Associations of insulin-like growth factor-I and its binding proteins and testosterone with frailty in older men

Authors


Correspondence: Bu Beng Yeap, School of Medicine and Pharmacology, Level 2, T Block, Fremantle Hospital, Alma Street, Fremantle, WA 6160, Australia. Tel.: +61 (8) 94313229; Fax: +61 (8) 94312977; E-mail: byeap@cyllene.uwa.edu.au

Summary

Objective

Ageing is associated with frailty and decreased anabolic hormones, insulin-like growth factor-I (IGF-I) and testo;?>sterone. We hypothesized that components of the IGF-I system, in conjunction with testosterone, modulate frailty risk in the elderly. We examined associations between IGF-I, its binding proteins IGFBP1 and IGFBP3 and testosterone with frailty in men.

Design

Observational study of 3 447 community-dwelling men aged 70–89 years assessed in 2001–04, with 1 654 reassessed in 2008–09.

Methods

Baseline total IGF-I, IGFBP1, IGFBP3 and testosterone were assayed. Frailty was assessed using the FRAIL scale, comprising 5 domains: fatigue; difficulty climbing stairs; difficulty walking >100 m; >5 illnesses; weight loss >5%. Men with ≥ 3 domains were considered frail.

Results

At baseline, 527 men (15·3%) were frail. Frail men had lower IGFBP3 (3 630 ng/ml vs not frail: 3 800 ng/ml, P < 0·001) and comparable IGFBP1 (23·5 vs 21·5 ng/ml, P = 0·09). In multivariate analyses, higher IGFBP1 was associated with increased prevalence of frailty (highest vs lowest quartile Q4:Q1, adjusted odds ratio [OR] = 1·39, 95% CI = 1·03–1·88). New-onset frailty arose in 260 (17·5%) of 1 484 men. Lower baseline IGF-I predicted new-onset frailty (Q1:Q4 OR = 1·48, 95% CI = 1·00–2·20) as did higher IGFBP1 (Q4:Q1 OR = 1·59, 95% CI = 1·01–2·50). Men with both IGF-I and free testosterone in Q1 had greater odds of prevalent frailty (OR = 2·13, 95% CI = 1·54–2·95).

Conclusions

Older men with higher IGFBP1 level, or both lower IGF-I and testosterone, are more likely to be frail, while those with lower IGF-I and higher IGFBP1 are more likely to become frail. Components of the IGF-I system may be biomarkers or independent predictors of frailty.

Ancillary