Effects of chronic slow release-lanreotide treatment on insulin-like growth factor system and metabolic parameters in acromegalic patients.

ABSTRACT

Insulin and IGF binding protein (IGFBP)-1 are linked by negative association. Somatostatin (SS) reduces insulin secretion by acting on pancreatic ß-cell and also by decreasing GH secretion. SS analogues in acromegaly reduce total IGF-I levels inhibiting GH hypersecretion, but they also reduce free IGF-I bioactivity increasing IGFBP-1 levels by inducing insulin decrease. In 13 acromegalic patients we studied GH, IGF system, insulin, and glucagon levels at baseline and at 7 days, 1 and 6 months under treatment with slow release (SR)-lanreotide (LAN) (60 mg im monthly). The hormonal and metabolic response to arginine (ARG) (0.5 g/kg iv in 30 min) was also studied at each time point. LAN decreased GH, total IGF-I, and IGFBP-3 levels at each time point. Insulin and glucagon levels were reduced, while IGFBP-1 and free IGF-I levels were increased by LAN at day 7 and after 1 month only. LAN did not modify the GH, insulin, glucagon, glucose, and IGFBP-1 responses to ARG. At each time point ARG-induced insulin increase was coupled to increase in glucagon and IGFBP-1 levels. This study shows that acromegalic patients under chronic treatment with LAN display a) inhibition of GH and total IGF-I levels, not coupled to persistent decrease in free IGF-I levels; b) persistent decrease in IGFBP- 3 but transient decrease and increase in insulin and IGFBP- 1, respectively; c) unchanged hormonal and metabolic response to ARG. Our findings also show that ARG stimulates IGFBP-1 despite marked increase in insulin secretion; this escape from the negative relationship linking insulin and IGFBP- 1 would likely reflect the ARG-induced glucagon increase.