title: Significance of urinary glycosaminoglycans/proteoglycans in the evaluation of type 1 and type 2 diabetes complications.
abstract: Because of the high incidence of kidney disease in diabetic patients, the early diagnosis of renal impairment is a key point for intervention and management. Although urinary albumin excretion currently represents the accepted standard to assess both diabetic nephropathy and cardiovascular risk, it has some limitations as structural changes in the glomerular basement membrane may occur before the onset of microalbuminuria. It is therefore important to identify urinary markers that may provide greater sensitivity, earlier detection, and greater predictive power for diabetes complications. In this respect, urinary glycosaminoglycans/proteoglycans (GAGs/PGs) have been long associated with several kidney diseases as well as diabetic nephropathies as their levels increase more readily than albuminuria. In particular, heparan sulfate, a key component of the glomerular basement membrane responsible for its charge-dependent permeability, is excreted into urine at higher concentrations during the early kidney remodeling events caused by the altered glucose metabolism in diabetes. Over the past few years, also urinary trypsin inhibitor has been linked to a chronic inflammatory condition in both type 1 and 2 diabetes. The underlying mechanisms of such increase are not completely known since either a systemic inflammatory condition or a more localized early renal impairment could play a role. Nevertheless, the association with other inflammatory markers and a detailed urinary trypsin inhibitor structural characterization in diabetes remain to be elucidated. This review will discuss a great deal of information on the association between urinary GAGs/PGs and type 1 and 2 diabetes, with particular emphasis on renal involvement, and their potential as markers useful in screening, diagnosis and follow up to be associated with the current standard tests.
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Via Muroni 25, 07100, Sassari, Italy. Electronic address: ajlepedda@uniss.it.
authors.forename: Antonio Junior
authors.initials: AJ
authors.lastname: Lepedda
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Via Muroni 25, 07100, Sassari, Italy. Electronic address: demuro@uniss.it.
authors.forename: Pierina
authors.initials: P
authors.lastname: De Muro
authors.affiliation: Gynecologic and Obstetric Clinic, Department of Surgical, Microsurgical and Medical Sciences, University of Sassari, Viale San Pietro 12, 07100, Sassari, Italy. Electronic address: capobia@uniss.it.
authors.forename: Giampiero
authors.initials: G
authors.lastname: Capobianco
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Via Muroni 25, 07100, Sassari, Italy. Electronic address: formato@uniss.it.
authors.forename: Marilena
authors.initials: M
authors.lastname: Formato
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003928:Diabetic Nephropathies / Q000097:blood / Q000503:physiopathology / Q000652:urine*; D018450:Disease Progression; D006025:Glycosaminoglycans / Q000097:blood / Q000652:urine*; D006801:Humans; D007668:Kidney / Q000503:physiopathology*; D011509:Proteoglycans / Q000097:blood / Q000652:urine*; D051437:Renal Insufficiency / Q000097:blood / Q000503:physiopathology / Q000652:urine*
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans; D011509:Proteoglycans
keywords: Chronic inflammation; Diabetic nephropathy; Glycosaminoglycans; Proteoglycans; Urinary trypsin inhibitor