Circulating human epidermal growth factor receptor 2 (HER2) is associated with hyperglycaemia and insulin resistance

Abstract

Background: Type 2 diabetes mellitus (T2DM) and human epidermal growth factor receptor 2 (HER2) are associated with cancer, although the role of HER2 in T2DM is not well defined. The aim of this study was to investigate the association between HER2 levels and T2DM and whether that association differed in Swedish people born in Iraq or Sweden.

Methods: Circulating HER2 levels were analyzed by the Luminex assay in 95 Iraqi-born and 75 Swedish-born Swedes.

Results: There were significant differences in HER2 among those with normal glucose tolerance (NGT), impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT), and T2DM in the entire population after adjusting for age, sex, and body mass index (BMI; P = 0.03). Stratification of data according to country of birth revealed significant differences in HER2 levels among NGT, IFG/IGT, and T2DM groups only in Swedes (P = 0.007). For the entire study population, there was a positive association between HER2 and hyperglycemia (IFG and/or IGT + T2DM; P = 0.011), BMI, waist circumference, serum insulin, homeostatic model assessment of β-cell function, HbA1c, triglycerides, and C-peptide (P < 0.05), and a negative association between HER2 and insulin sensitivity index (ISI; P < 0.0001). Bivariate and multivariate linear regression analyses on the whole study population revealed that the associations between hyperglycemia and HER2, as well as between ISI and HER2, were independent of factors known to be associated with T2DM and insulin resistance (e.g. demographics, obesity, lipids, sedentary lifestyle, a family history of T2DM, C-peptide, and C-reactive protein).

Conclusions: There is an independent association between HER2 levels and hyperglycemia and insulin resistance that is not modified by country of birth.

Keywords: epidermal growth factor receptor; ethnicity; human epidermal growth factor receptor 2 (HER2); insulin sensitivity; type 2 diabetes mellitus; 关键词：表皮生长因子受体，种族，人类表皮生长因子受体2，胰岛素敏感性，2型糖尿病。.