Objectives: To test the hypothesis that intensive metabolic treatment with insulin-glucose infusion followed by multidose insulin treatment in patients with diabetes mellitus and acute myocardial infarction improves the prognosis. Design: Patients with diabetes mellitus and acute myocardial infarction were randomly allocated standard treatment plus insulin-glucose infusion for at least 24 hours followed by multidose insulin treatment or standard treatment (controls). Subjects: 620 patients were recruited, of whom 306 received intensive insulin treatment and 314 served as controls. Main outcome measure: Long term all cause mortality. Results: The mean (range) follow up was 3.4 (1.6-5.6) years. There were 102 (33%) deaths in the treatment group compared with 138 (44%) deaths in the control group (relative risk (95% confidence interval) 0.72 (0.55 to 0.92); P=0.011).The effect was most pronounced among the predefined group that included 272 patients without previous insulin treatment and at a low cardiovascular risk (0.49 (0.30 to 0.80); P=0.004). Conclusion: Insulin-glucose infusion followed by intensive subcutaneous insulin in diabetic patients with acute myocardial infarction improves long term survival, and the effect seen at one year continues for at least 3.5 years, with an absolute reduction in mortality of 11%. This means that one life was saved for nine treated patients. The effect was most apparent in patients who had not previously received insulin treatment and who were at a low cardiovascular risk. Key messages Diabetes mellitus is common among patients with acute myocardial infarction Diabetic patients with myocardial infarction have a poor short and long term prognosis Poor metabolic control is common among diabetic patients with myocardial infarction Improved metabolic control by means of acute insulin-glucose infusion followed by long term intensive insulin treatment improves long term prognosis among these patients

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Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(02)09089-X.pdf

Glucose metabolism in patients with acute myocardial infarction and no previous diagnosis of diabetes mellitus: a prospective study

Objectives To undertake a systematic review of the long-term effects of obesity treatments on body weight, risk factors for disease, and disease. Methods The study encompassed three systematic reviews that examined different aspects of obesity treatments. (1) A systematic review of obesity treatments in adults where the methods of the Cochrane Collaboration were applied and randomised controlled trials (RCTs) with a follow-up of at least 1 year were evaluated. (2) A systematic epidemiological review, where studies were sought on long-term effects of weight loss on morbidity and/or mortality, and examined through epidemiological modelling. (3) A systematic economic review that sought reports with both costs and outcomes of treatment, including recent reports that assessed the cost-effectiveness of pharmaceutical and surgical interventions. A Markov model was also adopted to examine the cost-effectiveness of a low-fat diet and exercise intervention in adults with obesity and impaired glucose tolerance. Results The addition of the drugs orlistat or sibutramine was associated with weight loss and generally improved risk factors, apart from diastolic blood pressure for sibutramine. Metformin was associated with decreased mortality after 10 years in obese people with type 2 diabetes. Low-fat diets were associated with continuing weight loss for 3 years and improvements in risk factors, as well as prevention of type 2 diabetes and improved control of hypertension. Insufficient evidence was available to demonstrate the benefits of low calorie or very low calorie diets. The addition of an exercise or behaviour programme to diet was associated with improved weight loss and risk factors for at least 1 year. Studies combining low-fat diets, exercise and behaviour therapy suggested improved hypertension and cardiovascular disease. Family therapy was associated with improved weight loss for 2 years compared to individual therapy. There was insufficient evidence to conclude that individual therapy was more beneficial than group therapy. Weight lost more quickly (within 1 year), from the epidemiology review, may be more beneficial with respect to the risk of mortality. The effects of intentional weight loss need further investigation. Weight loss from surgical and non-surgical interventions for people suffering from obesity was associated with decreased risk of development of diabetes, and a reduction in low-density lipoprotein cholesterol, total cholesterol and blood pressure, in the long term. Targeting high-risk individuals with drugs or surgery was likely to result in a cost per additional life-year or quality-adjusted life-year (QALY) of no more than 13,000 British pounds. There was also suggestive evidence of cost saving from treatment of people with type 2 diabetes with metformin. Targeting surgery on people with severe obesity and impaired glucose tolerance was likely to be more cost-effective at 2329 British pounds per additional life-year. Economic modelling over 6 years for diet and exercise for people with impaired glucose tolerance was associated with a high initial cost per additional QALY, but by the sixth year the cost per QALY was 13,389 British pounds. Results did not include cost savings from diseases other than diabetes, and therefore may be conservative. Conclusions The drugs orlistat and sibutramine appear beneficial for the treatment of adults with obesity, and metformin for obese patients with type 2 diabetes. Exercise and/or behaviour therapy appear to improve weight loss when added to diet. Low-fat diets with exercise, or with exercise and behaviour therapy are associated with the prevention of type 2 diabetes and hypertension. Long-term weight loss in epidemiological studies was associated with reduced risk of type 2 diabetes, and may be beneficial for cardiovascular disease. Low-fat diets and exercise interventions in individuals at risk of obesity-related illness are of comparable cost to drug treatments. Long-term pragmatic RCTs of obesity treatments in populations with obesity-related illness or at high risk of developing such illness are needed (to include an evaluation of risk factors, morbidity, quality of life and economic evaluations). Drug trials that include dietary advice, plus exercise and/or behaviour therapy are also needed. Research exploring effective types of exercise, diet or behaviour and also interventions to prevent obesity in adults is required.

Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement

Background—The Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) study addressed prognostic factors and the effects of concomitant treatment and glycometabolic control in diabetic patients with myocardial infarction (AMI). Methods and Results—Of 620 diabetic patients with AMI, 306 were randomly assigned to a ≥24-hour insulin-glucose infusion followed by multidose subcutaneous insulin. Three hundred fourteen patients were randomized as controls, receiving routine antidiabetic therapy. Thrombolysis and β-blockers were administered when possible. Univariate and multivariate statistical analyses were applied to study predictors of long-term mortality. During an average follow-up of 3.4 years (range, 1.6 to 5.6 years), 102 patients (33%) in the intensive insulin group and 138 (44%) in the control group died (P=0.011). Old age, previous heart failure, diabetes duration, admission blood glucose, and admission Hb AIc were independent predictors of mortality in the total cohort, whereas...

Glycometabolic State at Admission: Important Risk Marker of Mortality in Conventionally Treated Patients With Diabetes Mellitus and Acute Myocardial Infarction Long-Term Results From the Diabetes and Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) Study

Therapeutic strategies to protect the ischemic myocardium have been studied extensively. Reperfusion is the definitive treatment for acute coronary syndromes, especially acute myocardial infarction; however, reperfusion has the potential to exacerbate lethal tissue injury, a process termed "reperfusion injury." Ischemia/reperfusion injury may lead to myocardial infarction, cardiac arrhythmias, and contractile dysfunction. Ischemic preconditioning of myocardium is a well described adaptive response in which brief exposure to ischemia/reperfusion before sustained ischemia markedly enhances the ability of the heart to withstand a subsequent ischemic insult. Additionally, the application of brief repetitive episodes of ischemia/reperfusion at the immediate onset of reperfusion, which has been termed "postconditioning," reduces the extent of reperfusion injury. Ischemic pre- and postconditioning share some but not all parts of the proposed signal transduction cascade, including the activation of survival protein kinase pathways. Most experimental studies on cardioprotection have been undertaken in animal models, in which ischemia/reperfusion is imposed in the absence of other disease processes. However, ischemic heart disease in humans is a complex disorder caused by or associated with known cardiovascular risk factors including hypertension, hyperlipidemia, diabetes, insulin resistance, atherosclerosis, and heart failure; additionally, aging is an important modifying condition. In these diseases and aging, the pathological processes are associated with fundamental molecular alterations that can potentially affect the development of ischemia/reperfusion injury per se and responses to cardioprotective interventions. Among many other possible mechanisms, for example, in hyperlipidemia and diabetes, the pathological increase in reactive oxygen and nitrogen species and the use of the ATP-sensitive potassium channel inhibitor insulin secretagogue antidiabetic drugs and, in aging, the reduced expression of connexin-43 and signal transducer and activator of transcription 3 may disrupt major cytoprotective signaling pathways thereby significantly interfering with the cardioprotective effect of pre- and postconditioning. The aim of this review is to show the potential for developing cardioprotective drugs on the basis of endogenous cardioprotection by pre- and postconditioning (i.e., drug applied as trigger or to activate signaling pathways associated with endogenous cardioprotection) and to review the evidence that comorbidities and aging accompanying coronary disease modify responses to ischemia/reperfusion and the cardioprotection conferred by preconditioning and postconditioning. We emphasize the critical need for more detailed and mechanistic preclinical studies that examine car-dioprotection specifically in relation to complicating disease states. These are now essential to maximize the likelihood of successful development of rational approaches to therapeutic protection for the majority of patients with ischemic heart disease who are aged and/or have modifying comorbid conditions.

Interaction of Cardiovascular Risk Factors with Myocardial Ischemia/Reperfusion Injury, Preconditioning, and Postconditioning

Effect of diabetes mellitus on short- and long-term mortality rates of patients with acute myocardial infarction: A statewide study

Persistence of normotension after discontinuation of lifestyle intervention in the Trial of TONE

Traumatic tricuspid regurgitation with cyanosis: Diagnosis by transesophageal echocardiography

Non-drug therapy for hypertension : Do effects on weight and sodium intake persist after discontinuation of intervention?

Most studies on the relation between ventricular ectopic activity and hypertension have been performed in patients with diastolic hypertension. There are no data on the prevalence or characteristics of ventricular ectopic activity in patients with isolated systolic hypertension.1–9 We performed 24-hour ambulatory electrocardiography in 238 patients with isolated systolic hypertension who participated in the Systolic Hypertension in the Elderly Program (SHEP), and in a group of 100 age- and sex-matched normotensive control subjects.10

Daniel M. Shindler

Papers

Effect of diabetes mellitus on short- and long-term mortality rates of patients with acute myocardial infarction: A statewide study

Persistence of normotension after discontinuation of lifestyle intervention in the Trial of TONE

Traumatic tricuspid regurgitation with cyanosis: Diagnosis by transesophageal echocardiography

Non-drug therapy for hypertension : Do effects on weight and sodium intake persist after discontinuation of intervention?

Frequency of ventricular ectopic activity in isolated systolic systemic hypertension.