The effect of diabetes mellitus on prognosis and serial left ventricular function after acute myocardial infarction: contribution of both coronary disease and diastolic left ventricular dysfunction to the adverse prognosis. The MILIS Study Group

Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115.

Patients with diabetes mellitus experience a more adverse outcome after acute myocardial infarction compared with nondiabetic patients, although the mechanisms responsible for these findings are not clear. From the Multicenter Investigation of the Limitation of Infarct Size (MILIS) study, the course of acute infarction in 85 diabetic patients was compared with that in 415 nondiabetic patients, all of whom had serial assessments of left ventricular function. The diabetic patients experienced a more complicated in-hospital and postdischarge course than did the nondiabetic patients, including a higher incidence of postinfarction angina, infarct extension, heart failure and death, despite the development of a smaller infarct size and similar levels of left ventricular ejection fraction. Although diabetic patients had a worse profile of cardiovascular risk factors at the time of the index infarction, the increased incidence of adverse outcomes among them persisted despite adjustment for these baseline imbalances. Diabetic women had a poor baseline risk profile compared with the other groups categorized by gender and diabetic status, and experienced an almost twofold increase in cardiac mortality despite development of the smallest infarct size during the index event. The duration of diabetes and the use of insulin at the time of the index infarction were associated with a better in-hospital mortality rate, but the duration of diabetes did not exert a major influence on the outcome of the diabetic patients. The factors responsible for the increased incidence of adverse outcomes among diabetic patients may be related to an acceleration of the atherosclerotic process, diastolic left ventricular dysfunction associated with diabetic cardiomyopathy or other unidentified unfavorable processes.

This article has been cited by other articles:

				S. J. Nicholls, E. M. Tuzcu, S. Kalidindi, K. Wolski, K.-W. Moon, I. Sipahi, P. Schoenhagen, and S. E. Nissen Effect of Diabetes on Progression of Coronary Atherosclerosis and Arterial Remodeling: A Pooled Analysis of 5 Intravascular Ultrasound Trials J. Am. Coll. Cardiol., July 22, 2008; 52(4): 255 - 262. [Abstract] [Full Text] [PDF]

				T. Kinnaird, E. Stabile, S. Zbinden, M.-S. Burnett, and S. E. Epstein Cardiovascular risk factors impair native collateral development and may impair efficacy of therapeutic interventions Cardiovasc Res, May 1, 2008; 78(2): 257 - 264. [Abstract] [Full Text] [PDF]

				T H Marwick Diabetic heart disease Postgrad. Med. J., April 1, 2008; 84(990): 188 - 192. [Abstract] [Full Text] [PDF]

				J. F. Navarro, C. Mora, M. Gomez, M. Muros, C. Lopez-Aguilar, and J. Garcia Influence of renal involvement on peripheral blood mononuclear cell expression behaviour of tumour necrosis factor-{alpha} and interleukin-6 in type 2 diabetic patients Nephrol. Dial. Transplant., March 1, 2008; 23(3): 919 - 926. [Abstract] [Full Text] [PDF]

				I. Lekli, G. Szabo, B. Juhasz, S. Das, M. Das, E. Varga, L. Szendrei, R. Gesztelyi, J. Varadi, I. Bak, et al. Protective mechanisms of resveratrol against ischemia-reperfusion-induced damage in hearts obtained from Zucker obese rats: the role of GLUT-4 and endothelin Am J Physiol Heart Circ Physiol, February 1, 2008; 294(2): H859 - H866. [Abstract] [Full Text] [PDF]

				L. van Heerebeek, N. Hamdani, M. L. Handoko, I. Falcao-Pires, R. J. Musters, K. Kupreishvili, A. J.J. Ijsselmuiden, C. G. Schalkwijk, J. G.F. Bronzwaer, M. Diamant, et al. Diastolic Stiffness of the Failing Diabetic Heart: Importance of Fibrosis, Advanced Glycation End Products, and Myocyte Resting Tension Circulation, January 1, 2008; 117(1): 43 - 51. [Abstract] [Full Text] [PDF]

				E. van Lunteren and M. Moyer Oxidoreductase, morphogenesis, extracellular matrix, and calcium ion-binding gene expression in streptozotocin-induced diabetic rat heart Am J Physiol Endocrinol Metab, September 1, 2007; 293(3): E759 - E768. [Abstract] [Full Text] [PDF]

				M. P. Chandler, E. E. Morgan, T. A. McElfresh, T. A. Kung, J. H. Rennison, B. D. Hoit, and M. E. Young Heart failure progression is accelerated following myocardial infarction in type 2 diabetic rats Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1609 - H1616. [Abstract] [Full Text] [PDF]

				A. Pelletier and L. Coderre Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1325 - E1332. [Abstract] [Full Text] [PDF]

				S. Jesmin, S. Zaedi, N. Shimojo, M. Iemitsu, K. Masuzawa, N. Yamaguchi, C. N. Mowa, S. Maeda, Y. Hattori, and T. Miyauchi Endothelin antagonism normalizes VEGF signaling and cardiac function in STZ-induced diabetic rat hearts Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1030 - E1040. [Abstract] [Full Text] [PDF]

				C. J. Schofield, G. Libby, G. M. Brennan, R. R. MacAlpine, A. D. Morris, G. P. Leese, and for the DARTS/MEMO Collaboration Mortality and Hospitalization in Patients After Amputation: A comparison between patients with and without diabetes Diabetes Care, October 1, 2006; 29(10): 2252 - 2256. [Abstract] [Full Text] [PDF]

				D. An and B. Rodrigues Role of changes in cardiac metabolism in development of diabetic cardiomyopathy Am J Physiol Heart Circ Physiol, October 1, 2006; 291(4): H1489 - H1506. [Abstract] [Full Text] [PDF]

				S. Sulfi and A. D Timmis Review: Heart failure complicating acute myocardial infarction in patients with diabetes: pathophysiology and management strategies The British Journal of Diabetes & Vascular Disease, September 1, 2006; 6(5): 191 - 196. [Abstract] [PDF]

				N. Chaowalit, A. L. Arruda, R. B. McCully, K. R. Bailey, and P. A. Pellikka Dobutamine Stress Echocardiography in Patients With Diabetes Mellitus: Enhanced Prognostic Prediction Using a Simple Risk Score J. Am. Coll. Cardiol., March 7, 2006; 47(5): 1029 - 1036. [Abstract] [Full Text] [PDF]

				R. E. Gilbert, K. Connelly, D. J. Kelly, C. A. Pollock, and H. Krum Heart Failure and Nephropathy: Catastrophic and Interrelated Complications of Diabetes Clin. J. Am. Soc. Nephrol., March 1, 2006; 1(2): 193 - 208. [Abstract] [Full Text] [PDF]

				T H Marwick Diabetic heart disease Heart, March 1, 2006; 92(3): 296 - 300. [Abstract] [Full Text] [PDF]

				M. Saha and A. D Timmis Review: Diabetic autonomic dysfunction: adverse effects on presentation, management and outcomes of acute coronary syndromes The British Journal of Diabetes & Vascular Disease, September 1, 2005; 5(5): 260 - 264. [Abstract] [PDF]

				B. Verges, M. Zeller, J. Desgres, G. Dentan, Y. Laurent, L. Janin-Manificat, I. L'Huillier, G. Rioufol, J.-C. Beer, H. Makki, et al. High plasma N-terminal pro-brain natriuretic peptide level found in diabetic patients after myocardial infarction is associated with an increased risk of in-hospital mortality and cardiogenic shock Eur. Heart J., September 1, 2005; 26(17): 1734 - 1741. [Abstract] [Full Text] [PDF]

				M. Suleiman, D. Aronson, R. Asleh, M. R. Kapeliovich, A. Roguin, S. R. Meisel, M. Shochat, A. Sulieman, S. A. Reisner, W. Markiewicz, et al. Haptoglobin Polymorphism Predicts 30-Day Mortality and Heart Failure in Patients With Diabetes and Acute Myocardial Infarction Diabetes, September 1, 2005; 54(9): 2802 - 2806. [Abstract] [Full Text] [PDF]

				J Figueras, C Pena, and J Soler-Soler Thirty day prognosis of patients with acute pulmonary oedema complicating acute coronary syndromes Heart, July 1, 2005; 91(7): 889 - 893. [Abstract] [Full Text] [PDF]

				I. S. Thrainsdottir, T. Aspelund, G. Thorgeirsson, V. Gudnason, T. Hardarson, K. Malmberg, G. Sigurdsson, and L. Ryden The Association Between Glucose Abnormalities and Heart Failure in the Population-Based Reykjavik Study Diabetes Care, March 1, 2005; 28(3): 612 - 616. [Abstract] [Full Text] [PDF]

				B S Rana, P O Lim, A A O Naas, S A Ogston, R W Newton, R T Jung, A D Morris, and A D Struthers QT interval abnormalities are often present at diagnosis in diabetes and are better predictors of cardiac death than ankle brachial pressure index and autonomic function tests Heart, January 1, 2005; 91(1): 44 - 50. [Abstract] [Full Text] [PDF]

				R. V. Donthi, G. Ye, C. Wu, D. A. McClain, A. J. Lange, and P. N. Epstein Cardiac Expression of Kinase-deficient 6-Phosphofructo-2-kinase/Fructose-2,6-bisphosphatase Inhibits Glycolysis, Promotes Hypertrophy, Impairs Myocyte Function, and Reduces Insulin Sensitivity J. Biol. Chem., November 12, 2004; 279(46): 48085 - 48090. [Abstract] [Full Text] [PDF]

				A. M. Murcia, C. H. Hennekens, G. A. Lamas, M. Jimenez-Navarro, J. L. Rouleau, G. C. Flaker, S. Goldman, H. Skali, E. Braunwald, and M. A. Pfeffer Impact of Diabetes on Mortality in Patients With Myocardial Infarction and Left Ventricular Dysfunction Arch Intern Med, November 8, 2004; 164(20): 2273 - 2279. [Abstract] [Full Text] [PDF]

				N. Carrabba, R. Valenti, G. Parodi, G. M. Santoro, and D. Antoniucci Left Ventricular Remodeling and Heart Failure in Diabetic Patients Treated With Primary Angioplasty for Acute Myocardial Infarction Circulation, October 5, 2004; 110(14): 1974 - 1979. [Abstract] [Full Text] [PDF]

				D. Aguilar, S. D. Solomon, L. Kober, J.-L. Rouleau, H. Skali, J. J.V. McMurray, G. S. Francis, M. Henis, C. M. O'Connor, R. Diaz, et al. Newly Diagnosed and Previously Known Diabetes Mellitus and 1-Year Outcomes of Acute Myocardial Infarction: The Valsartan in Acute Myocardial Infarction (VALIANT) Trial Circulation, September 21, 2004; 110(12): 1572 - 1578. [Abstract] [Full Text] [PDF]

				K. Bibbins-Domingo, F. Lin, E. Vittinghoff, E. Barrett-Connor, S. B. Hulley, D. Grady, and M. G. Shlipak Predictors of Heart Failure Among Women With Coronary Disease Circulation, September 14, 2004; 110(11): 1424 - 1430. [Abstract] [Full Text] [PDF]

				H. S. Lim, R. J. MacFadyen, and G. Y. H. Lip Diabetes Mellitus, the Renin-Angiotensin-Aldosterone System, and the Heart Arch Intern Med, September 13, 2004; 164(16): 1737 - 1748. [Abstract] [Full Text] [PDF]

				R. Marfella, K. Esposito, F. Nappo, M. Siniscalchi, F. C. Sasso, M. Portoghese, M. Pia Di Marino, A. Baldi, S. Cuzzocrea, C. Di Filippo, et al. Expression of Angiogenic Factors During Acute Coronary Syndromes in Human Type 2 Diabetes Diabetes, September 1, 2004; 53(9): 2383 - 2391. [Abstract] [Full Text] [PDF]

				P. Raggi, L. J. Shaw, D. S. Berman, and T. Q. Callister Prognostic value of coronary artery calcium screening in subjects with and without diabetes J. Am. Coll. Cardiol., May 5, 2004; 43(9): 1663 - 1669. [Abstract] [Full Text] [PDF]

				I. Gustafsson, B. Brendorp, M. Seibaek, H. Burchardt, P. Hildebrandt, L. Kober, C. Torp-Pedersen, and DIAMOND Study Group Influence of diabetes and diabetes-gender interaction on the risk of death in patients hospitalized with congestive heart failure J. Am. Coll. Cardiol., March 3, 2004; 43(5): 771 - 777. [Abstract] [Full Text] [PDF]

				P L Sanchez, J L Morinigo, P Pabon, F Martin, I Piedra, I F Palacios, and C Martin-Luengo Prognostic relations between inflammatory markers and mortality in diabetic patients with non-ST elevation acute coronary syndrome Heart, March 1, 2004; 90(3): 264 - 269. [Abstract] [Full Text] [PDF]

				C. D. Lee, A. R. Folsom, J. S. Pankow, F. L. Brancati, and For the Atherosclerosis Risk in Communities (ARIC) Cardiovascular Events in Diabetic and Nondiabetic Adults With or Without History of Myocardial Infarction Circulation, February 24, 2004; 109(7): 855 - 860. [Abstract] [Full Text] [PDF]

				D. S.H. Bell Heart Failure: The frequent, forgotten, and often fatal complication of diabetes Diabetes Care, August 1, 2003; 26(8): 2433 - 2441. [Abstract] [Full Text] [PDF]

				T. Shiomi, H. Tsutsui, M. Ikeuchi, H. Matsusaka, S. Hayashidani, N. Suematsu, J. Wen, T. Kubota, and A. Takeshita Streptozotocin-induced hyperglycemia exacerbates left ventricular remodeling and failure after experimental myocardial infarction J. Am. Coll. Cardiol., July 2, 2003; 42(1): 165 - 172. [Abstract] [Full Text] [PDF]

				C. Borghi, S. Bacchelli, D. D. Esposti, and E. Ambrosioni Effects of the Early ACE Inhibition in Diabetic Nonthrombolyzed Patients With Anterior Acute Myocardial Infarction Diabetes Care, June 1, 2003; 26(6): 1862 - 1868. [Abstract] [Full Text] [PDF]

				D. A. Alter, Y. Khaykin, P. C. Austin, J. V. Tu, and J. E. Hux Processes and Outcomes of Care for Diabetic Acute Myocardial Infarction Patients in Ontario: Do physicians undertreat? Diabetes Care, May 1, 2003; 26(5): 1427 - 1434. [Abstract] [Full Text] [PDF]

				K Foo, J Cooper, A Deaner, C Knight, A Suliman, K Ranjadayalan, and A D Timmis A single serum glucose measurement predicts adverse outcomes across the whole range of acute coronary syndromes Heart, May 1, 2003; 89(5): 512 - 516. [Abstract] [Full Text] [PDF]

				B. N. Finck, X. Han, M. Courtois, F. Aimond, J. M. Nerbonne, A. Kovacs, R. W. Gross, and D. P. Kelly A critical role for PPARalpha -mediated lipotoxicity in the pathogenesis of diabetic cardiomyopathy: Modulation by dietary fat content PNAS, February 4, 2003; 100(3): 1226 - 1231. [Abstract] [Full Text] [PDF]

				T.-M. Lee and T.-F. Chou Impairment of Myocardial Protection in Type 2 Diabetic Patients J. Clin. Endocrinol. Metab., February 1, 2003; 88(2): 531 - 537. [Abstract] [Full Text] [PDF]

				A. M. Calafiore, M. Di Mauro, G. Di Giammarco, M. Contini, G. Vitolla, A. Lorena Iaco, C. Canosa, and S. D'Alessandro Effect of diabetes on early and late survival after isolated first coronary bypass surgery in multivessel disease J. Thorac. Cardiovasc. Surg., January 1, 2003; 125(1): 144 - 154. [Abstract] [Full Text] [PDF]

				D. Chyun, V. Vaccarino, J. Murillo, L. H. Young, and H. M. Krumholz Cardiac Outcomes After Myocardial Infarction in Elderly Patients With Diabetes Mellitus Am. J. Crit. Care., November 1, 2002; 11(6): 504 - 519. [Abstract] [Full Text] [PDF]

				A. F.L. Schinkel, A. Elhendy, R. T. van Domburg, J. J. Bax, E. C. Vourvouri, F. B. Sozzi, R. Valkema, J. R.T.C. Roelandt, and D. Poldermans Prognostic Value of Dobutamine-Atropine Stress Myocardial Perfusion Imaging in Patients With Diabetes Diabetes Care, September 1, 2002; 25(9): 1637 - 1643. [Abstract] [Full Text] [PDF]

				L. E. Egede and D. Zheng Modifiable Cardiovascular Risk Factors in Adults With Diabetes: Prevalence and Missed Opportunities for Physician Counseling Arch Intern Med, February 25, 2002; 162(4): 427 - 433. [Abstract] [Full Text] [PDF]

				Z S Kyriakides, S Psychari, N Chrysomallis, M Georgiadis, E Sbarouni, and D T Kremastinos Type II diabetes does not prevent the recruitment of collateral vessels and the normal reduction of myocardial ischaemia on repeated balloon inflations during angioplasty Heart, January 1, 2002; 87(1): 61 - 66. [Abstract] [Full Text] [PDF]

				J. C. LaRosa Prevention and Treatment of Coronary Heart Disease: Who Benefits? Circulation, October 2, 2001; 104(14): 1688 - 1692. [Abstract] [Full Text] [PDF]

				S. Ghosh, N. B. Standen, and M. Galinanes Failure to precondition pathological human myocardium J. Am. Coll. Cardiol., March 1, 2001; 37(3): 711 - 718. [Abstract] [Full Text] [PDF]

				I. Gustafsson and P. Hildebrandt Early Failure of the Diabetic Heart Diabetes Care, January 1, 2001; 24(1): 3 - 4. [Full Text]

				I Gustafsson, P Hildebrandt, M Seibaek, T Melchior, C Torp-Pedersen, L Kober, and P Kaiser-Nielsen Long-term prognosis of diabetic patients with myocardial infarction: relation to antidiabetic treatment regimen Eur. Heart J., December 1, 2000; 21(23): 1937 - 1943. [Abstract] [PDF]

				K. Malmberg, S. Yusuf, H. C. Gerstein, J. Brown, F. Zhao, D. Hunt, L. Piegas, J. Calvin, M. Keltai, A. Budaj, et al. Impact of Diabetes on Long-Term Prognosis in Patients With Unstable Angina and Non-Q-Wave Myocardial Infarction : Results of the OASIS (Organization to Assess Strategies for Ischemic Syndromes) Registry Circulation, August 29, 2000; 102(9): 1014 - 1019. [Abstract] [Full Text] [PDF]

				A. Norhammar and K. Malmberg Heart failure and glucose abnormalities: an increasing combination with poor functional capacity and outcome Eur. Heart J., August 2, 2000; 21(16): 1293 - 1294. [PDF]

				S Kennon, K Barakat, A Suliman, P K MacCallum, K Ranjadayalan, P Wilkinson, and A D Timmis Influence of previous aspirin treatment and smoking on the electrocardiographic manifestations of injury in acute myocardial infarction Heart, July 1, 2000; 84(1): 41 - 45. [Abstract] [Full Text] [PDF]

				R. H. Mehta, T. J. Ruane, P. A. McCargar, K. A. Eagle, and E. J. Stalhandske The Treatment of Elderly Diabetic Patients With Acute Myocardial Infarction: Insight From Michigan's Cooperative Cardiovascular Project Arch Intern Med, May 8, 2000; 160(9): 1301 - 1306. [Abstract] [Full Text] [PDF]

				B Almbrand, M Johannesson, B Sjostrand, K Malmberg, and L Ryden Cost-effectiveness of intense insulin treatment after acute myocardial infarction in patients with diabetes mellitus. Results from the DIGAMI study Eur. Heart J., May 1, 2000; 21(9): 733 - 739. [Abstract] [PDF]

				D. Hasdai, C. B. Granger, S. S. Srivatsa, D. A. Criger, S. G. Ellis, R. M. Califf, E. J. Topol, and D. R. Holmes Jr. Diabetes mellitus and outcome after primary coronary angioplasty for acute myocardial infarction: lessons from the GUSTO-IIb angioplasty substudy J. Am. Coll. Cardiol., May 1, 2000; 35(6): 1502 - 1512. [Abstract] [Full Text] [PDF]

				K.-H. Mak and E. J. Topol Emerging concepts in the management of acute myocardial infarction in patients with diabetes mellitus J. Am. Coll. Cardiol., March 1, 2000; 35(3): 563 - 568. [Abstract] [Full Text] [PDF]

				I. I. Joffe, K. E. Travers, C. L. Perreault-Micale, T. Hampton, S. E. Katz, J. P. Morgan, and P. S. Douglas Abnormal cardiac function in the streptozotocin-induced, non-insulin-dependent diabetic rat: Noninvasive assessment with Doppler echocardiography and contribution of the nitric oxide pathway J. Am. Coll. Cardiol., December 1, 1999; 34(7): 2111 - 2119. [Abstract] [Full Text] [PDF]

				K. A. Eagle, R. A. Guyton, R. Davidoff, G. A. Ewy, J. Fonger, T. J. Gardner, J. P. Gott, H. C. Herrmann, R. A. Marlow, W. C. Nugent, et al. ACC/AHA guidelines for coronary artery bypass graft surgery: A report of the American College of Cardiology/ American Heart Association task force on Practice Guidelines (Committee to revise the 1991 Guidelines for Coronary Artery Bypass Graft Surgery) J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1262 - 1347. [Full Text] [PDF]

				S. M. Grundy, R. Pasternak, P. Greenland, S. Smith Jr, and V. Fuster Assessment of cardiovascular risk by use of multiple-risk-factor assessment equations: A statement for healthcare professionals from the American Heart Association and the American College of Cardiology J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1348 - 1359. [Full Text] [PDF]