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GRACE: Effects of Insulin Glargin and of Polyunsaturated Fatty Acids on Carotid Intima Media Thickness in High-Risk Diabetes

See the press release:
Munich, Germany – August 27 2012: A sub-study of the Outcome Reduction with an Initial Glargine Intervention (ORIGIN) trial, designed to investigate the effect of insulin glargine and omega-3 fatty acids on atherosclerosis progression, has found that, compared to standard care, only insulin glargine (a long-acting insulin) had a "modest" statistically non-significant reducing effect on the primary outcome of rate of change in maximum carotid intima media thickness (CIMT) at 12 carotid sites...
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Presenter: Eva Lonn | see Discussant report

List of Authors: Eva M. Lonn, MD, MSc, Jackie Bosch, MSc,  Rafael Diaz, MD, Patricio Lopez-Jaramillo, MD, Ambady Ramachandran MD,  Nicolae Hâncu, MD, PhD, Markolf Hanefeld, MD, Krum Henry, MBBS, PhD,  Lars Ryden, MD, PhD, Sandra Smith, RDMS, Matthew J. McQueen, MD, PhD, Leanne Dyal, MSc, Salim Yusuf MD, DPhil, Hertzel C. Gerstein, MD, MSc, for the GRACE and ORIGIN Investigators.


People with dysglycemia are at increased risk for atherosclerosis and cardiovascular (CV) events. Effects of basal insulin titrated to normalize fasting plasma glucose or with n-3 fatty acid supplements on atherosclerosis progression in this population are unknown.

To evaluate effects of insulin glargine and of n-3 fatty acid supplements on carotid intima media thickness (CIMT).
Design, Setting and Participants: Randomized multicenter international 2-by-2 factorial design trial of 1184 people (mean age, 63years) with known CV disease and/or CV risk factors plus impaired fasting glucose, impaired glucose tolerance, or type 2 diabetes.

Participants received open label insulin glargine (with a target fasting blood glucose level of ≤95 mg per deciliter [5.3 mmol per liter]) in addition to standard care or standard glycemic care alone and double-blind therapy with a 1-g capsule of ethyl esters of n–3 fatty acids or placebo. 

Main Outcome Measures:
The primary outcome was the annualized rate of change in maximum CIMT for 12 carotid sites. Secondary outcomes were the annualized rates of change in maximum CIMT for the common carotid artery and for the common carotid plus bifurcation sites. Baseline, followed by annual ultrasounds were obtained during a median follow-up of 4.9 years. 

Compared to standard care, insulin glargine reduced the primary CIMT outcome, but the difference was not statistically significant (difference =0.0030 ± 0.0021 mm/year; p=0.145) and significantly reduced the secondary CIMT outcomes (differences of 0.0033 ± 0.0017  mm/year; p=0.049 and 0.0045 ± 0.0021 mm/year; p=0.032, respectively). There were no differences in the primary and secondary outcomes between the n-3 fatty acid supplement and placebo groups.

In people with known CV disease and/or CV risk factors and dysglycemia insulin glargine used to target normoglycemia, modestly reduced CIMT progression, while daily supplementation with 1 g of n-3 fatty acid supplements, had no effect on CIMT progression.

Discussant: John Eric Deanfield | see Presenter abstract


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The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.