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

Abstract

Objective: Ageing is associated with frailty and decreased anabolic hormones, insulin-like growth factor-I (IGF-I) and testosterone. 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.