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    Raffaele De Caterina, Rosalinda Madonna.European heart Journal 2010; 31: 1557-1564

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    ` The Euro Heart Survey on Diabetes and the

    Heart1, and European Heart Journal data2indicate a high prevalence of diabetes,undiagnosed diabetes or pre diabetic states -impaired glucose tolerance (IGT) or impaired

    fasting glucose in coronary heart disease(CHD)

    1. Bolk J, van der Ploeg T, Cornel JH, Arnold AE, Sepers J, Umans VA.Impaired glucose metabolism predicts mortality after a myocardialinfarction. Int J Cardiol 2001;79:207214.

    2. Wascher TC, Sourij H, Roth M, Dittrich P. Prevalence of pathologicalglucose metabolism in patients undergoing elective coronary angiography.Atherosclerosis 2004;176:419421.

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    ` CHD is the number 1 cause of deathworldwide with diabetes increasing by 2-3

    times the risk of CHD

    Mathers C et al. The Global Burden of Disease in 2002: Data

    Sources, Methods and Results, Geneva: World Health Organization;

    2003

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    1. Review the evidence linking hyperglycaemia in

    patients with acute coronary syndrome (ACS)

    with an adverse prognosis

    2. Review strategies adopted so far to controlhyperglycaemia in acute cardiac care setting

    3. Hypothesize a role for recently developed

    drugs incretin analogues and mimetics

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    ` Hyperglycaemia is an acute stress response3

    associated with less favourable outcome inpatient with or without known diabetes4

    3.Bartnik M, Malmberg K, Norhammar A, Tenerz A, Ohrvik J, Ryden L. Newlydetected abnormal glucose tolerance: an important predictor of long-termoutcome after myocardial infarction. Eur Heart J 2004;25:19901997.

    4.Capes SE, Hunt D, Malmberg K, Gerstein HC. Stress hyperglycaemia and

    increased risk of death after myocardial infarction in patients with and withoutdiabetes: a systematic overview. Lancet 2000;355:773778.

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    ` GAMI (Glucose Tolerance in Patients withAcute Myocardial Infarction) trial

    aim at assessing the prevalence of abnormalglucose regulation using oral glucose

    tolerance test (OGTT) in patient withoutknown diabetes admitted for ACS

    Bartnik M, Malmberg K, Norhammar A, Tenerz A, Ohrvik J, Ryden L. Newly detectedabnormal glucose tolerance: an important predictor of long-term outcome after myocardialinfarction. Eur Heart J 2004;25:19901997.

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    Table 1: Glucose metabolism after discharge from a coronary care unit

    and after 3 months in patients with AMI

    BLOOD

    GLUCOSE

    AFTER OGTT

    NORMOGLYCAEMI

    A

    11.1mmol/L

    After hospital

    discharge

    (n=164)

    34% (n=55) 35% (n=58) 31% (n=51)

    Three months

    after discharge

    (n=144)

    35% (n=50) 40% (n=58) 25% (n=36)

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    Points :

    - Hyperglycaemia after an ACS is not a

    mere stress response

    - The existence of a pancreatic beta cell

    dysfunction and insulin resistance before

    the ischaemic event seems more probable

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    ` Follow up of GAMI population indicatedthat there is substantially increased risk of

    for further CHD events in patients with noknown diabetes with abnormal glucose

    metabolism

    Cakmak M et al. The value of admission glycosylated haemoglobin

    level in patient with acute myocardial infarction. Canadian Journal ofCardiology2008; 24: 375-378

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    1. GIK regime (glucose, insulin infusion and

    potassium)

    ` OASIS-6 GIK5 and CREATE-ECLA6 trial :GIK infusion has no effects on mortality,

    cardiac arrest or cardiogenic shock inACS

    5. Diaz R et al. Glucose-insulin-potassium therapy in patients with ST-segmentelevation myocardial infarction. JAMA 2007; 298: 2399-2405

    6. Mehta SR et al. Effect of glucose-insulin-potassium infusion on mortality in patientswith acute ST-segment elevation myocardial infarction:the CREATE-ECLArandomized controlled trial. JAMA 2005;293:437446.

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    Problems with GIK :

    ` Harmful in the early phase of ACS due to

    hyperkalaemia and fluid challenge

    ` Mean glucose level increased during

    therapy (CREATEECLA) baseline

    glucose level 9mmol/L to 10.4mmol/L after6 hours of GIK

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    2. DIGAMI 1 trial (Diabetes mellitus, Insulin-

    Glucose Infusion in AMI)

    ` Insulin-glucose infusion for 24hours afterhospital admission, followed by intensiveinsulin therapy after discharge was superiorto conventional treatment in improving acuteand long term glycaemic control

    Malmberg KA, Efendic S, Ryden LE.F

    easibility of insulin-glucose infusion indiabetic patients with acute myocardial infarction. A report from the multi center trial:DIGAMI. Diabetic Care 1994; 17: 1007-1014

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    ` 1 year mortality

    18.6% in the infusion group vs 26.1% in

    control group

    ` Long term mortality (3-4 years)

    11% reduction

    ` Main benefit was seen during early postinfarction period no reinfarction and

    reduced rate of heart failure

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    3. DIGAMI 2 trial larger trial

    i. Insulin infusion (24h) and then

    subcutaneous insulin

    ii. Insulin infusion (24h) and then standard

    long term therapy

    iii. Conventional therapy

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    Limitation of DIGAMI 2 trial

    ` Premature stop slow recruitment rate

    ` Statistical power drop to below 50%

    ` Interpretation is uncertain

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    DIGAMI 1 vs DIGAMI 2

    ` 1-year mortality 12.1%, but did not differbetween groups

    ` Gylcaemic control was better during insulin

    infusion but no difference between groups andreduction in HbA1c could not be achieved

    ` Glucose level at admission was a strong and

    independent predictor of long term mortality

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    SYMPHONY studies

    ` Glucose lowering therapy associated with 90-day death, ACS and severe recurrentischaemia

    i. Only insulin and/or sulfonylureas - 12%

    ii. Biguanide only and/or thiazolidinedione

    5%McGuire DK et al. Association of diabetes mellitus and glycemic control strategieswith clinical outcomes after acute coronary syndromes. Am Heart J 2004;147:246252.

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    MINAP Myocardial Infarction National Audit

    Project

    ` Conducted in 201 hospitals in England andWales

    ` Determined the effect of insulin in themanagement of hyperglycaemia in non-diabetic patients presenting with ACS

    Weston C, Walker L, Birkhead J. Early impact of insulin treatment on mortality for

    hyperglycaemic patients without known diabetes who present with an acute coronarysyndrome. Heart 2007;93:15421546.

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    INSULIN WITHOUT

    INSULIN

    MORTALITY

    7 days

    30 days

    11.6%

    15.8%

    16.5%

    22.1%

    RELATIVE

    RISK OF

    DEATH

    7 days

    30 days

    56%

    51%

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    CARDINAL trial database

    ` Non-diabetic patients higher baselineglucose predicted higher mortality, and

    greater 24h change in glucose predictedlower mortality at 30 days

    Goyal A et al. Prognostic significance of the change in glucose level in thefirst 24 h after acute myocardial infarction: results from the CARDINALstudy. Eur Heart J 2006;27:12891297.

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    ` The European Society of Cardiology(ESC)/European Association for the Studyof Diabetes (EASD) recommends bloodglucose control by intensive insulin

    treatment after heart surgery and inpatient with AMI

    Ryden L et al. Guidelines on diabetes, pre-diabetes, and cardiovasculardiseases: executive summary. The Task Force on Diabetes andCardiovascular Diseases of the European Society of Cardiology (ESC) andof the European Association for the Study of Diabetes (EASD). Eur Heart J2007;28:88136.

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    ` 2008 ESC guidelines on ST-elevation MI

    i. target glucose level 5-7.8mmol/L andavoiding blood glucose (BG) level 10mmol/Lregardless of prior diabetes history

    iii. Non-ICU setting maintaining BG

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    1. Glucagon-like-peptide 1 (GLP1)

    ` Incretin hormone contributes to glucose

    regulation

    ` Reduces hyperglycaemia but does not

    induce hypoglycaemia

    ` GLP1 analogue such as exenatide

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    2.Inhibitors of DPP-4 (dipeptidyl peptidase-4)Incretin enhancers/gliptins such assitagliptin

    ` Prevent breakdown of endogenous GLP1

    ` Less nausea, less effect of hypoglycaemia

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    GLP1 in ACS?

    ` Improves myocardial glucose uptake

    ` Improves left ventricular systolic function

    ` Reduces ischaemia/reperfusion injury in

    experimental models

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    ` Diabetic patients with heart failure left

    ven