympic athletes

Author: Lok, R., Zerbini, G., Gordijn, M. C. M., Beersma, D. G. M., and Hut, R. A.
Published: 2020
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6. Retinopathy as an independent predictor of all-cause mortality in individuals with type 2 diabetes

Author: Orsi, E, Solini, A, Bonora, E, Vitale, M, Garofolo, M, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Zerbini, G, Nicolucci, A, Pugliese, G, Orsi, Emanuela, Solini, Anna, Bonora, Enzo, Vitale, Martina, Garofolo, Monia, Fondelli, Cecilia, Trevisan, Roberto, Vedovato, Monica, Cavalot, Franco, Zerbini, Gianpaolo, Nicolucci, Antonio, Pugliese, Giuseppe, Orsi, E, Solini, A, Bonora, E, Vitale, M, Garofolo, M, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Zerbini, G, Nicolucci, A, Pugliese, G, Orsi, Emanuela, Solini, Anna, Bonora, Enzo, Vitale, Martina, Garofolo, Monia, Fondelli, Cecilia, Trevisan, Roberto, Vedovato, Monica, Cavalot, Franco, Zerbini, Gianpaolo, Nicolucci, Antonio, and Pugliese, Giuseppe
Abstract: Aims: To assess whether the presence and grade of diabetic retinopathy (DR) predict all-cause mortality, independent of risk factors for cardiovascular disease (CVD) and other complications, including diabetes-related kidney disease (DKD) and CVD, in individuals with type 2 diabetes mellitus. Methods: Prospective cohort study that enroled 15,773 patients in 19 Italian centers in 2006–2008. DR ascertained by fundoscopy, DKD by albuminuria and estimated glomerular filtration rate, and prior CVD by hospital discharge records. All-cause mortality retrieved for 15,656 patients on 31 October 2015. Results: The adjusted risk of death was increased in patients with any DR (hazard ratio, 1.136 [95% confidence interval, 1.054;1.224] P < 0.0001), advanced DR, including severe non-proliferative and proliferative DR and diabetic macula edema (1.213 [1.097;1.340] P < 0.0001), and especially proliferative DR alone (1.381 [1.207;1.580] P < 0.0001), compared with those without DR. The impact of DR was more evident in patients without than in those with DKD or CVD. Mortality risk was increased in participants with DR alone, though much less than in those with DKD or CVD alone and particularly in those with both DR and DKD or CVD. DR grade was related to mortality in individuals without DKD or CVD, whereas it conferred no additional risk to those with albuminuric or nonalbuminuric DKD or established CVD. Conclusions: In patients with type 2 diabetes mellitus, the excess mortality risk conferred by DR is relatively small and higher in those without DKD and CVD, suggesting that it may be mediated by the concurrent presence of these complications, even at a subclinical level.
Published: 2023

7. Die Messung von Schlafproblemen und der Beeinträchtigung der Tagesform mittels der Athens Insomnia Scale for Non-Clinical Application (AIS-NCA) in deutscher und englischer Sprache

Author: Sattler, S., Seddig, D., and Zerbini, G.
Subjects: Schlafqualität, Funktionsfähigkeit am Tag, Schlafprobleme, Tagesform, Schlaf
Abstract: Die „Athens Insomnia Scale for Non-Clinical Application (AIS-NCA)“ erfasst Schlafprobleme (anhand von vier Items) und die Beeinträchtigung der Tagesform (anhand von drei Items). Es ist auch möglich alle sieben Items als Gesamtskala zu verwenden. Die AIS-NCA wurde für nicht-klinischen Anwendungen entwickelt und liegt sowohl in deutscher (AIS-NCA-G) als auch englischer Sprache (AIS-NCA-E) vor., Zusammenstellung sozialwissenschaftlicher Items und Skalen (ZIS)
Published: 2023
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8. Topical nerve growth factor prevents neurodegenerative and vascular stages of diabetic retinopathy

Author: Zerbini, G., Maestroni, S., Leocani, L., Mosca, A., Godi, M., Paleari, R., Belvedere, A., Gabellini, D., Tirassa, P., Castoldi, V., Viganò, I., Galbiati, S., Turco, V., Lambiase, A., and Rama, P.
Subjects: Pharmacology, diabetic retinopathy, topical treatment, nerve growth factor, neurodegeneration, prevention, Pharmacology (medical), Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Abstract: Specific and effective preventive treatment for diabetic retinopathy (DR) is presently unavailable, mostly because the early stages of the complication have been, until recently, poorly understood. The recent demonstration that the vascular phase of DR is preceded and possibly caused by the neurodegeneration of retinal ganglion cells suggests that DR could, at least theoretically, be prevented through an early neuroprotective approach. The aims of our study were to clarify the natural history of diabetes-driven retinal neurodegeneration and to verify the possibility to prevent DR using topical nerve growth factor (NGF). The results of the study show that retinal neurodegeneration, characterized by the loss of retinal ganglion cells represents a relatively early phenomenon of diabetes (between 5 and 16 weeks of age), which tends to be self-limiting in the long run. Neurodegeneration is followed by the development of DR-related vascular dysfunctions, as confirmed by the development of acellular capillaries and the loss of retinal pericytes. Both retinal neurodegeneration and subsequent vascular dysfunction can be successfully prevented by topical NGF administration. These findings suggest that: 1) The first stage of DR consists in a self-limiting retinal neurodegeneration 2) The demonstrated effectiveness of topical NGF in the prevention of DR could be rapidly translated into clinical practice.
Published: 2022

9. Sodium-glucose cotransporter 2 inhibition prevents renal fibrosis in cyclosporine nephropathy

Author: Castoldi, G, Carletti, R, Ippolito, S, Colzani, M, Barzaghi, F, Stella, A, Zerbini, G, Perseghin, G, Zatti, G, di Gioia, C, Castoldi G., Carletti R., Ippolito S., Colzani M., Barzaghi F., Stella A., Zerbini G., Perseghin G., Zatti G., di Gioia C. R. T., Castoldi, G, Carletti, R, Ippolito, S, Colzani, M, Barzaghi, F, Stella, A, Zerbini, G, Perseghin, G, Zatti, G, di Gioia, C, Castoldi G., Carletti R., Ippolito S., Colzani M., Barzaghi F., Stella A., Zerbini G., Perseghin G., Zatti G., and di Gioia C. R. T.
Abstract: Aims: Sodium-glucose cotransporter 2 (SGLT2) inhibitors, a new class of antidiabetic drugs, are nephroprotective in case of diabetes, but whether a similar beneficial effect may be detectable also in case of chronic non-diabetic kidney diseases remains still unknown. The aim of this study was to evaluate the effects of empagliflozin, a SGLT-2 inhibitor, on the progression of cyclosporine nephropathy, in the absence of diabetes. Methods: Sprague Dawley rats (n = 27) have been fed with low-salt diet starting 10 days before the beginning and finished at the end of the experimental period. Cyclosporine-A (CsA, 15 mg/kg/day, intraperitoneal injection, n = 8) and CsA plus empagliflozin (Empa, 10 mg/kg/day, per os, n = 7) were administered for 4 weeks. The control groups were treated with placebo (Control, n = 7) or empagliflozin (Control + Empa, n = 5). Blood pressure (plethysmographic method) was measured at the beginning and at the end of the experimental period. At the end of the experimental protocol, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates (monocytes/macrophages), type I and type IV collagen expression, and tyrosine hydroxylase expression, used as marker of sympathetic nerve activity. Results: CsA-treated rats showed a significant increase (p < 0.01) in blood pressure, which was reduced by administration of empagliflozin (p < 0.05). CsA administration caused an increase in glomerular and tubulo-interstitial fibrosis (p < 0.05), renal inflammatory infiltrates (p < 0.05), type I and type IV collagen expression (p < 0.01), and tyrosine hydroxylase expression (p < 0.01) as compared to the control rats and control + Empa-treated rats. Treatment with empagliflozin in CsA-treated rats reduced glomerular (p < 0.01) and tubulo-interstitial fibrosis (p < 0.05), type I and type IV collagen expression (p < 0.01), inflammatory cell infiltr
Published: 2021

10. Insulin resistance, diabetic kidney disease, and all-cause mortality in individuals with type 2 diabetes: a prospective cohort study

Author: Penno, G, Solini, A, Orsi, E, Bonora, E, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Zerbini, G, Lamacchia, O, Nicolucci, A, Pugliese, G, Laviola, L, Penno G., Solini A., Orsi E., Bonora E., Fondelli C., Trevisan R., Vedovato M., Cavalot F., Zerbini G., Lamacchia O., Nicolucci A., Pugliese G., Laviola L., Penno, G, Solini, A, Orsi, E, Bonora, E, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Zerbini, G, Lamacchia, O, Nicolucci, A, Pugliese, G, Laviola, L, Penno G., Solini A., Orsi E., Bonora E., Fondelli C., Trevisan R., Vedovato M., Cavalot F., Zerbini G., Lamacchia O., Nicolucci A., Pugliese G., and Laviola L.
Abstract: Background: It is unclear whether insulin resistance (IR) contributes to excess mortality in patients with type 2 diabetes independent of diabetic kidney disease (DKD), which is strongly associated with IR and is a major risk factor for cardiovascular disease (CVD), the main cause of death in these individuals. We tested this hypothesis in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian Multicentre Study. Methods: This observational, prospective, cohort study enrolled 15,773 patients with type 2 diabetes attending 19 Italian Diabetes Clinics in 2006–2008. Insulin sensitivity was assessed as estimated glucose disposal rate (eGDR), which was validated against the euglycaemic-hyperinsulinemic clamp technique. Vital status on October 31, 2015, was retrieved for 15,656 patients (99.3%). Participants were stratified by eGDR tertiles from T1 (≥ 5.35 mg/kg/min) to T3 (≤ 4.14 mg/kg/min, highest IR). Results: CVD risk profile was worse in T2 and T3 vs T1. eGDR tertiles were independently associated with micro- and macroalbuminuria and the albuminuric DKD phenotypes (albuminuria with preserved or reduced estimated glomerular filtration rate [eGFR]) as well as with eGFR categories or the nonalbuminuric DKD phenotype. Over a 7.4-year follow-up, unadjusted death rates and mortality risks increased progressively across eGDR tertiles, but remained significantly elevated after adjustment only in T3 vs T1 (age- and gender- adjusted death rate, 22.35 vs 16.74 per 1000 person-years, p < 0.0001, and hazard ratio [HR] adjusted for multiple confounders including DKD, 1.140 [95% confidence interval [CI], 1.049–1.238], p = 0.002). However, eGDR was independently associated with mortality in participants with no DKD (adjusted HR, 1.214 [95% CI, 1.072–1.375], p = 0.002) and in those with nonalbuminuric DKD (1.276 [1.034–1.575], p = 0.023), but not in those with the albuminuric DKD phenotypes. Moreover, the association was stronger in males and i
Published: 2021

11. Renal Anti-Fibrotic Effect of Sodium Glucose Cotransporter 2 Inhibition in Angiotensin II-Dependent Hypertension

Author: Castoldi, G, Carletti, R, Ippolito, S, Colzani, M, Barzaghi, F, Stella, A, Zerbini, G, Perseghin, G, Di Gioia, C, Castoldi G., Carletti R., Ippolito S., Colzani M., Barzaghi F., Stella A., Zerbini G., Perseghin G., Di Gioia C. R. T., Castoldi, G, Carletti, R, Ippolito, S, Colzani, M, Barzaghi, F, Stella, A, Zerbini, G, Perseghin, G, Di Gioia, C, Castoldi G., Carletti R., Ippolito S., Colzani M., Barzaghi F., Stella A., Zerbini G., Perseghin G., and Di Gioia C. R. T.
Abstract: Background: Clinical trials have shown that empagliflozin (Empa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, promotes nephroprotective effects in diabetic patients. The mechanisms underlying nephroprotection are not completely known and it is not known whether the renal beneficial action is present even in non-diabetic kidney disease. The aim of this study was to evaluate the effect of Empa administration on the development of renal fibrosis in an experimental model of angiotensin II (Ang II)-dependent hypertension. Methods: Sprague Dawley rats (n = 31) were divided into 4 experimental groups. Ang II (200 ng/kg/min, osmotic minipumps, s.c., n = 9) or Ang II + Empa (10 mg/kg/day, per os, n = 10) were administered for 2 weeks. Control rats were treated with placebo (physiological saline, n = 6), and another group was treated with placebo plus Empa (n = 6) for the same period. Blood pressure (plethysmographic method) was measured at the beginning and at the end of the experimental protocol. After 2 weeks, the rats were euthanized and the kidneys were excised for histomorphometric evaluation of glomerular and tubulo-interstitial fibrosis and for the immunohistochemical evaluation of inflammatory infiltrates (monocytes/macrophages) and types I and IV collagen expression. Results: The administration of Ang II resulted in an increase in blood pressure (p < 0.01), glomerular (p < 0.05) and tubulo-interstitial (p < 0.01) fibrosis, renal inflammatory infiltrates (p < 0.01) and type I (p < 0.01) and type IV collagen expression (p < 0.05) compared to the control group. Treatment with Empa did not significantly modify the increase in blood pressure due to Ang II, but prevented the development of renal glomerular and tubulo-interstitial fibrosis, and the increase in inflammatory infiltrates and types I and IV collagen expression in Ang II-treated rats (p < 0.01). Conclusions: These data demonstrate that the treatment with Empa prevents the developmen
Published: 2020

12. Angiotensin II Modulates Calcium/Phosphate Excretion in Experimental Model of Hypertension: Focus on Bone

Author: Castoldi, G, Carletti, R, Ippolito, S, Villa, I, Palmisano, B, Bolamperti, S, Rubinacci, A, Zerbini, G, Meani, M, Zatti, G, di Gioia, C, Castoldi, Giovanna, Carletti, Raffaella, Ippolito, Silvia, Villa, Isabella, Palmisano, Biagio, Bolamperti, Simona, Rubinacci, Alessandro, Zerbini, Gianpaolo, Meani, Michela, Zatti, Giovanni, di Gioia, Cira R. T., Castoldi, G, Carletti, R, Ippolito, S, Villa, I, Palmisano, B, Bolamperti, S, Rubinacci, A, Zerbini, G, Meani, M, Zatti, G, di Gioia, C, Castoldi, Giovanna, Carletti, Raffaella, Ippolito, Silvia, Villa, Isabella, Palmisano, Biagio, Bolamperti, Simona, Rubinacci, Alessandro, Zerbini, Gianpaolo, Meani, Michela, Zatti, Giovanni, and di Gioia, Cira R. T.
Abstract: A link between hypertension and long-term bone health has been suggested. The aim of this study was to investigate the effects of chronic angiotensin II administration on urinary calcium/phosphate excretion, bone mineral density, bone remodeling and osteoblast population in a well-established experimental model of hypertension, in the absence of possible confounding factors that could affect bone metabolism. Male Sprague–Dawley rats, divided in the following groups: (a) Angiotensin II (Ang II, 200 ng/kg/min, osmotic minipumps, sub cutis, n = 8); (b) Ang II+losartan (Los, 50 mg/kg/day, per os, n = 6); (c) control group (physiological saline, sub cutis, n = 9); and (d) control+losartan (n = 6) were treated for four weeks. During the experimental period, 24-hour diuresis, urinary calcium, phosphate and sodium excretion were measured prior to the treatment, at two weeks of treatment, and at the end of the treatment. Systolic blood pressure was measured by plethysmography technique (tail cuff method). At the end of the experimental protocol, the rats were euthanized and peripheral quantitative computed tomography at the proximal metaphysis and at the diaphysis of the tibiae and quantitative bone histomorphometry on distal femora were performed. Angiotensin II-dependent hypertension is associated with increased calcium and phosphate excretion. AT1 receptor blockade prevented the increase of blood pressure and phosphate excretion but did not affect the increase of calcium excretion. These changes took place without significantly affecting bone density, bone histology or osteoblast population. In conclusion, in our experimental conditions, angiotensin II-dependent hypertension gave rise to an increased urinary excretion of calcium and phosphate without affecting bone density.
Published: 2022

13. [OP.4B.05] MIR-30A-3P EXPRESSION IN THE HEARTS OF DIABETIC RATS: EFFECTS OF ANGIOTENSIN TYPE 1 (AT1) AND ANGIOTENSIN TYPE 2 (AT2) RECEPTORS

Author: Castoldi, G., Di Gioia, C., Roma, F., Carletti, R., Sinico, R.A., Stella, A., Zerbini, G., and Perseghin, G.
Published: 2017
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14. SIK1 localizes with nephrin in glomerular podocytes and its polymorphism predicts kidney injury

Author: Ferrandi, M., Molinari, I., Matafora, V., Zerbini, G., Trevisani, F., Rastaldi, M. P., Simonini, M., Giardino, L., Ferrari, P., and Manunta, P.
Published: 2017
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15. Zoom Slit Lamp Adapter for Ophthalmological Green Laser

Author: Rossi, G., Zerbini, G., Castro, G. C., Ortega, T. A., Mota, A. D., Yasuoka, F. M. M., Magjarevic, Ratko, editor, Dössel, Olaf, editor, and Schlegel, Wolfgang C., editor
Published: 2009
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16. Insulin resistance, diabetic kidney disease, and all-cause mortality in individuals with type 2 diabetes: a prospective cohort study

Author: Penno G., Solini A., Orsi E., Bonora E., Fondelli C., Trevisan R., Vedovato M., Cavalot F., Zerbini G., Lamacchia O., Nicolucci A., Pugliese G., Laviola L., Penno, G, Solini, A, Orsi, E, Bonora, E, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Zerbini, G, Lamacchia, O, Nicolucci, A, Pugliese, G, and Laviola, L
Subjects: Male, medicine.medical_specialty, Mellitu, lcsh:Medicine, 030209 endocrinology & metabolism, Type 2 diabetes, 030204 cardiovascular system & hematology, Type 2 diabete, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Insulin resistance, Risk Factors, Diabetes mellitus, Internal medicine, Diabetes Mellitus, medicine, Humans, Albuminuria, Diabetic Nephropathies, Prospective Studies, Risk factor, Diabetic kidney disease, Prospective cohort study, albuminuria, all-cause mortality, diabetic kidney disease, estimated glucose disposal rate, glomerular filtration rate, mellitus, type 2 diabetes, Cause of death, Aged, Estimated glucose disposal rate, business.industry, Mortality rate, lcsh:R, General Medicine, medicine.disease, All-cause mortality, Survival Analysis, Glomerular filtration rate, Mellitus, Diabetes Mellitus, Type 2, Female, Insulin Resistance, medicine.symptom, business, Type 2, Research Article
Abstract: Background It is unclear whether insulin resistance (IR) contributes to excess mortality in patients with type 2 diabetes independent of diabetic kidney disease (DKD), which is strongly associated with IR and is a major risk factor for cardiovascular disease (CVD), the main cause of death in these individuals. We tested this hypothesis in patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events Italian Multicentre Study. Methods This observational, prospective, cohort study enrolled 15,773 patients with type 2 diabetes attending 19 Italian Diabetes Clinics in 2006–2008. Insulin sensitivity was assessed as estimated glucose disposal rate (eGDR), which was validated against the euglycaemic-hyperinsulinemic clamp technique. Vital status on October 31, 2015, was retrieved for 15,656 patients (99.3%). Participants were stratified by eGDR tertiles from T1 (≥ 5.35 mg/kg/min) to T3 (≤ 4.14 mg/kg/min, highest IR). Results CVD risk profile was worse in T2 and T3 vs T1. eGDR tertiles were independently associated with micro- and macroalbuminuria and the albuminuric DKD phenotypes (albuminuria with preserved or reduced estimated glomerular filtration rate [eGFR]) as well as with eGFR categories or the nonalbuminuric DKD phenotype. Over a 7.4-year follow-up, unadjusted death rates and mortality risks increased progressively across eGDR tertiles, but remained significantly elevated after adjustment only in T3 vs T1 (age- and gender- adjusted death rate, 22.35 vs 16.74 per 1000 person-years, p p = 0.002). However, eGDR was independently associated with mortality in participants with no DKD (adjusted HR, 1.214 [95% CI, 1.072–1.375], p = 0.002) and in those with nonalbuminuric DKD (1.276 [1.034–1.575], p = 0.023), but not in those with the albuminuric DKD phenotypes. Moreover, the association was stronger in males and in younger individuals and was observed in those without but not with prior CVD, though interaction was significant only for age. Conclusions The proxy of insulin sensitivity eGDR predicts all-cause mortality in type 2 diabetes, independent of confounders including DKD. However, the impact of IR in individuals with albuminuric DKD may be mediated by its relationship with albuminuria. Trial registration ClinicalTrials.gov, NCT00715481, retrospectively registered 15 July 2008.
Published: 2021

17. Is resistant hypertension an independent predictor of all-cause mortality in individuals with type 2 diabetes? A prospective cohort study

Author: Solini, A, Penno, G, Orsi, E, Bonora, E, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Lamacchia, O, Baroni, M, Nicolucci, A, Pugliese, G, Bollanti, L, Alessi, E, Vitale, M, Cirrito, T, Cavallo-Perin, P, Gruden, G, Lorenzati, B, Trovati, M, Di Martino, L, Mazzaglia, F, Zerbini, G, Martina, V, Maestroni, S, Capuano, V, Palmieri, E, Lunati, E, Grancini, V, Resi, V, Pontiroli, A, Veronelli, A, Zecchini, B, Arosio, M, Montefusco, L, Rossi, A, Adda, G, Corsi, A, Albizzi, M, Zoppini, G, Avogaro, A, Pucci, L, Lucchesi, D, Russo, E, Garofolo, M, Dotta, F, Nigi, L, Morano, S, Filardi, T, Turinese, I, Rossetti, M, Buzzetti, R, Foffi, C, Cignarelli, M, Pinnelli, S, Monaco, L, Giorgino, F, Laviola, L, Natalicchio, A, Sesti, G, Andreozzi, F, Frau, G, Boi, A, Solini A., Penno G., Orsi E., Bonora E., Fondelli C., Trevisan R., Vedovato M., Cavalot F., Lamacchia O., Baroni M. G., Nicolucci A., Pugliese G., Bollanti L., Alessi E., Vitale M., Cirrito T., Cavallo-Perin P., Gruden G., Lorenzati B., Trovati M., Di Martino L., Mazzaglia F., Zerbini G., Martina V., Maestroni S., Capuano V., Palmieri E., Lunati E., Grancini V., Resi V., Pontiroli A., Veronelli A., Zecchini B., Arosio M., Montefusco L., Rossi A., Adda G., Corsi A., Albizzi M., Zoppini G., Avogaro A., Pucci L., Lucchesi D., Russo E., Garofolo M., Dotta F., Nigi L., Morano S., Filardi T., Turinese I., Rossetti M., Buzzetti R., Foffi C., Cignarelli M., Pinnelli S., Monaco L., Giorgino F., Laviola L., Natalicchio A., Sesti G., Andreozzi F., Frau G., Boi A., Solini, A, Penno, G, Orsi, E, Bonora, E, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Lamacchia, O, Baroni, M, Nicolucci, A, Pugliese, G, Bollanti, L, Alessi, E, Vitale, M, Cirrito, T, Cavallo-Perin, P, Gruden, G, Lorenzati, B, Trovati, M, Di Martino, L, Mazzaglia, F, Zerbini, G, Martina, V, Maestroni, S, Capuano, V, Palmieri, E, Lunati, E, Grancini, V, Resi, V, Pontiroli, A, Veronelli, A, Zecchini, B, Arosio, M, Montefusco, L, Rossi, A, Adda, G, Corsi, A, Albizzi, M, Zoppini, G, Avogaro, A, Pucci, L, Lucchesi, D, Russo, E, Garofolo, M, Dotta, F, Nigi, L, Morano, S, Filardi, T, Turinese, I, Rossetti, M, Buzzetti, R, Foffi, C, Cignarelli, M, Pinnelli, S, Monaco, L, Giorgino, F, Laviola, L, Natalicchio, A, Sesti, G, Andreozzi, F, Frau, G, Boi, A, Solini A., Penno G., Orsi E., Bonora E., Fondelli C., Trevisan R., Vedovato M., Cavalot F., Lamacchia O., Baroni M. G., Nicolucci A., Pugliese G., Bollanti L., Alessi E., Vitale M., Cirrito T., Cavallo-Perin P., Gruden G., Lorenzati B., Trovati M., Di Martino L., Mazzaglia F., Zerbini G., Martina V., Maestroni S., Capuano V., Palmieri E., Lunati E., Grancini V., Resi V., Pontiroli A., Veronelli A., Zecchini B., Arosio M., Montefusco L., Rossi A., Adda G., Corsi A., Albizzi M., Zoppini G., Avogaro A., Pucci L., Lucchesi D., Russo E., Garofolo M., Dotta F., Nigi L., Morano S., Filardi T., Turinese I., Rossetti M., Buzzetti R., Foffi C., Cignarelli M., Pinnelli S., Monaco L., Giorgino F., Laviola L., Natalicchio A., Sesti G., Andreozzi F., Frau G., and Boi A.
Abstract: Background: Resistant hypertension is independently associated with an increased risk of death in the general hypertensive population. We assessed whether resistant hypertension is an independent predictor of all-cause mortality in individuals with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study. Methods: On 31 October 2015, vital status information was retrieved for 15,656 of the 15,773 participants enrolled in 2006-2008. Based on baseline blood pressure (BP) values and treatment, participants were categorized as normotensive, untreated hypertensive, controlled hypertensive (i.e., on-target with < 3 drugs), uncontrolled hypertensive (i.e., not on-target with 1-2 drugs), or resistant hypertensive (i.e., uncontrolled with > 3 drugs or controlled with > 4 drugs). Kaplan-Meier and Cox proportional hazards regression analyses were used to assess the association with all-cause mortality. Results: Using the 130/80 mmHg targets for categorization, crude mortality rates and Kaplan-Meier estimates were highest among resistant hypertension participants, especially those with controlled resistant hypertension. As compared with resistant hypertension, risk for all-cause mortality was significantly lower for all the other groups, including individuals with controlled hypertension (hazard ratio 0.81 [95% confidence interval 0.74-0.89], P < 0.0001), but became progressively similar between resistant and controlled hypertension after adjustment for cardiovascular risk factors and complications/comorbidities. Also when compared with controlled resistant hypertension, mortality risk was significantly lower for all the other groups, including controlled hypertension, even after adjusting for cardiovascular risk factors (0.77 [0.63-0.95], P = 0.012), but not for complications/comorbidities (0.88 [0.72-1.08], P = 0.216). BP was well below target in the controlled hypertensive groups (resistant and non-resistant) and values < 120/7
Published: 2019

18. EMPAGLIFLOZIN ADMINISTRATION PREVENTS THE DEVELOPMENT OF MYOCARDIAL FIBROSIS IN ANGIOTENSIN II-DEPENDENT HYPERTENSION

Author: Colzani, M, Di Gioia, C, Carletti, R, Ippolito, S, Barzaghi, F, Stella, A, Zerbini, G, Perseghin, G, Castoldi, G, Colzani, M., Di Gioia, C., Carletti, R., Ippolito, S., Barzaghi, F., Stella, A., Zerbini, G., Perseghin, G., Castoldi, G., Colzani, M, Di Gioia, C, Carletti, R, Ippolito, S, Barzaghi, F, Stella, A, Zerbini, G, Perseghin, G, Castoldi, G, Colzani, M., Di Gioia, C., Carletti, R., Ippolito, S., Barzaghi, F., Stella, A., Zerbini, G., Perseghin, G., and Castoldi, G.
Published: 2019

19. Improved Function of Circulating Angiogenic Cells Is Evident in Type 1 Diabetic Islet-Transplanted Patients

Author: Petrelli, A., Maestroni, A., Fadini, G.P., Belloni, D., Venturi, M., Albero, M., Kleffel, S., Mfarrej, B.G., Del Maschio, A., Maffi, P., Avogaro, A., Ferrero, E., Zerbini, G., Secchi, A., and Fiorina, P.
Published: 2010
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20. SGLT2 INHIBITION PREVENTS RENAL FIBROSIS IN CYCLOSPORINE NEPHROPATHY

Author: Castoldi, G, Carletti, R, Ippolito, S, Colzani, M, Barzaghi, F, Stella, A, Zerbini, G, Perseghin, G, Zatti, G, Di Gioia, C, Castoldi, G, Carletti, R, Ippolito, S, Colzani, M, Barzaghi, F, Stella, A, Zerbini, G, Perseghin, G, Zatti, G, and Di Gioia, C
Subjects: diabete, MED/13 - ENDOCRINOLOGIA
Published: 2020

21. Different expression of Fibrinopeptide A and related fragments in serum of type 1 diabetic patients with nephropathy

Author: Gianazza, E., Mainini, V., Castoldi, G., Chinello, C., Zerbini, G., Bianchi, C., Galbusera, C., Stella, A., Mauri, G., Zoppis, I., Magni, F., and Kienle, M. Galli
Published: 2010
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22. Communication skills of medical students: Evaluation of a new communication curriculum at the University of Augsburg

Author: Zerbini, Giulia, Reicherts, Philipp, Reicherts, Miriam, Roob, Nina, Schneider, Pia, Dankert, Andrea, Greiner, Sophie-Kathrin, Kadmon, Martina, Lechner, Veronika, Roos, Marco, Schimmel, Mareike, Strube, Wolfgang, Temizel, Selin, Uhrmacher, Luise, and Kunz, Miriam
Subjects: communication, empathy, education, communication skills, medical curriculum, simulated patients, Special aspects of education, LC8-6691, Medicine
Abstract: Objectives: Teaching communication skills plays a pivotal role in medical curricula. The aim of this article is to describe and evaluate a new communication curriculum developed at the Faculty of Medicine, University of Augsburg (KomCuA), which was conceptualized by an interdisciplinary team based on recommended quality standards (i.e., helical, integrated, longitudinal).Methods: A total of 150 medical students enrolled in the 1, 3, and ≥5 semester participated in the study. They completed an online survey (numerical rating scales and validated questionnaires) evaluating their current communication skills, how these developed across the curriculum in terms of quality and self-confidence, and how helpful they considered practicing in small group tutorials with simulated patients. The students’ attitudes towards communication and empathy in the context of medical care were additionally assessed. The students’ responses were compared across semesters using one-way univariate analysis of variance (ANOVA).Results: Overall, students reported improved communications skills due to attending the KomCuA and further considered practicing with simulated patients as being very helpful (large effect sizes). Compared to 1 semester students, 3 and ≥5 semester students reported better communication skills (medium to large effect sizes). Additionally, ≥5 semester students showed stronger agreement towards the relevance of empathy in the context of medical care (medium effect size) compared to both 1 and 3 semester students. Conclusion: The KomCuA has shown to be an effective communication curriculum to support medical students in the development of their communication skills and positive attitudes towards empathy. Additional studies assessing students’ communication skills and empathic attitudes longitudinally are warranted to confirm the present results and to gain further knowledge on how these essential skills and attitudes develop across medical curricula.
Published: 2024
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23. SIK1 localizes with nephrin in glomerular podocytes and its polymorphism predicts kidney injury

Author: Ferrandi, M., Molinari, I., Matafora, V., Zerbini, G., Trevisani, F., Rastaldi, M.P., Simonini, M., Giardino, L., Ferrari, P., and Manunta, P.
Published: 2014
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24. Defining the contribution of chronic kidney disease to all-cause mortality in patients with type 2 diabetes: the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study

Author: Penno, G, Solini, A, Bonora, E, Orsi, E, Fondelli, C, Zerbini, G, Trevisan, R, Vedovato, M, Cavalot, F, Laviola, L, Nicolucci, A, Pugliese, G, Penno G., Solini A., Bonora E., Orsi E., Fondelli C., Zerbini G., Trevisan R., Vedovato M., Cavalot F., Laviola L., Nicolucci A., Pugliese G., Penno, G, Solini, A, Bonora, E, Orsi, E, Fondelli, C, Zerbini, G, Trevisan, R, Vedovato, M, Cavalot, F, Laviola, L, Nicolucci, A, Pugliese, G, Penno G., Solini A., Bonora E., Orsi E., Fondelli C., Zerbini G., Trevisan R., Vedovato M., Cavalot F., Laviola L., Nicolucci A., and Pugliese G.
Abstract: Aims: To define the contribution of chronic kidney disease (CKD) to excess mortality in patients with type 2 diabetes and identify the baseline variables associated with all-cause death in those with and without CKD using the RECursive Partitioning and Amalgamation (RECPAM) method. Methods: This observational, longitudinal, cohort study enrolled 15,773 consecutive non-dialytic patients with type 2 diabetes in 19 Diabetes Clinics throughout Italy in 2006–2008. Based on the presence of albuminuria ≥ 30 mg day−1 and/or estimated glomerular filtration rate (eGFR) < 60 mL min−1·1.73 m−2 at baseline, patients were classified as having or not CKD. Vital status was verified on October 31, 2015 for 99.26% of patients. Results: Mortality increased with increasing albuminuria and eGFR category. Excess risk versus the general population was maximal in patients aged < 55 years in the worse albuminuria or eGFR category. Conversely, in subjects aged ≥ 75 years with albuminuria < 10 mg day−1 or eGFR ≥ 75 mL min−1·1.73 m−2, excess mortality was no longer detectable. At RECPAM analysis, the main correlates of death in the whole cohort were albuminuria > 44 mg day−1, prevalent CVD, and eGFR < ~ 75 mL min−1·1.73 m−2; gender, prevalent CVD, and higher albuminuria in the normoalbuminuric range, in patients without CKD; and CVD, eGFR ~ < 50 mL min−1·1.73 m−2, and albuminuria > 53 mg day−1, in those with CKD. Conclusions: CKD is a major contributor to excess mortality in type 2 diabetes, conferring a very high risk in younger patients and fully accounting for excess risk in the older ones. Higher albuminuria and lower eGFR, even in the normal range, identify individuals with increased mortality risk. Trial registration ClinicalTrials.gov (NCT00715481; https://clinicaltrials.gov/ct2/show/NCT00715481).
Published: 2018

25. Psychosocial burden of healthcare professionals in times of COVID-19 - a survey conducted at the University Hospital Augsburg

Author: Zerbini, G, Ebigbo, A, Reicherts, P, Kunz, M, and Messman, H
Subjects: health resources, Gesundheitsressourcen, ddc: 610, psychische Gesundheit, Pflegerinnen, Ärztinnen, COVID-19, Pfleger, Ärzte, health personnel, mental health, psychological burnout, Arbeitsbelastung
Abstract: Objective: The outbreak of COVID-19 was declared a pandemic by the WHO in March 2020. Studies from China, where the virus first spread, have reported increased psychological strain in healthcare professionals. The aim of this study was to investigate the psychosocial burden of physicians and nurses depending on their degree of contact with COVID-19 patients. In addition, we explored which supportive resources they used and which supportive needs they experienced during the crisis.Methods: Data were collected between March and April 2020 at the University Hospital Augsburg. A total of 75 nurses and 35 physicians, working either in a special COVID-19 ward or in a regular ward, took part in the survey. The participants filled in two standardized questionnaires (the Patient Health Questionnaire, PHQ; and the Maslach Burnout Inventory, MBI), and reported their fear of a COVID-19 infection and stress at work on a 10-point Likert scale. Finally, they answered three open-ended questions about causes of burden, supportive resources and needs during the crisis.Results: Nurses working in the COVID-19 wards reported higher levels of stress, exhaustion, and depressive mood, as well as lower levels of work-related fulfilment compared to their colleagues in the regular wards. Physicians reported similar scores independent of their contact with COVID-19 patients. The most common causes for burden were job strain and uncertainty about the future. Psychosocial support as well as leisure time were listed as important resources, and a better infrastructure adjustment to COVID-19 at the hospital (e.g. sufficient staff, keeping teams and working schedules stable) as suggestion for improvement.Conclusions: Our findings indicate that especially nurses working in COVID-19 wards are affected psychologically by the consequences of the pandemic. This might be due to a higher workload and longer time in direct contact with COVID-19 patients, compared to physicians. Ziel: Im März 2020 wurde der Ausbruch von COVID-19 von der WHO zur Pandemie erklärt, nachdem sich der Virus zunächst vor allem in China ausbreitete. Erste Studien berichteten von einer erhöhten psychologischen Belastung der Beschäftigten im chinesischen Gesundheitssystem. Das Ziel der vorliegenden Studie war es, die besonderen psychosozialen Belastungen von Ärztinnen und Ärzten im Vergleich zu Pflegerinnen und Pflegern durch COVID-19 zu erfassen, unter Berücksichtigung des Ausmaßes der Exposition zu COVID-19-Patientinnen und -Patienten. Zusätzlich wollten wir besonders relevante Ressourcen und Möglichkeiten zur Entlastung eruieren.Methoden: Die Datenerhebung erfolgte zwischen März und April 2020 am Universitätsklinikum Augsburg. Insgesamt nahmen 75 Pflegerinnen und Pfleger sowie 35 Ärztinnen und Ärzte an der Untersuchung teil, die entweder in regulären oder speziellen COVID-19-Stationen tätig waren. Neben zwei Standardinstrumenten (Gesundheitsfragebogen PHQ und Fragebogen zur Arbeitsbelastung MBI) bewerteten die Teilnehmenden ihre Angst, sich mit COVID-19 zu infizieren, und das Ausmaß der Belastung am Arbeitsplatz auf 10-stufigen numerischen Ratingskalen. Zusätzlich wurden drei offene Fragen zu den größten Belastungen, Ressourcen und Bedürfnissen durch bzw. in der Krise beantwortet.Ergebnisse: Insbesondere Pflegerinnen und Pfleger auf COVID-19-Stationen berichteten mehr Stress, Ermüdung, depressive Symptome und geringere Erfüllung am Arbeitsplatz als ihre Kolleginnen und Kollegen auf den regulären Stationen. Ärztinnen und Ärzte hingegen erzielten unabhängig von der spezifischen Exposition zu COVID-19-Patientinnen und -Patienten ähnliche Ergebnisse. Am häufigsten wurden von den Teilnehmenden das Arbeitspensum und die Ungewissheit hinsichtlich der weiteren Entwicklung als Ursache ihrer Belastung benannt. Psychosoziale Unterstützung und Freizeit wurden als wichtige Ressourcen aufgelistet. Die Teilnehmenden mahnten u.a. an, auf ausreichendes Personal, Kontinuität der Teamzusammensetzung und Schichtplanung zu achten.Schlussfolgerungen: Unsere Ergebnisse zeigen, dass insbesondere das Pflegepersonal - im Kontrast zu Ärztinnen und Ärzten - auf COVID-19-Stationen psychosozial unter den Folgen der Pandemie leidet, vermutlich als Konsequenz der Mehrarbeit und des höheren Expositionsrisikos.
Published: 2020

26. Association between On-Treatment Haemoglobin A1c and All-Cause Mortality in Individuals with Type 2 Diabetes: Importance of Personalized Goals and Type of Anti-Hyperglycaemic Treatment

Author: Orsi, E, Bonora, E, Solini, A, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Zerbini, G, Morano, S, Nicolucci, A, Penno, G, Pugliese, G, Orsi, Emanuela, Bonora, Enzo, Solini, Anna, Fondelli, Cecilia, Trevisan, Roberto, Vedovato, Monica, Cavalot, Franco, Zerbini, Gianpaolo, Morano, Susanna, Nicolucci, Antonio, Penno, Giuseppe, Pugliese, Giuseppe, Orsi, E, Bonora, E, Solini, A, Fondelli, C, Trevisan, R, Vedovato, M, Cavalot, F, Zerbini, G, Morano, S, Nicolucci, A, Penno, G, Pugliese, G, Orsi, Emanuela, Bonora, Enzo, Solini, Anna, Fondelli, Cecilia, Trevisan, Roberto, Vedovato, Monica, Cavalot, Franco, Zerbini, Gianpaolo, Morano, Susanna, Nicolucci, Antonio, Penno, Giuseppe, and Pugliese, Giuseppe
Abstract: The increased mortality reported with intensive glycaemic control has been attributed to an increased risk of treatment-related hypoglycaemia. This study investigated the relationships of haemoglobin (Hb) A(1c), anti-hyperglycaemic treatment, and potential risks of adverse effects with all-cause mortality in patients with type 2 diabetes. Patients (n = 15,773) were stratified into four categories according to baseline HbA(1c) and then assigned to three target categories, based on whether HbA(1c) was <= 0.5% below or above (on-target), >0.5% below (below-target) or >0.5% above (above-target) their HbA(1c) goal, personalized according to the number of potential risks among age > 70 years, diabetes duration > 10 years, advanced complication(s), and severe comorbidity (ies). The vital status was retrieved for 15,656 patients (99.26%). Over a 7.4-year follow-up, mortality risk was increased among patients in the highest HbA(1c) category (>= 8.5%) (adjusted hazard ratio, 1.34 (95% confidence interval, 1.22-1.47), p < 0.001) and those above-target (1.42 (1.29-1.57), p < 0.001). Risk was increased among individuals in the lowest HbA(1c) category (<6.5%) and those below-target only if treated with agents causing hypoglycaemia (1.16 (1.03-1.29), p = 0.01 and 1.10 (1.01-1.22), p = 0.04, respectively). These data suggest the importance of setting both upper and lower personalized HbA(1c) goals to avoid overtreatment in high-risk individuals with type 2 diabetes treated with agents causing hypoglycaemia.
Published: 2020

27. Gender differences in cardiovascular disease risk factors, treatments and complications in patients with type 2 diabetes: the RIACE Italian multicentre study

Author: Penno, G., Solini, A., Bonora, E., Fondelli, C., Orsi, E., Zerbini, G., Trevisan, R., Vedovato, M., Gruden, G., Laviola, L., Nicolucci, A., and Pugliese, G.
Published: 2013
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28. C-peptide: a redundant relative of insulin?

Author: Luzi, L., Zerbini, G., and Caumo, A.
Published: 2007
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29. Increased clonogenic potential of circulating endothelial progenitor cells in patients with type 1 diabetes and proliferative retinopathy

Author: Asnaghi, V., Lattanzio, R., Mazzolari, G., Pastore, M. R., Ramoni, A., Maestroni, A., Ruggieri, D., Luzi, L., Brancato, R., and Zerbini, G.
Published: 2006
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30. Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen

Author: SALEM, R. M., TODD, J. N., SANDHOLM, N., COLE, J. B., CHEN, W. M., Andrews, D., PEZZOLESI, M. G., MCKEIGUE, P. M., HIRAKI, L. T., Qiu, C., Nair, V., DI LIAO, C., Cao, J. J., VALO, E., ONENGUT-GUMUSCU, S., SMILES, A. M., MCGURNAGHAN, S. J., HAUKKA, J. K., HARJUTSALO, V., BRENNAN, E. P., VAN ZUYDAM, N., AHLQVIST, E., Doyle, R., AHLUWALIA, T. S., LAJER, M., HUGHES, M. F., Park, J., SKUPIEN, J., SPILIOPOULOU, A., Liu, A., Menon, R., BOUSTANY-KARI, C. M., KANG, H. M., NELSON, R. G., Klein, R., KLEIN, B. E., Lee, K. E., Gao, X., Mauer, M., MAESTRONI, S., CARAMORI, M. L., DE BOER, I. H., MILLER, R. G., Guo, J., BORIGHT, A. P., TREGOUET, D., Gyorgy, B., SNELL-BERGEON, J. K., MAAHS, D. M., BULL, S. B., CANTY, A. J., PALMER, C. N. A., STECHEMESSER, L., PAULWEBER, B., WEITGASSER, R., SOKOLOVSKA, J., ROVITE, V., PIRAGS, V., PRAKAPIENE, E., RADZEVICIENE, L., VERKAUSKIENE, R., PANDURU, N. M., GROOP, L. C., McCarthy, M. I., GU, H. F., MOLLSTEN, A., FALHAMMAR, H., Brismar, K., Martin, F., ROSSING, P., COSTACOU, T., ZERBINI, G., Marre, M., Hadjadj, S., MCKNIGHT, A. J., FORSBLOM, C., McKay, G., GODSON, C., Maxwell, A. P., KRETZLER, M., SUSZTAK, K., COLHOUN, H. M., KROLEWSKI, A., PATERSON, A. D., GROOP, P. H., RICH, S. S., HIRSCHHORN, J. N., FLOREZ, J. C., Bordeaux population health (BPH), and Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: VINTAGE, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, urologic and male genital diseases
Abstract: BACKGROUND: Although diabetic kidney disease demonstrates both familial clustering and single nucleotide polymorphism heritability, the specific genetic factors influencing risk remain largely unknown. METHODS: To identify genetic variants predisposing to diabetic kidney disease, we performed genome-wide association study (GWAS) analyses. Through collaboration with the Diabetes Nephropathy Collaborative Research Initiative, we assembled a large collection of type 1 diabetes cohorts with harmonized diabetic kidney disease phenotypes. We used a spectrum of ten diabetic kidney disease definitions based on albuminuria and renal function. RESULTS: Our GWAS meta-analysis included association results for up to 19,406 individuals of European descent with type 1 diabetes. We identified 16 genome-wide significant risk loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain (COL4A3) gene, which encodes a major structural component of the glomerular basement membrane (GBM). Mutations in COL4A3 are implicated in heritable nephropathies, including the progressive inherited nephropathy Alport syndrome. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of diabetic kidney disease, including albuminuria and ESKD, and demonstrated a significant association with GBM width; protective allele carriers had thinner GBM before any signs of kidney disease, and its effect was dependent on glycemia. Three other loci are in or near genes with known or suggestive involvement in this condition (BMP7) or renal biology (COLEC11 and DDR1). CONCLUSIONS: The 16 diabetic kidney disease-associated loci may provide novel insights into the pathogenesis of this condition and help identify potential biologic targets for prevention and treatment.
Published: 2019

31. Activity and expression of the Na+/H+ exchanger in human endothelial cells cultured in high glucose

Author: Zerbini, G., Roth, T., Podestá, E., Cagliero, E., Doria, A., Canessa, M., and Lorenzi, M.
Published: 1995
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32. Activation of angiotensin type 2 (AT2) receptors prevents myocardial hypertrophy in Zucker diabetic fatty rats

Author: Castoldi, G, di Gioia, C, Roma, F, Carletti, R, Manzoni, G, Stella, A, Zerbini, G, Perseghin, G, Castoldi, Giovanna, di Gioia, Cira R. T., Roma, Francesca, Carletti, Raffaella, Manzoni, Giuseppina, Stella, Andrea, Zerbini, Gianpaolo, Perseghin, Gianluca, Castoldi, G, di Gioia, C, Roma, F, Carletti, R, Manzoni, G, Stella, A, Zerbini, G, Perseghin, G, Castoldi, Giovanna, di Gioia, Cira R. T., Roma, Francesca, Carletti, Raffaella, Manzoni, Giuseppina, Stella, Andrea, Zerbini, Gianpaolo, and Perseghin, Gianluca
Abstract: Aims: Compound 21 (C21), selective AT2 receptor agonist, has cardioprotective effects in experimental models of hypertension and myocardial infarction. The aims of the study was to evaluate the effect of C21, losartan, or both in Zucker diabetic fatty (ZDF) rats (type 2 diabetes) on (1) the prevention of myocardial hypertrophy; (2) myocardial expression of phosphatase and tensin homolog (PTEN), a target gene of miR-30a-3p, involved in myocardial remodelling. Methods: Experiments were performed in ZDF (n = 33) and in control Lean (8) rats. From the 6th to the 20th week of age, we administered C21 (0.3 mg/kg/day) to 8 ZDF rats. 8 ZDF rats were treated with losartan (10 mg/kg/day), 8 rats underwent combination treatment, C21+ losartan, and 9 ZDF rats were left untreated. Blood glucose and blood pressure were measured every 4 weeks. At the end of the study the hearts were removed, the apex was cut for the quantification of PTEN mRNA and miR-30a-3p expression (realtime-PCR). Myocardial hypertrophy was evaluated by histomorphometric analysis, and nitrotyrosine expression (as marker of oxidative stress) by immunohistochemistry. Results: ZDF rats had higher blood glucose (p < 0.0001) with respect to control Lean rats, while blood pressure did not change. Both parameters were not modified by C21 treatment, while losartan and losartan + C21 reduced blood pressure in ZDF rats (p < 0.05). miR-30a-3p expression was increased in ZDF rats (p < 0.01) and PTEN mRNA expression was decreased (p < 0.05). ZDF rats developed myocardial hypertrophy (p < 0.01) and increased oxidative stress (p < 0.01), both were prevented by C21 or losartan, or combination treatment. C21 or losartan normalized the expression of miR-30a-3p and PTEN. Conclusions: Activation of AT2 receptors or AT1 receptor blockade prevents the development of myocardial hypertrophy in ZDF rats. This occurs through the modulation of the miR-30a-3p/PTEN interaction.
Published: 2019

33. Magnetic resonance imaging of the kidney in Type 1 (insulin-dependent) diabetes mellitus

Author: Mangili, R., Sironi, S., Rankel, G., Makarovic, M., Zerbini, G., Del Maschio, A., and Pozza, G.
Published: 1992
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34. Clinical significance of nonalbuminuric renal impairment in type 2 diabetes

Author: Penno, G., Solini, A., Bonora, E., Fondelli, C., Orsi, E., Zerbini, G., Trevisan, R., Vedovato, M., Gruden, G., Cavalot, F., Cignarelli, M., Laviola, L., Morano, S., Nicolucci, A., Pugliese, G., RIACE Study Group, Pugliese, G, Penno, G, Solini, A, Bonora, E, Orsi, E, Trevisan, R, Laviola, L, Nicolucci, A, De Cosmo, S, Gruden, G, Morano, S, Pugliese, F, Zerbini, G, Simonelli, P, Negro, A, Salvi, L, Bazuro, A, Frasheri, A, Cavallo Perin, P, Lorenzati, B, Trovati, M, Anfossi, G, Cavalot, F, Chirio, M, Martina, V, Dolci, A, Pontiroli, A, Laneri, M, Arosio, M, Rossi, A, Montefusco, L, Corsi, A, Zoppini, G, Avogaro, A, Vedovato, M, Pagnin, E, Pucci, L, Lucchesi, D, Storti, E, Dotta, Francesco, Fondelli, C, Nigi, L, Gatti, A, Mandosi, E, Fallarino, M, Buzzetti, R, Leto, G, Cignarelli, M, Lamacchia, O, Pinnelli, S, Giorgino, F, Perrini, S, Sesti, G, Andreozzi, F, Baroni, Mg, Frau, G., Penno, G, Solini, A, Bonora, E, Fondelli, C, Orsi, E, Zerbini, G, Trevisan, R, Vedovato, M, Gruden, G, Cavalot, F, Cignarelli, M, Laviola, L, Morano, S, Nicolucci, A, and Pugliese, G
Subjects: Male, albuminuria, cardiovascular disease, gfr, type 2 diabetes, medicine.medical_specialty, Physiology, Cardiovascular risk factors, MEDLINE, Renal function, Type 2 diabetes, GFR, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, Clinical significance, albuminuria, cardiovascular disease, GFR, type 2 diabetes, type 2 diabete, business.industry, medicine.disease, chronic kidney disease, Diabetes Mellitus, Type 2, Albuminuria, Female, Kidney Diseases, medicine.symptom, Cardiology and Cardiovascular Medicine, business, Glomerular Filtration Rate
Abstract: Objective: In type 2 diabetes, prevalence of nonalbuminuric renal impairment is increasing worldwide, though its clinical significance remains unclear. This large-cohort study aimed at evaluating the association of this phenotype with cardiovascular risk factors and other complications. Methods: Type 2 diabetic patients from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study (n=15773), visiting consecutively 19 hospital-based Diabetes Clinics in years 2007-2008, were examined. Serum creatinine was assessed by the Jaffe method; albuminuria was measured by immunonephelometry or immunoturbidimetry. Results: Of patients with renal impairment, as identified by an estimated glomerular filtration rate (eGFR) less than 60ml/min per 1.73m, 56.6% were normoalbuminuric, 30.8% were microalbuminuric, and 12.6% were macroalbuminuric. Percentages were similar when GFR was estimated using the more accurate Chronic Kidney Disease Epidemiology Collaboration equation instead of the simplified Modification of Diet in Renal Disease formula, and were independent of age, thus indicating that the increasing prevalence of this phenotype does not reflects misclassification of elderly patients. Nonalbuminuric renal impairment was not associated with HbA1c and correlated less strongly with retinopathy and hypertension than albuminuria, either alone or associated with reduced eGFR. It was associated with a higher prevalence of cardiovascular disease (CVD) than albuminuria alone, but lower than albuminuric renal impairment. Female sex correlated with nonalbuminuric renal impairment and male sex with the albuminuric forms. Conclusion:S: These data show that type 2 diabetic patients with nonalbuminuric renal impairment exhibit distinct clinical features, suggesting predominance of macroangiopathy as underlying renal pathology, and that this phenotype is associated with significant CVD burden.
Published: 2011

35. EMPAGLIFLOZIN ADMINISTRATION PREVENTS THE DEVELOPMENT OF MYOCARDIAL FIBROSIS IN ANGIOTENSIN II-DEPENDENT HYPERTENSION

Author: Colzani, M., primary, Di Gioia, C., additional, Carletti, R., additional, Ippolito, S., additional, Barzaghi, F., additional, Stella, A., additional, Zerbini, G., additional, Perseghin, G., additional, and Castoldi, G., additional
Published: 2019
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36. New genetic loci link adipose and insulin biology to body fat distribution

Author: Shungin, D, Winkler, T, Croteau Chonka, D, Ferreira, T, Locke, A, Mägi, R, Strawbridge, R, Pers, T, Fischer, K, Justice, A, Workalemahu, T, Wu, J, Buchkovich, M, Heard Costa, N, Roman, T, Drong, A, Song, C, Gustafsson, S, Day, F, Esko, T, Fall, T, Kutalik, Z, Luan, J, Randall, J, Scherag, A, Vedantam, S, Wood, A, Chen, J, Fehrmann, R, Karjalainen, J, Kahali, B, Liu, C, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bragg Gresham, J, Buyske, S, Demirkan, A, Ehret, G, Feitosa, M, Goel, A, Jackson, A, Johnson, T, Kleber, M, Kristiansson, K, Mangino, M, Leach, I, Medina Gomez, C, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Stanca'Kova', A, Sung, Y, Tanaka, T, Teumer, A, Van Vliet Ostaptchouk, J, Yengo, L, Zhang, W, Albrecht, E, Ärnlöv, J, Arscott, G, Bandinelli, S, Barrett, A, Bellis, C, Bennett, A, Berne, C, Blüher, M, Böhringer, S, Bonnet, F, Böttcher, Y, Bruinenberg, M, Carba, D, Caspersen, I, Clarke, R, Daw, E, Deelen, J, Deelman, E, Delgado, G, Doney, A, Eklund, N, Erdos, M, Estrada, K, Eury, E, Friedrich, N, Garcia, M, Giedraitis, V, Gigante, B, Go, A, Golay, A, Grallert, H, Grammer, T, Gräsler, J, Grewal, J, Groves, C, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heikkilä, K, Herzig, K, Helmer, Q, Hillege, H, Holmen, O, Hunt, S, Isaacs, A, Ittermann, T, James, A, Johansson, I, Juliusdottir, T, Kalafati, I, Kinnunen, L, Koenig, W, Kooner, I, Kratzer, W, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindström, J, Lobbens, S, Lorentzon, M, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Menni, C, Merger, S, Mihailov, E, Milani, L, Mills, R, Moayyeri, A, Monda, K, Mooijaart, S, Mühleisen, T, Mulas, A, Müller, G, Müller Nurasyid, M, Nagaraja, R, Nalls, M, Narisu, N, Glorioso, N, Nolte, I, Olden, M, Rayner, N, Renstrom, F, Ried, J, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Sennblad, B, Seufferlein, T, Sitlani, C, Smith, A, Stirrups, K, Stringham, H, Sundström, J, Swertz, M, Swift, A, Syvänen, A, Tayo, B, Thorand, B, Thorleifsson, G, Tomaschitz, A, Troffa, C, Van Oort, F, Verweij, N, Vonk, J, Waite, L, Wennauer, R, Wilsgaard, T, Wojczynski, M, Wong, A, Zhang, Q, Zhao, J, Brennan, E, Choi, M, Eriksson, P, Folkersen, L, Franco Cereceda, A, Gharavi, A, Hedman, A, Hivert, M, Huang, J, Kanoni, S, Karpe, F, Keildson, S, Kiryluk, K, Liang, L, Lifton, R, Ma, B, Mcknight, A, Mcpherson, R, Metspalu, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Olsson, C, Perry, J, Reinmaa, E, Salem, R, Sandholm, N, Schadt, E, Scott, R, Stolk, L, Vallejo, E, Westra, H, Zondervan, K, Amouyel, P, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Brown, M, Burnier, M, Campbell, H, Chakravarti, A, Chines, P, Claudi Boehm, S, Collins, F, Crawford, D, Danesh, J, De Faire, U, De Geus, E, Dörr, M, Erbel, R, Eriksson, J, Farrall, M, Ferrannini, E, Ferrières, J, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gieger, C, Gudnason, V, Haiman, C, 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Abstract: Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, we conducted genome-wide association meta-analyses of waist and hip circumference-related traits in up to 224,459 individuals. We identified 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (WHRadjBMI) and an additional 19 loci newly associated with related waist and hip circumference measures (P<5×10-8). Twenty of the 49 WHRadjBMI loci showed significant sexual dimorphism, 19 of which displayed a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation, and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms.
Published: 2015

37. Genetic studies of body mass index yield new insights for obesity biology

Author: Locke, A, Kahali, B, Berndt, S, Justice, A, Pers, T, Day, F, Powell, C, Vedantam, S, Buchkovich, M, Yang, J, Croteau-Chonka, D, Esko, T, Fall, T, Ferreira, T, Gustafsson, S, Kutalik, Z, Luan, J, Magi, R, Randall, J, Winkler, T, Wood, A, Workalemahu, T, Faul, J, Smith, J, Zhao, J, Zhao, W, Chen, J, Fehrmann, R, Hedman, A, Karjalainen, J, Schmidt, E, Absher, D, Amin, N, Anderson, D, Beekman, M, Bolton, J, Bragg-Gresham, J, Buyske, S, Demirkan, A, Deng, G, Ehret, G, Feenstra, B, Feitosa, M, Fischer, K, Goel, A, Gong, J, Jackson, A, Kanoni, S, Kleber, M, Kristiansson, K, Lim, U, Lotay, V, Mangino, M, Leach, I, Medina-Gomez, C, Medland, S, Nalls, M, Palmer, C, Pasko, D, Pechlivanis, S, Peters, M, Prokopenko, I, Shungin, D, Stancakova, A, Strawbridge, R, Sung, Y, Tanaka, T, Teumer, A, Trompet, S, van der Laan, S, van Setten, J, Van Vliet-Ostaptchouk, J, Wang, Z, Yengo, L, Zhang, W, Isaacs, A, Albrecht, E, Arnlov, J, Arscott, G, Attwood, A, Bandinelli, S, Barrett, A, Bas, I, Bellis, C, Bennett, A, Berne, C, Blagieva, R, Bluher, M, Bohringer, S, Bonnycastle, L, Bottcher, Y, Boyd, H, Bruinenberg, M, Caspersen, I, Chen, Y, Clarke, R, Daw, E, de Craen, A, Delgado, G, Dimitriou, M, Doney, A, Eklund, N, Estrada, K, Eury, E, Folkersen, L, Fraser, R, Garcia, M, Geller, F, Giedraitis, V, Gigante, B, Go, A, Golay, A, Goodall, A, Gordon, S, Gorski, M, Grabe, H, Grallert, H, Grammer, T, Grassler, J, Gronberg, H, Groves, C, Gusto, G, Haessler, J, Hall, P, Haller, T, Hallmans, G, Hartman, C, Hassinen, M, Hayward, C, Heard-Costa, N, Helmer, Q, Hengstenberg, C, Holmen, O, Hottenga, J, James, A, Jeff, J, Johansson, A, Jolley, J, Juliusdottir, T, Kinnunen, L, Koenig, W, Koskenvuo, M, Kratzer, W, Laitinen, J, Lamina, C, Leander, K, Lee, N, Lichtner, P, Lind, L, Lindstrom, J, Lo, K, Lobbens, S, Lorbeer, R, Lu, Y, Mach, F, Magnusson, P, Mahajan, A, Mcardle, W, Mclachlan, S, Menni, C, Merger, S, Mihailov, E, Milani, L, Moayyeri, A, Monda, K, Morken, M, Mulas, A, Muller, G, Muller-Nurasyid, M, Musk, A, Nagaraja, R, Nothen, M, Nolte, I, Pilz, S, Rayner, N, Renstrom, F, Rettig, R, Ried, J, Ripke, S, Robertson, N, Rose, L, Sanna, S, Scharnagl, H, Scholtens, S, Schumacher, F, Scott, W, Seufferlein, T, Shi, J, Smith, A, Smolonska, J, Stanton, A, Steinthorsdottir, V, Stirrups, K, Stringham, H, Sundstrom, J, Swertz, M, Swift, A, Syvanen, A, Tan, S, Tayo, B, Thorand, B, Thorleifsson, G, Tyrer, J, Uh, H, Vandenput, L, Verhulst, F, Vermeulen, S, Verweij, N, Vonk, J, Waite, L, Warren, H, Waterworth, D, Weedon, M, Wilkens, L, Willenborg, C, Wilsgaard, T, Wojczynski, M, Wong, A, Wright, A, Zhang, Q, Brennan, E, Choi, M, Dastani, Z, Drong, A, Eriksson, P, Franco-Cereceda, A, Gadin, J, Gharavi, A, Goddard, M, Handsaker, R, Huang, J, Karpe, F, Kathiresan, S, Keildson, S, Kiryluk, K, Kubo, M, Lee, J, Liang, L, Lifton, R, Ma, B, Mccarroll, S, Mcknight, A, Min, J, Moffatt, M, Montgomery, G, Murabito, J, Nicholson, G, Nyholt, D, Okada, Y, Perry, J, Dorajoo, R, Reinmaa, E, Salem, R, Sandholm, N, Scott, R, Stolk, L, Takahashi, A, Van't Hooft, F, Vinkhuyzen, A, Westra, H, Zheng, W, Zondervan, K, Heath, A, Arveiler, D, Bakker, S, Beilby, J, Bergman, R, Blangero, J, Bovet, P, Campbell, H, Caulfield, M, Cesana, G, Chakravarti, A, Chasman, D, Chines, P, Collins, F, Crawford, D, Cupples, L, Cusi, D, Danesh, J, de Faire, U, Den Ruijter, H, Dominiczak, A, Erbel, R, Erdmann, J, Eriksson, J, Farrall, M, Felix, S, Ferrannini, E, Ferrieres, J, Ford, I, Forouhi, N, Forrester, T, Franco, O, Gansevoort, R, Gejman, P, Gieger, C, Gottesman, O, Gudnason, V, Gyllensten, U, Hall, A, Harris, T, Hattersley, A, Hicks, A, Hindorff, L, Hingorani, A, Hofman, A, Homuth, G, Hovingh, G, Humphries, S, Hunt, S, Hypponen, E, Illig, T, Jacobs, K, Jarvelin, M, Jockel, K, Johansen, B, Jousilahti, P, Jukema, J, Jula, A, Kaprio, J, Kastelein, J, Keinanen-Kiukaanniemi, S, Kiemeney, L, Knekt, P, Kooner, J, Kooperberg, C, Kovacs, P, Kraja, A, Kumari, M, Kuusisto, J, Lakka, T, Langenberg, C, Marchand, L, Lehtimaki, T, Lyssenko, V, Mannisto, S, Marette, A, Matise, T, Mckenzie, C, Mcknight, B, Moll, F, Morris, A, Murray, J, Nelis, M, Ohlsson, C, Oldehinkel, A, Ong, K, Madden, P, Pasterkamp, G, Peden, J, Peters, A, Postma, D, Pramstaller, P, Price, J, Qi, L, Raitakari, O, Rankinen, T, Rao, D, Rice, T, Ridker, P, Rioux, J, Ritchie, M, Rudan, I, Salomaa, V, Samani, N, Saramies, J, Sarzynski, M, Schunkert, H, Schwarz, P, Sever, P, Shuldiner, A, Sinisalo, J, Stolk, R, Strauch, K, Tonjes, A, Tregouet, D, Tremblay, A, Tremoli, E, Virtamo, J, Vohl, M, Volker, U, Waeber, G, Willemsen, G, Witteman, J, Zillikens, M, Adair, L, Amouyel, P, Asselbergs, F, Assimes, T, Bochud, M, Boehm, B, Boerwinkle, E, Bornstein, S, Bottinger, E, Bouchard, C, Cauchi, S, Chambers, J, Chanock, S, Cooper, R, de Bakker, P, Dedoussis, G, Ferrucci, L, Franks, P, Froguel, P, Groop, L, Haiman, C, Hamsten, A, Hui, J, Hunter, D, Hveem, K, Kaplan, R, Kivimaki, M, Kuh, D, Laakso, M, Liu, Y, Martin, N, Marz, W, Melbye, M, Metspalu, A, Moebus, S, Munroe, P, Njolstad, I, Oostra, B, Pedersen, N, Perola, M, Perusse, L, Peters, U, Power, C, Quertermous, T, Rauramaa, R, Rivadeneira, F, Saaristo, T, Saleheen, D, Sattar, N, Schadt, E, Schlessinger, D, Slagboom, P, Snieder, H, Spector, T, Thorsteinsdottir, U, Stumvoll, M, Tuomilehto, J, Uitterlinden, A, Uusitupa, M, van der Harst, P, Walker, M, Wallaschofski, H, Wareham, N, Watkins, H, Weir, D, Wichmann, H, Wilson, J, Zanen, P, Borecki, I, Deloukas, P, Fox, C, Heid, I, O'Connell, J, Strachan, D, Stefansson, K, van Duijn, C, Abecasis, G, Franke, L, Frayling, T, Mccarthy, M, Visscher, P, Scherag, A, Willer, C, Boehnke, M, Mohlke, K, Lindgren, C, Beckmann, J, Barroso, I, North, K, Ingelsson, E, Hirschhorn, J, Loos, R, Speliotes, E, Thompson, J, Goldstein, B, Konig, I, Cazier, J, Grundberg, E, Havulinna, A, Ho, W, Hopewell, J, Eriksson, N, Lundmark, P, Lyytikainen, L, Rafelt, S, Tikkanen, E, Van Zuydam, N, Voight, B, Ziegler, A, Altshuler, D, Balmforth, A, Braund, P, Burgdorf, C, Claudi-Boehm, S, Cox, D, Do, R, El Mokhtari, N, Fontanillas, P, Hager, J, Han, B, Kang, H, Kessler, T, Knowles, J, Kolovou, G, Langford, C, Lokki, M, Lundmark, A, Meisinger, C, Melander, O, Maouche, S, Nikus, K, Rasheed, A, Rosinger, S, Rubin, D, Rumpf, M, Schafer, A, Sivananthan, M, Song, C, Stewart, A, Thorgeirsson, G, van der Schoot, C, Wagner, P, Wells, G, Wild, P, Tsun-Po, Y, Basart, H, Brambilla, P, Cambien, F, Cupples, A, Dehghan, A, Diemert, P, Epstein, S, Evans, A, Ferrario, M, Gauguier, D, Hazen, S, Holm, H, Iribarren, C, Jang, Y, Kahonen, M, Kee, F, Kim, H, Klopp, N, Kuulasmaa, K, Laaksonen, R, Ouwehand, W, Parish, S, Park, J, Rader, D, Shah, S, Stark, K, Wallentin, L, Zimmermann, M, Nieminen, M, Sandhu, M, Pastinen, T, Zalloua, P, Siegbahn, A, Schreiber, S, Ripatti, S, Blankenberg, S, O'Donnell, C, Reilly, M, Collins, R, Roberts, R, Pattaro, C, Kottgen, A, Garnaas, M, Boger, C, Fuchsberger, C, Olden, M, Chen, M, Tin, A, Taliun, D, Li, M, Gao, X, Yang, Q, Hundertmark, C, Foster, M, O'Seaghdha, C, Glazer, N, Liu, C, Struchalin, M, Li, G, Johnson, A, Gierman, H, Hwang, S, Atkinson, E, Lohman, K, Cornelis, M, Chouraki, V, Holliday, E, Sorice, R, Deshmukh, H, Ulivi, S, Chu, A, Murgia, F, Imboden, M, Kollerits, B, Pistis, G, Launer, L, Aspelund, T, Eiriksdottir, G, Mitchell, B, Schmidt, H, Cavalieri, M, Rao, M, Hu, F, de Andrade, M, Turner, S, Ding, J, Andrews, J, Freedman, B, Doring, A, Kolcic, I, Zemunik, T, Boban, M, Minelli, C, Wheeler, H, Igl, W, Zaboli, G, Wild, S, Ellinghaus, D, Nothlings, U, Jacobs, G, Biffar, R, Endlich, K, Ernst, F, Kroemer, H, Nauck, M, Stracke, S, Volzke, H, Aulchenko, Y, Polasek, O, Hastie, N, Vitart, V, Helmer, C, Wang, J, Ruggiero, D, Bergmann, S, Viikari, J, Nikopensius, T, Province, M, Ketkar, S, Colhoun, H, Robino, A, Giulianini, F, Kramer, B, Portas, L, Buckley, B, Adam, M, Thun, G, Paulweber, B, Haun, M, Sala, C, Metzger, M, Mitchell, P, Ciullo, M, Kim, S, Vollenweider, P, Gasparini, P, Pirastu, M, Probst-Hensch, N, Kronenberg, F, Toniolo, D, Coresh, J, Schmidt, R, Siscovick, D, Kardia, S, Curhan, G, Franke, A, Parsa, A, Goessling, W, Kao, W, de Boer, I, Peralta, C, Akylbekova, E, Kramer, H, Arking, D, Franceschini, N, Egan, J, Hernandez, D, Townsend, R, Lumley, T, Psaty, B, Kestenbaum, B, Haritunians, T, Mooser, V, Florez, J, Meigs, J, Lu, X, Leak, T, Aasarod, K, Skorpen, F, Baumert, J, Devuyst, O, Mychaleckyj, J, Kedenko, L, Coassin, S, Hallan, S, Navis, G, Shlipak, M, Bull, S, Paterson, A, Rotter, J, Dreisbach, A, Anderson, C, Guo, Q, Henders, A, Lambert, A, Lee, S, Kraft, P, Kennedy, S, Macgregor, S, Missmer, S, Painter, J, Roseman, F, Treloar, S, Wallace, L, Forsblom, C, Isakova, T, Mckay, G, Williams, W, Sadlier, D, Makinen, V, Swan, E, Boright, A, Ahlqvist, E, Keller, B, Huang, H, Ahola, A, Fagerholm, E, Gordin, D, Harjutsalo, V, He, B, Heikkila, O, Hietala, K, Kyto, J, Lahermo, P, Lehto, M, Osterholm, A, Parkkonen, M, Pitkaniemi, J, Rosengard-Barlund, M, Saraheimo, M, Sarti, C, Soderlund, J, Soro-Paavonen, A, Syreeni, A, Thorn, L, Tikkanen, H, Tolonen, N, Tryggvason, K, Waden, J, Gill, G, Prior, S, Guiducci, C, Mirel, D, Taylor, A, Hosseini, M, Parving, H, Rossing, P, Tarnow, L, Ladenvall, C, Alhenc-Gelas, F, Lefebvre, P, Rigalleau, V, Roussel, R, Maestroni, A, Maestroni, S, Falhammar, H, Gu, T, Mollsten, A, Cimponeriu, D, Mihai, I, Mota, M, Mota, E, Serafinceanu, C, Stavarachi, M, Hanson, R, Nelson, R, Kretzler, M, Panduru, N, Gu, H, Brismar, K, Zerbini, G, Hadjadj, S, Marre, M, Lajer, M, Waggott, D, Savage, D, Bain, S, Martin, F, Godson, C, Groop, P, Maxwell, A, Sengupta, S, Peloso, G, Ganna, A, Mora, S, Chang, H, Den Hertog, H, Donnelly, L, Freitag, D, Gurdasani, D, Heikkila, K, Johnson, T, Kaakinen, M, Kettunen, J, Li, X, Montasser, M, Petersen, A, Saxena, R, Service, S, Sidore, C, Surakka, I, Teslovich, T, Van den Herik, E, Volcik, K, Wu, Y, Asiki, G, Been, L, Burnett, M, Elliott, P, Eyjolfsson, G, Goodarzi, M, Gravito, M, Hartikainen, A, Hung, Y, Jones, M, Kaleebu, P, Khaw, K, Kim, E, Komulainen, P, Lin, S, Narisu, N, Nieminen, T, Nsubuga, R, Olafsson, I, Palotie, A, Papamarkou, T, Pomilla, C, Pouta, A, Ruokonen, A, Seeley, J, Silander, K, Tiret, L, van Pelt, L, Wainwright, N, Wijmenga, C, Young, E, Bennett, F, Boomsma, D, Burnier, M, Feranil, A, Freimer, N, Hsiung, C, Kesaniemi, A, Koudstaal, P, Krauss, R, Kyvik, K, Meneton, P, Moilanen, L, Sanghera, D, Sheu, W, Whitfield, J, Wolffenbuttel, B, Ordovas, J, Rich, S, Johnson, L, Larson, M, Levy, D, Newton-Cheh, C, O'Reilly, P, Palmas, W, Rice, K, Snider, H, Tobin, M, Verwoert, G, Pihur, V, Heath, S, Sober, S, Arora, P, Zhang, F, Lucas, G, Milaneschi, Y, Parker, A, Fava, C, Fox, E, Go, M, Sjogren, M, Vinay, D, Alexander, M, Tabara, Y, Shaw-Hawkins, S, Whincup, P, Shi, G, Seielstad, M, Sim, X, Nguyen, K, Matullo, G, Gaunt, T, Onland-Moret, N, Cooper, M, Platou, C, Org, E, Hardy, R, Dahgam, S, Palmen, J, Kuznetsova, T, Uiterwaal, C, Adeyemo, A, Ludwig, B, Tomaszewski, M, Tzoulaki, I, Palmer, N, Chang, Y, Steinle, N, Grobbee, D, Morrison, A, Najjar, S, Hadley, D, Brown, M, Connell, J, Day, I, Lawlor, D, Lawrence, R, Ongen, H, Li, Y, Young, J, Bis, J, Chaturvedi, N, Islam, M, Jafar, T, Kulkarni, S, Howard, P, Guarrera, S, Ricceri, F, Emilsson, V, Plump, A, Weder, A, Sun, Y, Scott, L, Peltonen, L, Vartiainen, E, Brand, S, Staessen, J, Wang, T, Burton, P, Artigas, M, Dong, Y, Wang, X, Zhu, H, Rudock, M, Heckbert, S, Smith, N, Wiggins, K, Doumatey, A, Shriner, D, Veldre, G, Viigimaa, M, Kinra, S, Prabhakaran, D, Tripathy, V, Langefeld, C, Rosengren, A, Thelle, D, Corsi, A, Singleton, A, Hilton, G, Salako, T, Iwai, N, Kita, Y, Ogihara, T, Ohkubo, T, Okamura, T, Ueshima, H, Umemura, S, Eyheramendy, S, Meitinger, T, Cho, Y, Scott, J, Sehmi, J, Hedblad, B, Nilsson, P, Smith, G, Raffel, L, Yao, J, Schwartz, S, Ikram, M, W, L, Mosley, T, Seshadri, S, Shrine, N, Wain, L, Zitting, P, Cooper, J, van Gilst, W, Janipalli, C, Mani, K, Yajnik, C, Mattace-Raso, F, Lakatta, E, Orru, M, Scuteri, A, Ala-Korpela, M, Kangas, A, Soininen, P, Tukiainen, T, Wurtz, P, Ong, R, Dorr, M, Galan, P, Hercberg, S, Lathrop, M, Zelenika, D, Zhai, G, Meschia, J, Sharma, P, Terzic, J, Kumar, M, Denniff, M, Zukowska-Szczechowska, E, Wagenknecht, L, Fowkes, F, Charchar, F, Guo, X, Rotimi, C, Bots, M, Brand, E, Talmud, P, Nyberg, F, Laan, M, Palmer, L, van der Schouw, Y, Casas, J, Vineis, P, Ganesh, S, Wong, T, Tai, E, Morris, R, Marmot, M, Miki, T, Chandak, G, Zhu, X, Elosua, R, Soranzo, N, Sijbrands, E, Uda, M, Vasan, R, Alizadeh, B, de Boer, R, Boezen, H, Hillege, H, van der Klauw, M, Ormel, J, Rosmalen, J, Slaets, J, Lagou, V, Welch, R, Wheeler, E, Rehnberg, E, Rasmussen-Torvik, L, Lecoeur, C, Johnson, P, Sennblad, B, Salo, P, Timpson, N, Evans, D, St Pourcain, B, Bielak, L, Horikoshi, M, Navarro, P, Raychaudhuri, S, Chen, H, Rybin, D, Willems, S, Song, K, An, P, Marullo, L, Jansen, H, Pankow, J, Edkins, S, Varga, T, Oksa, H, Antonella, M, Kong, A, Herder, C, Antti, J, Small, K, Miljkovic, I, Atalay, M, Kiess, W, Smit, J, Campbell, S, Fowkes, G, Rathmann, W, Maerz, W, Watanabe, R, de Geus, E, Penninx, B, Toenjes, A, Peyser, P, Korner, A, Dupuis, J, Cucca, F, Balkau, B, Bouatia-Naji, N, Purcell, S, Musunuru, K, Ardissino, D, Mannucci, P, Anand, S, Engert, J, Morgan, T, Spertus, J, Stoll, M, Girelli, D, Mckeown, P, Patterson, C, Merlini, P, Berzuini, C, Bernardinelli, L, Peyvandi, F, Tubaro, M, Celli, P, Fetiveau, R, Marziliano, N, Casari, G, Galli, M, Ribichini, F, Rossi, M, Bernardi, F, Zonzin, P, Piazza, A, Yee, J, Friedlander, Y, Marrugat, J, Subirana, I, Sala, J, Ramos, R, Williams, G, Nathan, D, Macrae, C, Berglund, G, Asselta, R, Duga, S, Spreafico, M, Daly, M, Nemesh, J, Korn, J, Surti, A, Gianniny, L, Parkin, M, Burtt, N, Gabriel, S, Wright, B, Ball, S, Schunkert, I, Linsel-Nitschke, P, Lieb, W, Fischer, M, Grosshennig, A, Preuss, M, Scholz, M, Chen, Z, Wilensky, R, Matthai, W, Qasim, A, Hakonarson, H, Devaney, J, Pichard, A, Kent, K, Satler, L, Lindsay, J, Waksman, R, Knouff, C, Scheffold, T, Berger, K, Huge, A, Martinelli, N, Olivieri, O, Corrocher, R, Xie, C, Ahmadi, K, Ainali, C, Bataille, V, Bell, J, Buil, A, Dermitzakis, E, Dimas, A, Durbin, R, Glass, D, Hassanali, N, Ingle, C, Knowles, D, Krestyaninova, M, Lowe, C, Meduri, E, Di Meglio, P, Montgomery, S, Nestle, F, Nica, A, Nisbet, J, O'Rahilly, S, Parts, L, Potter, S, Sekowska, M, Shin, S, Surdulescu, G, Travers, M, Tsaprouni, L, Tsoka, S, Wilk, A, Yang, T, Higashio, J, Williams, R, Nato, A, Ambite, J, Deelman, E, Manolio, T, Heiss, G, Taylor, K, Avery, C, Graff, M, Lin, D, Quibrera, M, Cochran, B, Kao, L, Umans, J, Cole, S, Maccluer, J, Person, S, Gross, M, Fornage, M, Durda, P, Jenny, N, Patsy, B, Arnold, A, Buzkova, P, Haines, J, Murdock, D, Glenn, K, Brown-Gentry, K, Thornton-Wells, T, Dumitrescu, L, Bush, W, Mitchell, S, Goodloe, R, Wilson, S, Boston, J, Malinowski, J, Restrepo, N, Oetjens, M, Fowke, J, Spencer, K, Pendergrass, S, Le Marchand, L, Park, L, Tiirikainen, M, Kolonel, L, Cheng, I, Wang, H, Shohet, R, Stram, D, Henderson, B, Monroe, K, Anderson, G, Carlson, C, Prentice, R, Lacroix, A, Wu, C, Carty, C, Rosse, S, Young, A, Kocarnik, J, Lin, Y, Jackson, R, Duggan, D, Kuller, L, He, C, Sulem, P, Barbalic, M, Broer, L, Byrne, E, Gudbjartsson, D, Mcardle, P, Porcu, E, van Wingerden, S, Zhuang, W, Lauc, L, Broekmans, F, Burri, A, Chen, C, Corre, T, Coviello, A, D'Adamo, P, Davies, G, Deary, I, Ebrahim, S, Fauser, B, Ferreli, L, Folsom, A, Hankinson, S, Hass, M, Janssens, A, Karasik, D, Keyzer, J, Kiel, D, Lahti, J, Lai, S, Laisk, T, Laven, J, Liu, J, Lopez, L, Louwers, Y, Marongiu, M, Klaric, I, Masciullo, C, Melzer, D, Newman, A, Pare, G, Peeters, P, Pop, V, Raikkonen, K, Salumets, A, Stacey, S, Starr, J, Stathopoulou, M, Styrkarsdottir, U, Tenesa, A, Tryggvadottir, L, Tsui, K, van Dam, R, van Gils, C, van Nierop, P, Vink, J, Voorhuis, M, Widen, E, Wijnands-Van Gent, C, Yerges-Armstrong, L, Zgaga, L, Zygmunt, M, Buring, J, Crisponi, L, Demerath, E, Streeten, E, Murray, A, Visser, J, Lunetta, K, Elks, C, Cousminer, D, Koller, D, Lin, P, Smith, E, Warrington, N, Alavere, H, Berenson, G, Blackburn, H, Busonero, F, Chen, W, Couper, D, Easton, D, Foroud, T, Kilpelainen, T, Li, S, Murray, S, Ness, A, Northstone, K, Peacock, M, Pennell, C, Pharoah, P, Rafnar, T, Rice, J, Ring, S, Schork, N, Segre, A, Sovio, U, Srinivasan, S, Tammesoo, M, van Meurs, J, Young, L, Bierut, L, Econs, M, Locke A. E., Kahali B., Berndt S. I., Justice A. E., Pers T. H., Day F. R., Powell C., Vedantam S., Buchkovich M. L., Yang J., Croteau-Chonka D. C., Esko T., Fall T., Ferreira T., Gustafsson S., Kutalik Z., Luan J., Magi R., Randall J. C., Winkler T. W., Wood A. R., Workalemahu T., Faul J. D., Smith J. A., Zhao J. H., Zhao W., Chen J., Fehrmann R., Hedman A. K., Karjalainen J., Schmidt E. M., Absher D., Amin N., Anderson D., Beekman M., Bolton J. L., Bragg-Gresham J. L., Buyske S., Demirkan A., Deng G., Ehret G. B., Feenstra B., Feitosa M. F., Fischer K., Goel A., Gong J., Jackson A. U., Kanoni S., Kleber M. E., Kristiansson K., Lim U., Lotay V., Mangino M., Leach I. M., Medina-Gomez C., Medland S. E., Nalls M. A., Palmer C. D., Pasko D., Pechlivanis S., Peters M. J., Prokopenko I., Shungin D., Stancakova A., Strawbridge R. J., Sung Y. J., Tanaka T., Teumer A., Trompet S., van der Laan S. W., van Setten J., Van Vliet-Ostaptchouk J. 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L., Goodloe R., Wilson S., Boston J., Malinowski J., Restrepo N., Oetjens M., Fowke J., Spencer K., Pendergrass S., Le Marchand L., Park L., Tiirikainen M., Kolonel L., Cheng I., Wang H., Shohet R., Stram D., Henderson B., Monroe K., Anderson G., Carlson C., Prentice R., Lacroix A., Wu C., Carty C., Rosse S., Young A., Kocarnik J., Lin Y., Jackson R., Duggan D., Kuller L., He C., Sulem P., Barbalic M., Broer L., Byrne E. M., Gudbjartsson D. F., McArdle P. F., Porcu E., van Wingerden S. W., Zhuang W. V., Lauc L. B., Broekmans F. J., Burri A., Chen C., Corre T., Coviello A. D., D'adamo P., Davies G., Deary I. J., Ebrahim S., Fauser B. C., Ferreli L., Folsom A. R., Hankinson S. E., Hass M., Janssens A. C., Karasik D., Keyzer J., Kiel D. P., Lahti J., Lai S., Laisk T., Laven J. S., Liu J., Lopez L. M., Louwers Y. V., Marongiu M., Klaric I. M., Masciullo C., Melzer D., Newman A. B., Pare G., Peeters P. H., Pop V. J., Raikkonen K., Salumets A., Stacey S. N., Starr J. M., Stathopoulou M. G., Styrkarsdottir U., Tenesa A., Tryggvadottir L., Tsui K., van Dam R. M., van Gils C. H., van Nierop P., Vink J. M., Voorhuis M., Widen E., Wijnands-Van Gent C. J., Yerges-Armstrong L. M., Zgaga L., Zygmunt M., Buring J. E., Crisponi L., Demerath E. W., Streeten E. A., Murray A., Visser J. A., Lunetta K. L., Elks C. E., Cousminer D. L., Koller D. L., Lin P., Smith E. N., Warrington N. M., Alavere H., Berenson G. S., Blackburn H., Busonero F., Chen W., Couper D., Easton D. F., Eriksson J., Foroud T., Kilpelainen T. O., Li S., Murray S. S., Ness A. R., Northstone K., Peacock M., Pennell C. E., Pharoah P., Rafnar T., Rice J. P., Ring S. M., Schork N. J., Segre A. V., Sovio U., Srinivasan S. R., Tammesoo M. L., van Meurs J. B., Young L., Bierut L. J., and Econs M. J.
Abstract: Obesity is heritable and predisposes to many diseases. To understand the genetic basis of obesity better, here we conduct a genome-wide association study and Metabochip meta-analysis of body mass index (BMI), a measure commonly used to define obesity and assess adiposity, in up to 339,224 individuals. This analysis identifies 97 BMI-associated loci (P < 5 × 10-8), 56 of which are novel. Five loci demonstrate clear evidence of several independent association signals, and many loci have significant effects on other metabolic phenotypes. The 97 loci account for ∼2.7% of BMI variation, and genome-wide estimates suggest that common variation accounts for >20 % of BMI variation. Pathway analyses provide strong support for a role of the central nervous system in obesity susceptibility and implicate new genes and pathways, including those related to synaptic function, glutamate signalling, insulin secretion/action, energy metabolism, lipid biology and adipogenesis.
Published: 2015

38. Chronic kidney disease in type 2 diabetes: Lessons from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study

Author: Pugliese, G, Solini, A, Bonora, E, Fondelli, C, Orsi, E, Nicolucci, A, Penno, G, RIACE Study Group, Trevisan, R, Laviola, L, De Cosmo, S, Gruden, G, Morano, S, Pugliese, F, Zerbini, G, Salvi, L, Bollanti, L, Bazuro, A, Cavallo Perin, P, Lorenzati, B, Trovati, M, Anfossi, G, Cavalot, F, Chirio, M, Martina, V, Maestroni, S, Montefusco, L, Zimbalatti, D, Pontiroli, A, Veronelli, A, Zecchini, B, Arosio, M, Dolci, A, Corsi, A, Zoppini, G, Avogaro, A, Vedovato, M, Pagnin, E, Pucci, L, Lucchesi, D, Russo, E, Garofolo, M, Dotta, Francesco, Nigi, L, Gatti, A, Buzzetti, R, Foffi, C, Cignarelli, M, Lamacchia, O, Pinnelli, S, Monaco, L, Giorgino, F, Perrini, S, Sesti, G, Andreozzi, F, Baroni, Mg, and Frau, G.
Subjects: Male, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Medicine (miscellaneous), Renal function, Type 2 diabetes, urologic and male genital diseases, End stage renal disease, Coronary artery disease, Sex Factors, Albuminuria, cardiovascular disease, Chronic kidney disease, Diabetic retinopathy, eGFR, Risk Factors, Internal medicine, Prevalence, medicine, Humans, Hypoglycemic Agents, Multicenter Studies as Topic, Renal Insufficiency, Chronic, Intensive care medicine, Glycated Hemoglobin, Nutrition and Dietetics, business.industry, riace, medicine.disease, Metformin, Observational Studies as Topic, Sulfonylurea Compounds, Diabetes Mellitus, Type 2, Italy, Cardiovascular Diseases, Cohort, Female, type 2 diabetes, medicine.symptom, Cardiovascular disease, EGFR, Cardiology and Cardiovascular Medicine, business, Glomerular Filtration Rate, Kidney disease
Abstract: The Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicentre Study is an ongoing observational survey that examines the role of estimated glomerular filtration rate (eGFR) as an independent predictor of cardiovascular and renal outcomes in 15,773 Italian subjects with type 2 diabetes. The analysis of data collected at the enrollment visit provided a picture of chronic kidney disease (CKD) and its association with other complications, risk factors for cardiovascular disease (CVD) and treatments in a large contemporary cohort. Main results of this analysis were that (a) non-albuminuric renal impairment is the predominant clinical phenotype in patients, particularly women, with reduced eGFR; (b) concordance between CKD and diabetic retinopathy is low, with only a minority of patients with renal dysfunction presenting with any or advanced retinal lesions; (c) the non-albuminuric form is associated with a significant prevalence of CVD, especially at the level of the coronary vascular bed; (d) CKD is associated with hemoglobin (Hb) A1c variability more than with average HbA1c, whereas retinopathy and CVD are not; (e) in elderly individuals with moderate-to-severe eGFR reduction, use of agents which are not recommended, such as sulphonylureas and metformin, is still frequent; and (f) though complications are generally more prevalent in men (except non-albuminuric renal impairment) women show a less favorable CVD risk profile and achieve therapeutic targets to a lesser extent than men, despite the fact that treatment intensity is not lower. These data update existing information on the natural history of CKD in patients with type 2 diabetes.
Published: 2014

39. Angiotensina e fibrosi renale: ruolo dei microRNA

Author: CASTOLDI, GIOVANNA, ROMA, FRANCESCA, STELLA, ANDREA, Di Gioia, C, Giollo,F, Carletti, R, Bombardi, C, Zerbini, G, Castoldi, G, Di Gioia, C, Giollo, F, Carletti, R, Bombardi, C, Roma, F, Zerbini, G, and Stella, A
Subjects: angiotensina II, microRNA, fibrosi renale
Published: 2015

40. The influence of sleep and time of day on school performance: causes, consequences and possible remedies

Author: Zerbini, G, additional, van der Vinne, V, additional, Otto, L, additional, Siersema, A, additional, Pieper, A, additional, Krijnen, W, additional, Hut, RA, additional, Kantermann, T, additional, Roenneberg, T, additional, and Merrow, M, additional
Published: 2018
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41. Distribution of cardiovascular disease and retinopathy in patients with type 2 diabetes according to different classification systems for chronic kidney disease: a cross-sectional analysis of the renal insufficiency and cardiovascular events (RIACE) Italian multicenter study

Author: Pugliese, G, Solini, A, Bonora, E, Orsi, E, Zerbini, G, Fondelli, C, Gruden, G, Cavalot, F, Lamacchia, O, Trevisan, R, Vedovato, M, Penno, G, Pugliese G, Solini A, Bonora E, Orsi E, Zerbini G, Fondelli C, Gruden G, Cavalot F, Lamacchia O, Trevisan R, Vedovato M, Penno G, Pugliese, G, Solini, A, Bonora, E, Orsi, E, Zerbini, G, Fondelli, C, Gruden, G, Cavalot, F, Lamacchia, O, Trevisan, R, Vedovato, M, Penno, G, Pugliese G, Solini A, Bonora E, Orsi E, Zerbini G, Fondelli C, Gruden G, Cavalot F, Lamacchia O, Trevisan R, Vedovato M, and Penno G
Abstract: Background: The National Kidney Foundation's Kidney Disease Outcomes Quality Initiative (NKF's KDOQI) staging system for chronic kidney disease (CKD) is based primarily on estimated GFR (eGFR). This study aimed at assessing whether reclassification of subjects with type 2 diabetes using two recent classifications based on both eGFR and albuminuria, the Alberta Kidney Disease Network (AKDN) and the Kidney Disease: Improving Global Outcomes (KDIGO), provides a better definition of burden from cardiovascular disease (CVD) and diabetic retinopathy (DR) than the NKF's KDOQI classification.Methods: This is a cross-sectional analysis of patients with type 2 diabetes (n = 15,773) from the Renal Insufficiency And Cardiovascular Events Italian Multicenter Study, consecutively visiting 19 Diabetes Clinics throughout Italy in years 2007-2008. Exclusion criteria were dialysis or renal transplantation. CKD was defined based on eGFR, as calculated from serum creatinine by the simplified Modification of Diet in Renal Disease Study equation, and albuminuria, as measured by immunonephelometry or immunoturbidimetry. DR was assessed by dilated fundoscopy. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events.Results: Though prevalence of complications increased with increasing CKD severity with all three classifications, it differed significantly between NKF's KDOQI stages and AKDN or KDIGO risk categories. The AKDN and KDIGO systems resulted in appropriate reclassification of uncomplicated patients in the lowest risk categories and a more graded independent association with CVD and DR than the NKF's KDOQI classification. However, CVD, but not DR prevalence was higher in the lowest risk categories of the new classifications than in the lowest stages of the NKF's KDOQI, due to the inclusion of subjects with reduced eGFR without albuminuria. CVD prevalence differed also among eGFR and albuminuria categories grouped
Published: 2014

42. [OP.4B.05] MIR-30A-3P EXPRESSION IN THE HEARTS OF DIABETIC RATS

Author: Castoldi, G, Di Gioia, C, Roma, F, Carletti, R, Sinico, R, Stella, A, Zerbini, G, Perseghin, G, ROMA, FRANCESCA, Sinico, RA, Castoldi, G, Di Gioia, C, Roma, F, Carletti, R, Sinico, R, Stella, A, Zerbini, G, Perseghin, G, ROMA, FRANCESCA, and Sinico, RA
Published: 2017

43. 5.17 Effects of Chronic Angiotensin II Administration on MicroRNA Expression in Rat Cardiovascular System

Author: Castoldi, G., di Gioia, C., Bombardi, C., Mancini, M., Leopizzi, M., Corradi, B., Zerbini, G., and Stella, A.
Published: 2008
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44. 4.24 Chronic AC-SDKP Administration Reduces Cardiac and Renal Perivascular Fibrosis in Diabetic Rats

Author: Castoldi, G., di Gioia, C., Perego, L., Bombardi, C., Mancini, M., Travaglini, C., Zerbini, G., and Stella, A.
Published: 2007
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45. Gender differences in cardiovascular disease risk factors, treatments and complications in patients with type 2 diabetes: the RIACE Italian multicentre study

Author: Penno, G, Solini, A, Bonora, E, Fondelli, C, Orsi, E, Zerbini, G, Trevisan, R, Vedovato, M, Gruden, G, Laviola, L, Nicolucci, A, Pugliese, G, Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, Trevisan R, Vedovato M, Gruden G, Laviola L, Nicolucci A, Pugliese G, Penno, G, Solini, A, Bonora, E, Fondelli, C, Orsi, E, Zerbini, G, Trevisan, R, Vedovato, M, Gruden, G, Laviola, L, Nicolucci, A, Pugliese, G, Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, Trevisan R, Vedovato M, Gruden G, Laviola L, Nicolucci A, and Pugliese G
Abstract: Objectives: Poorer control of risk factors for cardiovascular disease (CVD) has been reported in diabetic women, as compared with diabetic men. It has been proposed that this finding is due to gender disparities in treatment intensity. We investigated this hypothesis in a large contemporary cohort of subjects with type 2 diabetes. Design: Observational, cross-sectional study. Subjects and setting: Consecutive patients with type 2 diabetes from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicentre study (n = 15 773), attending 19 hospital-based diabetes clinics in 2007-2008. Main outcome measures: Traditional CVD risk factors, macro- and microvascular complications and current glucose-, lipid- and blood pressure (BP)-lowering treatments were assessed. Results: Although CVD was more prevalent in men, women showed a less favourable CVD risk profile and worse performance in achieving treatment targets for haemoglobin A1c, LDL, HDL and non-HDL cholesterol, systolic blood pressure (BP) and in particular obesity [body mass index (BMI) and waist circumference], but not for triglycerides and diastolic BP. However, women were more frequently receiving pharmacological treatment for hypertension and to a lesser extent hyperglycaemia and dyslipidaemia than men, and female gender remained an independent predictor of unmet therapeutic targets after adjustment for confounders such as treatments, BMI, duration of diabetes and, except for the systolic BP goal, age. Conclusions: In women with type 2 diabetes from the RIACE cohort, a more adverse CVD risk profile and a higher likelihood of failing treatment targets, compared with men, were not associated with treatment differences. This suggests that factors other than gender disparities in treatment intensity are responsible.
Published: 2013

46. Hemoglobin A(1c) variability as an independent correlate of cardiovascular disease in patients with type 2 diabetes: a cross-sectional analysis of the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study

Author: Penno, G, Solini, A, Zoppini, G, Orsi, E, Fondelli, C, Zerbini, G, Morano, S, Cavalot, F, Lamacchia, O, Trevisan, R, Vedovato, M, Pugliese, G, Penno G, Solini A, Zoppini G, Orsi E, Fondelli C, Zerbini G, Morano S, Cavalot F, Lamacchia O, Trevisan R, Vedovato M, Pugliese G, Penno, G, Solini, A, Zoppini, G, Orsi, E, Fondelli, C, Zerbini, G, Morano, S, Cavalot, F, Lamacchia, O, Trevisan, R, Vedovato, M, Pugliese, G, Penno G, Solini A, Zoppini G, Orsi E, Fondelli C, Zerbini G, Morano S, Cavalot F, Lamacchia O, Trevisan R, Vedovato M, and Pugliese G
Abstract: Background: Previous reports have clearly indicated a significant relationship between hemoglobin (Hb) A1c change from one visit to the next and microvascular complications, especially nephropathy (albuminuria and albuminuric chronic kidney disease, CKD). In contrast, data on macrovascular disease are less clear. This study was aimed at examining the association of HbA1c variability with cardiovascular disease (CVD) in the large cohort of subjects with type 2 diabetes from the Renal Insufficiency and Cardiovascular Events (RIACE) Italian Multicenter Study.Methods: Serial (3-5) HbA1c values obtained during the 2-year period preceding recruitment, including that obtained at the enrolment, were available from 8,290 subjects from 9 centers (out of 15,773 patients from 19 centers). Average HbA1c and HbA1c variability were calculated as the intra-individual mean (HbA1c-MEAN) and standard deviation (HbA1c-SD), respectively, of 4.52±0.76 values. Prevalent CVD, total and by vascular bed, was assessed from medical history by recording previous documented major acute events. Diabetic retinopathy (DR) was assessed by dilated fundoscopy. CKD was defined based on albuminuria, as measured by immunonephelometry or immunoturbidimetry, and estimated glomerular filtration rate, as calculated from serum creatinine.Results: HbA1c-MEAN, but not HbA1c-SD, was significantly higher (P<0.0001) in subjects with history of any CVD (n. 2,133, 25.7%) than in those without CVD (n. 6,157, 74.3%). Median and interquartile range were 7.78 (7.04-8.56) and 7.49 (6.81-8.31), respectively, for HbA1c-MEAN, and 0.47 (0.29-0.75) and 0.46 (0.28-0.73), respectively, for HbA1c-SD. Logistic regression analyses showed that HbA1c-MEAN, but not HbA1c-SD (and independent of it), was a significant correlate of any CVD. Similar findings were observed in subjects with versus those without any coronary or cerebrovascular event or myocardial infarction. Conversely, none of these measures were associated with stroke
Published: 2013

47. Rate and Determinants of Association Between Advanced Retinopathy and Chronic Kidney Disease in Patients With Type 2 Diabetes The Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study

Author: Penno, G, Solini, A, Zoppini, G, Orsi, E, Zerbini, G, Trevisan, R, Gruden, G, Cavalot, F, Laviola, L, Morano, S, Nicolucci, A, Pugliese, G, Penno G, Solini A, Zoppini G, Orsi E, Zerbini G, Trevisan R, Gruden G, Cavalot F, Laviola L, Morano S, Nicolucci A, Pugliese G, Penno, G, Solini, A, Zoppini, G, Orsi, E, Zerbini, G, Trevisan, R, Gruden, G, Cavalot, F, Laviola, L, Morano, S, Nicolucci, A, Pugliese, G, Penno G, Solini A, Zoppini G, Orsi E, Zerbini G, Trevisan R, Gruden G, Cavalot F, Laviola L, Morano S, Nicolucci A, and Pugliese G
Abstract: OBJECTIVE - To evaluate the rate and determinants of concordance between advanced diabetic retinopathy (DR) and chronic kidney disease (CKD), as assessed by both albuminuria and estimated glomerular fi ltration rate (eGFR), in the large cohort of the Renal Insuf ficiency And Cardiovascular Events (RIACE) Italian multicenter study. RESEARCH DESIGN AND METHODS - Patients with type 2 diabetes (n = 15,773) visiting consecutively 19 hospital -based diabetes clinics in years 2007 and 2008 were examined. DR was assessed by dilated fundoscopy. CKD was de fined based on albuminuria and eGFR. RESULTS - CKD was present in 58.64%of subjects with advanced DR, whereas advanced DR was detectable only in 15.28%of individuals with any CKD and correlated with the albuminuric CKD phenotypes more than with the nonalbuminuric phenotype. Age, male sex, diabetes duration, hemoglobin A 1c, hypertension, triglycerides, previous cardiovascular disease, and, inversely, HDL-cholesterol correlated independently with the presence of any CKD in individuals with advanced DR; correlates differed according to the presence of albuminuria, reduced eGFR, or both. Conversely, factors associated with the presence of advanced DR in subjects with any CKD were diabetes treatment, previous cardiovascular disease, albuminuria, and, inversely, smoking, eGFR, and age at diagnosis. CONCLUSIONS - Concordance of CKD with advanced DR is low in subjects with type 2 diabetes, and CKD without advanced DR ismore frequent than isolated advanced DR, at variance with type 1 diabetes. Factors independently associated with the presence of any CKD in individuals with advanced DR differ, at least in part, from those correlating with the presence of advanced DR in subjects with any CKD and by CKD phenotype.
Published: 2012

48. Clinical significance of nonalbuminuric renal impairment in type 2 diabetes

Author: Penno, G, Solini, A, Bonora, E, Fondelli, C, Orsi, E, Zerbini, G, Trevisan, R, Vedovato, M, Gruden, G, Cavalot, F, Cignarelli, M, Laviola, L, Morano, S, Nicolucci, A, Pugliese, G, Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, Trevisan R, Vedovato M, Gruden G, Cavalot F, Cignarelli M, Laviola L, Morano S, Nicolucci A, Pugliese G, Penno, G, Solini, A, Bonora, E, Fondelli, C, Orsi, E, Zerbini, G, Trevisan, R, Vedovato, M, Gruden, G, Cavalot, F, Cignarelli, M, Laviola, L, Morano, S, Nicolucci, A, Pugliese, G, Penno G, Solini A, Bonora E, Fondelli C, Orsi E, Zerbini G, Trevisan R, Vedovato M, Gruden G, Cavalot F, Cignarelli M, Laviola L, Morano S, Nicolucci A, and Pugliese G
Abstract: Objective: In type 2 diabetes, prevalence of nonalbuminuric renal impairment is increasing worldwide, though its clinical significance remains unclear. This large-cohort study aimed at evaluating the association of this phenotype with cardiovascular risk factors and other complications. Methods: Type 2 diabetic patients from the Renal Insufficiency And Cardiovascular Events (RIACE) Italian Multicenter Study (n=15773), visiting consecutively 19 hospital-based Diabetes Clinics in years 2007-2008, were examined. Serum creatinine was assessed by the Jaffe method; albuminuria was measured by immunonephelometry or immunoturbidimetry. Results: Of patients with renal impairment, as identified by an estimated glomerular filtration rate (eGFR) less than 60ml/min per 1.73m, 56.6% were normoalbuminuric, 30.8% were microalbuminuric, and 12.6% were macroalbuminuric. Percentages were similar when GFR was estimated using the more accurate Chronic Kidney Disease Epidemiology Collaboration equation instead of the simplified Modification of Diet in Renal Disease formula, and were independent of age, thus indicating that the increasing prevalence of this phenotype does not reflects misclassification of elderly patients. Nonalbuminuric renal impairment was not associated with HbA1c and correlated less strongly with retinopathy and hypertension than albuminuria, either alone or associated with reduced eGFR. It was associated with a higher prevalence of cardiovascular disease (CVD) than albuminuria alone, but lower than albuminuric renal impairment. Female sex correlated with nonalbuminuric renal impairment and male sex with the albuminuric forms. Conclusion:S: These data show that type 2 diabetic patients with nonalbuminuric renal impairment exhibit distinct clinical features, suggesting predominance of macroangiopathy as underlying renal pathology, and that this phenotype is associated with significant CVD burden.
Published: 2011

49. Rate and Determinants of Association Between Advanced Retinopathy and Chronic Kidney Disease in Patients With Type 2 Diabetes: The Renal Insufficiency And Cardiovascular Events (RIACE) Italian multicenter study

Author: Penno, G., Solini, A., Zoppini, G., Orsi, E., Zerbini, G., Trevisan, R., Gruden, G., Cavalot, F., Laviola, L., Morano, Susanna, Nicolucci, A., Pugliese, Giuseppe, Cardiovascular Events Study Group For The Renal Insufficiency And, Penno, G, Solini, A, Zoppini, G, Orsi, E, Zerbini, G, Trevisan, R, Gruden, G, Cavalot, F, Laviola, L, Morano, S, Nicolucci, A, and Pugliese, G
Subjects: Male, ALBUMINURIA, NEPHROPATHY, urologic and male genital diseases, GLOMERULAR-FILTRATION-RATE, ARTERIAL-HYPERTENSION, MICROALBUMINURIA, PREVALENCE, COMPLICATIONS, EPIDEMIOLOGY, IMPAIRMENT, EQUATION, advanced diabetic retinopathy, chronic kidney disease, type 2 diabetes, glomerular filtration rate, albuminuria, Diabetes Mellitus, Humans, Diabetic Nephropathies, Renal Insufficiency, Renal Insufficiency, Chronic, Chronic, Pathophysiology/Complications, Original Research, Aged, Albuminuria, Diabetes Mellitus, Type 2, Diabetic Retinopathy, Female, Glomerular Filtration Rate, Logistic Models, Middle Aged, female genital diseases and pregnancy complications, Type 2
Abstract: OBJECTIVE - To evaluate the rate and determinants of concordance between advanced diabetic retinopathy (DR) and chronic kidney disease (CKD), as assessed by both albuminuria and estimated glomerular fi ltration rate (eGFR), in the large cohort of the Renal Insuf ficiency And Cardiovascular Events (RIACE) Italian multicenter study. RESEARCH DESIGN AND METHODS - Patients with type 2 diabetes (n = 15,773) visiting consecutively 19 hospital -based diabetes clinics in years 2007 and 2008 were examined. DR was assessed by dilated fundoscopy. CKD was de fined based on albuminuria and eGFR. RESULTS - CKD was present in 58.64%of subjects with advanced DR, whereas advanced DR was detectable only in 15.28%of individuals with any CKD and correlated with the albuminuric CKD phenotypes more than with the nonalbuminuric phenotype. Age, male sex, diabetes duration, hemoglobin A 1c, hypertension, triglycerides, previous cardiovascular disease, and, inversely, HDL-cholesterol correlated independently with the presence of any CKD in individuals with advanced DR; correlates differed according to the presence of albuminuria, reduced eGFR, or both. Conversely, factors associated with the presence of advanced DR in subjects with any CKD were diabetes treatment, previous cardiovascular disease, albuminuria, and, inversely, smoking, eGFR, and age at diagnosis. CONCLUSIONS - Concordance of CKD with advanced DR is low in subjects with type 2 diabetes, and CKD without advanced DR ismore frequent than isolated advanced DR, at variance with type 1 diabetes. Factors independently associated with the presence of any CKD in individuals with advanced DR differ, at least in part, from those correlating with the presence of advanced DR in subjects with any CKD and by CKD phenotype.
Published: 2012

50. Angiotensin type-2 (AT-2)-receptor activation reduces renal fibrosis in cyclosporine nephropathy: Evidence for blood pressure independent effect

Author: Castoldi, G, Di Gioia, C, Carletti, R, Roma, F, Zerbini, G, Stella, A, Di Gioia, CRT, ROMA, FRANCESCA, STELLA, ANDREA, Castoldi, G, Di Gioia, C, Carletti, R, Roma, F, Zerbini, G, Stella, A, Di Gioia, CRT, ROMA, FRANCESCA, and STELLA, ANDREA
Abstract: Synopsis Compound 21 (C21), selective agonist of angiotensin type-2 (AT-2) receptors, shows anti-inflammatory effects in experimental models of hypertension and nephroprotection in diabetes. The aim of the present study was to evaluate the effects of C21 in cyclosporine nephropathy, which is characterized mainly by tubulo-interstitial fibrosis. Ten days before and during the experimental periods, low-salt diet was administered to Sprague-Dawley rats. Cyclosporine-A (CsA; 15 mg/kg per day, intraperitoneal injection) and CsA plus C21 (0.3 mg/kg per day, intraperitoneal injection) were administered for 1 and 4 weeks. Control groups were left without any treatment. Blood pressure (plethysmographic method) and 24 h urinary albumin excretion were measured once a week. At the end of the experimental protocols, the kidneys were excised for histomorphometric analysis of renal fibrosis and for immunohistochemical evaluation of inflammatory infiltrates and type I and type IV collagen expression. After 1 and 4 weeks, the rats treated with CsA showed a significant increase (P<0.01) in blood pressure, no significant changes in urinary albumin excretion and a significant increase (P<0.01) in glomerular and tubulo-interstitial fibrosis and inflammatory infiltrates as compared with the control rats. Treatment with C21 did not modify the CsA dependent increase of blood pressure, which was higher than in control rats, but after 4 weeks of treatment significantly reduced (P<0.01) glomerular and tubulo-interstitial fibrosis, type 1 collagen expression and macrophage infiltration, as compared with rats treated with cyclosporine. The administration of C21 showed a protective effect on cyclosporine nephropathy, decreasing renal fibrosis and macrophage infiltration. These data suggest that C21 may counteract tubulo-interstitial fibrosis, the most potent predictor of the progression of renal diseases.
Published: 2016

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