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The impact of admission plasma glucose on long-term mortality after STEMI and NSTEMI myocardial infarction
International Journal of Cardiology 121 (2007) 215 – 217 www.elsevier.com/locate/ijcard
Letter to the Editor
The impact of admission plasma glucose on long-term mortality after STEMI and NSTEMI myocardial infarction A. Dirkali, Tj. van der Ploeg, M. Nangrahary, J.H. Cornel, V.A.W.M. Umans ⁎ Department of Cardiology, Medisch Centrum Alkmaar, The Netherlands Received 4 August 2006; accepted 11 August 2006 Available online 6 December 2006
Abstract Diabetes mellitus is a widely recognized risk factor for cardiovascular disease. Type 2 diabetics have a 3-fold increased risk of CAD; prediabetics, without chronic hyperglycemia, have a 2-fold increased risk compared with normal subjects. We determined in 615 consecutive acute infarction patients whether the admission plasma glucose level remains associated with major adverse cardiovascular events (MACE) in an unselected patient population with myocardial infarction. Of these, the mean age of 66 ± 12 years (range 36–90) and 69% were men and mean APG and HbA1c level were 8.2 ± 4.0 mmol/l and 6.1 ± 1.1% respectively. 13.2% of total study population was already known with diabetes. We recorded 132 deaths (21.5%), of whom 23.6% were known diabetic patients during 2.5 years of follow-up Multivariate statistical analysis identified APG, older age and previous MI as independent mortality predictors. Conclusion: Increased APG levels are significantly and independently correlated with poor prognosis after myocardial infarction, and this underlines the need for better medical treatment of hyperglycemic state and aggressive screening for early detection of diabetes. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Diabetes; Myocardial infarction; Reperfusion
1. Introduction Patients with or without a history of diabetes may present with hyperglycemia during acute myocardial infarction (AMI) Several studies have demonstrated a relationship between hyperglycemia upon admission and increased adverse events, such as left ventricular failure, cardiogenic shock and death [1–12]. We determined whether the admission plasma glucose level remains associated with major adverse cardiovascular events (MACE) in an unselected patient population (irreAbbreviations: APG, admission plasma glucose; AMI, acute myocardial infarction; CABG, coronary artery bypass grafting; CAD, coronary artery disease; CK, creatine kinase; DM, diabetes mellitus; FU, follow-up; HbA1c, glycosylated hemoglobin; IGT, impaired glucose tolerance; MACE, major adverse cardiac events (death, revascularization and reinfarction); MI, myocardial infarction; PCI, percutaneous coronary intervention. ⁎ Corresponding author. E-mail address: [email protected] (V.A.W.M. Umans). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.08.107
spective of the diagnosis of diabetes) with myocardial infarction in the reperfusion era. 2. Methods 2.1. Definitions Diabetes mellitus (DM) was considered present if a patient had been given the diagnosis and was receiving treatment according to the WHO definition. Patients without this diagnosis but with a blood glucose level of ≥ 11.1 mmol/l on admission were classified as having newly detected DM [13]. Impaired glucose tolerance was defined as an admission plasma glucose level N 5.6 mmol/l but b11.1 mmol/l. 2.2. Study population All 615 consecutive patients admitted to the coronary care unit at the Medical Center Alkmaar in 1996 and 1999 with a
216
A. Dirkali et al. / International Journal of Cardiology 121 (2007) 215–217
Table 1 Patient characteristics according to admission plasma glucose (APG) status Variable
Age (years) (SD)
Group Group Group I⁎ II# III§ (n = 125) (n = 296) (n = 98)
0.001±
23 (18.4) 7 (5.6) 6 (4.8)
41 (13.9) 4 (1.4) 9 (3.0)
14 (14.3) 6 (6.1) 7 (7.1)
19 (19.8) 2 (2.1) 7 (7.3)
0.388
45 (36.0) Hypercholesterolemia 55 (%) (44.0) Smoking (%) 66 (52.8) Family history of 42 CAD (%) (33.6) Diabetes mellitus (%) 4 (3.2)
76 (25.7) 107 (36.1) 128 (43.2) 92 (31.1) 9 (3.0)
2 (1.6)
8 (2.7)
2 (1.6)
1 (0.3)
47 (49.0) 41 (42.7) 32 (33.3) 15 (15.6) 49 (51.1) 30 (31.3) 19 (19.8)
b0.001
Oral hypoglycemic (%) Insulin (%)
26 (26.5) 38 (38.8) 38 (38.8) 20 (20.4) 19 (19.4) 11 (11.2) 8 (8.2)
45 (36.0)
125 (42.2)
42 (42.9)
52 (54.2)
0.059
3 (2.4) 49 (39.2) 73 (58.4)
7 (2.4) 186 (62.8) 103 (34.8)
1 (1.0) 55 (56.1) 42 (42,8)
2 (2.1) 38 (39.6) 56 (58.3)
0.898 b0.001
PCI (%) CABG (%) Risk factors Hypertension (%)
Infarct localization Anterolateral (%) Initial therapy PCI (%) Thrombolysis (%) No reperfussion ind (%)
65.27 (12.77) 26.4 6.7 (0.8)
66.62 (12.00) 30.6 9.4 (0.7)
pvalue
71.38 (11.25) 55.2 15.7 (4.9) 5.6 (0.6) 5.9 (0.7) 6.4 (1.0) 7.8 (1.8)
Female (%) Mean APG (mmol/L) (SD) Mean HbA1c (SD) (183 pts) History MI (%)
64.06 (12.65) 20.0 4.9 (0.5)
Group IV¶ (n = 96)
b0.001 b0.001
compared with the chi-square and Fisher's exact test as appropriate. 3. Results 3.1. Patient characteristics
b0.001
There were 624 patients hospitalized with AMI in Medical Center Alkmaar in the years 1996 and 1999, of whom 615 fulfilled the entry criteria. The baseline and treatment characteristics are given in Table 1. At hospital admission, the mean APG and HbA1c level was 8.2 ± 4.0 mmol/l and 6.1 ± 1.1% respectively. 13.2% of total study population was already known with diabetes. 16.2% had elevated HbA1c level and the patients who were not known with previous DM formed 7.6% of total study population. 64% of 615 patients presented with mild or severe impaired glucose levels at the time of hospital admission with acute myocardial infarction. Diabetic patients were older and more likely to be female than nondiabetic patients. 15.7% of these patients had previous myocardial infarction, while 7.8% had undergone a PCI or CABG. There were no significant differences in previous MI, PCI and CABG among the groups.
b0.001
3.2. Long-term follow-up
b0.001
0.047 0.214
0.047 0.004 0.001
b0.001
b0.001
During long-term follow-up all patients were followed for a mean of 2.5 years. None of the patients were lost to followup. There were 132 deaths (21.5%), of whom 23.6% were known diabetic patients. The mortality rates for pre-specified groups are given in Fig. 1 and were significantly higher in patients with impaired APG level when compared to patients with a normal APG level. Multivariate statistical analysis identified older age, APG, and previous MI as independent mortality predictors.
⁎Group I: Patients with an APG level b5.6 mmol/l. #Group II: Mild impaired glucose tolerance (APG 5.6–8.3 mmol/l). §Group III: Severe impaired glucose tolerance (APG 8.4–11.0 mmol/l). ¶Group IV: Patients with APG ≥ 11.1 mmol/l. SD: Standard deviation. ±p-value is significant between group I-II and IV. Ind = indication.
recorded diagnosis of acute ST-elevation and/or ST-depression myocardial infarction and available APG levels were included. We also stratified the patients according to the presence or absence of the history of DM. The study population was followed for 2.5 years with regular outpatient clinic visits and telephone interviews. 2.3. Statistics Standard statistical methods were applied by using SPSS statistical package. The categorical data are presented as proportions, and continuous data are presented as mean (SD). Continuous variables between two groups were compared with the Student's t test, more than two groups were compared with ANOVA analysis. Categorical variables were
Fig. 1. Survival curve after admission for acute myocardial infarction. Group I: Patients with an APG level b5.6 mmol/l. Group II: Mild impaired glucose tolerance (APG 5.6–8.3 mmol/l). Group III: Severe impaired glucose tolerance (APG 8.4–11.0 mmol/l). Group IV: Patients with APG ≥11.1 mmol/l.
A. Dirkali et al. / International Journal of Cardiology 121 (2007) 215–217
4. Discussion Our findings in an unselected patient population are in line with other previous studies [10,11,14–17] and showed that patients who are hyperglycemic on admission for AMI are at increased risk of mortality. Overall 2.5-year mortality is 21.3% and is higher with increasing APG levels. The association of glucose with risk of cardiovascular events starts in the nondiabetic range and progresses exponentially within the diabetic glucose range. Cardiovascular risk is predicted by the degree of glucose elevation and not by the presence or absence of diabetes mellitus. The significance of hyperglycemia among patients with myocardial infarction has been recognized in the DIGAMI study [11] as there was a linear relationship between APG and long-term mortality, indicating that hyperglycemia at admission is not only related to stress but also identifies patients with previously undiagnosed diabetes. Norhammar et al. [12] concluded that APG level in nondiabetic patients with AMI was an independent predictor of long-term cardiovascular morbidity and mortality. This findings indicate that high APG during an acute coronary event is a “stress hyperglycemia”, but it may also characterize patients who are at a high risk for future development of diabetes and cardiovascular events. The HbAc can be used to distinguish between stress hyperglycemia and hyperglycemia caused by diabetes. The degree of hyperglycemia, as measured using either a plasma glucose level or HbA1c level, is progressively related to the risk for a new or recurrent cardiovascular event. In a recent epidemiological analysis of UKPDS [18] data, 1% reduction in HbA1c was associated with a 14% reduction in the risk for myocardial infarctions. The results of prospective studies [19,20] have clearly documented the importance of glycemic control in reducing cardiovascular mortality and morbidity in diabetics. Intensive treatment with insulin caused a 40% reduction in cardiovascular events in the Diabetes Control and Complications Trial. In another prospective study [11], the long-term mortality in diabetic patients admitted for AMI was reduced to 28% with 24 h insulin-glucose infusion followed by multidose insulin treatment. 5. Conclusion Increased APG levels are significantly and independently correlated with poor prognosis after myocardial infarction, and this underlines the need for better medical treatment of hyperglycemic state and aggressive screening for early detection of diabetes. References [1] Hsueh WA, et al. Cardiovascular risk continuum: implications of insulin resistance and diabetes. Am J Med 1998;105(1A):4S–14S.
217
[2] Haffner SM, Stern MP, Hazuda HP, et al. Cardiovascular risk factors in confirmed prediabetic individuals: does the clock for coronary heart disease ticking before the onset of clinical diabetes? JAMA 1990;263:2893–8. [3] Kenny SJ, et al. Prevalence and incidence of non-insulin-dependent diabetes. In: Harris MI, editor. Diabetes in America. Washington, DC: National Institutes of Health, vol. 47–67. National Institute of diabetes and Digestive and Kidney Diseases NIH publication, 2nd ed. 1995. p. 95–1468 [4] Bolk J, van der Ploeg T, Cornel JH, Arnold AE, Sepers J, Umans VA. Impaired glucose metabolism predicts mortality after a myocardial infarction. Int J Cardiol 2001;79:207–14. [5] Wahab NN, Cowden EA, Pearce NJ, et al. Is blood glucose an independent predictor of mortality in acute myocardial infarction in the thrombolytic era? J Am Coll Cardiol 2002;40:1748–54. [6] Iwasaka T, Takahashi N, Nakamura S, et al. Residual left ventricular function pump function after acute myocardial function in NIDDM patients. Diabetes Care 1992;15:1522–6. [7] O'Sullivan J, Conroy R, Robinson K, et al. In-hospital prognosis of patients with fasting hyperglycemia after first myocardial infarction. Diabetes Care 1991;14:758–60. [8] Oswald G, Smith C, Betteridge J, et al. Determinants and importance of stress hyperglycaemia in non-diabetic patients with myocardial infarction. BMJ 1986;293:917–22. [9] Fava S, Aquilina O, Azzopardi J, et al. The prognostic value of blood glucose in diabetic patients with acute myocardial infarction. Diabet Med 1996;13:80–3. [10] Capes SE, Hunt D, Malmberg K, et al. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 2000;355:773–8. [11] Malmberg K, Norhammar A, Wedel H, Ryden L. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the diabetes and insulin-glucose infusion in acute myocardial infarction (DIGAMI) study. Circulation 1999;99:2626–32. [12] Norhammar AM, Ryden L, Malmberg K. Admission plasma glucose: independent risk factor for long-term prognosis after myocardial infarction even in nondiabetic patients. Diabetes Care 1999;22:1827–31. [13] American Diabetes Association. Report of the expert committee on the diagnosis and the classification of diabetes mellitus. Diabetes Care 1997;20:1183–7. [14] Malmberg K, Rydén L. Myocardial infarction in patients with diabetes mellitus. Eur Heart J 1988;9:256–64. [15] Abbud Z, Shindler D, Wilson A, Kostis J. Effect of diabetes mellitus on short- and long-term mortality rates of patients with acute myocardial infarction: a statewide study. Am Heart J 1995;130:51–8. [16] Woodfield SL, Lundergan CF, Reiner JS, et al. Angiographic findings and outcome in diabetic patients treated with thrombolytic therapy for acute myocardial infarction: the GUSTO-I experience. J Am Coll Cardiol 1996;28:1661–9. [17] Norhammar A, Tenerz Å, Nilsson G, et al. Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet 2002;359:2140–4. [18] Stratton IM, Adler AI, Neil HAW, et al, on behalf of the UK Prospective Diabetes Study Group. Association of glycaemia with macrovascular and microvascular complications on type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405–12. [19] The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–86. [20] Laakso M. Glycemic control and the risk for coronary heart disease in patients with non-insulin-dependent diabetes mellitus. Ann Intern Med 1996;124:127–30.
Letter to the Editor
The impact of admission plasma glucose on long-term mortality after STEMI and NSTEMI myocardial infarction A. Dirkali, Tj. van der Ploeg, M. Nangrahary, J.H. Cornel, V.A.W.M. Umans ⁎ Department of Cardiology, Medisch Centrum Alkmaar, The Netherlands Received 4 August 2006; accepted 11 August 2006 Available online 6 December 2006
Abstract Diabetes mellitus is a widely recognized risk factor for cardiovascular disease. Type 2 diabetics have a 3-fold increased risk of CAD; prediabetics, without chronic hyperglycemia, have a 2-fold increased risk compared with normal subjects. We determined in 615 consecutive acute infarction patients whether the admission plasma glucose level remains associated with major adverse cardiovascular events (MACE) in an unselected patient population with myocardial infarction. Of these, the mean age of 66 ± 12 years (range 36–90) and 69% were men and mean APG and HbA1c level were 8.2 ± 4.0 mmol/l and 6.1 ± 1.1% respectively. 13.2% of total study population was already known with diabetes. We recorded 132 deaths (21.5%), of whom 23.6% were known diabetic patients during 2.5 years of follow-up Multivariate statistical analysis identified APG, older age and previous MI as independent mortality predictors. Conclusion: Increased APG levels are significantly and independently correlated with poor prognosis after myocardial infarction, and this underlines the need for better medical treatment of hyperglycemic state and aggressive screening for early detection of diabetes. © 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Diabetes; Myocardial infarction; Reperfusion
1. Introduction Patients with or without a history of diabetes may present with hyperglycemia during acute myocardial infarction (AMI) Several studies have demonstrated a relationship between hyperglycemia upon admission and increased adverse events, such as left ventricular failure, cardiogenic shock and death [1–12]. We determined whether the admission plasma glucose level remains associated with major adverse cardiovascular events (MACE) in an unselected patient population (irreAbbreviations: APG, admission plasma glucose; AMI, acute myocardial infarction; CABG, coronary artery bypass grafting; CAD, coronary artery disease; CK, creatine kinase; DM, diabetes mellitus; FU, follow-up; HbA1c, glycosylated hemoglobin; IGT, impaired glucose tolerance; MACE, major adverse cardiac events (death, revascularization and reinfarction); MI, myocardial infarction; PCI, percutaneous coronary intervention. ⁎ Corresponding author. E-mail address: [email protected] (V.A.W.M. Umans). 0167-5273/$ - see front matter © 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.ijcard.2006.08.107
spective of the diagnosis of diabetes) with myocardial infarction in the reperfusion era. 2. Methods 2.1. Definitions Diabetes mellitus (DM) was considered present if a patient had been given the diagnosis and was receiving treatment according to the WHO definition. Patients without this diagnosis but with a blood glucose level of ≥ 11.1 mmol/l on admission were classified as having newly detected DM [13]. Impaired glucose tolerance was defined as an admission plasma glucose level N 5.6 mmol/l but b11.1 mmol/l. 2.2. Study population All 615 consecutive patients admitted to the coronary care unit at the Medical Center Alkmaar in 1996 and 1999 with a
216
A. Dirkali et al. / International Journal of Cardiology 121 (2007) 215–217
Table 1 Patient characteristics according to admission plasma glucose (APG) status Variable
Age (years) (SD)
Group Group Group I⁎ II# III§ (n = 125) (n = 296) (n = 98)
0.001±
23 (18.4) 7 (5.6) 6 (4.8)
41 (13.9) 4 (1.4) 9 (3.0)
14 (14.3) 6 (6.1) 7 (7.1)
19 (19.8) 2 (2.1) 7 (7.3)
0.388
45 (36.0) Hypercholesterolemia 55 (%) (44.0) Smoking (%) 66 (52.8) Family history of 42 CAD (%) (33.6) Diabetes mellitus (%) 4 (3.2)
76 (25.7) 107 (36.1) 128 (43.2) 92 (31.1) 9 (3.0)
2 (1.6)
8 (2.7)
2 (1.6)
1 (0.3)
47 (49.0) 41 (42.7) 32 (33.3) 15 (15.6) 49 (51.1) 30 (31.3) 19 (19.8)
b0.001
Oral hypoglycemic (%) Insulin (%)
26 (26.5) 38 (38.8) 38 (38.8) 20 (20.4) 19 (19.4) 11 (11.2) 8 (8.2)
45 (36.0)
125 (42.2)
42 (42.9)
52 (54.2)
0.059
3 (2.4) 49 (39.2) 73 (58.4)
7 (2.4) 186 (62.8) 103 (34.8)
1 (1.0) 55 (56.1) 42 (42,8)
2 (2.1) 38 (39.6) 56 (58.3)
0.898 b0.001
PCI (%) CABG (%) Risk factors Hypertension (%)
Infarct localization Anterolateral (%) Initial therapy PCI (%) Thrombolysis (%) No reperfussion ind (%)
65.27 (12.77) 26.4 6.7 (0.8)
66.62 (12.00) 30.6 9.4 (0.7)
pvalue
71.38 (11.25) 55.2 15.7 (4.9) 5.6 (0.6) 5.9 (0.7) 6.4 (1.0) 7.8 (1.8)
Female (%) Mean APG (mmol/L) (SD) Mean HbA1c (SD) (183 pts) History MI (%)
64.06 (12.65) 20.0 4.9 (0.5)
Group IV¶ (n = 96)
b0.001 b0.001
compared with the chi-square and Fisher's exact test as appropriate. 3. Results 3.1. Patient characteristics
b0.001
There were 624 patients hospitalized with AMI in Medical Center Alkmaar in the years 1996 and 1999, of whom 615 fulfilled the entry criteria. The baseline and treatment characteristics are given in Table 1. At hospital admission, the mean APG and HbA1c level was 8.2 ± 4.0 mmol/l and 6.1 ± 1.1% respectively. 13.2% of total study population was already known with diabetes. 16.2% had elevated HbA1c level and the patients who were not known with previous DM formed 7.6% of total study population. 64% of 615 patients presented with mild or severe impaired glucose levels at the time of hospital admission with acute myocardial infarction. Diabetic patients were older and more likely to be female than nondiabetic patients. 15.7% of these patients had previous myocardial infarction, while 7.8% had undergone a PCI or CABG. There were no significant differences in previous MI, PCI and CABG among the groups.
b0.001
3.2. Long-term follow-up
b0.001
0.047 0.214
0.047 0.004 0.001
b0.001
b0.001
During long-term follow-up all patients were followed for a mean of 2.5 years. None of the patients were lost to followup. There were 132 deaths (21.5%), of whom 23.6% were known diabetic patients. The mortality rates for pre-specified groups are given in Fig. 1 and were significantly higher in patients with impaired APG level when compared to patients with a normal APG level. Multivariate statistical analysis identified older age, APG, and previous MI as independent mortality predictors.
⁎Group I: Patients with an APG level b5.6 mmol/l. #Group II: Mild impaired glucose tolerance (APG 5.6–8.3 mmol/l). §Group III: Severe impaired glucose tolerance (APG 8.4–11.0 mmol/l). ¶Group IV: Patients with APG ≥ 11.1 mmol/l. SD: Standard deviation. ±p-value is significant between group I-II and IV. Ind = indication.
recorded diagnosis of acute ST-elevation and/or ST-depression myocardial infarction and available APG levels were included. We also stratified the patients according to the presence or absence of the history of DM. The study population was followed for 2.5 years with regular outpatient clinic visits and telephone interviews. 2.3. Statistics Standard statistical methods were applied by using SPSS statistical package. The categorical data are presented as proportions, and continuous data are presented as mean (SD). Continuous variables between two groups were compared with the Student's t test, more than two groups were compared with ANOVA analysis. Categorical variables were
Fig. 1. Survival curve after admission for acute myocardial infarction. Group I: Patients with an APG level b5.6 mmol/l. Group II: Mild impaired glucose tolerance (APG 5.6–8.3 mmol/l). Group III: Severe impaired glucose tolerance (APG 8.4–11.0 mmol/l). Group IV: Patients with APG ≥11.1 mmol/l.
A. Dirkali et al. / International Journal of Cardiology 121 (2007) 215–217
4. Discussion Our findings in an unselected patient population are in line with other previous studies [10,11,14–17] and showed that patients who are hyperglycemic on admission for AMI are at increased risk of mortality. Overall 2.5-year mortality is 21.3% and is higher with increasing APG levels. The association of glucose with risk of cardiovascular events starts in the nondiabetic range and progresses exponentially within the diabetic glucose range. Cardiovascular risk is predicted by the degree of glucose elevation and not by the presence or absence of diabetes mellitus. The significance of hyperglycemia among patients with myocardial infarction has been recognized in the DIGAMI study [11] as there was a linear relationship between APG and long-term mortality, indicating that hyperglycemia at admission is not only related to stress but also identifies patients with previously undiagnosed diabetes. Norhammar et al. [12] concluded that APG level in nondiabetic patients with AMI was an independent predictor of long-term cardiovascular morbidity and mortality. This findings indicate that high APG during an acute coronary event is a “stress hyperglycemia”, but it may also characterize patients who are at a high risk for future development of diabetes and cardiovascular events. The HbAc can be used to distinguish between stress hyperglycemia and hyperglycemia caused by diabetes. The degree of hyperglycemia, as measured using either a plasma glucose level or HbA1c level, is progressively related to the risk for a new or recurrent cardiovascular event. In a recent epidemiological analysis of UKPDS [18] data, 1% reduction in HbA1c was associated with a 14% reduction in the risk for myocardial infarctions. The results of prospective studies [19,20] have clearly documented the importance of glycemic control in reducing cardiovascular mortality and morbidity in diabetics. Intensive treatment with insulin caused a 40% reduction in cardiovascular events in the Diabetes Control and Complications Trial. In another prospective study [11], the long-term mortality in diabetic patients admitted for AMI was reduced to 28% with 24 h insulin-glucose infusion followed by multidose insulin treatment. 5. Conclusion Increased APG levels are significantly and independently correlated with poor prognosis after myocardial infarction, and this underlines the need for better medical treatment of hyperglycemic state and aggressive screening for early detection of diabetes. References [1] Hsueh WA, et al. Cardiovascular risk continuum: implications of insulin resistance and diabetes. Am J Med 1998;105(1A):4S–14S.
217
[2] Haffner SM, Stern MP, Hazuda HP, et al. Cardiovascular risk factors in confirmed prediabetic individuals: does the clock for coronary heart disease ticking before the onset of clinical diabetes? JAMA 1990;263:2893–8. [3] Kenny SJ, et al. Prevalence and incidence of non-insulin-dependent diabetes. In: Harris MI, editor. Diabetes in America. Washington, DC: National Institutes of Health, vol. 47–67. National Institute of diabetes and Digestive and Kidney Diseases NIH publication, 2nd ed. 1995. p. 95–1468 [4] Bolk J, van der Ploeg T, Cornel JH, Arnold AE, Sepers J, Umans VA. Impaired glucose metabolism predicts mortality after a myocardial infarction. Int J Cardiol 2001;79:207–14. [5] Wahab NN, Cowden EA, Pearce NJ, et al. Is blood glucose an independent predictor of mortality in acute myocardial infarction in the thrombolytic era? J Am Coll Cardiol 2002;40:1748–54. [6] Iwasaka T, Takahashi N, Nakamura S, et al. Residual left ventricular function pump function after acute myocardial function in NIDDM patients. Diabetes Care 1992;15:1522–6. [7] O'Sullivan J, Conroy R, Robinson K, et al. In-hospital prognosis of patients with fasting hyperglycemia after first myocardial infarction. Diabetes Care 1991;14:758–60. [8] Oswald G, Smith C, Betteridge J, et al. Determinants and importance of stress hyperglycaemia in non-diabetic patients with myocardial infarction. BMJ 1986;293:917–22. [9] Fava S, Aquilina O, Azzopardi J, et al. The prognostic value of blood glucose in diabetic patients with acute myocardial infarction. Diabet Med 1996;13:80–3. [10] Capes SE, Hunt D, Malmberg K, et al. Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview. Lancet 2000;355:773–8. [11] Malmberg K, Norhammar A, Wedel H, Ryden L. Glycometabolic state at admission: important risk marker of mortality in conventionally treated patients with diabetes mellitus and acute myocardial infarction: long-term results from the diabetes and insulin-glucose infusion in acute myocardial infarction (DIGAMI) study. Circulation 1999;99:2626–32. [12] Norhammar AM, Ryden L, Malmberg K. Admission plasma glucose: independent risk factor for long-term prognosis after myocardial infarction even in nondiabetic patients. Diabetes Care 1999;22:1827–31. [13] American Diabetes Association. Report of the expert committee on the diagnosis and the classification of diabetes mellitus. Diabetes Care 1997;20:1183–7. [14] Malmberg K, Rydén L. Myocardial infarction in patients with diabetes mellitus. Eur Heart J 1988;9:256–64. [15] Abbud Z, Shindler D, Wilson A, Kostis J. Effect of diabetes mellitus on short- and long-term mortality rates of patients with acute myocardial infarction: a statewide study. Am Heart J 1995;130:51–8. [16] Woodfield SL, Lundergan CF, Reiner JS, et al. Angiographic findings and outcome in diabetic patients treated with thrombolytic therapy for acute myocardial infarction: the GUSTO-I experience. J Am Coll Cardiol 1996;28:1661–9. [17] Norhammar A, Tenerz Å, Nilsson G, et al. Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study. Lancet 2002;359:2140–4. [18] Stratton IM, Adler AI, Neil HAW, et al, on behalf of the UK Prospective Diabetes Study Group. Association of glycaemia with macrovascular and microvascular complications on type 2 diabetes (UKPDS 35): prospective observational study. BMJ 2000;321:405–12. [19] The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977–86. [20] Laakso M. Glycemic control and the risk for coronary heart disease in patients with non-insulin-dependent diabetes mellitus. Ann Intern Med 1996;124:127–30.