glycometabolic status and acute myocardial infarction: has the time come for...

Internal Medicine Journal 2003; 33: 443–449

REVIEW

Glycometabolic status and acute myocardial infarction: has the time come for glucose-insulin-(potassium) therapy?V. WONG, N. W. CHEUNG and S. C. BOYAGES

Department of Diabetes and Endocrinology, Westmead Hospital, Sydney, New South Wales, Australia

AbstractGlucose-insulin-potassium infusion as a metabolictherapy was first advocated for the management of acutemyocardial infarction (AMI) in 1960s. Over the subse-quent decades, enthusiasm for its use has been patchy,especially with the availability of other effective treat-ments such as reperfusion therapy for AMI. Several clin-ical studies in the mid-1990s revived the interest in theglycometabolic aspects of patients with AMI. The some-what conflicting results of these recent studies have gen-erated debate over the significance of the glycometabolic

state following acute coronary occlusion and the role ofinsulin-based infusion therapy. Although most of theavailable evidence is in favour of an insulin-based ther-apy, there are still many aspects of this therapy thatrequire clarification. More evidence will be requiredfrom further clinical trials before it is adopted in routineclinical practice. (Intern Med J 2003; 33: 443–449)

Key words: insulin, hyperglycaemia, acute myocardial infarction, diabetes mellitus, reperfusion therapy.

INTRODUCTIONOver the last 20 years, although we have seen advancesin coronary reperfusion techniques and the availability ofa wide range of new medical therapies, hospital mortalityrates for acute myocardial infarction (AMI) remain1.5–2-times higher in diabetic than in non-diabeticpatients.1 Whereas diabetic subjects may have moreextensive concomitant cardiovascular risk factors, poorcardiac reserve and diffuse coronary artery disease,2 it ispossible that metabolic factors, including suboptimalglycaemic control at the time of AMI, also contribute topoor outcomes.

People without a known history of diabetes oftendevelop hyperglycaemia during times of extreme stress,such as AMI, and this group of patients has been shownto have less favourable outcomes following acutecoronary occlusion.3 There is evidence that insulin-based therapy may be effective in reducing cardiacmortality and morbidity after AMI, although this has notnecessarily been aimed at treating stress-induced hyper-glycaemia. The purpose of the present review is toexamine the potential role of active management of theglycometabolic state during AMI and to review theevidence that the use of insulin-glucose or glucose-insulin-potassium (GIK) infusion for patients at the timeof AMI confers clinical benefit.

STRESS-INDUCED HYPERGLYCAEMIADuring acute physiological stress, counter-regulatoryhormones such as glucagon, catecholamines and cortisolare released, while cytokines such as tumour necrosisfactor-α and interleukin-1 become elevated.4 Conse-quent to the activated sympathetic nervous systemduring acute stress, lipolysis is also increased, leading toelevation of free fatty acids (FFA) levels. All these eithercontribute to insulin resistance or may directly inhibitinsulin secretion, causing a ‘relative insulin deficient’state and raised blood glucose levels.3 Despite the hyper-glycaemia, cellular glucose metabolism such as glycolysisdecreases. It is believed that the sicker the patient, thegreater the release of these hormones and cytokines, andthe more likely the occurrence of stress hyperglycaemia.4

Whereas chronic hyperglycaemia results in the devel-opment of diabetic cardiomyopathy, acute hyper-glycaemia can also cause injury to the myocardium.Animal studies have shown that acute hyperglycaemia inlow insulin state activates pro-apoptotic processes incardiomyocytes5 and, at the same time, attenuates cardi-omyocyte contractility.6 Furthermore, acute hyper-glycaemia may lead to generation of reactive oxygenspecies in cardiomyocytes and impair collateral flow inthe coronary vessels by interfering with the nitric oxidepathways.7

Recently, a meta-analysis of 15 studies in theprethrombolytic era found that patients without diabeteswho were hyperglycaemic at the time of their AMIadmission had a 3.9-fold higher risk of death than thosewho had normal glucose levels.3 These patients also hada 3.1-fold higher risk of congestive cardiac failure orcardiogenic shock when compared to normoglycaemicpatients. In the reperfusion era, the relation between

Correspondence to: Vincent Wong, Department of Diabetes and Endocrinology, Westmead Hospital, PO Box 533, Wentworthville, NSW 2145, Australia. Email: [email protected]

Received 1 May 2002; accepted 7 January 2003.

Funding: None

Conflicts of interest: None

444 Wong et al.


hyperglycaemia and adverse cardiac outcomes persists.This was evaluated prospectively in a study of 336consecutive AMI patients, approximately 50% of whomreceived reperfusion therapy.8 The 1-year mortality ofthose with admission blood sugar level (BSL) greaterthan 11.1 mmol/L was 44%, compared to less than 10%in those with normoglycaemia (BSL <5.6 mmol/L).Moreover, a lower admission BSL was associated withsignificantly smaller infarcts based on peak creatinephosphokinase values. Although only 12% of thesubjects were known to have diabetes, 65% of allpatients were hyperglycaemic (BSL >8.4 mmol/L) at thetime of admission. In a different study of 197 patientswithout known diabetes presenting with AMI, admissionBSL was strongly associated with non-fatal re-infarction,major cardiovascular events and re-admission forcongestive cardiac failure.9

The nature of the relationship between hyper-glycaemia and poor outcomes following AMI isuncertain, because it has been argued that hyper-glycaemia could represent a marker for more severedisease rather than being directly deleterious to themyocardium.10 It is possible that the insulin-insufficientstate, not hyperglycaemia per se, is actually moreharmful for the ischaemic myocardium.3 The issue ofwhether the glycometabolic status of AMI patients needsto be tightly controlled remains a point of contention.

GLUCOSE-INSULIN-POTASSIUM INFUSION FOR AMIGIK was first advocated for the management of patientswith AMI in the early 1960s.11 The mechanism of thepostulated benefit is still unknown, but the rationale wasbased on the ability of GIK to stimulate potassium re-uptake, suppress FFA metabolism and enhance glycol-ysis in the ischaemic myocardium.12,13 An increase inglycolytic flux results in higher free-energy yield as ittraps inorganic phosphate and adenosine diphosphate,whereas glycolytically derived ATP helps maintainmyocardial calcium and sodium homeostasis in times ofischaemia.14,15 In contrast, high levels of FFA followingAMI have been shown to depress myocardial contrac-tility, suppress glycolysis and increase myocardial oxygendemands, effects that are hazardous to the ischaemic orreperfused myocardium.16,17 More recently, insulin wasfound to have other cardioprotective effects. Forinstance, insulin has a vasodilative effect on coronaryarteries in normoglycaemic as well as type 1 diabeticsubjects.18 Animal studies also showed that insulin mayimprove myocardial contractility19 and inhibit cardiomy-ocyte apoptosis following ischaemia-reperfusion.20

The results of several clinical trials of GIK conductedin the prethrombolytic era were inconclusive, mainlybecause of the small number of recruits in each study,the study design and methodological differencesbetween the trials. The conflicting results of these trialscontributed to the lack of enthusiasm for the clinical useof GIK therapy. In the mid-1990s, a meta-analysis ofrandomized trials in the prethrombolytic era on GIKtherapy for AMI was conducted.21 With a pooled total of

1932 patients (with or without diabetes), the authorsfound that GIK therapy had a proportional hospitalmortality reduction of 28% following AMI compared toplacebo. In particular, four studies (with 288 patients)employed a higher dose of insulin in the infusion, andthe proportional hospital mortality reduction reached48%. The dose of insulin given in these four trials wasdeemed sufficient to suppress systemic FFA levels andmyocardial FFA uptake.12 However, the small numberof patients and the heterogeneity of the study protocolsin these four trials limited the applicability of thisfinding. Nevertheless, this meta-analysis rekindledinterest for the use of GIK in the reperfusion era, andthree important trials using insulin-based infusion forAMI were conducted around that time.

The Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) studyThe aim of the DIGAMI study was to evaluate whethertight metabolic control early in the course of AMIimproves survival in diabetic patients.22 Eligible subjectshad an AMI within the preceding 24 h and plasmaglucose exceeding 11 mmol/L, even if they were notpreviously known to have diabetes. Subjects randomizedto the treatment group were given high-dose insulin-glucose infusion for at least 24 h to keep plasma glucosebetween 7 mmol/L and 10 mmol/L. This was to befollowed by subcutaneous insulin injections four timesper day for at least 3 months following AMI (Table 1).

More than 80% of the 620 recruited subjects wereknown to have diabetes. Apart from the metabolictherapy, other treatments were not different between thetwo groups, with almost 50% of all patients receivingthrombolytic therapy. Baseline blood glucose andHbA1c at randomization did not differ, however theblood glucose levels 24 h after randomization and athospital discharge were already significantly lower in thetreatment group. The incidence of hypoglycaemia washigher in the intensive treatment group (15% vs. 0% inthe control group; P < 0.0001), and their mean serumpotassium level 24 h after randomization was lowercompared to the control group (4.0 mmol/L vs.4.2 mmol/L; P < 0.001). Despite the protocol, only 87%of subjects in the treatment group were on subcutaneousinsulin therapy at discharge, compared with 43% ofpatients in the control group.23 During follow-up,glycaemic control was better in the treatment group,with the HbA1c decreasing by 1.1% (vs. 0.4% in controlgroup; P < 0.0001) after 3 months.

Mortality was not significantly different between thetwo groups at discharge and at 3 months; however, atthe end of 12 months there was a 29% (P = 0.027)relative mortality reduction for the treatment group.22

This protective effect of intensive metabolic therapypersisted for at least 3.4 years.23 Congestive cardiacfailure accounted for 66% of all deaths within the firstyear, but the cause of death did not differ between thetwo groups.24 When patients were divided into fourstrata based on their premorbid cardiovascular riskprofile and previous insulin use, those with lowpremorbid cardiovascular risks who were not previously

Glycometabolic control for AMI 445


Tab

le 1

Infu

sion

pro

toco

ls fo

r th

e in

tens

ive

arm

, mai

n be

nefit

s an

d co

mm

ents

of t

he t

hree

insu

lin-b

ased

clin

ical

tri

als

for

AM

I22,2

7,30

Tri

alP

roto

col f

or in

tens

ive

arm

Insu

lin d

ose†

Sum

mar

y of

mai

n fin

ding

sC

omm

ent

DIG

AM

I(6

20 s

ubje

cts)

5% d

extr

ose

(500

mL

)80

U o

f sol

uble

insu

linSt

art w

ith 3

0 m

L/h

[rat

e ca

n th

en b

e tit

rate

d],

for

24 h

to

keep

blo

od s

ugar

leve

l 7–

10 m

mol

/L)

Fol

low

ed b

y 3

mon

ths

of s

ubcu

tane

ous

insu

lin in

ject

ions

four

tim

es p

er d

ay.

4.8

units

/h29

% r

educ

tion

in m

orta

lity

afte

r 1

year

Surv

ival

ben

efit

pers

iste

d af

ter

3 ye

ars

Tho

se w

ith lo

w c

ardi

ovas

cula

r ri

sk a

nd n

ot

prev

ious

ly o

n in

sulin

der

ived

mos

t be

nefit

Una

ble

to d

iffer

entia

te t

he b

enefi

ts fr

om

insu

lin-g

luco

se in

fusi

on o

r im

prov

ed lo

ng-

term

gly

cem

ic c

ontr

olC

onfin

ed m

ainl

y to

dia

betic

sub

ject

s

EC

LA

(407

sub

ject

s)H

igh

dose

:– 2

5% g

luco

se (

1000

mL

)–

50 U

of s

olub

le in

sulin

– 80

mm

ol/L

of K

Cl (

star

t w

ith

1.5

mL

/kg

per

h fo

r 24

h)

Low

dos

e–

10%

glu

cose

(10

00 m

L)

– 20

U o

f sol

uble

insu

lin–

40 m

mol

/L o

f KC

l (st

art

with

1.0

mL

/kg

per

h or

24

h)

Hig

h do

se (

5.3

U/h

)

Low

dos

e (1

.4 U

/h)

66%

red

uctio

n of

hos

pita

l mor

talit

y in

re

perf

used

pat

ient

s w

ho r

ecei

ved

GIK

63%

red

uctio

n of

1-y

ear

mor

talit

y in

hig

h-do

se G

IK p

atie

nts

com

pare

d to

con

trol

Smal

l sam

ple

size

, ins

uffic

ient

pow

er to

stu

dy

man

y ou

tcom

e pa

ram

eter

s in

var

ious

su

bgro

ups

Sele

ctio

n cr

iteri

a fo

r re

perf

usio

n th

erap

y no

t cl

ear,

har

d to

exp

lain

the

hig

h m

orta

lity

in

repe

rfus

ed c

ontr

ol g

roup

Pol-

GIK

(954

sub

ject

s)–

10%

dex

tros

e (1

000

mL

)–

20–3

2 un

its s

olub

le in

sulin

– 6.

0 g

of p

otas

sium

chl

orat

e in

1lit

re (

sic)

(inf

usio

n at

42

mL

/h, f

or 2

4 h)

0.8–

1.3

U/h

Hig

her

tota

l mor

talit

y in

GIK

gro

up a

fter

35

day

sH

ighe

r to

tal m

orta

lity

in G

IK g

roup

aft

er

6 m

onth

sN

o si

gnifi

cant

diff

eren

ces

in c

ardi

ac d

eath

s af

ter

35 d

ays

Exc

lusi

on o

f ins

ulin

-req

uiri

ng d

iabe

tic

subj

ects

lim

its g

enen

alis

abili

tyE

xclu

sion

of s

ubje

cts

with

con

gest

ive

card

iac

failu

re a

t tim

e of

AM

IIn

sulin

dos

e to

o lo

w

AM

I, a

cute

myo

card

ial i

nfar

ctio

n; D

IGA

MI,

The

Dia

bete

s M

ellit

us I

nsul

in G

luco

se I

nfus

ion

in A

cute

Myo

card

ial I

nfar

ctio

n St

udy;

EC

LA

, The

Est

udio

Car

diol

ogic

os L

atin

oam

eric

a St

udy;

GIK

, glu

cose

-in

sulin

-pot

assi

um;

Pol-

GIK

, The

Pol

ish-

GIK

tri

al. †

The

sta

rtin

g in

sulin

dos

e ca

lcul

ated

for

a 70

-kg

pers

on.

446 Wong et al.


on insulin therapy derived the greatest benefit fromintensive treatment. The mortality reduction in thisstratum was already apparent at the time of hospitaldischarge (58%) and maintained at 1 year (52%).25 Inthe other three strata (‘no insulin-high risk’; ‘previousinsulin use-low risk’; and ‘previous insulin use-high risk’strata), mortality rates were not significantly differentbetween the treatment and control groups.

The omission of potassium from the infusion, theinclusion of mainly diabetic patients and the commence-ment of subcutaneous insulin following the peri-infarctperiod set this trial apart from others. Because of thestudy design, it was impossible to establish whether thebenefit resulted from the peri-infarct insulin-glucoseinfusion or from the improved long-term glycaemiccontrol, especially because mortality reduction was onlystatistically significant at the end of 1 year. The studymay not have sufficient power for the subgroup analyses,but it is difficult to explain why the ‘no insulin/low risk’stratum derived such great benefits from intensive treat-ment. Cessation of oral hypoglycaemic drugs may havecontributed to the better results in the treatment group,although the potential harm caused by the sulphonylureagroup of drugs is unproven.26 It is also unclear whetherinsulin therapy enhances the benefits of reperfusiontherapy following AMI in this study.

The Estudio Cardiologicos Latinoamerica (ECLA) StudyThe ECLA study was a randomized trial that examinedthe effects of high- and low-dose GIK infusion for 24 hon the outcomes of AMI in the thrombolytic era(Table 1).27 In contrast to the DIGAMI study, the trialinvestigated the FFA-suppression aspect of GIK ratherthan aiming at tight glycaemic control. The dose in thehigh-dose GIK arm was considered sufficient tocompletely suppress FFA, even though serum FFAlevels were not measured.12,14 The mean plasma glucoselevel of patients pre-randomization was <155 mg/dL(8.6 mmol/L), which was substantially lower than thatfor the DIGAMI study (mean admission plasma glucose>15 mmol/L). In total, 407 patients were included, andreperfusion therapy was given in 61.9% of patients, ofwhom 95% received thrombolysis and the remaining 5%had primary angioplasty. Diabetic patients representedonly 16% of all subjects. Reperfusion strategies wereused at the discretion of the treating physicians.

At hospital discharge, there was a 66% mortalityreduction for patients who received reperfusion therapyin the combined GIK group compared to control. Incontrast, non-reperfused patients did not seem to derivemuch benefit from GIK. Other outcomes, such asheart failure, cardiogenic shock and life-threateningarrhythmia, did not differ significantly between thegroups. After 1 year, the high-dose GIK group had a63% reduction in mortality compared with control(P = 0.046). Mortality did not differ between the low-dose GIK group and the controls after 1 year.

Because ECLA study was a pilot study, the samplesize was small and it was not powered to assess varioussecondary end-points. Whereas control patients who

were not reperfused had a hospital mortality rate of6.7%, the mortality rate was particularly high amongcontrol patients who received reperfusion therapy(15.2%). Although the selection for reperfusion therapywas not standardized, it is likely that patients whoreceived reperfusion therapy were sicker and had largerinfarcts. The fact that the reperfused patients given GIKhad the lowest hospital mortality (5.2%) could implythat GIK is most beneficial when combined with reper-fusion therapy. There is little doubt that reperfusion isultimately vital for myocardial salvage, but it may alsocontribute to arrhythmia and accelerate myocardialinjury.28 There is evidence from animal studies that GIKreduces this reperfusion injury and complements thecardioprotective effects of reperfusion therapy.29

Although Diaz et al. favoured the use of high-dose GIKbecause of the benefits seen at the end of 1 years, thevalue of the low-dose regime, at least in the short term,is not clearly defined.

The Polish-GIK trial (Pol-GIK)The other large clinical trial conducted in the modernera is the Pol-GIK.30 In the Pol-GIK study, 954 patientswith AMI were enrolled, with half of the subjects rand-omized to receive a low-dose GIK infusion over 24 h.The dose of insulin over 24 h was reduced from 32 U to20 U following the high incidence of hypoglycaemia(9.5%) during the first phase of the study. Thrombolytictherapy was administered in 57–60% of patients. Only6.3% of all patients were known to have diabetes. At35 days, there were no differences in cardiac mortality orthe incidence of cardiac events between the two groups.However, total mortality at 35 days was significantlyhigher in the GIK than the control group (8.9% vs.4.8%; P = 0.01).

The outcomes of the Pol-GIK study were contrastedwith the two studies outlined above. Certain aspects ofthe trial protocol perhaps could explain these divergentresults. First, following the dose reduction, the rate ofinsulin infusion given was only 15% of that used in thehigh-dose GIK arm of the ECLA study, and this isdeemed insufficient to adequately suppress FFA.14

Second, with the exclusion of subjects with insulin-requiring diabetes and of those who had overt congestivecardiac failure on presentation of their AMI, therecruited patients had lower blood glucose levels(median plasma glucose 7.0 mmol/L) and the degree oftheir myocardial injury might have been smaller. GIKtherapy may not be as useful in this subtype of patients.The excess mortality in the GIK group was also mainlyattributed to non-cardiac causes such as stroke, gastro-intestinal bleeding and neoplastic disease. Whether thehigh incidence of hypoglycaemia in the GIK groupcontributed to the adverse outcomes was unclear.Furthermore, patients in the GIK group were slightlyolder, and more of them had hypertension, hyper-lipidaemia, diabetes and a previous history of cardiacfailure. Although these differences were not statisticallysignificant in each category, the GIK group may have aworse overall premorbid status. Therefore, despite thelack of cardiac protection of low-dose GIK in this large



trial, the design of the Pol-GIK study and the patientselection criteria need to be taken into consideration ininterpreting the results.

INSULIN INFUSION IN OTHER CLINICAL SITUATIONSIntensive insulin therapy in coronary artery surgeryThe possible role of insulin-based infusion has also beeninvestigated in patients undergoing coronary arterybypass grafting. During the bypass procedure, themyocardium is subjected to a period of elective aorticclamping, and thus represents a model of modifiedmyocardial ischaemia followed by reperfusion. In aprospective study, 30 non-diabetic patients withunstable angina were included.31 The patients wererandomized to receive either dextrose or GIK infusion.The infusion was commenced at the time of anaestheticinduction, stopped during cardiopulmonary bypass, andrecommenced when the aorta was unclamped for 12 h.The results showed higher cardiac indices, lowerinotropic requirement, lower incidence of atrial fibril-lation, and shorter duration of ventilatory support in theGIK group. The higher postoperative cardiac indicespersisted even after the GIK infusion was ceased. Othersimilar studies for diabetic patients also supported theuse of GIK therapy.32,33 There was no mortality in eitherarm of these studies, mainly because of the small samplesizes. Long-term outcomes of peri-operative GIKtherapy are not known.

Intensive insulin therapy in critically ill patientsThe benefits of insulin infusion may not be limited topatients with acute coronary syndromes. Recently, tightglycaemic control by insulin infusion for the treatment ofcritically ill patients was evaluated.34 A total of 1548ventilated patients in a surgical intensive care unit (ICU)was randomized to receive either intensive treatment(glucose level kept between 4.4 and 6.1 mmol/L byinsulin infusion) or conventional treatment (glucoselevel kept below 11.9 mmol/L) for the duration of stay inthe unit. Thirteen per cent of patients were known tohave diabetes in each arm of the study. The medianinsulin dose required in the intensive group was 3.0 U/h(compared to 1.4 U/h for the control group). The resultsdemonstrated that those in the intensive group had a32% reduction in mortality during ICU admission(P < 0.04) and a 34% reduction in overall in-hospitalmortality (P = 0.01). Furthermore, the incidence ofsepticaemia and renal failure requiring dialysis in theintensive group was decreased by 46% and 41%, respec-tively (P < 0.01). Other secondary outcomes – such ascritical illness-polyneuropathy, the need for prolongedventilatory support and the need for red-cell transfusion– were all significantly reduced in the intensive group.No differences in cardiac outcomes were reported,although of the subjects who underwent cardiac surgery,there was a non-significant reduction of mortality rate inthose in the intensive group (2.1 vs. 5.1%). As expected,hypoglycaemia (defined as glucose level <2.2 mmol/L)

was more common in the intensive group (5.1% vs.0.1%).

The mechanisms for these benefits remain difficult toexplain, but the suppressive effect of insulin on pro-inflammatory cytokines could play a role.35 Because thesubjects were mainly confined to surgical patients, onecould not directly extrapolate these findings to criticalmedical patients, such as those in cardiogenic shockfollowing AMI. Nevertheless, the study of van denBerghe et al. is the first large study to demonstrate thebenefits of treating stress hyperglycaemia with insulininfusion during a wide range of extreme physiologicalstress.

Are we ready for GI(K) in AMI?Overall, there seems to be a good rationale for thehypothesis that glucose-insulin (with or without potas-sium) therapy is beneficial for patients presenting withAMI. However, results from the DIGAMI, ECLA andPol-GIK trials (two positive and one negative) suggestthat further studies will be required to convince clin-icians of its role. The inability to conduct a study in atruly blinded fashion is always a weakness for these trials.Clarification is required regarding the appropriateinsulin/glucose doses, the need to include potassium aspart of the infusion and the type of patients who wouldderive most benefit.

Because the cardioprotective effect of GI(K) is likelyto be on multiple levels, it is difficult to establish what isthe most important component (i.e. suppression of FFAby insulin, or the maintenance of strict glycaemic controlduring the peri-infarct period). DIGAMI is the onlystudy that aimed to treat hyperglycaemia in diabeticsubjects using insulin, but there are not yet convincingclinical data to show that maintaining tight glycemiccontrol is cardioprotective. In contrast, if the FFA-suppression aspect of insulin is the vital component, ahigher dose of insulin (0.075 Ukg–1 h–1) should beadministered to adequately suppress FFA, as in the high-dose arm of the ECLA study.12,27 Consequently, moreglucose must be administered simultaneously to avoidhypoglycaemia. Whereas a faster rate of glucose infusionmay potentially cause fluid overload, a higher concentra-tion of glucose can induce phlebitis in the peripheralvein.28

In the ICU and the DIGAMI studies, which did notinclude potassium in the infusion regime, efficacy fromthe insulin-based therapy was observed without anyadverse effect from hypokalaemia. Thus, the importanceof potassium as part of the infusion is uncertain.Although the infusion was given for 24 h in these trials,it is not known whether longer duration of infusion mayconfer greater benefit. As a result of all these uncertain-ties, an effective yet practical and safe infusion regimemust be clearly defined before this treatment gains wide-spread acceptance. Although it is desirable to maintaingood long-term glycaemic control for diabetic subjectspost-AMI, there is not enough evidence to recommendroutine commencement of intensive subcutaneousinsulin therapy following their discharge from hospital.In the United Kingdom Prospective Diabetes Study,

448 Wong et al.


long-term tight glycaemic control by insulin therapy didnot have a significant impact in preventing cardiacmortality and morbidity.36

The selection of the appropriate patients for GI(K)therapy is also an area of controversy. At the moment,there is confusion over whether GI(K) therapy should beconfined to diabetic subjects, limited to those with stresshyperglycaemia, or extended to all patients followingAMI. Subgroup analyses of ECLA and DIGAMIsuggest that subjects likely to benefit include those whoreceived concomitant reperfusion therapy, and diabeticsubjects not previously on insulin therapy who had lowpremorbid cardiovascular risks. In contrast, thosewithout hyperglycaemia who did not develop leftventricular dysfunction following AMI may derive leastbenefit, as seen in the Pol-GIK.

In conclusion, the current evidence suggests that thepatient’s glycometabolic status is important during theperi-infarct period, and that GI(K) infusion is likely tohave some role in the acute management of AMI.However there is currently a lack of consensus regardinghow GI(K) should be administered, and who shouldreceive this therapy. We eagerly await the results ofongoing large trials such as the DIGAMI2 and ECLA-GIK II, which may shed some light in theseuncertainties.

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