Administration of human recombinant insulin-like growth factor-I to patients following major gastrointestinal surgery.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 1283730 · doi:10.1111/j.1365-2265.1992.tb01486.x
What was done
A double-blind, placebo-controlled randomized trial evaluated the pharmacokinetics and acute biological effects of a single subcutaneous dose of recombinant human IGF-I (rhIGF-I, 40 micrograms/kg, n = 20) versus placebo (n = 10) in 30 patients 24 hours following major gastric or colonic surgery. Serum and urine samples were collected over 72 hours to measure immunoreactive IGF-I, IGF-II, IGFBP-1, IGFBP-3, growth hormone, insulin, cartilage bioactivity, renal parameters, lipids, and electrolytes.
What was found
Peak serum immunoreactive IGF-I occurred at 4 hours (1.09 +/- 0.12 U/ml), stayed elevated for 15 hours, and returned to baseline by 24 hours (Tmax 5.0 +/- 0.43 hours; elimination half-life 10.8 +/- 1.2 hours; volume of distribution 0.33 +/- 0.05 l/kg; clearance 25 ml/min). IGF bioactivity increased by 57% at 6 hours. Compared to placebo, rhIGF-I caused: - Transient insulin suppression at 30 minutes (16.9 +/- 3.0 mU/l vs 32.3 +/- 7.1 mU/l, P = 0.02). - A decrease in serum creatinine (-6.3 +/- 3.0 mmol/l vs +7.2 +/- 6.2 mmol/l, P = 0.03) and an increase in creatinine clearance from 71.6 +/- 7.5 ml/min to 83.2 +/- 7.6 ml/min (P = 0.02). - A reduction in serum cholesterol (-0.20 +/- 0.05 mmol/l vs +0.20 +/- 0.14 mmol/l, P = 0.006). - A transient reduction in potassium from 4.1 +/- 0.1 mmol/l to 3.8 +/- 0.1 at 4 hours (P = 0.002) and 3.6 +/- 0.1 at 10 hours (P = 0.001), resolving to 4.0 +/- 0.1 at 24 hours (P = 0.293). No significant changes occurred in IGF-II, IGFBP-1, IGFBP-3, GH, free fatty acids, or triglycerides.
Why it matters
This study provides baseline pharmacokinetic and pharmacodynamic data for rhIGF-I in acute post-surgical catabolism, showing short-term biological activity and renal enhancement without immediate adverse events.
Limits
The trial evaluated only a single dose in a small cohort (n = 30) with an unequal 2:1 allocation. Clinical recovery outcomes, sustained anabolic markers (such as nitrogen balance), and long-term safety were not evaluated.
Cited by
- supports The half-life of insulin-like growth factor 1 (IGF-1) in serum is approximately 12 hours.