Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): Effects on mortality at 1 year

Malmberg, Klas; Rydén, Lars; Efendić, Suad; Herlitz, Johan; Nicol, Peter; Waldenström, Anders; Wedel, Hans; Welin, Lennart

doi:10.1016/0735-1097(95)00126-k

Cited by 1,388 publications

(830 citation statements)

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“…40 In combination with hypertension, Fukui et al 41 observed that DM accelerates LV diastolic dysfunction via renin-angiotensin system in hypertensive rats. Taken together, hypertension and DM could synergistically deteriorate diastolic function in human.…”

Section: Renin-angiotensin System and Opn Expressionmentioning

confidence: 99%

Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population

et al. 2011

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Heart failure with preserved ejection fraction is recently highlighted as a major health problem, and diastolic dysfunction associated with hypertension has a dominant role in the development of heart failure with preserved ejection fraction. Osteopontin (OPN) is a secreted phosphoprotein, which mediates fibrosis. In animal models, OPN is upregulated in response to pressure overload and is thought to be involved in systolic dysfunction. However, the functional role of OPN in diastolic dysfunction is unknown. The guanine base insertion polymorphism at À156 position of the OPN promoter is postulated to upregulate the transcription of OPN in human. To investigate whether À156del/G polymorphism of OPN promoter is associated with diastolic dysfunction in hypertensive hearts, the patients with hypertension have been genotyped for variants of À156del/G polymorphism by genomic sequencing. Diastolic function of the left ventricle was estimated as the ratio of early to atrial filling (E/A ratio), obtained by pulsed-Doppler derived transmitral flow in echocardiographic analysis. The patients with À156G allele displayed lower E/A ratio compared with those with À156del/del genotype, suggesting exacerbated diastolic function. Notably, in case of the population with diabetes mellitus, the patients with À156G allele showed significant association with lower E/A ratio, compared with À156del/À156del patients. Multiple linear regression analysis revealed that prevalence of À156G allele was an independent factor for lowering E/A ratio. The À156del/G genetic variants of OPN promoter were associated with decreased E/A ratio in hypertensive patients. These results suggest that OPN has a functional role in the development of diastolic dysfunction in hypertensive hearts.

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Section: Renin-angiotensin System and Opn Expressionmentioning

confidence: 99%

Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population

et al. 2011

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“…Moreover, a positive association between hyperglycaemia at the time of the event and subsequent mortality from myocardial infarction has been reported [3]. Although the mechanisms underlying this association are not fully understood, evidence that the use of insulin to lower glucose concentrations decreases mortality in patients with diabetes who have myocardial infarction [4] suggests that hyperglycaemia is not simply an epiphenomenon of a stress response. Consequently, hyperglycaemia at the time of myocardial infarction could be an important and potentially modifiable risk factor for poor outcome.…”

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confidence: 99%

Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1

et al. 2002

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Aims/hypothesis. This study aimed to evaluate the effects of hyperglycaemia on the evolution of myocardial infarction and the expression of the transcriptional factor for angiogenesis hypoxia-inducible factor 1α (HIF-1α) in the rat. Methods. We studied the effects of streptozotocin induced diabetes on infarct size and HIF-1α gene expression. These parameters were also evaluated in isolated hearts of non-diabetic rat, in condition of high glucose concentration. Results. In streptozotocin (STZ)-diabetic rats (in vivo study), myocardial infarct size was greater (p<0.01) in hyperglycaemic rats (22 mmol/l) than in normoglycaemic (7 mmol/l) or non-diabetic rats. In euglycaemic conditions, basal expression of HIF-1α mRNA was not appreciable, but increased steadily after ischaemia (762±86%, p<0.001); this response was blunted in hyperglycaemic STZ-rats (6.8±6% of the control, p<0.001) and improved in euglycaemic STZ-rats (58±10%). The changes in myocardial Rac1 mRNA expression paralleled those of HIF-1α. In isolated hearts from non-diabetic rats (in vitro study), perfusion with high glucose (33 mmol/l) produced an infarct size (58±2% of the area at risk) not different from that obtained in hyperglycaemic STZ-rats (57±2%). Similar changes in the expression of HIF-1α and Rac1, which were prevented by glutathione infusion (0.3 mmol/l) were also observed. Conclusion/interpretation. Both hyperglycaemia and high glucose concentrations increased basal HIF-1α and Rac1 expression, suggesting a state of pseudohypoxia. These findings show that myocardial infarct size in the rat is increased in hyperglycaemic conditions and is associated with a reduced expression of the HIF-1α gene. These changes are reversed, totally or partially, by normoglycaemia or glutathione suggesting a role for reactive oxygen species generation brought about by hyperglycaemia. [Diabetologia (2002[Diabetologia ( ) 45:1172[Diabetologia ( -1181

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“…It was suggested that there is probably a link between hyperglycemia and the lack of efficacy of GIK infusion in patients with ACS. Therapy with GIK has long been prescribed during the acute phase of myocardial infarction, but available data on its benefit have been controversial 2, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14. In the DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) 1 study6 where GIK administration was associated with aggressive glucose lowering, a significant reduction in 1‐year mortality was demonstrated in patients with ST‐segment elevation myocardial infarction 4.…”

Section: Discussionmentioning

confidence: 99%

“…The potential mechanisms by which GIK could improve clinical outcomes in ACS includes the decrease of the amount of circulating free fatty acids while enhancing the use of glucose as the primary energy substrate for myocardial tissue 3, 4. Although early trials have shown some benefit of GIK treatment,5, 6, 7, 8, 9 other studies have not demonstrated such benefit 2, 10, 11, 12, 13, 14. It was suggested that the inability of GIK to improve outcome might partly be attributable to the tendency of GIK to increase serum glucose levels 15, 16.…”

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confidence: 99%

One‐Year Outcome of Intensive Insulin Therapy Combined to Glucose‐Insulin‐Potassium in Acute Coronary Syndrome: A Randomized Controlled Study

Bouida

Beltaïef

Msolli

et al. 2017

JAHA

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BackgroundA number of factors may offset the cardioprotective effects of glucose‐insulin‐potassium (GIK) on outcome of patients with acute coronary syndrome, such as hyperglycemia induced by this cocktail infusion. We performed a study to evaluate the effect of intensive insulin therapy in association with GIK on 1‐year outcome in patients hospitalized for acute coronary syndrome.Methods and ResultsIn a randomized prospective controlled trial we included 772 patients with non–ST‐segment elevation acute coronary syndrome. Patients were randomized into 3 groups: GIKI2 group, who received GIK with intensive insulin therapy for 24 hours; GIK group, who received GIK with nonintensive insulin therapy; and control group, who received usual care. The primary outcome criteria were the rates of major cardiovascular events combining death, reinfarction, and stroke rate at 1 year. In addition, we measured platelet function assay‐100 and plasminogen activator inhibitor‐1 at admission and 24 hours later. Based on an intention‐to‐treat analysis, major cardiovascular events at 1 year was 12.8% in the GIKI2 group, 15.5% in the GIK group, and 20.5% in the placebo group; the difference was significant between the GIK2 and control groups (P=0.01). Platelet function assay‐100 at 24 hours decreased significantly from baseline in the control group but not in the GIKI2 group. Plasminogen activator inhibitor‐1 decreased significantly in the GIKI2 group but significantly increased in the control group. Minor hypoglycemic events were more frequent in the GIKI2 group compared with other groups.ConclusionsGIKI2 led to improvement of 1‐year outcome rates in patients with non–ST‐segment elevation acute coronary syndrome. This beneficial effect was associated with a decrease in platelet reactivity and an increase on fibrinolysis tests.Clinical Trial RegistrationURL: https://www.clinicaltrials.gov. Unique identifier: NCT00965406.

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Randomized trial of insulin-glucose infusion followed by subcutaneous insulin treatment in diabetic patients with acute myocardial infarction (DIGAMI study): Effects on mortality at 1 year

Abstract: Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infarction.

Cited by 1,388 publications

References 59 publications

Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population

Association between osteopontin promoter variants and diastolic dysfunction in hypertensive heart in the Japanese population

Myocardial infarction in diabetic rats: role of hyperglycaemia on infarct size and early expression of hypoxia-inducible factor 1

One‐Year Outcome of Intensive Insulin Therapy Combined to Glucose‐Insulin‐Potassium in Acute Coronary Syndrome: A Randomized Controlled Study

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