The prevalence of diabetes was 25.8% in this study, 2.37 fold higher than the 2013 nationwide survey, which estimated the prevalence of diabetes as 10.9%1. In the studied population, the severity of coronary stenosis, quantified as Gensini score, was positively correlated with FBG, PBG, glycated albumin, and HbA1c even after adjustments for all known factors. In contrast, no correlation of Gensini score with fasting insulin, postprandial insulin, HOMAIR or HOMAB remained significant after adjustments for age and gender. Two previous studies in Caucasian men, including 363 men without a diabetes history and 234 men with NGT, observed significant correlations between the number of involved vessels and postload glycemia, HbA1c, fasting insulin, and postload insulin, suggesting that the severity of atherosclerosis was positively correlated with both glucose and insulin resistance10,11. Nevertheless, this was not supported by the findings of the present study. Although hyperinsulinemia or insulin resistance has been regarded as a risk factor for developing cardiovascular disease12,13,14, most East Asian patients with diabetes have much more moderate BMI compared with Caucasians. Impaired insulin secretion was reported to contribute more to the incidence of diabetes than insulin resistance15. Therefore, the significance of insulin resistance in the development of CHD might also be different from that of Caucasians. In fact, our result was in agreement with a previous Korean study of 230 patients, which also concluded that postchallenge hyperglycemia, but not hyperinsulinemia, was associated with CHD assessed by angiography16. The UKPDS study reported that in patients with type 2 diabetes, each 1% reduction in mean HbA1c was associated with a 14% reduction in the risk of myocardial infarction17.

Hyperglycemia itself is an independent risk factor for cardiovascular diseases. Therapies targeting postprandial glucose, including acarbose and insulin, prevent CVD in diabetic patients18,19, whose beneficial effects are independent of improving insulin resistance. It is generally accepted that hyperglycemia leads to atherosclerosis via mechanisms unified as overproduction of ROS and consequent oxidative stress20. Recently more mechanisms have been proposed. Firstly, hyperglycemia can cause epigenetic changes, especially dysregulation of microRNAs. These microRNA changes can lead to dysfunction of endothelial cells, vascular smooth muscle cells, platelets, and macrophage, as well as abnormal lipid metabolism, all of which are involved in atherosclerosis21,22,23. Secondly, the ROS overproduction caused by hyperglycemia triggers redox modifications and malfunction of ion channels in cardiomyocytes, e.g. the type 2 ryanodine receptor (RyR2) on the endoplasmic reticulum (ER). This direct effect may worsen the cardiovascular function observed in chronic hyperglycemia. Thirdly, hyperglycemia alters signaling pathways in atherosclerotic plaques. Plaques from patients with diabetes had more NF-kB expression and less SIRT6 expression, indicating a less stable plaque phenotype24,25,26,27. Collectively, these studies highlighted the contributions of hyperglycemia to the development of cardiovascular injury in diabetes.

The outstanding importance of PBG was supported by both linear and logistic regression analyses. PBG had the most significant correlation with prevalence and severity of CHD amongst the three glycemic parameters. The effects of FBG and HbA1c were completely masked by PBG when they were simultaneously included in the analysis. In logistic regression analysis, PBG stands in line with well-known risk factors like age, gender, and LP(a). Although HbA1c depicted a chronic glycemic profile, glucose fluctuations during postprandial periods triggered oxidative stress more than chronic sustained hyperglycemia. On the contrary, fasting hyperglycemia played a major role as soon as the HbA1c level rises above 8.4%28. Postprandial glucose was more sensitive than HbA1c in screening for prediabetes. 2-h Glucose level and IGT were stronger predictors of CVD than HbA1c29. Kataoka et al.30 reported that diffuse coronary artery narrowing (calculated by averaged vessel diameter and lesion length) was associated with postprandial hyperglycemia in 534 Japanese patients using quantitative coronary angiography. Later in a larger Caucasian cohort of 1040 patients, Saely et al.31 reported that PBG was associated with the number of significant coronary stenoses and the Gensini score. These results were consistent with our findings that PBG was associated with Gensini score, reiterating the importance of PBG in the natural development of coronary artery disease.

Another important finding in the present study was the correlation of PBG with the severity of atherosclerosis (quantified by Gensini score) was independent of the duration of diabetes. This finding may have important clinical implications. The duration of diabetes is known to contribute significantly to CVD risks. A 1.38-fold increased risk for CHD and a 1.86-fold higher risk for CVD death has been reported for each 10-year increase in duration of diabetes by the Framingham Heart Study32. Although the macrovascular complications of diabetes increase with duration, based on our findings, we suggest PBG should be closely monitored for early identification of CHD patients. In other words, aggressive screening of CHD is justified, provided that PBG is elevated, whether diabetes is newly diagnosed or diagnosed long ago.

The strengths of our study resided in the large study population and the use of the “gold standard” coronary angiography for assessing coronary stenosis. However, this study also had some important limitations: 1) As a cross-sectional study, we were unable to establish any causal relationships. 2) Our study focused on a highly selected group of patients, i.e. symptomatic inpatients. We didn’t have an independent population which was more general and less severe to validate the findings. 3) Also, the study involved only Asians, therefore the results may not be generalized to other racial or ethnic groups. 4)The female sample size was relatively small and thus did not allow separate analyses by gender. 5) The superiority of PBG was not validated in another independent population.

In conclusion, the severity of CHD was associated with glucose rather than insulin resistance in a large Chinese inpatient population scheduled for coronary angiography. Postprandial hyperglycemia was independently correlated with the presence and severity of coronary atherosclerosis in this population. These results suggest that the timing of screening should be based on postprandial glucose level, which outperformed FBG, HbA1c and insulin levels. Nevertheless, these findings still need to be validated in another independent population if we want to extend the significance of current study to a more general scenario. Follow-up studies are also needed to investigate the predictive power of postprandial glucose for future cardiovascular events.