Urinary PC-1 and N-acetyl-beta-D-glucosaminidase activity in patients with type 2 diabetes treated with metformin, gliclazide or glibenclamide.

BACKGROUND: Insulin resistance is a key feature of type 2 diabetes mellitus. Plasma cell differentiation antigen (PC-1) is an inhibitor of insulin receptor tyrosine kinase, and has been implicated in the pathogenesis of insulin resistance. METHODS: Urinary excretion of PC-1 was determined in 45 newly detected, obese diabetic patients treated with metformin (16 patients), gliclazide (14 patients) or glibenclamide (15 patients). Urinary N-acetyl-beta-D-glucosaminidase (NAGA), a lysosomal enzyme, was determined as a marker of tubular damage in diabetes. RESULTS: Basal urinary PC-1 excretion in all three groups of diabetic patients was at the level of healthy controls. Treatment with oral hypoglycaemic drugs did not change significantly the group level or the number of patients in each group with increased PC-1 activity. Urinary excretion of NAGA in patients with type 2 diabetes was not statistically different from the control level. Metformin and gliclazide treatment did not change significantly the group levels of NAGA excretion. However, glibenclamide treatment produced an increased urinary NAGA excretion in the whole group, and in about twice as many patients as in the pre-treatment period.

Urinary PC-1 activity in patients with type 1 diabetes mellitus.

BACKGROUND: Insulin resistance characterizes type 1 diabetes mellitus with nephropathy. The molecular mechanisms of insulin resistance are not completely understood. Recently some advances have been made in identification of transmembrane glycoprotein PC-1 as a potential factor of insulin resistance. METHODS: We measured urinary excretion of PC-1 (alkaline phosphodiesterase I), a potential factor of insulin resistance, and N-acetyl-beta-D-glucosaminidase (NAGA) in 62 type 1 diabetic patients with different damage to the kidney. RESULTS: In newly detected type 1 diabetes patients, before insulin therapy, urine PC-1 excretion was significantly increased (P<0.05) over the control level. However, in patients after 12.4 years of therapy, urinary PC-1 was significantly decreased (P<0.05). Decreased urine PC-1 activity (P<0.05) was found also in type 1 diabetes patients with microalbuminuria and manifest nephropathy, including those with renal failure. Urinary NAGA excretion was found to be significantly increased (P=0.001) in all but the group of type 1 diabetes patients without nephropathy. CONCLUSION: This study of urinary PC-1 in patients with type 1 diabetes shows increased excretion in newly detected patients with poor glycaemic control, but decreased excretion in patients with micro-/macroalbuminuria as well as in those without apparent kidney damage. In patients with primary glomerulonephritis, urinary excretion of PC-1 was significantly decreased and that of NAGA significantly increased compared with the excretion in healthy controls.