title: Abdominal adiposity largely explains associations between insulin resistance, hyperglycemia and subclinical atherosclerosis: the NEO study.
abstract: OBJECTIVE
  The relative importance of insulin resistance and hyperglycemia to the development of atherosclerosis remains unclear. Furthermore, adiposity may be responsible for observed associations. Our aim was to study the relative contributions of adiposity, insulin resistance and hyperglycemia to subclinical atherosclerosis.
  
  
  METHODS
  In this cross-sectional analysis of the Netherlands Epidemiology of Obesity (NEO) study, a cohort of persons of 45-65 years, BMI, waist circumference (WC), fasting glucose (FPG), HbA1c and insulin concentrations were measured and the revised HOMA-IR was calculated. The carotid Intima-Media Thickness (cIMT) was measured by ultrasound. We performed linear regression analyses between standardized values of FPG, HbA1c, HOMA-IR, BMI, WC with cIMT, and subsequently included age, sex, ethnicity, education and smoking, HOMA-IR, HbA1c and FPG, BMI and WC in the models.
  
  
  RESULTS
  After exclusion of participants with glucose lowering therapy (n = 356) or missing data (n = 252), this analysis included 6065 participants, 43% men, and mean (SD) cIMT of 616 (92) μm. Differences in cIMT (95% CI) per SD were: FPG: 16 (10,21); HbA1c: 12 (7,16); HOMA-IR: 11 (6,16) μm. These associations attenuated after adjustments, and attenuated most strongly after adjustment for WC. Differences in cIMT (95% CI) per SD in the full model were: FPG: 4 (0,7); HbA1c: 2 (-1,5); HOMA-IR: 0 (-3,3); BMI 16 (13,19); WC: 18 (14,21) μm.
  
  
  CONCLUSIONS
  In middle-aged individuals, we observed similar contributions of insulin resistance and hyperglycemia to subclinical atherosclerosis. These contributions were largely explained by abdominal adiposity, emphasizing the importance of weight management.
authors.affiliation: Department of Clinical Epidemiology, Leiden University Medical Center, PO Box 9600, 2300 RC Leiden, The Netherlands. k.b.gast@lumc.nl
authors.forename: Karin B
authors.initials: KB
authors.lastname: Gast
authors.forename: Johannes W A
authors.initials: JW
authors.lastname: Smit
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
authors.forename: Saskia
authors.initials: S
authors.lastname: Middeldorp
authors.forename: Ralph C A
authors.initials: RC
authors.lastname: Rippe
authors.forename: Saskia
authors.initials: S
authors.lastname: le Cessie
authors.forename: Eelco J P
authors.initials: EJ
authors.lastname: de Koning
authors.forename: J W
authors.initials: JW
authors.lastname: Jukema
authors.forename: Ton J
authors.initials: TJ
authors.lastname: Rabelink
authors.forename: Albert
authors.initials: A
authors.lastname: de Roos
authors.forename: Frits R
authors.initials: FR
authors.lastname: Rosendaal
authors.forename: Renée
authors.initials: R
authors.lastname: de Mutsert
mesh_terms: D050153:Abdominal Fat / Q000378:metabolism*; D000368:Aged; D050197:Atherosclerosis / Q000453:epidemiology / Q000378:metabolism*; D015992:Body Mass Index; D059168:Carotid Intima-Media Thickness; D003430:Cross-Sectional Studies; D005260:Female; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000453:epidemiology / Q000378:metabolism*; D007333:Insulin Resistance / Q000502:physiology*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009765:Obesity / Q000453:epidemiology / Q000378:metabolism*; D011446:Prospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D055105:Waist Circumference
keywords: Adiposity; Atherosclerosis; Cardiovascular disease; Hyperglycemia; Insulin resistance; Intima-media thickness; Waist circumference