BACKGROUND AND OBJECTIVES Insulin and IGF-I interact at many levels. L
ittle is known about the insulin-like growth factor-I/insulin-Iike gro
wth factor binding proteins (IGF-I/IGFBP) system in congenital partial
lipodystrophy, a syndrome characterized by insulin resistance, hyperi
nsulinaemia and absence of truncal and limb fat. Some cases have acrom
egaloid features with thick skin and large hands and feet in associati
on with normal levels of circulating growth hormone. METHODS In four f
emales known with congenital partial lipodystrophy, hyperinsulinaemia
with acromegaloid features, the number and affinity of the IGF-I recep
tors on peripheral blood mononuclear cells (PBMCs), and the concentrat
ion of circulating insulin, total and free IGF-I, IGFBP-1 and IGFBP-3
levels were measured in the fasting and the fed state. Cultures of PBM
Cs of the patients with lipodystrophy were also used to study the effe
ct of IGF-I stimulation on thymidine uptake in vitro. MEASUREMENTS In
the subjects with lipodystrophy the affinity and the number of the IGF
-I receptors on peripheral mononuclear cells (PBMCs) and erythrocytes
did not differ significantly from controls in the fasting state. Insul
in levels were significantly higher in subjects with lipodystrophy bot
h in the fasting as well in the fed state. Total IGF-I, free IGF-I and
IGFBP-3 levels did not differ but serum IGFBP-1 levels were lower in
lipodystrophy subjects than in healthy controls. The free IGF-I/IGFBP-
1 ratio was increased in lipodystrophy subjects both in the fasting an
d the fed states. The effects of IGF-I stimulation on thymidine uptake
by PBMCs of lipodystrophy subjects in the absence of IGFBP-1 were not
different from healthy controls cultures in vitro. When a combination
of IGFBP-1 tin a concentration comparable to the fasting serum IGFBP-
1 levels in lipodystrophy patients found in our study) and IGF-I was a
dded to PBMC cultures from lipodystrophy patients no decrease in thymi
dine uptake by PBMCs was found. CONCLUSIONS In the four subjects with
lipodystrophy hyperinsulinaemia, lowered free IGF-I and IGFBP-1 levels
, but increased free IGF-I/IGBP-1 ratios were observed. Low IGFBP-1 co
ncentrations in culture media did not reduce the stimulating IGF-I eff
ect on thymidine uptake by PBMCs from lipodystrophy patients. Our data
suggest that the observed increased IGF-I/IGFBP-1 ratio in lipodystro
phy patients contributes to an unopposed biological effect of IGF-I on
IGF-I receptors, thereby inducing the development of acromegaloid fea
tures, acanthosis nigricans and polycystic ovaries in some patients wi
th congenital partial lipodystrophy.