Introduction
Diabetes mellitus (DM) is a well-established risk factor for cardiovascular events.1 It is well known that cardiovascular risk is increased before the onset of DM as a state of pre-diabetes.2 In the American Diabetes Association (ADA) classification, a fasting blood glucose (FBG) range of 100–125 mg/dL is categorized as impaired fasting glucose (IFG).3 However, before 2003, an FBG range of 110–125 mg/dL was categorized as IFG in the ADA classification. In WHO criteria, an FBG range of 110–125 mg/dL is categorized as IFG. In the Japan Diabetes Society criteria, an FBG range of 110–125 mg/dL is categorized as pre-diabetes, and a range of 100–109 mg/dL is categorized as high normal blood glucose.4 The definition of IFG differs between countries and eras.
Endothelial dysfunction is known as the first step in the pathogenesis of atherosclerosis and is also known as a marker of cardiovascular events.5 6 Measurement of flow-mediated vasodilation (FMD) in the brachial artery is widely used for assessment of endothelial function. FMD is also well known as an independent predictor of cardiovascular events.7–11 In addition, measurement of FMD is an independent predictor of cardiovascular events in the general population, including individuals with DM. It has been established that DM is associated with endothelial dysfunction.12–14 However, the relationship between IFG and endothelial function is still controversial. Some investigators have shown that IFG is associated with endothelial dysfunction.15–18 On the other hand, Henry et al reported that IFG was not associated with endothelial dysfunction.13
There has been no study on the detailed relationships of FBG, including a normal range of glucose, pre-IFG range, and IFG range with endothelial function. First, we divided subjects into four groups according to the ADA classification, the WHO criteria and the Japan Diabetes Society criteria, FBG of <100, 100–109, 110–125, and ≥126 mg/dL or known DM, and assessed the FMD values. Furthermore, there is no information on from what level of FBG adversely affects endothelial function. Therefore, we divided FBG of <100 mg/dL, which was previously classified as normal blood glucose, into three groups, FBG of <90 md/dL, FBG of 90–94 mg/dL and FBG of 95–99 mg/dL, and evaluated the relationships of FBG levels of <90, 90–94, 95–99, 100–109, 110–125 and ≥126 mg/dL or known DM with FMD in multiple centers using a large sample size.