Diabetes mellitus affects 6% of the US population but is present in as many as 30% of patients hospitalized with acute coronary syndromes. It has been recognized for some time that diabetics experience a greater mortality during the acute phase of myocardial infarction (MI) and a higher morbidity in the postinfarction period (see recent reviews in References 1 and 2). Before the advent of coronary care as we know it today, mortality among diabetic patients in MI was reported to be as high as 40% 3 and at least double the mortality rate in patients without diabetes. More extensive coronary artery disease, additional cardiovascular risk factors, and other end-organ disease were thought to be largely responsible for this major difference in outcome. Current treatment of acute MI derived from large clinical trials has dramatically improved survival in both nondiabetic and diabetic patients. However, despite these improvements, diabetes still doubles the casefatality rate. In the GUSTO-1 angiography substudy report, 4 this twofold increase in relative risk of 30-day mortality persisted even after adjustment for the factors cited above. What is this “diabetic factor”? It is in this context that new information on this topic must be evaluated. In the December 16, 1997, issue of Circulation, the GISSI-3 investigators compare the effect of early administration (within 24 hours of admission) of lisinopril in patients with and without diabetes mellitus in MI. 5 Compared with placebo, lisinopril dramatically reduced both 6-week and 6-month mortality in diabetics versus nondiabetics (6 weeks, 30% versus 5% and 6 months, 20% and 0%, respectively). Furthermore, the incidence of drug-related adverse effects was similar between the two groups within the blood pressure and renal function parameters used in that study. This experience, along with the subgroup analyses of SAVE6 and TRACE, 7 should firmly establish an ACE inhibitor as part of the regimen for the diabetic patient with MI. In a recent meta-analysis of ACE inhibitor trials in acute MI, only a 6% relative mortality reduction (without regard to the presence or absence of diabetes mellitus) was found with early drug administration. 8 Despite these collective data, ACE inhibitors are generally withheld on the first day of acute MI to avoid causing hypotension. In CONSENSUS II, 9 hypotension in the enalapril-treated group negated any potential benefit of early ACE inhibition. This GISSI-3 report also suggests that the diabetic patient may have far more to gain than the nondiabetic when an ACE inhibitor is administered within the first day of an acute MI. The putative mechanisms responsible for the major benefit of lisinopril in these patients are presented below. In general, ACE inhibitors are grossly underprescribed in this setting, despite their recognized benefits. 10 The failure to use them in diabetic patients may be even more prevalent, for the following reasons:(1) fear of azotemia with or without preexistent renal disease;(2) fear that they may cause or contribute to hemodynamic instability, particularly if diabetesrelated autonomic neuropathy is suspected;(3) fear that they may induce hyperkalemia, because type 4 RTA or bilateral renal artery stenoses are more common in diabetics; and (4) preoccupation with the challenge of glycemic control. A similar paradox relates to the failure to administer ß-blockers to diabetic patients in acute MI. 11 Compared with placebo in this setting, ß-blockers provide two to three times the relative benefit in mortality reduction when diabetes is present compared with when it is absent. 12 However, the risk of masking the warning signs of hypoglycemia and disturbing glycemic control tends to limit their use …