The prevalence of type 2 diabetes mellitus (DM) has rapidly increased worldwide over the last decades and DM is increasingly perceived as an ongoing epidemic. There is a conclusive evidence implicating DM in complications of coronary heart disease (CHD)[1],[2],[3] and[4]. The risk of acute myocardial infarction (AMI) and death in diabetic subjects without CHD is similar to the risk of non-diabetic pts with previous AMI. Therefore, DM has gained the status of CHD risk equivalent[5]. Despite recent treatment improvements of AMI, patients with DM have worse prognosis after myocardial infarction in comparison to subjects without DM. There is also evidence that CHD patients have glucose abnormalities (GA) other than DM. Mozaffarian et al. as well as Bartnik et al. compared population-based cohorts of patients with AMI and found that AMI groups showed almost twice higher annual incidence-rates of impaired fasting glucose and diabetes. Therefore, they proposed that myocardial infarction may be a prediabetes equivalent[6] and[7]. However, the early and long-term outcome in AMI patients with glucose abnormalities other than DM remains unclear. The aim of our study was to assess the incidence and prognostic role of different glucose abnormalities in AMI patients treated with percutaneous coronary intervention (PCI) as well as to identify independent predictors of death in GA.

Results of several cohort studies revealed that glucose abnormalities other than DM are very frequent in patients with CHD[11],[12] and[13]. The Euro Heart Survey on Diabetes and the Heart showed that the rates of normal glucose tolerance were less common than abnormal ones in patients with diagnosed CHD and that over 50% of CHD subjects had IGT or newly detected DM[12] and[14]. Our results confirmed the high prevalence of abnormal glucose metabolism in AMI patients, with only 31% of subjects with normal glucose tolerance and a high proportion of DM, IGT and IFG (32, 22 and 15% respectively).

Published data indicates also that hyperglycaemia is associated with adverse outcomes regardless of diabetes status[15],[16] and[17]. Stress hyperglycaemia in a setting of AMI increases the risk of malignant ventricular tachyarrhythmias as well as in-hospital mortality[16]. In the observational registry of consecutive nondiabetic patients with STEMI Timmer et al. reported that acute admission hyperglycaemia was associated with increased 1-year and remote mortality[17]. However, by means of elevated admission glucose as well as HbA_1c the authors were able to identify the first parameter as the predictor of early adverse outcomes, while the latter one was independently associated with 1-year and long-term mortality. Similarly, Chan et al. showed that HbA_1c concentration in diabetic patients in a setting of acute coronary syndrome is not related to short-term cardiovascular outcome[18].

It is known that patients with both CHD and DM have worse outcomes than subjects with only one of these two conditions[5],[19] and[20]. However, to the best of our knowledge, there is very limited data on the impact of different glucose perturbations on early and late clinical outcomes in AMI patients treated with PCI in the acute phase of myocardial infarction. Lenzen et al. in a population of coronary artery disease showed that patients with previously recognized DM are at highest risk for adverse events, while those with newly detected DM are at intermediate risk. Nevertheless, IFG and IGT were not identified as independent predictors of worse outcome. What is more, acute coronary syndromes accounted for only 36% of patients in this study[14]. In GAMI study, the analysis of AMI population with coexisting abnormal glucose tolerance revealed that both IGT and newly diagnosed DM are strong and independent predictors of adverse cardiovascular events after myocardial infarction[13]. However, of note is that the GAMI population was relatively small and consisted of only 168 subjects. The group with abnormal glucose tolerance included 113 patients not only with IGT, but also with a newly detected DM. What is more, reperfusion therapy had been used only in 38% of patients with glucose abnormalities and in 51% with normal glucose regulation.

Our registry encompassed 2527 consecutive in-hospital AMI survivors, who were optimally treated, both pharmacologically and invasively (reperfusion by means of PCI only) in the acute phase of AMI. Total mortality rate of 8.6% in our study was relatively low. However, this may be a result of the study protocol, which was based on the analysis of in-hospital survivors (n = 2527, 92.5%) in order to assess properly the outcomes of AMI patients with different glucose abnormalities, in particular with GA other than previously diagnosed DM. Indeed, it would be impossible to diagnose accurately and reliably GA other than previously diagnosed DM in patients who died during hospitalization. Among 206 subjects with AMI (n = 7.5%) who died during index hospitalization 107 (52%) subjects had previously diagnosed DM. What is more, all consecutive patients with AMI were treated very homogenously and optimally both pharmacologically and invasively with modern therapy (PCI), in line with ESC recommendations and this may have contributed to the relatively low long-term mortality.

The main finding of our study is that IGT affects negatively the outcomes of AMI patients treated invasively in the acute phase of myocardial infarction. What is more, the long-term prognosis of patients with IGT is similar to the outcomes of AMI subjects with DM and significantly worse than in normoglycaemic patients. Both, IGT and DM increase significantly one year and remote mortality in AMI population.

Moreover, further multivariate analysis model identified independent predictors of death in subjects with glucose abnormalities. Impaired renal function along with depressed left ventricle ejection fraction appeared to be the strongest and common risk factors for death in both prediabetic and diabetic groups. On a similar study population Kowalczyk et al. found that the prognosis of diabetics with AMI is related to renal function and diabetes coexisting with chronic kidney disease (CKD) is one of the strongest independent risk factors for cardiovascular complications and total mortality[21]. Similarly, Kim et al. in a nationwide prospective Korea Acute Myocardial Infarction Registry (KAMIR) showed that compromised renal function, in particular in combination with diabetes, is associated with the occurrence of composite MACE and indicates poor prognosis in subjects with AMI[22]. The impact of abnormal glucose metabolism on left ventricular function and prognosis in AMI patients was assessed by Høfsten et al. who demonstrated a linear association between GA and left ventricular dysfunction[23]. What is more, Juana A Flores-Le Roux et al. reported that in subjects with acute decompensation of heart failure, a new onset diabetes is not only common, but also increases remote mortality in the same manner as previously diagnosed diabetes[24].

Our results thus confirmed an observation, that large proportion of AMI patients has IGT as well as that this type of abnormal glucose metabolism indicates the group of patients at a high risk of adverse cardiac events. Therefore, interventions which would improve the prognosis in this group of AMI patients should be considered. Published data indicates that smoking cessation, prevention of weight gain, and consumption of low-fat dairy products could substantially lower this risk[6] and[25]. However, although AMI individuals are usually scheduled to follow these recommendations, our results suggest that this type of strategy is insufficient.

Although it has been suggested, that IGT may be a more “benign” state than DM the results of our registry indicate, that both IGT and DM bear poor prognosis in AMI patients[6]. The intriguing convergence of survival Kaplan-Meier curves in diabetic and IGT-patients who survived AMI may be explained by different treatment strategies in both groups. Diabetic patients, in contrast to IGT subjects, receive glucose-lowering medications during acute AMI phase and throughout the follow-up period. Consequently, the beneficial effect of such a pharmacotherapy only in DM subjects could be responsible for similar long-term prognosis in both groups.

Up to date, only a few studies examined the effects of antidiabetic treatment in IGT subjects[25],[26] and[27]. However, the STOPNIDDM trial revealed very optimistic results[25] and[26]. In this randomized, placebo-controlled trial Acarbose – oral anti-diabetic agent, significantly prevented or delayed the progression of glucose intolerance to diabetes and, most importantly, significantly reduced the risk of cardiovascular events. These data provided a strong rationale for the use of similar agents as a part of treatment strategy in AMI patients with coexisting IGT to improve long-term prognosis.

Some recently published trials also indicated that lifestyle modification and various pharmacological agents can delay or prevent the development of glucose disturbances to overt diabetes. However, the expected rates of cardiovascular events in these studies were low and did not provide statistical power to evaluate the influence of such interventions on MACE[28],[29] and[30]. The recently published, promising study in this area was The Navigator trial. The study was designed to evaluate whether reducing postprandial hyperglycaemia and blockade of the renin-angiotensin-aldosterone system or both interventions reduce the risk of diabetes and cardiovascular events in patients with IGT[31]. However, after a median follow up of 6.5 years, neither valsartan nor nateglinide improved cardiovascular prognosis in the study population. What is more, nateglinide did not reduce the risk of new onset diabetes, while valsartan reduced this risk only by 14%[32] and[33]. The above mentioned conflicting data from different studies indicates the need for further randomized clinical trials in order to establish the position of glucose-lowering agents in prevention of adverse cardiovascular events in AMI patients.