True insulin and intact proinsulin levels in acromegalic patients

Abstract

To determine whether proinsulin (PI) contributes significantly to the immunoreactive insulin (IRI) concentrations in acromegalics, we measure PI, "true insulin" and IRI in a group of acromegalics compared with a control group. Serum PI was determined by the immunofluorimetric assay (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 with normal OGTT and body mass index < 25 kg/m2 (control group I), 10 controls with normal OGTT and body mass index > 25 kg/m2 (control group II), 15 patients with active acromegaly and normal OGTT and 11 patients with active acromegaly and IGT. Plasma glucose, serum GH, insulin and proinsulin were measured in all OGTT samples. Basal levels of insulin-like growth factor I (IGF-I) were measured in acromegalics. Mean body mass index in acromegalics with normal and impaired glucose tolerance were significantly higher compared with control group I and similar when compared with control group II. Proinsulin increased during OGTT in acromegalics with impaired glucose tolerance compared to control group I, and only fasting proinsulin compared to control group II. In 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 was measured by IFMA. These results suggest that in acromegalics, hyperinsulinism measured by RIA was at least in part due to hyperproinsulinism.

Avaliação do metabolismo da glicose em pacientes acromegálicos antes e após tratamento com octreotide LAR

“…Na acromegalia, RI com hiperinsulinemia e hiperproinsulinemia são dados freqüentemente descritos na literatura (14,(32)(33)(34). Concordante com isso, observam-se níveis aumentados de pró-insulina e HOMA-IR antes do início do tratamento medicamentoso com octreotide LAR.…”

“…Além da hiperinsulinemia, pacientes com acromegalia costumam ter níveis séricos de pró-insulina e peptídeo C mais elevados que controles normais (13,14), sendo o aumento dos níveis circulantes de pró-insulina considerado um reflexo da disfunção da célula-beta pancreática (14). Por outro lado, os níveis da proteína de ligação do IGF-I tipo 1 (insulin like growth factor binding protein type 1-IGFBP-1) tendem a ser baixos, visto sua regulação ser dependente da insulina, evidenciando sua relação inversa com a hiperinsulinemia existente (15)(16)(17).…”