Pre-Impaired Fasting Glucose State Is a Risk Factor for Endothelial Dysfunction: Flow-Mediated Dilation Japan (FMD-J) Study

Background: Diabetes mellitus is associated with endothelial dysfunction. However, there is little information on the relationships of fasting blood glucose (FBG) including high normal blood glucose and impaired fasting glucose (IFG) with endothelial function. The purpose of this study was to evaluate the relationship between FBG level and flow-mediated vasodilation (FMD) in detail using a large sample size. Methods: This study was a cross-sectional study. We measured FMD in 7265 subjects at 31 general hospitals. The subjects were divided into four groups based on FBG levels: <5·55 mmol/L, 5·55-6·05 mmol/L, 6·11-6·94 mmol/L, and ≥6·99 mmol/L or known diabetes. The subjects were also divided into six groups based on FBG levels: <5·00 mmol/L, 5·00-5·22 mmol/L, 5·27-5·50 mmol/L, 5·55-6·05 mmol/L, 6·11-6·94 mmol/L, and ≥6·99 mmol/L or known diabetes. Findings: FMD decreased in relation to increase in FBG level. There was a significant difference in FMD between the FBG of <5·55 mmol/L group and the other three groups (6·7±3·1% vs. 5·9±2·8%, 5·7±3·1%, and 5·1±2·6%; p<0·0001, respectively). After adjustment for confounding factors, the odds of having the lowest quartile of FMD was significantly higher in the FBG of 5·27-5·50 mmol/L, 5·55-6·05 mmol/L, 6·11-6·94 mmol/L, and ≥6·99 mmol/L or known diabetes groups than in the FBG of <5·00 mmol/L group. Interpretation: These findings suggest that FBG of 5·55-6·05 mmol/L and FBG of 6·11-6·94 mmol/L are similarly associated with endothelial dysfunction and that a pre-IFG state (FBG of 5·27-5·50 mmol/L) is also a risk for endothelial dysfunction compared with FBG of <5·00 mmol/L. Funding Statement: Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan (18590815 and 21590898 to Y.Higashi) and a Grant-in-Aid of Japanese Arteriosclerosis Prevention Fund (to Y.Higashi). Declaration of Interests: All authors have no conflicts of interests to report. Ethics Approval Statement: The Ethics Committee of Hiroshima University approved the study protocol. Written informed consent for participation in this study was obtained from all participants.