After an intravenous infusion of L-arginine to inhibit tubular reabsor
ption of albumin, glomerular clearance, renal clearance, and tubular r
eabsorption of unmodified albumin (UMA) and glycated albumin (GA) were
determined in 72 patients with NIDDM without (NIDDM-I; n = 47) or wit
h microalbuminuria (NIDDM-II; n = 25) and in 24 healthy control subjec
ts, Samples of serum albumin and dialyzed urine obtained 60 min before
and during L-arginine infusion were applied to an affinity column to
separate GA from UMA, and their albumin contents were assayed, The ser
um level of GA in NIDDM patients was higher than that in control subje
cts (P < 0.0001), Both UMA and GA were excreted in excess in NIDDIM-II
as compared with the other two groups (P < 0.0001), and UMA comprised
80% of total albumin excretion, In NIDDM-II, tile glomerular clearanc
e of UMA (2.5 +/- 0.16 > NIDDM-I [1.8 +/- 0.1] > control subjects [1.3
+/- 0.1 mu l/min], P < 0.001) and of GA (1.7 +/- 0.13 > NIDDM-I = con
trol subjects [1.1 +/- 0.1 mu l/min], P < 0.001) were enhanced, as com
pared with the other two groups, Renal clearance of UMA (1.3 +/- 0.13
mu l/min) and GA (0.89 +/- 0.09 mu l/min) in NIDDM-II was greater than
that in control subjects (0.27 +/- 0.03, 0.19 +/- 0.02 mu l/min) or i
n NIDDM-I (0.30 +/- 0.03, 0.11 +/- 0.01 mu l/min). Tubular reabsorptio
n of UMA, as assessed by the difference between glomerular and renal c
learances of albumin, in NIDDM-II (1.1 +/- 0.1 mu l/min) was less than
in NIDDM-I (1.50 +/- 0.09 mu l/min), and that of GA in NIDDM-II was l
ower than that in the other two groups, despite exaggerated glomerular
clearance of GA and UMA in NIDDM-II, In summary, microalbuminuria in
NIDDM is caused by increased excretion of UMA resulting from the decom
pensated ability of tubular reabsorption, which is exceeded by increas
ed glomerular clearance of UMA.