To the Editor,
First of all, we would like to thank the authors of the 2 very interesting letters your journal published regarding our paper,1 where we presented data on a new parameter to evaluate metabolic control in acute coronary syndrome (ACS) patients: magnitude of glycemia variation during hospitalization, which proved to be an independent predictor of long-term morbidity in non-diabetic, but not in diabetic patients.
Hyperglycemia in non-diabetics is more often a marker of stress response due to more extensive myocardial damage. A higher degree of stress is necessary to achieve the hyperglycemic state, because metabolic control in these persons is usually normal; in contrast, elevated glycemia after ACS in diabetics may be only a surrogate for poor glycemic control, not related with myocardial disease severity.
However, an important number of patients with no history of diabetes who develop hyperglycemia in stressful situations are true diabetics or have impaired glucose tolerance, and represent a higher risk cohort,2-4 as abnormal glucose regulation is very common in patients with coronary artery disease. Indeed, it was noted that patients with known or newly detected diabetes mellitus were at a particularly high risk for death and other cardiovascular events.
However, a recent study5 showed that two-thirds of ACS patients who had no previous diagnosis of diabetes had abnormal glucose tolerance by oral glucose tolerance test (OGTT) one week after the ACS, regardless of admission glucose levels, and admission hyperglycemia in non-diabetics did not represent previously undiagnosed abnormal glucose tolerance.
In accordance with European Society of Cardiology recommendations,6 in our coronary care unit ACS patients with no previous history of diabetes undergo an OGTT on day 5 of hospitalization. In a recent evaluation of our data (including 843 patients), we found that 246 patients (29.7%) had had a previous diagnosis of diabetes (type 2 diabetes in 90.1%), but after OGTT only 128 patients (15.2%) were found to have normal glucose metabolism (unpublished data). Of the remaining 715 (84.8%) patients, 27 were type 1 diabetics (3.8%), 425 (59.4%) had type 2 diabetes, 58 (8.1%) had impaired glucose tolerance and 205 (28.7%) impaired fasting glucose. Based on these results in a similar population from our coronary care unit, we can hypothesize that a large proportion of non-diabetic patients could be redefined as diabetics after OGTT results.
Nevertheless, our data on magnitude of glycemia variation clearly separated 2 ACS populations, depending on their prognosis: (long-term) diabetics and non-diabetics (or short-term/pre-diabetics - up to 78% of this patient population, based on our previous OGTT data).
If magnitude of glycemia variation were only a surrogate for undiagnosed diabetes, then its prognostic impact should be similar in both populations, given the high prevalence of undiagnosed diabetes and pre-diabetes in the population not previously known to be diabetic.
Available data on admission hyperglycemia and magnitude of glycemia variation seem to point to the existence of different responses to ACS stress by long-term diabetics and other patients (not known to be diabetic prior to ACS). Is there a "metabolic preconditioning" in long-term diabetics?
In order to answer this important question properly, we have to readdress the issue of OGTT data in "non-diabetic" ACS patients, as suggested in your letters. We are therefore in the process of retesting our non-diabetic ACS population with OGTT post-discharge, and will share the results with the scientific community as soon as they become available, thus contributing further to the clarification of the complex relationships between metabolism, cardiac ischemia and prognosis.