title: Insulin status and vascular responses to weight loss in obesity.
abstract: OBJECTIVE
  The aim of this study was to determine whether the effects of weight loss on arterial function are differentially modified by insulin status.
  
  
  BACKGROUND
  Clinical studies suggest that plasma insulin levels may predict the extent of cardiovascular benefit achieved with weight loss in obese individuals, but mechanisms are currently unknown.
  
  
  METHODS
  We prospectively followed 208 overweight or obese patients (body mass index [BMI] ≥25 kg/m(2)) receiving medical/dietary (48%) or bariatric surgical (52%) weight-loss treatment during a median period of 11.7 months (interquartile range: 4.6 to 13 months). We measured plasma metabolic parameters and vascular endothelial function using ultrasound at baseline and following weight-loss intervention and stratified analyses by median plasma insulin levels.
  
  
  RESULTS
  Patients age 45 ± 1 years, with BMI 45 ± 9 kg/m(2), experienced 14 ± 14% weight loss during the study period. In individuals with higher baseline plasma insulin levels (above median >12 μIU/ml; n = 99), ≥10% weight loss (compared with <10%) significantly improved brachial artery macrovascular flow-mediated vasodilation and microvascular reactive hyperemia (p < 0.05 for all). By contrast, vascular function did not change significantly in the lower insulin group (≤12 μIU/ml; n = 109) despite a similar degree of weight loss. In analyses using a 5% weight loss cut point, only microvascular responses improved in the higher insulin group (p = 0.02).
  
  
  CONCLUSIONS
  Insulin status is an important determinant of the positive effect of weight reduction on vascular function with hyperinsulinemic patients deriving the greatest benefit. Integrated improvement in both microvascular and macrovascular function was associated with ≥10% weight loss. Reversal of insulin resistance and endothelial dysfunction may represent key therapeutic targets for cardiovascular risk reduction in obesity.
authors: Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
authors: Sherman J
authors: SJ
authors: Bigornia
authors: Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
authors: Melissa G
authors: MG
authors: Farb
authors: Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
authors: Stephanie
authors: S
authors: Tiwari
authors: Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
authors: Shakun
authors: S
authors: Karki
authors: Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
authors: Naomi M
authors: NM
authors: Hamburg
authors: Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts.
authors: Joseph A
authors: JA
authors: Vita
authors: Department of General Surgery, Boston University School of Medicine, Boston, Massachusetts.
authors: Donald T
authors: DT
authors: Hess
authors: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
authors: Michael P
authors: MP
authors: Lavalley
authors: Department of Medicine, Section of Endocrinology, Diabetes and Nutrition, Boston University School of Medicine, Boston, Massachusetts.
authors: Caroline M
authors: CM
authors: Apovian
authors: Evans Department of Medicine and Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts. Electronic address: noyan.gokce@bmc.org.
authors: Noyan
authors: N
authors: Gokce
mesh_terms: D001783:Blood Flow Velocity / Q000502:physiology; D015992:Body Mass Index; D001916:Brachial Artery / Q000000981:diagnostic imaging*; D002784:Cholesterol / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007328:Insulin / Q000097:blood*; D008297:Male; D008833:Microcirculation / Q000502:physiology; D008875:Middle Aged; D009765:Obesity / Q000628:therapy*; D050177:Overweight / Q000628:therapy*; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000502:physiology; D014280:Triglycerides / Q000097:blood; D018617:Ultrasonography, Doppler, Pulsed; D015431:Weight Loss
chemical_list: D002784:Cholesterol; D006442:Glycated Hemoglobin; D007328:Insulin; D014280:Triglycerides; C517652:hemoglobin A1c protein, human
keywords: BMI; FMD; HDL; HOMA; HbA(1c); LDL; bariatric surgery; body mass index; flow-mediated dilation; glycosylated hemoglobin; high-density lipoprotein; homeostasis model assessment; hyperinsulinemia; low-density lipoprotein; obesity; vasculature; weight loss
references: J Clin Endocrinol Metab. 2006 May;91(5):1896-900
references: 16507636
references: J Am Coll Cardiol. 2002 Jan 16;39(2):257-65
references: 11788217
references: Endocrine. 2011 Oct;40(2):162-7
references: 21853297
references: Am J Physiol. 1996 Apr;270(4 Pt 2):H1435-40
references: 8967386
references: Eur J Nutr. 2013 Aug;52(5):1443-50
references: 23052625
references: Lancet. 2011 Aug 27;378(9793):815-25
references: 21872750
references: J Am Coll Cardiol. 2003 Oct 1;42(7):1149-60
references: 14522472
references: N Engl J Med. 2007 Aug 23;357(8):741-52
references: 17715408
references: Am J Epidemiol. 1995 Jun 15;141(12):1128-41
references: 7771451
references: Am J Cardiol. 2006 Apr 15;97(8):1250-4
references: 16616036
references: Circulation. 2002 Feb 5;105(5):576-82
references: 11827922
references: Nature. 2006 Dec 14;444(7121):860-7
references: 17167474
references: J Clin Endocrinol Metab. 2011 Oct;96(10):3242-9
references: 21849523
references: Circulation. 2011 Aug 16;124(7):840-50
references: 21844090
references: Obes Surg. 2012 Nov;22(11):1701-7
references: 22777211
references: J Clin Invest. 1996 Jun 1;97(11):2601-10
references: 8647954
references: Obesity (Silver Spring). 2013 Mar;21(3):504-9
references: 23404949
references: JAMA. 2002 Oct 9;288(14):1758-61
references: 12365960
references: Clin Nutr. 2013 Jun;32(3):346-52
references: 23111004
references: Circulation. 2000 Apr 25;101(16):1899-906
references: 10779454
references: Lancet. 2005 Oct 8;366(9493):1279-89
references: 16214598
references: N Engl J Med. 2007 Aug 23;357(8):753-61
references: 17715409
references: Arterioscler Thromb Vasc Biol. 2007 Oct;27(10):2113-9
references: 17717291
references: Am J Epidemiol. 1993 May 1;137(9):959-65
references: 8317453
references: N Engl J Med. 2007 Jun 14;356(24):2457-71
references: 17517853
references: Circulation. 2002 Feb 19;105(7):804-9
references: 11854119
references: JAMA. 2012 Feb 1;307(5):483-90
references: 22253364
references: Circulation. 2007 Mar 13;115(10):1285-95
references: 17353456
references: JAMA. 2012 Jan 4;307(1):56-65
references: 22215166
references: Am J Cardiol. 2008 Jan 1;101(1):82-8
references: 18157970
references: Rev Endocr Metab Disord. 2010 Mar;11(1):61-74
references: 20186491
references: JAMA. 2012 Feb 1;307(5):491-7
references: 22253363
references: Circulation. 2009 Aug 11;120(6):502-9
references: 19635967
references: N Engl J Med. 2013 Jul 11;369(2):145-54
references: 23796131
references: Circ Cardiovasc Imaging. 2011 Jul;4(4):348-50
references: 21772010
references: Hypertension. 2004 Aug;44(2):134-9
references: 15249547
references: J Am Coll Cardiol. 2001 Dec;38(7):1821-8
references: 11738280
references: Obes Res. 1998 Sep;6 Suppl 2:51S-209S
references: 9813653
references: N Engl J Med. 2012 Apr 26;366(17):1567-76
references: 22449319
references: Circulation. 2008 Jul 1;118(1):33-41
references: 18559705
references: N Engl J Med. 2008 Oct 9;359(15):1577-89
references: 18784090
references: Circulation. 2002 Apr 2;105(13):1567-72
references: 11927524
references: Lancet. 2009 Mar 28;373(9669):1083-96
references: 19299006
references: Diabetes Care. 2003 Jul;26(7):2119-25
references: 12832323
references: Circulation. 2011 Jan 18;123(2):163-9
references: 21200002
references: Arterioscler Thromb Vasc Biol. 2011 Sep;31(9):2063-9
references: 21680898
references: N Engl J Med. 2012 Apr 26;366(17):1577-85
references: 22449317