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Int J Epidemiol. 2019 Mar 3. pii: dyz053. doi: 10.1093/ije/dyz053. [Epub ahead of print]

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

Author information

1
Department of Medical Statistics, Informatics and Health Economics, Medical University of Innsbruck, Innsbruck, Austria.
2
Department of Global Public Health and Primary Care, University of Bergen, Bergen, Norway.
3
Cancer Registry of Norway, Oslo, Norway.
4
Institute of Epidemiology and Medical Biometry, Ulm University, Ulm, Germany.
5
Agency for Preventive and Social Medicine, Bregenz (aks), Austria.
6
Department of Surgery, Skåne University Hospital, Lund University, Malmö, Sweden.
7
Division of Mental and Physical Health, Norwegian Institute of Public Health, Bergen, Norway.
8
Department of Biobank Research, Umeå University, Umeå, Sweden.
9
Department of Surgical Sciences, Uppsala University, Uppsala, Sweden.
10
Department of Public Health and Clinical Medicine, Nutritional Research, Umeå University, Umeå, Sweden.
11
Department of Clinical Sciences Lund, Lund University, Lund, Sweden.
12
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.

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 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.

KEYWORDS:

Obesity; cancer; insulin resistance; longitudinal study; mediation analysis

PMID:
30945727
DOI:
10.1093/ije/dyz053

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