Diabetic microangiopathy and urinary glycosaminoglycans

Alterations in the metabolism of glycosaminoglycans (GAG) may play a role in the pathogenesis of diabetic-associated microangiopathy. Consequently, the relationship between diabetic nephropathy and retinopathy and urinary GAG distribution was assessed in 96 IDDM patients in comparison to 103 healthy controls. GAG concentration in 24h urine samples was determined by precipitation with cetylpyridinium chloride and potassium acetate in ethanol followed by a colorimetric test with carbazole. A marked difference (P = 0.0008) in urinary GAG excretion between patients (24.3 +/- 1.5 mg/24 h, mean +/- SEM) and controls (16.2 +/- 0.75 mg/24 h) could be detected. In patients with IDDM of longer duration, GAG excretion was increased (less than or equal to 10 yr: 20.8 +/- 2.1 vs >10 yr: 27.4 +/- 2.1 mg/24 h; P = 0.03). Furthermore, IDDM patients with class 4 nephropathy and retinopathy exhibited a markedly higher GAG excretion compared to those without nephropathy (33.1 +/- 3.0 vs 22.6 +/- 1.7 mg/24 h, P = 0.005) or retinopathy (29.7 +/- 2.8 vs 21.2 +/- 1.7 mg/24 h, P = 0.009). An increased urinary GAG concentration was detected in IDDM patients with albuminuria (>300 mg/24 h: 29.9 +/- 3.3 vs <30 mg/24 h: 23.0 +/- 1.7 mg/24 h; P = 0.048), proteinuria (>0.5 g/24 h: 30.3 +/- 3.7 vs <0.5 g/24 h: 22.7 +/- 1.6 mg/24 h) and in patients with augmented serum creatinine in comparison to those with normal values (>0.12 mg/L: 34.9 +/- 2.3 vs <0.12 mg/L: 22.4 +/- 1.6 mg/24 h; P = 0.01). The results demonstrate a close relationship between renal GAG excretion and the presence of microangiopathy in IDDM patients.