Abstract
Associations between insulin-like growth factor 1 (IGF1) and mortality have been reported to be female specific in mice and in human nonagenarians. Intervention in the growth hormone (GH)-IGF1 axis may particularly benefit patients with high risk of losing muscle mass, including renal transplant recipients (RTR). We investigated whether a potential association of circulating IGF1 with all-cause mortality in stable RTR could be female specific and mediated by variation in muscle mass. To this end, plasma IGF1 levels were measured in 277 female and 343 male RTR by mass spectrometry, and their association with mortality was assessed by Cox regression. During a median follow-up time of 5.4 years, 56 female and 77 male RTR died. In females, IGF1 was inversely associated with risk (hazard ratio (HR) per 1-unit increment in log2-transformed (doubling of) IGF1 levels, 95% confidence interval (CI)) of mortality (0.40, 0.24–0.65; p < 0.001), independent of age and the estimated Glomerular filtration rate (eGFR). In equivalent analyses, no significant association was observed for males (0.85, 0.56–1.29; p = 0.44), for which it should be noted that in males, age was negatively and strongly associated with IGF1 levels. The association for females remained materially unchanged upon adjustment for potential confounders and was furthermore found to be mediated for 39% by 24 h urinary creatinine excretion. In conclusion, low IGF1 levels associate with an increased risk of all-cause mortality in female RTR, which may link to conditions of low muscle mass that are known to be associated with poor outcomes in transplantation patients. For males, the strongly negative association of age with IGF1 levels may explain why low IGF1 levels were not found to be associated with an increased risk of all-cause mortality.
Highlights
The peptide hormone insulin-like growth factor 1 (IGF1) is a key mediator of the biochemical/endocrine effects of growth hormone (GH) [1]
Levels of serum creatinine, plasma albumin, plasma triglycerides, and 24 h urinary creatinine excretion were more likely to be higher whereas plasma aspartate transaminase (AST), gamma-glutamyltransferase (GGT), and high sensitivity C-reactive protein were more likely to be lower for these subjects
This study showed that low plasma IGF1 levels were independently associated with an increased risk of all-cause mortality in female renal transplant recipients (RTR)
Summary
The peptide hormone insulin-like growth factor 1 (IGF1) is a key mediator of the biochemical/endocrine effects of growth hormone (GH) [1]. A specific role for IGF1 receptor signaling in mammalian longevity was first established in IGF1 receptor-(haplo) insufficient mice. These mice lived 33% longer than their wildtype littermates, yet this effect was restricted to females [5], which was subsequently confirmed in two follow-up studies in mice [6,7]. IGF1 levels predict better survival in nonagenarians (i.e., people between the age of 90 and 99), and, notably, the corresponding association between IGF1 levels and longevity was found to be female specific [11]. Unclear whether circulating levels of IGF1 are associated with longevity in middle-aged subjects and whether such association is female specific
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