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The triglyceride-glucose index as a measure of insulin resistance and risk of obesity-related cancers

Fritz, Josef ; Bjørge, Tone LU ; Nagel, Gabriele ; Manjer, Jonas LU ; Engeland, Anders ; Häggström, Christel ; Concin, Hans ; Teleka, Stanley LU ; Tretli, Steinar and Gylling, Björn , et al. (2020) In International Journal of Epidemiology 49(1). p.193-204
Abstract

Background: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified. Methods: Altogether 510 471 individuals from six European cohorts, with a mean age of 43.1 years, were included. We used the triglyceride glucose product (TyG index) as a surrogate measure for insulin resistance. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with 10 common obesity-related cancers, and quantified the proportion of the effect of BMI mediated through TyG index on the log-transformed hazard ratio (HR) scale. Results: During a median follow-up of 17.2 years, 16 052 individuals... (More)

Background: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified. Methods: Altogether 510 471 individuals from six European cohorts, with a mean age of 43.1 years, were included. We used the triglyceride glucose product (TyG index) as a surrogate measure for insulin resistance. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with 10 common obesity-related cancers, and quantified the proportion of the effect of BMI mediated through TyG index on the log-transformed hazard ratio (HR) scale. Results: During a median follow-up of 17.2 years, 16 052 individuals developed obesity-related cancers. TyG index was associated with the risk of cancers of the kidney HR per one standard deviation increase 1.13, 95% confidence interval: 1.07 to 1.20], liver (1.13, 1.04 to 1.23), pancreas (1.12, 1.06 to 1.19), colon (1.07, 1.03 to 1.10) and rectum (1.09, 1.04 to 1.14). Substantial proportions of the effect of BMI were mediated by TyG index for cancers of the pancreas (42%), rectum (34%) and colon (20%); smaller proportions for kidney (15%) and liver (11%). Little or no mediation was observed for breast (postmenopausal), endometrial and ovarian cancer. Results were similar for males and females, except for pancreatic cancer where the proportions mediated were 20% and 91%, respectively. Conclusions: The TyG index was associated with increased risk of cancers of the digestive system and substantially mediated the effect of BMI, suggesting that insulin resistance plays a promoting role in the pathogenesis of gastrointestinal cancers.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cancer, Insulin resistance, Longitudinal study, Mediation analysis, Obesity
in
International Journal of Epidemiology
volume
49
issue
1
pages
12 pages
publisher
Oxford University Press
external identifiers
  • pmid:30945727
  • scopus:85077626556
ISSN
0300-5771
DOI
10.1093/ije/dyz053
language
English
LU publication?
yes
id
7879d8aa-1cdf-4d61-901a-61d746abe3ad
date added to LUP
2021-01-07 11:07:14
date last changed
2024-06-13 03:35:40
@article{7879d8aa-1cdf-4d61-901a-61d746abe3ad,
  abstract     = {{<p>Background: The role of insulin resistance as a mediator in the association of body mass index (BMI) with site-specific cancer risk has, to our knowledge, never been systematically quantified. Methods: Altogether 510 471 individuals from six European cohorts, with a mean age of 43.1 years, were included. We used the triglyceride glucose product (TyG index) as a surrogate measure for insulin resistance. We fitted Cox models, adjusted for relevant confounders, to investigate associations of TyG index with 10 common obesity-related cancers, and quantified the proportion of the effect of BMI mediated through TyG index on the log-transformed hazard ratio (HR) scale. Results: During a median follow-up of 17.2 years, 16 052 individuals developed obesity-related cancers. TyG index was associated with the risk of cancers of the kidney HR per one standard deviation increase 1.13, 95% confidence interval: 1.07 to 1.20], liver (1.13, 1.04 to 1.23), pancreas (1.12, 1.06 to 1.19), colon (1.07, 1.03 to 1.10) and rectum (1.09, 1.04 to 1.14). Substantial proportions of the effect of BMI were mediated by TyG index for cancers of the pancreas (42%), rectum (34%) and colon (20%); smaller proportions for kidney (15%) and liver (11%). Little or no mediation was observed for breast (postmenopausal), endometrial and ovarian cancer. Results were similar for males and females, except for pancreatic cancer where the proportions mediated were 20% and 91%, respectively. Conclusions: The TyG index was associated with increased risk of cancers of the digestive system and substantially mediated the effect of BMI, suggesting that insulin resistance plays a promoting role in the pathogenesis of gastrointestinal cancers.</p>}},
  author       = {{Fritz, Josef and Bjørge, Tone and Nagel, Gabriele and Manjer, Jonas and Engeland, Anders and Häggström, Christel and Concin, Hans and Teleka, Stanley and Tretli, Steinar and Gylling, Björn and Lang, Alois and Stattin, Pär and Stocks, Tanja and Ulmer, Hanno}},
  issn         = {{0300-5771}},
  keywords     = {{Cancer; Insulin resistance; Longitudinal study; Mediation analysis; Obesity}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{193--204}},
  publisher    = {{Oxford University Press}},
  series       = {{International Journal of Epidemiology}},
  title        = {{The triglyceride-glucose index as a measure of insulin resistance and risk of obesity-related cancers}},
  url          = {{http://dx.doi.org/10.1093/ije/dyz053}},
  doi          = {{10.1093/ije/dyz053}},
  volume       = {{49}},
  year         = {{2020}},
}