HER2/neu is a member of the epidermal growth factor receptor family
easily detectable in the serum of cancer patients. We aimed to evaluate
circulating HER-2 concentrations in association with insulin resistance in
healthy and obese subjects. METHODS: Insulin sensitivity (minimal model) and
serum HER-2 concentrations were evaluated in a cross sectional study in men
(cohort 1, n = 167) and longitudinally after weight loss in obese subjects
(cohort 2, n = 30). RESULTS: Serum HER-2 concentrations were positively
associated with BMI and waist circumference (both r = 0.18, p = 0.02), post-load
glucose (r = 0.28, p = 0.001) and fasting triglycerides (r = 0.26, p = 0.001);
and negatively associated with insulin sensitivity (r = -0.29, p = 0.002, n =
109). Subjects with type 2 diabetes showed significantly increased soluble serum
HER-2 concentrations. In different multivariate regression models, fasting
triglycerides emerged as the factor that independently contributed to 10-11% of
serum HER-2 variance.Serum HER-2 concentrations correlated significantly with
fasting triglycerides and insulin sensitivity index in subjects from cohort 2.
Weight loss led to a significant decrease of serum HER-2 concentrations. The
change in serum HER-2 concentrations were significantly associated with the
change in percent body fat and fasting triglycerides in young (below the median
age of the cohort) subjects. CONCLUSIONS: Serum HER-2 concentrations might be
implicated in the pathophysiology of insulin resistance and associated
comorbidities