The Relationship of Fasting Serum Radioimmune Insulin Levels to Incident Coronary Heart Disease in an Insulin-Treated Diabetic Cohort

Kronmal, Richard A.; Barzilay, Joshua I.; Tracy, Russell P.; Savage, Peter J.; Orchard, Trevor J.; Burke, Gregory L.

doi:10.1210/jc.2003-031822

Cited by 36 publications

(26 citation statements)

References 26 publications

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“…This finding was also reported in the PROactive cohort of type 2 patients with prior myocardial infarction who developed a second fatal or nonfatal myocardial infarction (4) and in the Cardiovascular Health Study (19), in which insulin was found to be associated with greater CVD mortality compared with oral agents. The association was true also when serum insulin concentrations were measured (20). In the DAI study, insulin treatment was an independent risk factor for IHD (12) and stroke (13) in patients free of CVD at baseline as well.…”

Section: Discussionmentioning

confidence: 84%

Recurrence of Cardiovascular Events in Patients With Type 2 Diabetes

Giorda

Avogaro

Maggini³

et al. 2008

Diabetes Care

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OBJECTIVE -The purpose of this study was to assess incidence of and risk factors for recurrent cardiovascular disease (CVD) in type 2 diabetes.RESEARCH DESIGN AND METHODS -We estimated the incidence of recurrent cardiovascular events in type 2 diabetic patients, aged 40 -97 years, followed by a network of diabetes clinics. The analysis was conducted separately for 2,788 patients with CVD at enrollment (cohort A) and for 844 patients developing the first episode during the observation period (cohort B).RESULTS -During 4 years of follow-up, in cohort A the age-adjusted incidence of a recurrent event (per 1,000 person-years) was 72.7 (95% CI 58.3-87.1) in men and 32.5 (21.2-43.7) in women, whereas in cohort B it was 40.1 (17.4 -62.9) in men and 22.4 (12.9 -32.0) in women. After controls were included for potential predictors (familial CVD, obesity, smoking, diabetes duration, glycemic control, microvascular complications, geographic area, and antihypertensive and lipid-lowering treatment), male sex, older age, and insulin use were significant independent risk predictors (cohort A) and serum triglyceride levels Ն1.69 mmol/l emerged as the only metabolic (negative) prognostic factor (cohort B). In both cohorts, a prior CVD episode, especially myocardial infarction, was by far the strongest predictor of recurrent CVD.CONCLUSIONS -Approximately 6% of unselected diabetic patients in secondary prevention develop recurrent major CVD every year. Those with long-standing previous CVD show a higher incidence of recurrence. Male sex, age, high triglyceride levels, and insulin use are additional predictors of recurrence.

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Section: Discussionmentioning

confidence: 84%

Recurrence of Cardiovascular Events in Patients With Type 2 Diabetes

Giorda

Avogaro

Maggini³

et al. 2008

Diabetes Care

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“…Most studies showed no relationship between IAs and changes in insulin dose requirements [9]. However, in a recent study, immune-reactive insulin levels were strongly correlated with IA levels, and elevated fasting immunoreactive insulin levels were an independent risk factor for coronary heart disease in insulin-treated older adults [60].…”

Section: Reduced Insulin Action and Risk Of Hyperglycaemiamentioning

confidence: 95%

Circulating insulin antibodies: influence of continuous subcutaneous or intraperitoneal insulin infusion, and impact on glucose control

Radermecker

Renard

Scheen

2009

Diabetes Metabolism Res

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The purification of animal insulin preparations and the use of human recombinant insulin have markedly reduced the incidence, but not completely suppressed, the development of anti-insulin antibodies (IAs). Advances in technologies concerning the mode of delivery of insulin, i.e. continuous subcutaneous insulin infusion (CSII), continuous peritoneal insulin infusion (CPII) and more recently inhaled insulin administration, appear to significantly increase circulating levels of immunoglobulin G (IgG) anti-IAs in diabetic patients. However, the increase is usually moderate and mostly transient as compared to previous observations with poorly purified animal insulin preparations. The clinical impact of these circulating anti-IAs remains unclear. Nevertheless, several studies have suggested that antibodies could retard insulin action, leading to a worsening of postprandial hyperglycaemia and/or serve as a carrier, thus leading to unexpected hypoglycaemia. CPII may be associated with more marked and sustained increase in IAs levels, possibly related to the use of an unstable insulin and the formation of immunogenic aggregates of insulin. The possible clinical consequences of these high levels of IAs remain to be evaluated because a low-glucose morning syndrome or severe insulin resistance with ketone bodies production have been reported in some cases. In conclusion, even if CSII and CPII may promote the development of circulating IAs, this increase does not lead to immunological insulin resistance, compared to that previously described with animal non-purified insulin preparations, and seems to have only marginal influence on blood glucose control or complications in most diabetic patients.

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“…Subsequently, the finding of highest mortality in the tolbutamide-treated group was attributed to reduced ischemic preconditioning seen predominantly, but not exclusively, with first-generation sulfonylureas. 8,9 Increased plasma insulin concentrations have been associated with adverse cardiovascular outcomes, regardless of whether the insulin source is exogenous (ie, administered therapeutically) 10 or endogenous in origin. 11 On the other hand, insulin treatment in both type 1 and type 2 diabetes mellitus has been associated with improved outcomes over the long term.…”

Section: Insulin-provisional Compared With Insulin-sensitization Thermentioning

confidence: 99%

Management of Diabetes Mellitus in Patients With Cardiovascular Disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial

Goldfine

Fonseca

2010

Circulation

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ardiovascular disease is the leading cause of morbidity and mortality for patients with type 2 diabetes mellitus (T2DM), accounting for two thirds of patient deaths. In addition to traditional cardiovascular risk factors, hyperglycemia and multiple other factors associated with T2DM such as obesity, insulin resistance, and inflammation play significant roles in cardiovascular disease risk. 1 Patients with diabetes mellitus have derived less benefit from multiple preventive and interventional advances. Indeed, in the Bypass Angioplasty Revascularization Investigation (BARI) trial, angioplasty appeared to provide very little benefit for patients with diabetes mellitus, 2 a finding supported by a meta-analysis of randomized interventional trials, 3 although modern revascularization techniques with the use of drug-eluting stents were not yet widely utilized.Therefore, the questions addressed in the BARI 2 Diabetes (BARI 2D) trial are of particular importance in determining optimal treatments to prevent mortality and major cardiovascular events in patients with T2DM and stable ischemic heart disease. Both prompt revascularization compared with intensive medical therapy alone or with delayed revascularization, and insulin-sensitization compared with insulin-provisional therapeutic strategies were evaluated in 2368 patients over 5 years with the use of a 2ϫ2 randomized factorial trial design. 4 With recognition of the cardiovascular benefits of optimal management of diabetes mellitus and cardiovascular risk factors in patients with diabetes mellitus, 5 the BARI 2D study was performed with guideline-driven targets for lipids, blood pressure, and aspirin use. Medical Therapy Compared With Prompt RevascularizationFirst, in a comparison of prompt revascularization with intensive medical therapy alone or with delayed revascularization, similar survival (88.3% versus 87.8%; Pϭ0.97) and freedom from cardiovascular event rates (77.2% versus 75.9%; Pϭ0.70) were demonstrated. However, a high proportion (42%) of subjects initially randomized to medical intervention received delayed revascularization. These findings extend those of the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE) trial, in which an initial management strategy of percutaneous coronary intervention (PCI) when added to optimal medical therapy did not reduce mortality or cardiovascular event rates, although only approximately one third of patients in this trial had diabetes mellitus. 6 Taken together, these trials support the use of optimal medical therapy for those with diabetes mellitus and stable coronary artery disease who prefer not to have an invasive procedure. Furthermore, because the treating cardiologist a priori selected the revascularization method, either coronary artery bypass grafting (CABG) or PCI, on the basis of clinical and angiographic factors, patients randomized to CABG compared with PCI more frequently had 3-vessel disease and proximal left anterior descending artery lesions and had more total occlusions...

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The Relationship of Fasting Serum Radioimmune Insulin Levels to Incident Coronary Heart Disease in an Insulin-Treated Diabetic Cohort

Cited by 36 publications

References 26 publications

Recurrence of Cardiovascular Events in Patients With Type 2 Diabetes

Recurrence of Cardiovascular Events in Patients With Type 2 Diabetes

Circulating insulin antibodies: influence of continuous subcutaneous or intraperitoneal insulin infusion, and impact on glucose control

Management of Diabetes Mellitus in Patients With Cardiovascular Disease in the Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) Trial

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