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Body mass index, triglyceride-glucose index, and prostate cancer death : a mediation analysis in eight European cohorts

Fritz, Josef LU ; Jochems, Sylvia H.J. LU ; Bjørge, Tone ; Wood, Angela M. ; Häggström, Christel LU ; Ulmer, Hanno ; Nagel, Gabriele ; Zitt, Emanuel ; Engeland, Anders and Harlid, Sophia , et al. (2023) In British Journal of Cancer
Abstract

Background: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited. Methods: We included 259,884 men from eight European cohorts, with 11,760 incident PCa’s and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index. Results: In the PCa-case-only analysis, baseline TyG... (More)

Background: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited. Methods: We included 259,884 men from eight European cohorts, with 11,760 incident PCa’s and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index. Results: In the PCa-case-only analysis, baseline TyG index was positively associated with PCa death (HR per 1-standard deviation: 1.11, 95% confidence interval (CI); 1.01–1.22), and mediated a substantial proportion of the baseline BMI effect on PCa death (HRtotal effect per 5-kg/m2 BMI: 1.24; 1.14–1.35, of which 28%; 4%–52%, mediated). In contrast, in the full cohort, the TyG index was not associated with PCa death (HR: 1.03; 0.94-1.13), hence did not substantially mediate the effect of BMI on PCa death. Conclusions: Insulin resistance could be an important pathway through which obesity accelerates PCa progression to death.

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publication status
epub
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in
British Journal of Cancer
publisher
Nature Publishing Group
external identifiers
  • pmid:38087039
  • scopus:85179305097
ISSN
0007-0920
DOI
10.1038/s41416-023-02526-1
language
English
LU publication?
yes
id
8aef2d84-e568-4efa-937f-11dae265ca68
date added to LUP
2024-01-11 10:38:13
date last changed
2024-04-26 06:24:58
@article{8aef2d84-e568-4efa-937f-11dae265ca68,
  abstract     = {{<p>Background: Insulin resistance is a hypothesised biological mechanism linking obesity with prostate cancer (PCa) death. Data in support of this hypothesis is limited. Methods: We included 259,884 men from eight European cohorts, with 11,760 incident PCa’s and 1784 PCa deaths during follow-up. We used the triglyceride-glucose (TyG) index as indicator of insulin resistance. We analysed PCa cases with follow-up from PCa diagnosis, and the full cohort with follow-up from the baseline cancer-free state, thus incorporating both PCa incidence and death. We calculated hazard ratios (HR) and the proportion of the total effect of body mass index (BMI) on PCa death mediated through TyG index. Results: In the PCa-case-only analysis, baseline TyG index was positively associated with PCa death (HR per 1-standard deviation: 1.11, 95% confidence interval (CI); 1.01–1.22), and mediated a substantial proportion of the baseline BMI effect on PCa death (HR<sub>total effect</sub> per 5-kg/m<sup>2</sup> BMI: 1.24; 1.14–1.35, of which 28%; 4%–52%, mediated). In contrast, in the full cohort, the TyG index was not associated with PCa death (HR: 1.03; 0.94-1.13), hence did not substantially mediate the effect of BMI on PCa death. Conclusions: Insulin resistance could be an important pathway through which obesity accelerates PCa progression to death.</p>}},
  author       = {{Fritz, Josef and Jochems, Sylvia H.J. and Bjørge, Tone and Wood, Angela M. and Häggström, Christel and Ulmer, Hanno and Nagel, Gabriele and Zitt, Emanuel and Engeland, Anders and Harlid, Sophia and Drake, Isabel and Stattin, Pär and Stocks, Tanja}},
  issn         = {{0007-0920}},
  language     = {{eng}},
  publisher    = {{Nature Publishing Group}},
  series       = {{British Journal of Cancer}},
  title        = {{Body mass index, triglyceride-glucose index, and prostate cancer death : a mediation analysis in eight European cohorts}},
  url          = {{http://dx.doi.org/10.1038/s41416-023-02526-1}},
  doi          = {{10.1038/s41416-023-02526-1}},
  year         = {{2023}},
}