Microalbuminuria in patients with essential hyper tension is a marker
of incipient glomerular dysfunction and clusters with lipid and hemody
namic abnormalities. Recent evidence has shown that hypertensive patie
nts with microalbuminuria have a hyperinsulinemic response to oral glu
cose, suggesting the presence of insulin resistance. To directly test
this possibility we studied insulin action in two accurately matched g
roups (n=10 each) of hypertensive patients with or without microalbumi
nuria (14+/-2 versus 52+/-7 mg . 24 h(-1), mean of three 24-hour colle
ctions). In response to glucose ingestion microalbuminuric patients sh
owed slight hyperglycemia (area under the curve, 928+/-43 versus 784=/
-19 mmol . L(-1). 2 h(-1), P<.02) and a marked hyperinsulinemia (26.8/-3.3 versus 49.8+/-3.7 nmol L(-1). 2 h(-1), P<.001). Basal arterial b
lood pressure, heart rate, and forearm blood flow were similar in the
two groups and did not change significantly during a 2-hour euglycemic
insulin clamp. Insulin-stimulated whole-body glucose uptake was 25% l
ower in microalbuminuric patients (33.5+/-2.5 versus 25.2+/-2.1 mu mol
. min(-1). kg(-1), P<.02). This difference was entirely due to a 40%
reduction in glycogen synthesis (12.9+/-1.8 versus 21.3+/-3.2 mu mol .
min(-1). kg(-1), P<.05) as glucose oxidation was similarly stimulated
in the two groups. In contrast, there was no difference in the abilit
y of insulin to suppress hepatic glucose production (by approximately
100% at the end of the clamp), to decrease fractional sodium and potas
sium excretions (by 35%), to lower circulating free fatty acids (by 80
%), and to reduce plasma potassium concentrations (by 10%). Insulin se
nsitivity was inversely related to albumin excretion rate even after a
djustment for body mass index (partial r=.51, P<.03). When both insuli
n sensitivity and the insulin area under the curve were entered into a
multiple regression equation, the insulin area was more strongly rela
ted to albumin excretion and, together with 24-hour mean blood pressur
e, explained approximately 60% of its variability (P<.001). In conclus
ion, microalbumin uria in essential hypertension signals the presence
of a selective impairment in peripheral insulin-mediated glucose uptak
e and an enhanced insulin secretory response to glucose. Insulin level
s rather than insulin sensitivity appear to be related to urinary albu
min excretion.