Association between glycosylated haemoglobin A(1c) and endothelial function in an adult non-diabetic population

Abstract

Objective: Endothelial dysfunction precedes apparent atherosclerosis in humans and is associated with a number of cardiovascular risk factors, including Type 2 diabetes. To investigate the impact of long-term glucose homeostasis on endothelial function in an adult non-diabetic population, we analysed the association of serum HbA(1c) levels with endothelial function.

Methods: We studied cross-sectional data from 1384 subjects (696 women), aged 25-85, without diabetes, from the population-based Study of Health in Pomerania (SHIP-1). Flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) measurements of the brachial artery were performed using standardised ultrasound techniques. Linear regression models were carried out to assess the association between serum HbA(1c) levels and FMD/NMD.

Results: Multivariable analyses disclosed an inverse association between serum HbA(1c) levels and FMD in women, but not in men. In women without current use of antihypertensive medication, increasing serum HbA(1c) levels were associated with decreasing FMD levels after adjustment for age, body mass index, smoking status, hypertension, low-density lipoprotein cholesterol, and sex-hormone medication (β=-1.17; 95% CI -2.03; -0.30, p=0.009). There was an inverse association between serum HbA(1c) levels and NMD in men (β=-1.68; 95% CI -2.83; -0.52, p=0.005), but not in women.

Conclusion: We conclude that higher serum HbA(1c) levels in non-diabetic subjects are inversely associated with FMD in women without antihypertensive medication, but not in men. The gender-specific aspects concerning the association of HbA(1c) levels and NMD in this population should be investigated in further studies. Our results support current considerations that subclinical disorders of glucose metabolism measured by serum HbA(1c) are associated with subclinical cardiovascular diseases detected by FMD, especially in women.