LETTERS

LETTERS

Managing the Diabetic Patient with AcuteMyocardial Infarction

Professor Yudkin’s article1 perhaps makesit timely to ask whether, before theDIGAMI study2 acquires the status of holywrit, we should go a little further inlooking carefully at the subgroup analysiswhich those authors present. Yudkinrightly says that this analysis hints at apossible adverse effect of sulphonylureas.To my eyes a rather more fundamentalpoint is that the subgroups who hadbeen defined as having a high priorcardiovascular risk (groups 2 and 4)did not appear to derive any benefitwhatsoever from intensive treatment withinsulin. Since, as Dr Fisher points out,3the institution of tight glycaemic controlin people with diabetes and myocardialinfarction has substantial resource impli-cations, it could be argued that we shouldconfine the use of DIGAMI-style intensivetreatment to those people who are, para-doxically, in the lower cardiovascular riskgroup since this is the only group forwhom we have evidence of benefit.

R.A. FiskenFriarage Hospital, Northallerton, NorthYorkshire, DL6 IJG, UK

References

1. Yudkin JS. Managing the diabeticpatient with acute myocardial infarc-tion. Diabetic Med 1998; 15: 276–281.

2. Malmberg K for the DIGAMI (DiabetesMellitus, Insulin Glucose Infusion inAcute Myocardial Infarction) StudyGroup. Br Med J 1997; 314: 1512–1515.

3. Fisher BM. Diabetes mellitus andmyocardial infarction: a time to actor a time to wait? Diabetic Med 1998;15: 275.

Managing the Diabetic Patient with AcuteMyocardial Infarction: Author’s Reply

The DIGAMI Study1 showed an approxi-mately 28 % reduction in deaths in dia-betic patients treated with insulin–glucoseinfusion, followed by subcutaneous insu-lin for at least 3 months after discharge,after an acute myocardial infarction. DrFisken2 raises the issue of sub-groupanalysis, suggesting that the benefits ofintensive insulin therapy achieved statisti-

980 CCC 0742–3071/98/110980–02$17.50 1998 John Wiley & Sons, Ltd. DIABETIC MEDICINE, 1998; 15: 980–981

cal significance only in those patients inthe study who were not previously treatedwith insulin and who were at low risk onthe basis of age, previous cardiac history,and digoxin treatment. The argument goesthat intensified treatment is necessary onlyin those not previously on insulin andwho are at low risk, this providing somereduction in demands on overstretchedresources.

I have previously argued the caseagainst sub-group analysis in diabeticpatients with cardiovascular disease.3 Ifwe had believed the sub-group analysisof the ISIS-2 study, we would not begiving aspirin to diabetic patients aftermyocardial infarction.4 As the ISIS-2authors point out, the lack of benefit ofaspirin in that particular study was alsoseen by those born under the astrologicalsigns of Gemini and Libra.3,4 Subsequentstudies have shown substantial benefitsof aspirin in diabetic, as in non-diabetic,patients.5 In the DIGAMI Study,1 thebenefits of intensified treatment werestatistically homogeneous across all foursub-groups, suggesting that this may be aparallel phenomenon.

The other point, namely that of resourceimplication, is unpersuasive. The no pre-vious insulin–low risk sub-group rep-resents nearly half of all myocardialinfarction patients, and another 35 % ofthe DIGAMI subjects were already oninsulin, and therefore not likely to betreated without insulin after their infarct.Thus insulin treatment, intensified or not,is indicated in some 80 % of all patients,so any savings in terms of resources arelikely to be pretty small.

Quite clearly, the DIGAMI Study needsconfirming in larger numbers of patients,which might be possible with the resultsof the DIGAMI-2 Study. In the meantime,I stand by my contention6 that we shouldbe treating all diabetic patients withintensive insulin therapy indefinitely aftera myocardial infarction.

J.S. YudkinDepartment of Medicine, University Col-lege London Medical School, WhittingtonHospital, London

References

1. Malmberg K. For the DIGAMI(Diabetes Mellitus, Insulin GlucoseInfusion in Acute MyocardialInfarction) Study Group. Prospectiverandomised study of intensive insulintreatment on long term survival afteracute myocardial infarction inpatients with diabetes mellitus. BrMed J 1997; 314: 1512–1515.

2. Fisken RA. Managing the diabeticpatient with acute myocardial infarc-tion. Diabetic Med 1998; 15: 980.

3. Yudkin JS. Assessing the evidence onaspirin in diabetes mellitus. Geminior Libra; lumping or splitting; surro-gate or hard; low or high; inter-ventionist or nihilist. Diabetologia:1996; 39: 1407–1408.

4. ISIS-2 (Second International Study ofInfarct Survival) Collaborative Group.Randomised trial of intravenous strep-tokinase, oral aspirin, both, or neitheramong 17 187 cases of suspectedacute myocardial infarction: ISIS-2.Lancet, 1988; ii: 349–360.

5. The Antiplatelet Trialists’ Collabor-ation. Collaborative overview of ran-domised trials of antiplatelet therapy.Prevention of death, myocardialinfarction, and stroke by prolongedantiplatelet therapy in various categ-ories of patients. Br Med J 1994; 308:81–106.

6. Yudkin JS. Managing the diabeticpatient with acute myocardial infarc-tion. Diabetic Med 1998; 15: 276–281.

The Elusive Diagnosis of GestationalDiabetes

Your Guest Editorial on ‘The ElusiveDiagnosis of Gestational Diabetes’1 wascomprehensive and well informed butmay have confused some who still believethat the Pedersen hypothesis2 providesthe physiological basis for understandingdiabetic pregnancy. This proposed thatmaternal hyperglycaemia leads to stimu-lation of the fetal pancreas and hyperinsul-inism, which is frequently manifest aslarge-for-dates babies and neonatal hypo-glycaemia. It must therefore have dis-turbed many readers to discover that ‘norelationship between maternal glycaemia,assessed at 28 weeks’ gestation, andneonatal hypoglycaemia was seen in alarge Canadian study of women with milddegrees of glucose intolerance’.3 Thisfinding is at variance with earlier work4

in which the area under the 28 week oralglucose tolerance test in 31 women withnormal or mildly impaired glucose toler-ance was found to correlate inverselywith the neonatal plasma glucose 2 hoursafter delivery r = 0.69, p , .0001). A simi-lar correlation was found with the rate ofglucose utilization during the first 2 hoursafter birth (incremental k value) andlow neonatal plasma glucose levels werefound to be associated with high plasmainsulin levels.

The Canadian workers excludedwomen with gestational diabetes accord-ing to the National Diabetes Data Groupcriteria. Although this group definesabnormality on the basis of 0, 1, 2, and3 h post-glucose values following a 50 gglucose load, it is possible to interpolate