OBJECTIVE: To examine whether subjects with impaired glucose tolerance (IGT) for more than 2 years have any abnormality in the kidney. RESEARCH DESIGN AND METHODS: We measured urinary excretion rate and clearance of various plasma proteins with different molecular radii and different isoelectric points in 22 Japanese men with IGT (IGT group) and 37 age-matched healthy control subjects (control group). RESULTS: Clearance of ceruloplasmin (molecular radius approximately 45 A; isoelectric point 4.4), IgG4 (molecular radius 55 A; isoelectric point 5.4), and IgG (molecular radius 55 A; isoelectric point 7.4) was significantly higher in the IGT group than in the control group, whereas there were no significant differences in urinary excretion rate of albumin (molecular radius 36 A; isoelectric points 4.8-5.2) and clearance of alpha 2-macroglobulin (molecular radius 88 A; isoelectric point 5.4) between the two groups. CONCLUSIONS: In the present study, we found that clearance of neutral-charged IgG, negatively charged IgG4, and ceruloplasmin with molecular radii of approximately 45-55 A was selectively increased in IGT subjects. This finding does not seem to be explained by impairment of charge and pore-size selectivity in the glomerulus. Therefore, considering the present result together with our recent finding that enhanced glomerular filtration rate (GFR) after acute protein loading in healthy subjects induced a selective increase in clearance of IgG, IgG4, and ceruloplasmin, we suggest that increased intraglomerular hydraulic pressure, although enhanced GFR was not demonstrated, may be at work in these mildly hyperglycemic subjects.

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