Urinary glycosaminoglycan and proteoglycan excretion in normoalbuminuric patients with type 1 diabetes mellitus.
BACKGROUND
Diabetic nephropathy may be related to an abnormal metabolism of glycosaminoglycans (GAG) in the glomerular basement membrane (GBM). The first manifestation of nephropathy is microalbuminuria, whose appearance indicates a loss of GBM selectivity. The present study evaluated whether GAG excretion becomes abnormal in parallel with microalbuminuria, and whether such abnormalities are also present in normoalbuminuric diabetic patients.


METHODS
We measured urinary GAG excretion in 60 patients with type 1 (insulin-dependent) diabetes mellitus and in 22 healthy subjects. GAG were isolated from 24-h urine using ion-exchange chromatography on DEAE Sephacel. GAG composition was determined by cellulose acetate electrophoresis and expressed as percentages by densitometric scanning of Alcian Blue stained strips.


RESULTS
On subgrouping for albuminuric status and glyco-metabolic control, we found high urinary GAG concentrations in all except the normoalbuminuric patients with good glyco-metabolic control. The urinary GAG electrophoretic pattern showed alterations in chondroitin sulphate (CS) and heparan sulphate (HS) relative contents. A higher frequency of low sulphated chondroitin sulphate-proteoglycan (LSC-PG) was observed in all patients, including those with normoalbuminuria and good glyco-metabolic control.


CONCLUSIONS
This urinary pattern may be indicative of an abnormal GBM metabolism. Since GAG play an important role in GBM permeability, these anomalies might consequently represent a first step towards selective changes of GBM in type 1 diabetes mellitus.
Department of Physiological, Biochemical and Cellular Science, Institute of Clinical Medicine, University of Sassari, Italy.
Pierina
P
De Muro
Pietro
P
Fresu
Marilena
M
Formato
Giancarlo
G
Tonolo
Marco
M
Mameli
Mario
M
Maioli
Giovanni Maria
GM
Sanna
Gian Mario
GM
Cherchi
D000328:Adult; D000419:Albuminuria / Q000150:complications* / Q000503:physiopathology / Q000652:urine*; D001485:Basement Membrane / Q000503:physiopathology; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000150:complications* / Q000503:physiopathology / Q000652:urine*; D003928:Diabetic Nephropathies / Q000209:etiology* / Q000503:physiopathology / Q000652:urine*; D005260:Female; D005500:Follow-Up Studies; D006025:Glycosaminoglycans / Q000652:urine*; D006801:Humans; D008297:Male; D017063:Outcome Assessment, Health Care; D011237:Predictive Value of Tests; D011509:Proteoglycans / Q000652:urine*; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors
D006025:Glycosaminoglycans; D011509:Proteoglycans; D003404:Creatinine