Are Abnormal IGF-1 Levels in the General Population a Cause for Concern?

Pavankumar Kamat

September 16, 2021

Both high and low levels of serum insulin-like growth factor 1 (IGF-1) may be associated with an increased risk of mortality in the general population, a new study published in the  European Journal of Endocrinology  suggests.

There is increasing evidence that modifiable risk factors for noncommunicable diseases, such as smoking, unhealthy diet, obesity and physical inactivity, may influence circulating IGF-1, which has a vital role in modulating development, homeostasis and aging. However, there is conflicting evidence from previous epidemiologic studies on the relationship between IGF-1 and mortality. Furthermore, there is a dearth of evidence from the general population.

Researchers assessed the association between baseline serum IGF-1 values and all-cause and cause-specific mortality in 380,997 UK Biobank participants who did not have a history of cancer, cardiovascular disease (CVD) or diabetes at baseline. Participants were categorized into deciles based on their baseline serum IGF-1 levels, with the fifth decile being the reference point.

After a median follow-up period of 8.8 years, 10,753 of the 380,997 participants had died. 56.8%, 18.1% and 15.0% of the deaths were attributable to cancer, CVD and other causes, respectively.

Dose-response analysis revealed a U-shaped association between IGF-1 and mortality, with both low and high IGF-1 levels linked to increased mortality risk. Compared with the fifth decile, the lowest decile was associated with 39% (95% CI, 29%-50%), 39% (95% CI, 14%-68%) and 20% (95% CI, 8%-34%) higher risk of all-cause, CVD and cancer mortality, respectively. Similarly, the highest decile vs the fifth decile was associated with 17% (95% CI, 7%-28%), 38% (95% CI, 11%-71%) and 38% (9%-76%) higher risk for all-cause, CVD, other mortality, respectively.

In the sensitivity analyses, the above associations remained significant after adjusting for C-reactive protein, glucose and lipids or exclusion of individuals who died within two years from baseline.

While the study included a large sample size and had a long follow-up duration, it also had some limitations. IGF-1 concentrations were measured only once at baseline which may not accurately reflect long-term exposure. Additionally, the UK Biobank comprises a predominantly White population, which limits the generalisability of the study results to other ethnic groups.

The authors said: "The findings contribute to the growing body of evidence that maintaining a normal range of IGF-1 concentrations is important for healthspan. More research is needed to fully understand the mechanisms and to investigate whether an intervention targeting IGF-1 concentration would improve lifespan."

The study was funded by the National Natural Science Foundation of China and others. The authors declared no competing interests.

Xie Y, Huang C, Zhu X, Wang J, Fan X, Fu Z, Ma Y, Hang D. Association between circulating insulin-like growth factor 1 and risk of all-cause and cause-specific mortality. Eur J Endocrinol. 2021 Sep 1 [Epub ahead of print]. doi: 10.1530/EJE-21-0573. PMID: 34478404

This article originally appeared on Univadis, part of the Medscape Professional Network.

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