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Background: Circulating insulin-like growth factor 1 (IGF-1) is positively associated with the risks of certain neurological disorders, including stroke, Alzheimer's disease, and Parkinson's disease. However, the association of IGF-1 with the risk of multiple sclerosis (MS) remains unclear., Methods: A total of 348,324 participants at baseline were included from the UK biobank in this prospective study. The association of circulating IGF-1 level with MS was analyzed by Cox proportional hazard models. Further, subgroup analyses were conducted to investigate the variables influencing these associations., Results: Among 348,324 individuals, lower circulating IGF-1 concentrations were associated with a reduced risk of MS (95 % CI, 0.5930-0.9700; P value = 0.02763). The association between lower IGF-1 levels and reduced risk of MS remains robust in older and female participants. Moreover, risk of MS appeared to be lower in IGF-1-low individuals who never smoked, currently drinking alcohol, with higher body mass index, and higher glucose concentrations., Conclusion: Our findings indicate that a lower concentration of serum IGF-1 was associated with a reduced risk of MS. The results provide evidence that the circulating IGF-1 may play a significant role in the pathogenesis of MS., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2025 Elsevier B.V. All rights reserved.)

Background: Adiposity is positively associated with risk of some cancer sites and other health conditions in men; however, it is unclear if endogenous hormones play a role in these associations. We examined how body composition, measured from magnetic resonance imaging (MRI) and common measures of adiposity (e.g., body mass index (BMI)), are related to hormone concentrations in men from the UK Biobank study., Methods: Up to 16,237 men with available body composition data (including visceral, subcutaneous, and liver fat, muscle fat infiltration (MFI), lean tissue, and common adiposity measures) and serum hormone measurements (insulin-like growth factor-I (IGF-I), total testosterone, sex hormone-binding globulin (SHBG), and calculated free testosterone) were included. Multivariable-adjusted linear regression models were used to determine the geometric mean hormone and SHBG concentrations across categories of each exposure., Results: Common measurements of adiposity were highly correlated with MRI measures of central and total adiposity (r = 0.76-0.91), although correlations with ectopic fat (liver fat and MFI) were lower (r = 0.43-0.54). Most adiposity measurements showed an inverse U- or J-shaped association with circulating IGF-I and free testosterone; however, MFI was linearly inversely associated, and lean tissue volume was positively associated with both IGF-I and free testosterone concentrations. All body composition measures were inversely associated with total testosterone and SHBG concentrations (relative geometric mean difference between Q5 vs. Q1: 20-30%)., Conclusion: Our results show that common adiposity and most MRI measures of adiposity relate similarly to serum hormone concentrations; however, associations with ectopic fat (particularly MFI) and lean tissue were different., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval: The UK Biobank has received ethics approval from the North West Multi-centre Research Ethics Committee (2021 approval reference 16/NW/0274). All participants provided informed consent to participate at recruitment. Our research required no additional ethical clearance., (© 2024. The Author(s).)

Aim: To test the hypothesis that liver-expressed antimicrobial peptide 2 (LEAP2) genetic variants might influence the susceptibility to human obesity., Methods: Using data from the UK Biobank, we identified independent LEAP2 gene single nucleotide polymorphisms (SNPs) and examined their associations with obesity traits and serum insulin-like growth factor-1 (IGF-1) concentration. These associations were evaluated for both individual SNPs and after combining them into a genetic risk score (GRS LEAP2 ) using linear and logistic regression models. Sex-stratified analyses were also conducted., Results: Five SNPs showed positive associations with obesity-related traits. rs57880964 was associated with body mass index (BMI) and waist-to-hip ratio adjusted for BMI (WHRadjBMI), in the total population and among women. Four independent SNPs were positively associated with higher serum IGF-1 concentrations in both men and women. GRS LEAP2 was associated with BMI and WHRadjBMI only in women and with serum IGF-1 concentration in both sexes., Conclusions: These findings reveal sex-specific associations between key LEAP2 gene variants and several obesity traits, while also indicating a strong independent association of LEAP2 variants with serum IGF-1 concentration., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)