Our main result was that stable STEMI patients without previously known diabetes have an excellent long-term prognosis independently of newly detected abnormal glucose regulation made by an OGTT screening either in-hospital or at three-month follow-up.
Large prospective studies have demonstrated both admission and fasting blood glucose levels to be independent predictors of long-term mortality in non-diabetic acute MI patients whether treated by primary PCI or not [19
]. However, data evaluating the prognostic importance of an OGTT performed during or early after an acute MI in patients without previously known diabetes are scarce. The timing of testing patients for abnormal glucose regulation after an acute MI is also uncertain. Recommendation of early screening of acute MI patients with an OGTT in order to detect high-risk patients in the recent European guidelines is mainly based on the follow-up study of the GAMI trial [8
]. In this follow-up study, abnormal glucose regulation classified by an OGTT day four or five post-MI was associated with worse clinical outcome during a median follow-up time of about three years [8
Our study is the second study (after the GAMI study) to evaluate early OGTT during an acute STEMI as a prognostic tool, in patients without previously known diabetes, and the first study who compared the prognostic value of an OGTT based classification in-hospital and after three months. The low event rate in the present study prevents firm conclusions about the prognostic value of OGTT screening in patients with acute STEMI. There was a non-significant trend towards increased hazard in patients with abnormal vs. normal glucose regulation and a real difference between groups may have been detected if the sample size was larger. However, our results are not in line with the similar sized GAMI study and may challenge the present guidelines, which emphasize the importance of early testing of all patients with acute MI, especially in the modern era of acute revascularization of STEMI patients.
The excellent prognosis found in our study, regardless of the glucometabolic status, may partly be explained by the low proportion of patients classified with type 2 diabetes in-hospital and at three-month (11% and 5%, respectively). Nevertheless, patients classified with abnormal compared to normal glucose regulation in-hospital and at three-month follow-up had significantly higher fasting values of HbA1c, circulating levels of insulin and proinsulin, and higher HOMA-IR score when measured both acutely and in a stable condition. These results correspond to another trial with acute MI patients showing that HbA1c and proinsulin were in the lowest range in patients with normal glucose regulation, intermediate in patients with impaired glucose tolerance, and highest in patients with type 2 diabetes [25
]. The present results suggest that the abnormal glucose regulation found in these STEMI patients not only seem to be a transient stress-induced response, but also may be a result of underlying insulin resistance.
The overall mortality rate in the present study was 2.7%. None died in-hospital and only one patient died during the first 30 days. Nine patients (7 with abnormal glucose regulation) experienced a new clinical event before the OGTT classification was performed at three-month follow-up. A low overall incidence of clinical events was found during the first three months of follow-up, suggesting that a early OGTT based classification of the glucometabolic status in order to identify high risk patients with worse prognosis is possibly of limited importance in low risk patients with a primary PCI treated STEMI.
The low overall incidence of clinical events reported in our study may partly be explained by the inclusion criteria. Unstable patients with cardiogenic shock, renal failure, ongoing chest pain, nausea and persistent hyperglycaemia were excluded from the study, probably making a selection bias towards more glucometabolically normal patients with better prognosis.
Furthermore, the patients included were relatively young and previous studies have shown a close relationship between newly diagnosed abnormal glucose regulation and age [8
]. Additionally, a high proportion of our patients were diagnosed with single-vessel disease during coronary angiography [10
], which may have contributed to the low event-rate observed in both groups.
Systematic use of recommended treatment (evidenced based medications and revascularisation) has been shown to have a favourable impact on one-year prognosis in patients with diabetes and coronary artery disease [29
]. Patients in the present study were all treated by primary PCI in addition to a high proportion of patients on evidence based secondary prevention. All patients were treated according to guidelines regardless of glucometabolic status and this may explain the excellent prognosis observed in this STEMI population. Transient hyperglycaemia in patients with acute MI without known diabetes is common and is associated with worse outcome [19
]. However, it has been difficult to prove that glucose control by insulin-glucose infusion [30
] or insulin-glucose-potassium infusion [31
], improve survival in patients with acute MI.
The European guidelines on diabetes, pre-diabetes, and cardiovascular diseases recommend that patients with cardiovascular disease without known diabetes should be investigated with an OGTT [9
], but whether the OGTT should be performed early after a first cardiovascular event or later in a stable condition is not defined. The present results suggest that OGTT screening of patients with acute STEMI without known diabetes should be performed in a stable condition during the post-MI follow-up.
The present study has certain limitations such as a possible selection bias towards more glucometabolically normal patients due to the exclusion of patients who were hemodynamically unstable, had severe renal failure and persistent hyperglycaemia. Accordingly, patients included, were somewhat younger than expected from a general STEMI population, had relatively few comorbidities and mainly one-vessel disease. It is possible that different results would be obtained in older MI patients since high age has been shown to be associated with ischemia related hyperglycaemia and poor glycemic control [28
All aspects taken together may explain the overall low incidence of clinical events during the follow-up period, but may also reflect the advances in modern treatment of STEMI with primary PCI in all patients and optimal post-infarction treatment. The association between abnormal glucose regulation classified by an OGTT and clinical outcome should be further investigated in forthcoming studies including primary PCI treated STEMI patients, with a prolonged follow-up period, using major cardiovascular events as a primary end-point.