Complication of diabetes
The aim of the resarch activity of the Complications of Diabetes Unit is to prevent the development of the microvascular complications of diabetes (in particular retinopathy and nephropathy) or, if they are already developed, to induce their remission.
- Diabetic Retinopathy: although laser photocoagulation and/or anti-VEGF treatment represent a valid therapeutical approach in case of established retinopathy, they have no effect in preventing the complication. The recent demonstration that the very early stage of diabetic retinopathy is characterized by a selective retinal neurodegeneration has totally changed the perspectives in the field. Prevention of the "classic" vascular stage of diabetic retinopathy through early retinal neuroprotection now appears as a promising goal. Studies aimed to verify the hypothesis are presently ongoing in our lab.
- Diabetic Nephropathy: despite an aggressive anti-hypertensive treatment started as soon as microalbuminuria (the first sign of nephropathy) develops, the possibility to prevent or treat the complication, particularly in case of type 2 diabetes, seems to be still out of reach. Probably the pathophysiologic mechanisms leading to the development of diabetic nephropathy are not yet fully understood. The recent demonstration that glomerular podocytes (the target cells of the complication) may survive the disease but are lost in large amount, still viable, with urine (a phenomenon known as podocyturia) has raised the hypothesis that diabetes might interfere with the adhesion of these cells to each other or to the glomerular basement membrane. Studies aimed to verify the hypothesis are presently ongoing in our lab.
Orsi E, Bonora E, Solini A, Fondelli C, Trevisan R, Vedovato M, Cavalot F, Zerbini G, Morano S, Nicolucci A, Penno G, Pugliese G. 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. J Clin Med. 2020 Jan 17;9(1).
Sacconi R, Lamanna F, Borrelli E, Mulinacci G, Casaluci M, Gelormini F, Carnevali A, Querques L, Zerbini G, Bandello F, Querques G. Morphofunctional analysis of the retina in patients with type 1 diabetes without complications after 30 years of disease. Sci Rep. 2020 Jan 14;10(1):206.
Castoldi G, Carletti R, Ippolito S, Colzani M, Barzaghi F, Stella A, Zerbini G, Perseghin G, di Gioia CRT. Renal Anti-Fibrotic Effect of Sodium Glucose Cotransporter 2 Inhibition in Angiotensin II-Dependent Hypertension. Am J Nephrol. 2020 Jan 7:1-11. doi: 10.1159/000505144
Salem RM, Todd JN, Sandholm N, Cole JB, Chen WM, Andrews D, Pezzolesi MG, McKeigue PM, Hiraki LT, Qiu C, Nair V, Di Liao C, Cao JJ, Valo E, Onengut-Gumuscu S, Smiles AM, McGurnaghan SJ, Haukka JK, Harjutsalo V, Brennan EP, van Zuydam N, Ahlqvist E, Doyle R, Ahluwalia TS, Lajer M, Hughes MF, Park J, Skupien J, Spiliopoulou A, Liu A, Menon R, Boustany-Kari CM, Kang HM, Nelson RG, Klein R, Klein BE, Lee KE, Gao X, Mauer M, Maestroni S, Caramori ML, de Boer IH, Miller RG, Guo J, Boright AP, Tregouet D, Gyorgy B, Snell-Bergeon JK, Maahs DM, Bull SB, Canty AJ, Palmer CNA, Stechemesser L, Paulweber B, Weitgasser R, Sokolovska J, Rovīte V, Pīrāgs V, Prakapiene E, Radzeviciene L, Verkauskiene R, Panduru NM, Groop LC, McCarthy MI, Gu HF, Möllsten A, Falhammar H, Brismar K, Martin F, Rossing P, Costacou T, Zerbini G, Marre M, Hadjadj S, McKnight AJ, Forsblom C, McKay G, Godson C, Maxwell AP, Kretzler M, Susztak K, Colhoun HM, Krolewski A, Paterson AD, Groop PH, Rich SS, Hirschhorn JN, Florez JC; SUMMIT Consortium, DCCT/EDIC Research Group, GENIE Consortium. Genome-Wide Association Study of Diabetic Kidney Disease Highlights Biology Involved in Glomerular Basement Membrane Collagen. J Am Soc Nephrol. 2019 Oct;30(10):2000-2016. doi: 10.1681/ASN.2019030218.
Sacconi R, Casaluci M, Borrelli E, Mulinacci G, Lamanna F, Gelormini F, Carnevali A, Querques L, Zerbini G, Bandello F, Querques G. Multimodal Imaging Assessment of Vascular and Neurodegenerative Retinal Alterations in Type 1 Diabetic Patients without Fundoscopic Signs of Diabetic Retinopathy. J Clin Med. 2019 Sep 8;8(9). pii: E1409. doi: 10.3390/jcm8091409.
Scotti F, Milani P, Setaccioli M, Maestroni S, Sidenius N, De Lorenzi V, Massacesi A, Bergamini F, Zerbini G. Increased soluble urokinase plasminogen activator receptor (suPAR) levels in neovascular age-related macular degeneration: a role for inflammation in the pathogenesis of the disease? Graefes Arch Clin Exp Ophthalmol. 2019 May;257(5):899-903. doi: 10.1007/s00417-018-04230-w.
Magagnotti C, Zerbini G, Fermo I, Carletti RM, Bonfanti R, Vallone F, Andolfo A. Identification of nephropathy predictors in urine from children with a recent diagnosis of type 1 diabetes. J Proteomics. 2018 Oct 24. doi: 10.1016/j.jprot.2018.10.010
Castoldi G, di Gioia CRT, Roma F, Carletti R, Manzoni G, Stella A, Zerbini G, Perseghin G. Activation of angiotensin type 2 (AT2) receptors prevents myocardial hypertrophy in Zucker diabetic fatty rats. Acta Diabetol. 2018 Sep 5. doi: 10.1007/s00592-018-1220-1.
Maestroni S, Zerbini G. Glomerular endothelial cells versus podocytes as the cellular target in diabetic nephropathy. Acta Diabetol. 2018 55:1105-1111.
Penno G, Solini A, Bonora E, Orsi E, Fondelli C, Zerbini G, Trevisan R, Vedovato M, Cavalot F, Laviola L, Nicolucci A, Pugliese G; Renal Insufficiency and Cardiovascular Events (RIACE) Study Group. 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. Acta Diabetol. 2018 55:603-612.
Buccarello L, Sclip A, Sacchi M, Castaldo AM, Bertani I, ReCecconi A, Maestroni S, Zerbini G, Nucci P, Borsello T. The c-jun N-terminal kinase plays a key role in ocular degenerative changes in a mouse model of Alzheimer disease suggesting a correlation between ocular and brain pathologies. Oncotarget. 2017 8:83038-83051.
Iacono P, Parodi MB, La Spina C, Zerbini G, Bandello F. Dynamic and static vessel analysis in patients with retinitis pigmentosa: A Pilot Study of Vascular Diameters and Functionality. Retina. 2017 37:998- 1002.
Castoldi G, di Gioia CR, Carletti R, Roma F, Zerbini G, Stella A. Angiotensin Type-2 (AT-2)-Receptor activation reduces renal fibrosis in cyclosporine nephropathy: Evidence for blood-pressure independent effect. Biosci Rep. 2016 Sep 27.
Zerbini G, Maestroni S, Turco V, Secchi A. The Eye as a Window to the Microvascular Complications of Diabetes. Dev Ophthalmol. 2017 60:6-15.
Carnevali A, Sacconi R, Corbelli E, Tomasso L, Querques L, Zerbini G, Scorcia V, Bandello F, Querques G. Optical coherence tomography angiography analysis of retinal vascular plexuses and choriocapillaris in patients with type 1 diabetes without diabetic retinopathy. Acta Diabetol. 2017 54:695-702.