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.
- 1MND Research Centre, Faculty of Medicine, Health and Human Sciences, Macquarie University
Abstract
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 {Delta}ALSFRS-R decline (95% CI: 0.03 to 2.77, p = 0.045). Generalised estimating equations yielded a similar association ({beta} = 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.
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BibTeX
@misc{lim2026circulating,
title = {{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.}},
author = {C. K. Lim and M. Brocardo and J. Hunter and J. A. Heads and D. B. Rowe and S. Furlong and J. D. Atkin},
howpublished = {medRxiv},
year = {2026},
month = nov,
doi = {10.64898/2026.11.05.26366903},
url = {https://www.medrxiv.org/content/10.64898/2026.11.05.26366903v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - 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.
AU - C. K. Lim
AU - M. Brocardo
AU - J. Hunter
AU - J. A. Heads
AU - D. B. Rowe
AU - S. Furlong
AU - J. D. Atkin
PY - 2026
DA - 2026/11/05
PB - medRxiv
DO - 10.64898/2026.11.05.26366903
UR - https://www.medrxiv.org/content/10.64898/2026.11.05.26366903v1
AB - 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 {Delta}ALSFRS-R decline (95% CI: 0.03 to 2.77, p = 0.045). Generalised estimating equations yielded a similar association ({beta} = 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.
ER -