Trial DesignRationale, design, and baseline characteristics for a large international trial of cardiovascular disease prevention in people with dysglycemia: The ORIGIN Trial (Outcome Reduction with an Initial Glargine Intervention)
Section snippets
Can insulin-mediated normoglycemia reduce cardiovascular disease?
Elevated fasting plasma glucose (FPG), 2-hour post-load glucose, and/or HbA1c levels all increase the risk for incident CV events in a progressive fashion. When both fasting and post-load glucose levels are known, the latter is a better predictor of CV risk5, 6, 7; however, studies in which the FPG is the only measure of glycemic status show a robust relationship with CV events. Thus, a meta-analysis of 17 cohort studies reported that every 1 mmol/L (18 mg/dL) increase in fasting glucose
Can ω-3 polyunsaturated FAs reduce cardiovascular death?
Essential long chain ω-3 polyunsaturated FAs (PUFA) including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are not efficiently synthesized by humans and are best derived from dietary sources such as fish oils.31 They inhibit platelet aggregation, are anti-inflammatory, reduce blood pressure and endothelial activation,32 and are antiarrhythmic.31 Higher intakes of fish or ω-3 PUFA predict a lower incidence of coronary heart disease and death,33, 34 and trials have generally
The ORIGIN trial
The ORIGIN trial is an international multicenter randomized controlled trial of 2 different interventions in dysglycemic individuals with IFG, IGT, newly detected diabetes, or established diabetes. It is determining whether providing sufficient basal insulin (as insulin glargine) to safely achieve fasting normoglycemia reduces the incidence of fatal and nonfatal CV events more than standard glycemic approaches in people with a modest degree of glucose elevation and high CV risk. At the same
Eligibility
Men and women aged ≥50 years were recruited if they were at high risk for a CV event and had either (a) IFG, IGT, or newly detected diabetes (ie, an FPG ≥6.1 mmol/L [110 mg/dL] or a 2-hour plasma glucose ≥7.8 mmol/L [140 mg/dL] after a 75-g oral glucose load); or (b) established type 2 diabetes on stable therapy with 0 or 1 oral agent for ≥3 months. To be eligible, the locally measured glycated hemoglobin level of participants with established diabetes was low enough to allow investigators to
Results
Between September 2003 and December 2005, 578 clinical sites in 40 countries screened 15 374 individuals and randomized 12 612 participants. The ratio of screened to randomized participants was 1.3:1. Of those randomized, 81.9% (n = 10 326) had previously diagnosed diabetes, 6.3% (n = 788) had biochemical evidence suggesting possible diabetes, and 11.5% (n = 1454) had either IFG or IGT. The mean FPG was 7.3 mmol/L (132 mg/dL) and the mean glycated hemoglobin was 6.5%. Baseline characteristics are
Discussion
The ORIGIN trial is determining whether insulin glargine (Lantus)–mediated normoglycemia reduces CV events more than standard approaches to managing glycemia in 12 612 high-risk individuals with IFG, IGT, newly detected, or relatively well-controlled diabetes. It targets normoglycemia with only 1 daily insulin injection daily; promotes self-titration; and measures both benefits and harms. Moreover, it is studying a population of individuals whose modest degree of dysglycemia is typical of most
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2020, American Journal of Human GeneticsCitation Excerpt :In this study, we used admixture mapping to investigate the impact of ancestry on the human serum proteome by conducting a comprehensive investigation of a multiplex biomarker panel. Specifically, we evaluated the effect of genetic ancestry on 237 serum biomarker concentrations measured in the Latin American population from the ORIGIN (Outcomes Reduction with an Initial Glargine Intervention) trial.21 Although ethnicity has been determined to be a strong predictor of biomarker concentrations, few studies have leveraged the genetic admixture in order to assess the impact of ancestry on biomarker variability that may, in turn, impact their risk of disease.
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NCT00069784@clinicaltrials.gov.