Long-Term Effect of Octreotide in Acromegaly on Insulin Resistance

Abstract

An important feature of acromegaly is a reduced action of insulin on hepatic gluconeogenesis and peripheral glucosal disposal. Octreotide (SMS) exerts complex effects on hormonal and metabolic regulations affecting glucose homeostasis. Eight patients with active acromegaly despite surgical intervention (age 44.8 ± 3.5 years, BMI 27.3 ± 1.6 kg/m², lean body mass (LBM) 70 ± 3.2%, blood glucose 5.24 ± 0.26 mmol/l, HbA1c ≤ 6.5%) were investigated before and after 6 months of treatment with SMS in an open trial. SMS was injected sc. at a dosage between 100 - 200 µg t.i.d. Mean GH and IGF1 levels during SMS therapy were significantly reduced (GH 9.6 ± 1.9 ng/ml vs. 4.9 ± 1.3 ng/ml, p < 0.05; IGF1 729.5 ± 84 ng/ml vs. 415 ± 49 ng/ml, p < 0.05). OGTT and euglycaemic-clamp-studies were performed before and after 6 months of SMS treatment. The glucosal disposal rate on average (insulin infusion rate 40 mU/m²/min) was not significantly changed following SMS treatment (McLBM before 3.60 ± 0.38, after 3.95 ± 0.41 mg/kg LBM/min). There was a positive correlation (r = 0.620) between the individual change of IGF1 and the change of McLBM. Additionally there was no significant difference of serum basal insulin levels (0.19 ± 0.01 vs. 0.23 ± 0.06 nmol/l) as well as basal C-peptide levels (0.19 ± 0.07 vs. 0.47 ± 0.04 nmol/l) before and with SMS treatment. We therefore conclude that long-term treatment of acromegalic patients with SMS, which achieves a successful reduction of GH and IGF1 levels, does not always guarantee a significant improvement in glucose metabolism. Therefore treatment of acromegalic patients requires individual adjustment of SMS-therapy as well as careful monitoring of glucose metabolism.

Key words

Acromegaly - Octreotide - Euglycaemic Clamp - Insulin Resistance