To determine whether proinsulin (PT) contributes significantly to the
immunoreactive insulin (IRI) concentrations in acromegalics, we measur
e PI, ''true insulin'' and IRI in a group of acromegalics compared wit
h a control group. Serum PI was determined by the immunofluorimetric a
ssay (IFMA). Insulin was also determined by an IFMA that measures true
insulin and by a radioimmunoassay (RIA). We performed an oral glucose
tolerance test (OGTT) in a total group of 46 subjects: 10 controls wi
th normal OGTT and body mass index < 25 kg/m(2) (control group I), 10
controls with normal OGTT and body mass index > 25 kg/m(2) (control gr
oup II), 15 patients with active acromegaly and normal OGTT and 11 pat
ients with active acromegaly and IGT. Plasma glucose, serum GH, insuli
n and proinsulin were measured in all OGTT samples. Basal levels of in
sulin-like growth factor I (IGF-I) were measured in acromegalics. Mean
body mass index in acromegalics with normal and impaired glucose tole
rance were significantly higher compared with control group I and simi
lar when compared with control group II. Proinsulin increased during O
GTT in acromegalics with impaired glucose tolerance compared to contro
l group I, and only fasting proinsulin compared to control group II, I
n normal OGTT acromegalics, only fasting proinsulin was increased. The
RIA insulin during OGTT was significantly higher for both acromegalic
groups compared to control group I and only at fasting when compared
with control group II. This difference was not evident when insulin wa
s measured by IFMA, These results suggest that in acromegalics, hyperi
nsulinism measured by RIA was at least in part due to hyperproinsulini
sm.