Circulating insulin-like growth factor 1 (IGF-1) and short-term functional change in amyotrophic lateral sclerosis (ALS): exploratory evidence for systemic trophic-metabolic reserve.

Amyotrophic lateral sclerosis (ALS) exhibit heterogeneous functional decline, potentially influenced by systemic metabolic reserve. We investigate whether circulating insulin-like growth factor 1 (IGF-1) is associated with subsequent functional change in ALS. Serum IGF-1 was measured in 37 participants with ALS and 25 healthy controls. Baseline levels were compared between groups, and across disease-duration defined progression categories. Lagged regression assessed whether prior visit IGF-1 level predicted change in Revised ALS Functional Rating Scale (ALSFRS-R) on the next visit, adjusting for inter-visit interval, body mass index, age and sex. Mixed-effects and sensitivity analyses assessed robustness. Baseline IGF-1 did not differ significantly between controls and ALS (mean + SD: 107.3 + 54.3 vs 132.2 + 68.3 ng/mL, p = 0.12), or across progression categories (F(2, 34) = 0.13, p = 0.88). Across 48 intervals from 23 ALS participants, each 1-SD higher IGF-1 from prior visit was associated with 1.40-point less subsequent ΔALSFRS-R decline (95% CI: 0.03 to 2.77, p = 0.045). Generalised estimating equations yielded a similar association (β = 1.50, p = 0.030), whereas small-cluster robust inference showed wider uncertainty (p = 0.084). Repeated IGF-1 showed an intraclass correlation coefficient of 0.69, and the lagged association remained positive in all 23 leave-one-participant-out analyses. The IGF-1-by-time interaction was not significant in a random-slope mixed model (p =0.254). Higher circulating IGF-1 may reflect systemic trophic-metabolic reserve associated with short-term functional preservation in ALS, but limited precision precludes definitive prognostic or causal conclusions.