Diabetes Mellitus , Insulin Glucose Infusion In Acute Myocardial Infarction Research Articles

Self-rated health predicts outcome in patients with type 2 diabetes and myocardial infarction: A DIGAMI 2 quality of life sub-study

The Diabetes mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Quality of Life (QoL) sub-study included 465 patients with type 2 diabetes and acute myocardial infarction (AMI) followed for 2 years. Self-rated health was reported by the rating scale (RS), graded 0 = death to 100 = perfect health. Prospective associations between RS and all-cause mortality, cardiovascular (CV) death and cardiovascular events (CVEs = CV death, non-fatal AMI, stroke) were assessed. Median age was 68 years (range 59-74), 68% male. Patients experiencing CVE (n = 132) or death (n = 71) had lower RS compared with patients free from events: 60 (50-79) versus 70 (55-81) (p < 0.001) and 60 (50-75) versus 70 (51-80) (p = 0.008). The RS score predicted CVE [hazard ratio (HR); 95% confidence interval (CI): 0.87; 0.80-0.95] and all-cause mortality (0.86; 0.76-0.97), and corresponding HRs after adjustment were 0.90; 0.83-0.99 and 0.90; 0.79-1.02, respectively. A low self-rated health is of prognostic importance in patients with type 2 diabetes and AMI and may serve as an easily obtainable indicator of high risk for CVEs supplementing traditional risk factors.

Management of Hyperglycemia in a Hospitalized Patient with Diabetes Mellitus and Cardiovascular Disease

Hyperglycemia in patients with and without known diabetes is a common finding in patients hospitalized with cardiovascular disease, and is associated with poor outcomes. Investigators have been examining the role of insulin to treat patients with acute myocardial infarction since the 1960's. Until the 1990's most studies evaluated fixed doses of glucose-insulin-potassium (GIK) infusions. The Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) trial, published in 1995, evaluated the role of adjustable-dose insulin infusion to lower blood glucose. Its promising results spurred further interest and a number of trials evaluating the use of insulin to lower blood glucose in hospitalized patients - many of which included patients with cardiovascular disease - have been conducted over the last two decades with conflicting results. This manuscript reviews the epidemiology and pathophysiology of hyperglycemia in hospitalized patients, summarizes the evidence for benefits and harms of using insulin to treat hyperglycemic patients hospitalized with cardiovascular disease, and offers some practical management considerations.

Prognostic implications of glucose-lowering treatment in patients with acute myocardial infarction and diabetes: experiences from an extended follow-up of the Diabetes Mellitus Insulin–Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Study

This post hoc analysis from the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 trial reports on extended long-term outcome in relation to glucose-lowering agents in patients with myocardial infarction and type 2 diabetes. Patients were randomised as follows: group 1, insulin-based treatment; group 2, insulin during hospitalisation followed by conventional glucose control; and group 3, conventional treatment. Treatment according to the above protocol lasted 2.1 years. Using the total DIGAMI 2 cohort as an epidemiological database, this study presents mortality rates in the randomised groups, and mortality and morbidity rates by glucose-lowering treatment during an extended period of follow-up (median 4.1 and max 8.1 years). Follow-up data were available in 1,145 of the 1,253 patients. The mortality rate was 31% (72% cardiovascular) without significant differences between treatment groups. The total number of fatal malignancies was 37, with a trend towards a higher risk in group 1. The HR for death from malignant disease, compared with group 2, was 1.77 (95% CI 0.87-3.61; p = 0.11) and 3.60 (95% CI 1.24-10.50; p = 0.02) compared with group 3. Insulin treatment was associated with non-fatal cardiovascular events (OR 1.89 95% CI 1.35-2.63; p = 0.0002), but not with mortality (OR 1.30, 95% CI 0.93-1.81; p = 0.13). Metformin was associated with a lower mortality rate (HR 0.65, 95% CI 0.47-0.90; p = 0.01) and a lower risk of death from malignancies (HR 0.25, 95% CI 0.08-0.83; p = 0.02). Patients with type 2 diabetes and myocardial infarction have a poor prognosis. Glucose-lowering drugs appear to be of prognostic importance. Insulin may be associated with an increased risk of non-fatal cardiac events, while metformin seems to be protective against risk of death.

Copeptin, IGFBP-1, and Cardiovascular Prognosis in Patients With Type 2 Diabetes and Acute Myocardial Infarction

OBJECTIVETo determine whether C-terminal provasopressin (copeptin) explains the prognostic importance of insulin growth factor binding protein-1 (IGFBP-1) in patients with myocardial infarction and type 2 diabetes.RESEARCH DESIGN AND METHODSCopeptin and IGFBP-1 were analyzed in 393 patients participating in the Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 trial.RESULTSCopeptin was associated with IGFBP-1 (Spearman rank correlation test, r = 0.53; P < 0.001). During follow-up there were 138 cardiovascular events (cardiovascular death, myocardial infarction, and stroke). In univariate Cox proportional hazard regression analyses both biomarkers were predictors of events: the hazard ratio for log copeptin was 1.59 (95% CI 1.41–1.81; P < 0.001) and for log IGFBP-1 was 1.49 (1.26–1.77; P < 0.001). In the final model, adjusting for age and renal function, copeptin was the only independent predictor (1.35 [1.16–1.57]; P < 0.001).CONCLUSIONSCopeptin is an independent predictor of cardiovascular events and appears to at least partly explain the prognostic impact of IGFBP-1 in patients with type 2 diabetes and myocardial infarction. Copeptin may be a pathogenic factor to address to improve outcome in these patients.

IGF Binding Protein 1 Predicts Cardiovascular Morbidity and Mortality in Patients With Acute Myocardial Infarction and Type 2 Diabetes

There are indications that the IGF system is related to both type 2 diabetes and cardiovascular disease (CVD). We tested the hypothesis that low IGF-I and high IGF-binding protein (IGFBP)-1 predict future cardiovascular mortality and morbidity in patients with acute myocardial infarction (AMI) and type 2 diabetes. The Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Trial recruited 1,253 patients with type 2 diabetes and AMI, of whom 575 were enrolled in a biochemical program with repeated blood sampling. Primary and secondary end points included adjudicated cardiovascular mortality and a composite of cardiovascular events (cardiovascular death, reinfarction, or stroke). Multiple Cox proportional hazard regression was used to study the relationship between the end points and the variables. Admission variables were used for the survival analysis and for blood glucose, and A1C updated mean values during follow-up were also available. During a median follow-up period of 2.2 years, 131 (23%) patients died from all-cause mortality and 102 (18%) from CVD, whereas 175 patients (30%) suffered from at least one cardiovascular event. The independent predictors for cardiovascular death in the Cox regression model were (as hazard ratio [HR] [95% CI]): ln updated mean blood glucose (12.2 [5.8-25.7]), age (+5 years) (1.5 [1.4-1.7]), ln IGFBP-1 (1.4 [1.1-1.8]), and ln serum creatinine at admission (2.4 [1.3-4.2]). The model predicting cardiovascular events contained the same variables (ln IGFBP-1 at admission, 1.2 [1.0-1.4]). High levels of IGFBP-1 at admission are associated with increased risk for cardiovascular mortality and morbidity in type 2 diabetes patients with AMI.

A national survey of in‐patient diabetes services in the United Kingdom

To examine in-patient diabetes services in all UK acute hospitals. We asked the diabetes specialist team in all UK acute hospitals to complete a structured questionnaire on in-patient diabetes management guidelines, in-patient referral patterns, diabetes in-patient specialist nurse (DISN) services and diabetes bed occupancy in their hospital. Of the 262 UK acute hospitals, 239 (91.2%) provided data (2005-2006). UK teams reported high levels of clinical risk associated with in-patient diabetes care. One-third did not have diabetes management guidelines for day surgery, endoscopy, barium studies or immediate management of the diabetic foot. Patients admitted with diabetic ketoacidosis were not immediately referred to the specialist team in one-third of hospitals. About half had no routine access to podiatry or dietetic care for in-patients with diabetes. The majority of UK hospitals either never adopted Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI)-1 protocols or had recently changed practice, and half do not endorse the use of in-patient subcutaneous insulin 'sliding-scales'. One in five UK hospitals survey in-patient diabetes treatment satisfaction. DISN numbers have increased rapidly-126 hospitals (51.4%) had a DISN, most (69.1%) appointed since 2002. Most (80.2%) hospitals without a DISN used the out-patient specialist nurse team to provide in-patient care. This survey has identified substantial gaps in in-patient diabetes care in the UK. The rapid increase in DISN numbers indicates increasing attention to in-patient diabetes care in UK hospitals.

Glycaemic control after myocardial infarction: The DIGAMI protocol

The diabetes mellitus, insulin glucose infusion in acute myocardial infarction (DIGAMI) study (Malmberg et al, 1994; 1995; 1996; 1997) assessed the effects of intravenous insulin and glucose, followed by multi-dose subcutaneous insulin, on mortality after acute myocardial infarction (AMI) in patients with hyperglycaemia. The study suggested improved survival rates in those patients who had received insulin and glucose. These results prompted many clinicians to question and alter their practice. However, the study did cause some controversy. The suggested regimen was not without problems and the trial raised questions about the importance of chronic versus acute metabolic control. The subsequent DIGAMI 2 study (Malmberg et al, 2005) sought to answer queries raised by the original study but was also controversial. It is important to note, however, that the DIGAMI study did identify the benefit of strict glycaemic control in patients with AMI. It is essential that nurses are aware of this to enable them to improve patient outcomes.

Impact of hyperglycemia on inpatient outcomes: A therapeutic target?

Patient survival after acute myocardial infarction (AMI) has improved considerably during the last several decades as percutaneous coronary intervention (PCI), fibrinolytic therapy, and other advances have entered clinical practice. Despite these improvements, the likelihood of death soon after AMI remains much greater among individuals with diabetes than among nondiabetic patients. It was long believed that the relationship between diabetes and heart disease could be explained by risk factors common to the 2 conditions. However, a number of studies have shown that hyperglycemia is directly associated with worse clinical outcomes after AMI, even after controlling for other clinical factors that are associated with diabetes. 1,2 Among nondiabetic patients, hyperglycemia at the time of AMI is associated with a high likelihood of death or heart failure, even when myocardial infarct sizes are relatively small. Acute hyperglycemia is also a significant predictor of long-term mortality after AMI. Several studies have demonstrated that there are abnormalities of myocardial blood flow in patients with diabetes and that hyperglycemia is associated with impairments of myocardial blood flow before and after PCI. Clinical studies that have investigated the therapeutic potential of insulin treatment in patients with AMI have produced conflicting results. In the Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) trial, insulin infusion improved clinical outcomes after AMI in patients with diabetes, especially among those with the highest baseline blood glucose levels. In the recent Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial Infarction Treatment E American Study Group (CREATE-ECLA), an infusion of a glucose-insulin-potassium (GIK) solution did not significantly improve clinical outcomes after AMI, although the treatment regimen used produced a significant increase in plasma glucose level from baseline soon after admission. The true benefit of insulin therapy for AMI and the best ways to incorporate insulin treatment into current treatment strategies require additional study.

How should we manage acute cardiovascular events in diabetes?

Summary Approximately one-third of patients admitted to hospitals for acute cardiovascular events have diabetes. Coronary artery disease associated with diabetes tends to be more extensive than in non-diabetic subjects. Diabetic cardiomyopathy may impair functioning of the non-infarcted myocardium, and autonomic neuropathy may critically diminish pain detection that could delay a person from seeking treatment. In the resting state, approximately 60% of myocardial energy is supplied by oxidation of free fatty acids, with the remainder coming from glucose. Insulin resistance and post-infarction myocardial free fatty acid utilisation may be arrhythmogenic and toxic to the myocardium. The Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study tested the hypothesis that high-dose insulin infusion followed by subcutaneous insulin at the time of infarction would improve survival in patients with diabetes. The study found a significant reduction in mortality rate through the 5-year follow-up. This result suggests that post-infarction treatments should include intensive insulin therapy to address the intrinsic metabolic status of diabetes.

Optimal care of patients with type 2 diabetes mellitus and coronary artery disease

Although cardiovascular mortality rates for the general population have declined during the past several decades, mortality among individuals with diabetes mellitus has increased. Given that the prevalence of type 2 diabetes is increasing dramatically and that current treatment strategies appear inadequate, there is a critical need for well-designed studies to address treatment of coronary artery disease in patients with diabetes to help guide clinical decision making in this setting. The Bypass Angioplasty Revascularization Investigation (BARI)–2D focuses on 2 specific treatment issues in the management of patients with type 2 diabetes. The first issue is the incremental value of early use of coronary revascularization procedures, and the second is the value of treating with an insulin-sensitizing agent versus an insulin-providing therapy. It is essential to determine whether treatment to enhance insulin sensitivity improves cardiovascular survival. Data indicate that outcomes of patients with diabetes and myocardial infarction are improved by administration of insulin or a regimen of glucose, insulin, and potassium (GIK). The Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study showed that administration of an insulin infusion followed by subcutaneous insulin therapy for ≥3 months improved the long-term prognosis of diabetic patients with acute myocardial infarction. However, there appears to be a lack of acceptance of these interventions by health care providers. Clinical trials of GIK and insulin sensitizers are needed to define further the optimal treatment of patients with type 2 diabetes and cardiovascular disease.

Ischemic heart disease in type 2 diabetes

Type 2 diabetes has reached epidemic proportions and an increasing proportion of patients with coronary artery disease (CAD) are diabetics. CAD in diabetics has specificities and, in particular, more extensive atherosclerosis; diabetic patients are also more frequently asymptomatic, with silent myocardial ischemia, which makes the diagnosis of CAD more difficult. In addition, diabetic patients with CAD have poorer outcomes than nondiabetics. The management of diabetic patients with CAD is based on intensive intervention on lifestyle and risk factors, together with the mandatory use of medications of proven benefit as regards secondary prevention in coronary patients: antiplatelet agents, statins, β-blockers, and angiotensin-converting enzyme (ACE) inhibitors. Glycemic control is also essential; although the use of sulfonylureas has been controversial, there is now a vast amount of data suggesting a beneficial effect, in particular when agents more specific for the pancreatic adenosine triphosphate-dependent potassium (K ATP) channels are used. At the acute stage of myocardial infarction, the Diabetes mellitus, Insulin Glucose infusion in Acute Myocardial Infarction (DIGAMI) trial suggested a beneficial effect of insulin therapy prolonged for 3 months after hospital discharge; these data will have to be confirmed by larger intervention trials. Finally, the respective roles of coronary angioplasty and coronary surgery in diabetics are debated; a post hoc analysis of the Bypass Angioplasty Revascularization Investigation (BARI) trial data showed increased mortality in diabetics with multivessel CAD treated with angioplasty compared with surgery, but the results of the more recent trials using intracoronary stents appear more balanced; in this regard, the effects of drug-eluting stents, which dramatically decrease the incidence of re-stenosis, seem promising.

DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction): theory and practice.

DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction): theory and practice.

Diabetes

The causes of accelerated atherogenesis in diabetes are unclear but the consequences in terms of cardiovascular morbidity and mortality are profound. Thus diabetes not only increases the risk of coronary heart disease but also increases the case fatality rate, ensuring that the majority of patients die of cardiovascular causes, often before the age of 50 years. The problem is compounded by autonomic neuropathy which alters the perception of cardiac pain, attenuating symptoms which are often atypical or absent. This may delay presentation or lead to inappropriate triage decisions such that access to defibrillators and specific treatment is denied. Central to the cardiovascular management of diabetes is vigorous risk factor modification although clear evidence that this leads to extra protection against coronary heart disease beyond that achieved in non-diabetic individuals has not been forthcoming. In other respects too, the management of diabetic patients with heart disease is underpinned by the same evidence-base as applies to non-diabetic patients, and it is noteworthy that 15-20% of the patients in most of the landmark clinical trials have been diabetic. Recently, however, trials such as the United Kingdom Prospective Diabetes Study (UKPDS), the Heart Outcomes Prevention Evaluation (HOPE) study, and the Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study have identified novel strategies for reducing cardiovascular risk in diabetes. These trials have already had a major impact on cardiological practice, emphasising the prime importance of blood pressure control and converting enzyme inhibition for reducing cardiovascular risk in diabetes as well as the value of insulin therapy for reducing mortality in diabetic myocardial infarction. Additional trials, already in progress, are expected to refine further the cardiovascular management of patients with diabetes in order to provide an effective challenge for a problem that shows no signs of going away.

Intensive insulin regimen reduced long-term mortality after MI in diabetes mellitus

Source Citation Malmberg K, for the DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ. 1997 May 24;314:1512-5.