This population-based cohort study was conducted among subjects with stable CVD without known diabetes with over a decade follow-up. We examined the associations between FPG and 2 h-PCPG, whether as continuous or categorical variables, and recurrent CVD/CHD and related hard outcomes. Firstly, we found out that as for FPG level, IFG-ADA was associated with 73% higher risk of hard CVD events and newly diagnosed diabetes was associated with 2-fold higher risk of recurrent CVD/CHD events, independent of traditional risk factors. Secondly, every 1.04 mmol/L increase in FPG was associated with 16% higher risk of CVD. Thirdly, as for 2 h-PCPG, subjects with newly diagnosed diabetes (2 h-PCPG ≥ 11.1 mmol/L) had moderately increased risk of hard coronary heart disease, moreover, every 3.49 mmol/L higher levels of 2 h-PCPG was associated with 19% risk of CVD. Fourthly, FPG and 2 h-PCPG, whether as continues or categorical variables were significant predictors of incident diabetes.
Impact of IFG, IGT and newly diagnosed diabetes on recurrent cardiovascular outcomes has been addressed in previous studies; however, there were significant differences between them as follows: Firstly, most of them were performed among admitted patients with high baseline risk for recurrent event i.e., those with MI [10, 11, 21–25] who had data on OGTT before discharging from hospital or those with history of PCI/CABG. Secondly, there was a great difference between studies in terms of sample size, follow-up duration, approaching FPG and 2 h-PCPG as a continuous or categorical variable and heterogeneity in outcome definitions (CVD, MACE, all-cause or cardiovascular mortality). To our knowledge, this is the first population-based study with a long-term follow-up to asses this association in a heterogenic and relatively low risk population with stable CVD.
Findings of previous studies regarding the association between FPG (whether as continuous or categorical variable) with recurrent CVD were heterogenic. Accordingly, FPG as a continuous variable was not associated [8, 9, 26] or had lower risk 0.85 [0.71–1.01), P = 0.06] of recurrent CVD [22, 27]; whereas each 1 mmol/L increase in FPG was associated with higher risk of MACE (28%) and cardiovascular mortality (51%) among post MI patients in UK; the risks however, were not significant in the models including both FPG and 2 h-PCPG . The finding of the current study showed that each 1.04 mmol/L increase in FPG was associated with 16% and 17% higher risk of CVD and CHD, respectively. When including both FPG and 2 h-PCPG in the same model, no association was found between glucose variables and different cardiovascular events.
Moreover, when using standard cut-offs among patients with prevalent CAD, IFG-WHO was not associated with MACE in the study of Tamita [1.86(0.86–3.87)] , any cardiac outcomes in the study by Kiviniemi et al  and composite endpoints (including cardiovascular mortality, non-fatal MI, stroke, or hospitalization for heart failure) in the study by Shahim et al.. Furthermore, in a population-based study among men in Japan, borderline hyperglycemia (FPG = 5.6–6.9 mmol/L) among those with prior CAD was not associated with recurrent CVD outcomes. Similarly, prediabetes (FPG of 5.6–6.9 mmol/L, and HbA1c < 39 mmol/L) was not associated with 2-year MACE and hard cardiovascular outcomes in Chinese patients after PCI. Besides, Lenzen et al  revealed that impaired glucose regulation (those with IFG and IGT) was not an independent predictor for hard CVD outcomes in the multicenter hospital-based setting. The findings of the current study, however, showed that among stable outpatient CAD patients, IFG-ADA was associated with 73% risk for hard CVD (including definite MI or stroke and CVD mortality) and was in line with the study conducted by Otten et al  that showed IFG-ADA was associated with a hazard of 1.66 [(1.05–2.61)] for MACE. Importantly, among general population, we have recently shown that the significant risk of IFG for CVD events was attributable to those population who converted from IFG state to diabetes. Unfortunately, in the current study, we did not have adequate power to check this possibility in a cohort of subjects with history of previous CVD.
Focusing on 2 h-PCPG, some studies suggest that 2 h-PCPG is a better determinant for assessing the prognosis of post ACS patients than FPG. Notably, some authors suggest that adding 2 h-PCPG (but not FPG) to the Global Registry of Acute Coronary Events (GRACE) score (an established risk model for recurrent cardiac events), can improve the prediction power of the model in post MI patients without known diabetes[22, 27]. Furthermore, the finding of the study by Chattopadhyay showed that 2 h-PCPG as a continues variable is a better predictor of adverse post MI outcomes compared to FPG . In this regard, our study showed a positive association between 2 h-PCPG as a continuous variable and recurrent CVD/CHD outcomes as each 3.49 mmol/L increase in 2 h-PCPG was associated with 19% and 22% higher risk of CVD and CHD, respectively. Moreover, finding of some studies showed that IGT was associated with worse post MI prognosis [9, 22] while some showed no significant risk  and study by George et al  revealed that IGT is associated with higher risk of MACE but not hard CVD outcomes. The findings of our study however, showed that the risk of CVD/CHD and the related hard outcomes does not increase among those with IGT; in line with other studies conducted among low risk population with prevalent CAD [8, 34].
Focusing on newly diagnosed diabetes, we found that newly diagnosed diabetes using FPG criteria was associated with CVD/CHD but not hard cardiovascular outcomes. In line with our study, the findings of a cohort study on Chinese patients who underwent PCI  showed that newly diagnosed diabetes (FPG ≥ 7.0 mmol/L or HbA1c ≥ 48 mmol/L) was an independent risk factor for MACE but not hard outcomes. Moreover, study conducted by George et al,  showed that newly diagnosed diabetes (FPG ≥ 7.0 and/or 2 h-PCPG ≥ 11.1mmom/L) was associated with CVD and related hard outcomes. However, in the EUROASPIRE IV study  newly diagnosed diabetes (FPG ≥ 7) was not associated with composite cardiovascular outcomes. Similarly, newly diagnosed diabetes was not associated with MI, stroke and hard CVD outcomes in the study among European population . Regarding the newly diagnosed diabetes using 2 h-PCPG criteria, most studies showed that newly diagnosed diabetes [21, 26] or AGT (newly diagnosed diabetes using 2 h-PCPG definition plus IGT) are independently associated with higher risk of different cardiovascular outcomes [9–11, 24–26]. In the current study however, when using 2 h-PCPG criteria, a moderate higher risk of hard CHD 2.02 [(0.91–4.47), P = 0.08] was seen among those with newly diagnosed diabetes. However, AGT was not associated with different cardiovascular outcomes.
Our findings showed that both FPG and 2 h-PCPG, whether as continuous or categorical are strong predictors of incident diabetes. This is while 2 h-PCPG but not FPG was a significant predictor in the EUROASPIRE IV study. However, as we have shown in our previous study history of CVD per se is not an independent risk factor for incident diabetes.
Strengths of the current study are its prospective, longitudinal design with a long-term follow-up, reliable measurements of different covariates and careful adjustment for potential confounders. Moreover, our study included a heterogenic group of subjects with history of CAD in the stable phase of the disease and evaluated a wide range of outcomes including hard CVD/CHD events. This study also had some limitation: Firstly, we did not have data to calculate GRACE score including the ejection fraction of subjects, however, the available variables of this score system such as heart rate, were included in the multivariate model. Secondly, we did not have data of HbA1c levels which may cause misclassification and underestimation of the risk associated with prediabetes. Finally, this study was conducted on an Iranian population and the findings cannot be extrapolated to other ethnicities.