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. 2023 Sep;149(11):8639-8648.
doi: 10.1007/s00432-023-04755-6. Epub 2023 Apr 27.

Association between metabolic syndrome, insulin resistance, and IGF-1 in breast cancer survivors of DIANA-5 study

Mauro De Santi #  1 , Giosuè Annibalini #  2 , Giuseppe Marano  3 , Giacomo Biganzoli  3 , Elisabetta Venturelli  4 , Massimo Pellegrini  5 , Francesco Lucertini  2 , Giorgio Brandi  1 , Elia Biganzoli  3 , Elena Barbieri  6 , Anna Villarini  7
Affiliations

Association between metabolic syndrome, insulin resistance, and IGF-1 in breast cancer survivors of DIANA-5 study

Mauro De Santi et al. J Cancer Res Clin Oncol. 2023 Sep.

Abstract

Purpose: Circulating insulin-like growth factor-1 (IGF-1) is positively associated with the risk of BC recurrence, and is more frequently dysregulated in older people, especially in those with metabolic syndrome (MetS) and obesity. This study aimed to analyze the association between IGF-1 levels and indices of MetS and insulin resistance in BC survivors.

Methods: Baseline data of 563 BC survivors enrolled in the DIet and ANdrogen-5 (DIANA-5; NCT05019989) study were analyzed.

Results: Lower circulating IGF-1 levels in subjects with MetS than in those without MetS were found. After stratification of the patients according to the diagnosis of MetS, we highlighted that the insulin was the main predictor of elevated IGF-1 levels only in subjects without MetS. Moreover, we found an interaction between high-density lipoprotein cholesterol (HDL-C), glycemia, and IGF-1 levels, showing a positive correlation between HDL-C and IGF-1, especially in subjects with higher values of glycemia and without a diagnosis of MetS.

Conclusions: While IGF-1 levels appear to be much more impaired in subjects diagnosed with MetS, in non-MetS subjects, IGF-1 levels may respond better to metabolic parameters and lifestyle changes. Further studies are needed to analyze the role of physical activity and/or dietary intervention in modulating IGF-1 concentrations in BC survivors.

Implications for cancer survivors: These results could have important clinical implications for planning customized strategies aimed at modulating IGF-1 levels in BC survivors. In fact, while the IGF-1 system seems to be much more compromised in subjects with a diagnosis of MetS, in noMetS subjects, IGF-1 levels could better respond to lifestyle changes.

Keywords: Breast cancer survivors; IGF-1; Metabolic syndrome; Tertiary cancer prevention.

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Conflict of interest statement

The authors declare no potential conflicts of interest.

Figures

Fig. 1
Fig. 1
IGF-1 levels in subjects stratifying by MetS factor numbers (A) and MetS diagnosis (B)
Fig. 2
Fig. 2
Effect plots showing the joint effect between HDL-C and glycemia on IGF-1 levels according to a linear (A, B) and semi-parametric smmothing model (C–F). A, B Linear interaction effect plots; C, D, surface plots; E, F contour plots showing the estimates of the average IGF-1 as a function of HDL-C and glycemia. Threshold for glycemia and HDL are shown (dashed lines)
See this image and copyright information in PMC

References

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