Diabetes mellitus is an important independent risk factor for coronary atherosclerotic heart disease (hereafter referred to as coronary heart disease). The results of a meta-analysis showed that each 1% increase in glycosylated hemoglobin (HbA1c) was associated with a 1.18-fold increase in the relative risk of cardiovascular events (95% confidence interval [95% CI] 1.10-1.26). The incidence of coronary heart disease in diabetic patients was found to be 30.2% in a cohort study of type 2 diabetes with 7 years of follow-up, which was not significantly different from the incidence of recurrent coronary heart disease in non-diabetic patients with coronary heart disease (18.8%). Therefore, the National Cholesterol Education Program 3rd Adult Committee Guidelines have considered diabetes as an equivocal risk for coronary artery disease. Although a clear correlation between chronic hyperglycemia and the development of cardiovascular disease has been established, the significance of hyperglycemia (with or without the presence of underlying diabetes) and treatment strategies for patients with acute coronary syndromes in the acute phase are not yet fully understood. I. Significance of hyperglycemia in the acute phase of ACS Hyperglycemia in the acute phase of ACS is not uncommon, and its incidence is reported in the literature to vary from 25% to >50%, and this difference is related to the different criteria for hyperglycemia used in each study. The relationship between blood glucose levels and prognosis Blood glucose levels at admission have now been shown in several studies to be associated with prognosis in patients with ACS. a study by Foo et al. found a linear correlation between the incidence of left heart failure and cardiogenic death and blood glucose levels at admission in patients with ACS. Another large retrospective study enrolling 141,680 elderly patients with myocardial infarction showed a significant association between glucose levels at admission and mortality, with an increase in 30-day mortality of 13%-77% and 1-year mortality of 7%-46% with increasing glucose levels; even after correcting for confounding factors such as comorbidity and disease severity, the short- and long-term mortality rates remained significantly higher. A prospective study measuring fasting glucose within 24 hours of acute myocardial infarction admission showed that 30-day mortality was higher in those with elevated fasting glucose than in those with normal glucose (1.7 times the risk of death in those with 8.0-10.0 mmol/L (95% CI 1.2-2.4). A recent meta-analysis reached a similar conclusion. This shows that elevated glucose on admission is directly related to the prognosis of patients with ACS, regardless of the presence or absence of underlying diabetes. Notably, ACS patients without underlying diabetes appear to have a worse prognosis when they present with hyperglycemia than those with underlying diabetes, the mechanism of which is still unclear. II. Diagnosis of hyperglycemia and diabetes mellitus in the acute phase of ACS From the above findings, it can be found that some ACS patients without underlying diabetes mellitus developed elevated blood glucose in the acute phase, so can these elevated blood glucose be used to diagnose diabetes mellitus? Is there a stress component? A recent study answered this question by enrolling 140 patients with ACS, all of whom were tested for glucose on admission and fasting glucose, and also underwent an oral glucose tolerance test (OGTT) 5-7 days after hospitalization. The sensitivity and specificity of the diagnosis of diabetes mellitus were 89.5% and 43.6%, respectively, using fasting blood glucose ≥ 5.6 mmol/L and blood glucose ≥ 7.8 mmol/L at admission as cut points. In another recent study, 88 patients with ACS underwent OGTT on day 2 after intervention, and 34% met the diagnostic criteria for diabetes and 41% met the criteria for impaired glucose tolerance; whereas only 18% of the 88 patients who repeated the OGTT 1 month later met the criteria for diabetes and 26% met the criteria for impaired glucose tolerance. Therefore, in the acute phase of ACS, blood glucose at admission and fasting blood glucose lack specificity for the diagnosis of diabetes, but if abnormal blood glucose occurs in the acute phase, OGTT should be considered, but OGTT is poorly reproducible in these patients, and there is no definite conclusion as to when the most appropriate time to perform OGTT is. The treatment of acute hyperglycemia in ACS is related to the prognosis of ACS, so can the control of acute hyperglycemia improve the prognosis of ACS patients? Previous studies have found that the use of an intensive glucose lowering strategy resulted in a significant reduction in mortality in critically ill patients in the ICU, as well as a reduction in the incidence of ICU-related complications such as renal insufficiency and sepsis. However, a subsequent large multicenter randomized controlled trial overturned this finding – that intensive glucose lowering therapy in ICU patients increased mortality. What does intensive glucose-lowering therapy mean for patients with ACS? The DIGAMI-1 study evaluated the impact of an intensive glucose-lowering regimen (continuous infusion of glucose + insulin for at least 24 hours, followed by multiple daily subcutaneous insulin injections for at least 3 months) versus a standard regimen (with or without insulin depending on the patient) on the prognosis of patients with acute myocardial infarction who had underlying diabetes. At 3.4 years of follow-up, the level of HbA1c decline was significantly lower in the intensive treatment group than in the standard treatment group, as well as the mortality rate of patients in the intensive group. digami-2 builds on this study and compares the effects of three different glucose-lowering strategies (group 1 with glucose + insulin continuous infusion over 24 hours + insulin-based long-term glucose-lowering therapy; group 2 group used glucose + insulin continuous infusion over 24 hours + standard glucose-lowering therapy; and group 3 used the conventional standard treatment directly). During the 2.1 years of follow-up, there were no significant differences in recurrent myocardial infarction, stroke and mortality between the three groups. However, it is worth noting that there was no significant difference in fasting glucose and HbA1c levels between the three groups at the end of follow-up, and the fasting level of 8.0 mmol/L in group 1 did not contribute to reaching the goal of the trial design (5-7 mmol/L), so the trial did not achieve the expected results. DIGAMI primarily studied diabetic ACS patients, but we have previously mentioned that non-diabetic patients with acute hyperglycemia have a worse prognosis, so the subsequent HI-5 enrolled both diabetic and non-diabetic hyperglycemic ACS patients, but its sample size was much smaller compared to the two studies above; similar to DIGAMI-1, the HI-5 study evaluated the effect of intensive glucose-lowering therapy and standard treatment on the prognosis of ACS, the results showed no significant difference in short- and long-term mortality between the two groups, but the incidence of 3-month internal insufficiency and recurrent myocardial infarction was lower in the intensive group than in the control group. It is also worth noting that the HI-5 study also showed no significant difference in blood glucose levels between the two groups during follow-up, and they found that regardless of the regimen used, patients with blood glucose control of 8.0 mmol/L or less within 24 hours had a 9% reduction in 6-month mortality compared to those with blood glucose >8.0 mmol/L. This shows that what is associated with the prognosis of ACS patients is their post-treatment blood glucose level, and there is no significant correlation with the method they use. Therefore, for ACS patients with acute hyperglycemia, it does not actually seem to be very important whether intensive hypoglycemic therapy is used or not, but rather the need to control blood glucose to a reasonable range is important.