Inverse correlation between insulin-like growth factor binding protein-1 and insulin in patients with acromegaly during treatment with the somatostatin analogue octreotide.
OBJECTIVE
Previous reports have shown an inverse relation between IGFBP-1 and insulin levels in healthy men, patients with insulin dependent diabetes mellitus, and insulinoma. We have investigated whether this inverse relation also exists in acromegaly, before and during treatment with octreotide, and whether changes in IGFBP-1 levels relate to GH and IGF-I levels.


METHODS
We studied short-term treatment with octreotide in a double-blind placebo-controlled 14-day clinical trial.


METHODS
Eighteen patients with acromegaly were studied.


METHODS
Plasma GH and serum IGFBP-1 levels were measured at hourly intervals from 0700 to 1800 h before randomization (day 0) and on days 4, 6, 8, 14 and 20. Serum insulin was determined at 0700, 0800 and 0900 h, and serum IGF-I at 0700 h.


RESULTS
Octreotide increased the daily mean IGFBP-1 level by 43% on day 8 and by 35% on day 14. The IGFBP-1 levels during octreotide were significantly higher (P < 0.05) compared to placebo, 29.9 +/- 3.9 vs 19.9 +/- 1.7 micrograms/l (mean +/- SEM) on day 8, and 28.3 +/- 3.2 vs 19.9 +/- 1.6 micrograms/l on day 14. Octreotide treatment significantly suppressed the insulin levels on all observation days by 40-48% compared to placebo. There was a significant inverse correlation between IGFBP-1 levels and insulin levels, both before treatment and on the last day of treatment (r = 0.79, P = 0.04; r = -0.90, P = 0.02, respectively). GH and IGF-I were significantly decreased in the octreotide group compared to the placebo group during the entire treatment period. The mean of age related standard deviation scores of IGF-I in the octreotide group decreased from a pretreatment value of 6.47 +/- 0.74 to 3.60 +/- 1.20 on day 14. There was no significant correlation between IGFBP-1 levels and levels of GH and IGF-I, either before or during treatment.


CONCLUSIONS
Octreotide treatment, in addition to reducing GH, IGF-I and insulin levels, is associated with an increase in IGFBP-1 concentrations in patients with acromegaly, and it is suggested that the rise in serum IGFBP-1 is a consequence of the decrease in insulin secretion.
Fredstorp
L
L
Department of Endocrinology, Karolinska Hospital, Stockholm, Sweden.
Werner
S
S
Bang
P
P
Hall
K
K
D000172:Acromegaly / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D013006:Growth Hormone / Q000097:blood; D006801:Humans; D018970:Insulin-Like Growth Factor Binding Protein 1; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D013002:Somatomedins / Q000378:metabolism*
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D015282:Octreotide