Introduction: The impact of glycemic status and insulin resistance on the risk of pancreatic cancer in the nondiabetic population remains uncertain. We aimed to examine the association of glycemic status and insulin resistance with pancreatic cancer mortality in individuals with and without diabetes.
Methods: This is a cohort study of 572,021 Korean adults without cancer at baseline, who participated in repeat screening examinations which included fasting blood glucose, hemoglobin A1c, and insulin, and were followed for a median of 8.4 years (interquartile range, 5.3 -13.2 years). Vital status and pancreatic cancer mortality were ascertained through linkage to national death records.
Results: During 5,211,294 person-years of follow-up, 260 deaths from pancreatic cancer were identified, with a mortality rate of 5.0 per 10 person-years. In the overall population, the risk of pancreatic cancer mortality increased with increasing levels of glucose and hemoglobin A1c in a dose-response manner, and this association was observed even in individuals without diabetes. In nondiabetic individuals without previously diagnosed or screen-detected diabetes, insulin resistance and hyperinsulinemia were positively associated with increased pancreatic cancer mortality. Specifically, the multivariable-adjusted hazard ratio (95% confidence intervals) for pancreatic cancer mortality comparing the homeostatic model assessment of insulin resistance ≥75th percentile to the <75th percentile was 1.49 (1.08-2.05), and the corresponding hazard ratio comparing the insulin ≥75th percentile to the <75th percentile was 1.43 (1.05-1.95). These associations remained significant when introducing changes in insulin resistance, hyperinsulinemia, and other confounders during follow-up as time-varying covariates.
Discussion: Glycemic status, insulin resistance, and hyperinsulinemia, even in individuals without diabetes, were independently associated with an increased risk of pancreatic cancer mortality.
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