The triglyceride-glucose index as a measure of insulin resistance and risk of obesity-related cancers.
Level 3 - non-randomized controlled study
Prospective observational cohort study with mediation analysis
PubMed 30945727 · doi:10.1093/ije/dyz053
What was done
Researchers pooled data from six European cohorts comprising 510,471 participants (mean age 43.1 years) followed for a median of 17.2 years. They evaluated the triglyceride-glucose (TyG) index as a surrogate measure of insulin resistance. Using multivariable Cox proportional hazards models, they assessed associations between the TyG index and 10 obesity-related cancers, and performed mediation analysis to estimate the proportion of the body mass index (BMI) effect on cancer risk mediated through the TyG index.
What was found
Across follow-up, 16,052 participants developed obesity-related cancers. Each one standard deviation increase in the TyG index was associated with higher risks of kidney cancer (HR 1.13, 95% CI 1.07 to 1.20), liver cancer (HR 1.13, 95% CI 1.04 to 1.23), pancreatic cancer (HR 1.12, 95% CI 1.06 to 1.19), rectal cancer (HR 1.09, 95% CI 1.04 to 1.14), and colon cancer (HR 1.07, 95% CI 1.03 to 1.10). TyG index mediated substantial proportions of BMI-associated risk for pancreatic (42%), rectal (34%), colon (20%), kidney (15%), and liver (11%) cancers, but showed little or no mediation for postmenopausal breast, endometrial, or ovarian cancers. Pancreatic cancer mediation showed sex differences (20% in males vs 91% in females).
Why it matters
This study provides large-scale epidemiological quantification showing that insulin resistance accounts for a meaningful fraction of the relationship between obesity and digestive system cancers, highlighting a specific metabolic pathway for risk stratification and intervention.
Limits
Insulin resistance was estimated solely using a surrogate biochemical index (TyG) rather than direct measures like hyperinsulinemic-euglycemic clamps. The study relied on European cohorts, limiting generalizability to other populations, and residual confounding cannot be ruled out due to the observational design.
Cited by
- partial Insulin resistance is an underlying driver of common cancers, including breast, pancreatic, ovarian, and colon cancer.