Circulating HER2/ErbB2 levels are associated with increased incidence of diabetes: A population-based cohort study

Abstract

OBJECTIVE HER2/ErbB2 is a member of the epidermal growth factor receptor family. It is widely used as a tumor marker, but it also has recently been associated with insulin resistance. Both ErbB2 and diabetes have been associated with cancer; however, the relationship between ErbB2 and diabetes has not been well explored. The aim of this population-based cohort study was to assess the association between plasma ErbB2 and incidence of diabetes. RESEARCH DESIGN AND METHODS The study population included participants from the Malmö Diet and Cancer-Cardiovascular Cohort (age range 46-68 years). After excluding participants with a history of diabetes and those missing data for ErbB2 and other covariates, the final study population consisted of 4,220 individuals. Incidence of diabetes was followed through linkages to local and national registers. Cox proportional hazards regression was used to assess the incidence of diabetes in relation to quartiles of ErbB2, adjusted for potential confounders. RESULTS Plasma ErbB2 was significantly and positively associated with glucose, insulin, and HbA1c after being adjusted for potential confounding factors. During a mean 6 SD follow-up period of 20.20 6 5.90 years, 615 participants (14.6%) were diagnosed with new-onset diabetes. Individuals with high levels of ErbB2 had a significantly higher risk of diabetes than those with low levels of ErbB2. The multivariableadjusted hazard ratio was 1.31 (95% CI 1.03-1.66; P < 0.05) for the highest versus the lowest quartile of ErbB2 and was 1.15 (95% CI 1.05-1.25; P < 0.05) per 1-SD increase in ErbB2. CONCLUSIONS Elevated levels of ErbB2 are associated with increased incidence of diabetes.