title: Effect of insulin glargine and n-3FA on carotid intima-media thickness in people with dysglycemia at high risk for cardiovascular events: the glucose reduction and atherosclerosis continuing evaluation study (ORIGIN-GRACE).
abstract: OBJECTIVE
  To evaluate the effects of insulin glargine and n-3 polyunsaturated fatty acid (n-3FA) supplements on carotid intima-media thickness (CIMT).
  
  
  METHODS
  We enrolled 1,184 people with cardiovascular (CV) disease and/or CV risk factors plus impaired fasting glucose, impaired glucose tolerance, or early type 2 diabetes in a randomized multicenter 2 × 2 factorial design trial. Participants received open-label insulin glargine (targeting fasting glucose levels ≤ 5.3 mmol/L [95 mg/dL]) or standard glycemic care and double-blind therapy with a 1-g capsule of n-3FA or placebo. The primary trial outcome was the annualized rate of change in maximum CIMT for the common carotid, bifurcation, and internal carotid artery segments. Secondary outcomes were the annualized rates of change in maximum CIMT for the common carotid and the common carotid plus bifurcation, respectively. Baseline followed by annual ultrasounds were obtained during a median follow-up of 4.9 years.
  
  
  RESULTS
  Compared with 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-3FA supplement and placebo groups.
  
  
  CONCLUSIONS
  In people with CV disease and/or CV risk factors and dysglycemia, insulin glargine used to target normoglycemia modestly reduced CIMT progression, whereas daily supplementation with n-3FA had no effect on CIMT progression.
authors.affiliation: Department of Medicine, McMaster University, Hamilton, Ontario, Canada. eva.lonn@phri.ca
authors.forename: Eva M
authors.initials: EM
authors.lastname: Lonn
authors.forename: Jackie
authors.initials: J
authors.lastname: Bosch
authors.forename: Rafael
authors.initials: R
authors.lastname: Diaz
authors.forename: Patricio
authors.initials: P
authors.lastname: Lopez-Jaramillo
authors.forename: Ambady
authors.initials: A
authors.lastname: Ramachandran
authors.forename: Nicolae
authors.initials: N
authors.lastname: Hâncu
authors.forename: Markolf
authors.initials: M
authors.lastname: Hanefeld
authors.forename: Henry
authors.initials: H
authors.lastname: Krum
authors.forename: Lars
authors.initials: L
authors.lastname: Ryden
authors.forename: Sandra
authors.initials: S
authors.lastname: Smith
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: McQueen
authors.forename: Leanne
authors.initials: L
authors.lastname: Dyal
authors.forename: Salim
authors.initials: S
authors.lastname: Yusuf
authors.forename: Hertzel C
authors.initials: HC
authors.lastname: Gerstein
mesh_terms: D000368:Aged; D050197:Atherosclerosis / Q000097:blood / Q000188:drug therapy*; D001786:Blood Glucose / Q000187:drug effects; D059168:Carotid Intima-Media Thickness; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012307:Risk Factors
chemical_list: D001786:Blood Glucose; D015525:Fatty Acids, Omega-3; D007004:Hypoglycemic Agents; D049528:Insulin, Long-Acting; D000069036:Insulin Glargine
references.citation: JAMA. 2007 Mar 28;297(12):1344-53
references.pmid: 17384434
references.citation: Circulation. 2001 Feb 20;103(7):919-25
references.pmid: 11181464
references.citation: JAMA. 2012 Sep 12;308(10):1024-33
references.pmid: 22968891
references.citation: J Am Coll Cardiol. 2008 Aug 5;52(6):417-24
references.pmid: 18672160
references.citation: Diabet Med. 2006 Jun;23(6):609-16
references.pmid: 16759301
references.citation: Am J Epidemiol. 2007 Mar 15;165(6):617-24
references.pmid: 17244636
references.citation: Arteriosclerosis. 1988 Mar-Apr;8(2):168-77
references.pmid: 3279941
references.citation: Am Heart J. 2008 Jan;155(1):26-32, 32.e1-6
references.pmid: 18082485
references.citation: Cardiovasc Diabetol. 2008 May 29;7:16
references.pmid: 18507868
references.citation: Cell Metab. 2011 Nov 2;14(5):575-85
references.pmid: 22055501
references.citation: Circulation. 2004 Feb 24;109(7):849-54
references.pmid: 14757687
references.citation: Stroke. 2003 Dec;34(12):2985-94
references.pmid: 14615619
references.citation: Ann Intern Med. 1999 Apr 6;130(7):554-62
references.pmid: 10189324
references.citation: J Am Coll Cardiol. 1995 Jun;25(7):1492-8
references.pmid: 7759696
references.citation: Diabetes Metab Res Rev. 2011 May;27(4):373-82
references.pmid: 21309063
references.citation: N Engl J Med. 2011 Mar 03;364(9):829-841
references.pmid: 21366474
references.citation: N Engl J Med. 1985 May 9;312(19):1205-9
references.pmid: 3990713
references.citation: N Engl J Med. 2005 Dec 22;353(25):2643-53
references.pmid: 16371630
references.citation: J Atheroscler Thromb. 2011;18(11):946-57
references.pmid: 21844660
references.citation: Cardiovasc Res. 2002 Apr;54(1):183-90
references.pmid: 12062374
references.citation: World Rev Nutr Diet. 1991;66:205-16
references.pmid: 2053338
references.citation: Lancet. 2007 Jul 14;370(9582):153-160
references.pmid: 17630038
references.citation: Arterioscler Thromb Vasc Biol. 2004 Feb;24(2):325-30
references.pmid: 14684428
references.citation: N Engl J Med. 2012 Jul 26;367(4):319-28
references.pmid: 22686416
references.citation: N Engl J Med. 2007 Apr 19;356(16):1620-30
references.pmid: 17387131
references.citation: Eur J Cardiovasc Prev Rehabil. 2006 Jun;13(3):325-33
references.pmid: 16926660
references.citation: BMJ. 2011 Jul 26;343:d4169
references.pmid: 21791495
references.citation: Curr Diab Rep. 2008 Jun;8(3):233-8
references.pmid: 18625122
references.citation: Lancet. 2007 Mar 31;369(9567):1090-8
references.pmid: 17398308
references.citation: Lancet. 1999 Aug 7;354(9177):447-55
references.pmid: 10465168
references.citation: Curr Atheroscler Rep. 2011 Apr;13(2):123-8
references.pmid: 21287301
references.citation: N Engl J Med. 2012 Jul 26;367(4):309-18
references.pmid: 22686415
references.citation: N Engl J Med. 2010 Mar 4;362(9):800-11
references.pmid: 20200384
references.citation: Lancet. 2010 Aug 14;376(9740):540-50
references.pmid: 20638121
references.citation: Lancet. 1989 Sep 30;2(8666):757-61
references.pmid: 2571009
references.citation: Lancet. 2010 Jun 26;375(9733):2215-22
references.pmid: 20609967
references.citation: J Am Coll Cardiol. 2009 Jun 2;53(22):2028-35
references.pmid: 19477351
references.citation: N Engl J Med. 2008 Oct 9;359(15):1577-89
references.pmid: 18784090
references.citation: Diabetologia. 2010 Dec;53(12):2509-17
references.pmid: 20711717
references.citation: Lancet. 2003 Feb 8;361(9356):477-85
references.pmid: 12583947