title: Obesity, Insulin Resistance, and Incident Small Vessel Disease on Magnetic Resonance Imaging: Atherosclerosis Risk in Communities Study.
abstract: OBJECTIVE
  The term metabolic syndrome describes the clustering of risk factors found in many individuals with obesity. Because of their pathophysiology, we hypothesized that 2 features of metabolic syndrome, central obesity and insulin resistance (IR), would be associated with cerebrovascular changes on magnetic resonance imaging, and specifically with incident lacunar disease and not white matter hyperintensity (WMH) progression.
  
  
  METHODS
  Risk factors were defined at study baseline in 934 participants in the Atherosclerosis Risk in Communities (ARIC) study, who completed 2 brain magnetic resonance imagings≈10 years apart. WMH progression and incident lacunes between the 2 magnetic resonance imagings were determined. An IR score for each participant was created using principal component analysis of 11 risk factors, including (among others): insulin, homeostatic model assessment-IR, body mass index, and waist circumference. Metabolic syndrome (presence/absence), using standard clinical definitions, and IR score at the first magnetic resonance imaging, were independent variables, evaluated in multivariate logistic regression to determine odds of WMH progression (Q5 versus Q1-Q4) and incident lacunes.
  
  
  RESULTS
  Metabolic syndrome (adjusted odds ratio, 1.98; 95% confidence interval, 1.28-3.05) and IR score (adjusted odds ratio per 1-SD increase, 1.33; 95% confidence interval, 1.05-1.68) were associated with incident lacunes but not with WMH progression. Insulin, homeostatic model assessment-IR, and body mass index were not associated with incident lacunes or WMH progression in separate models.
  
  
  CONCLUSIONS
  The IR score and central obesity are associated with incident lacunar disease but not WMH progression in individuals. Central obesity and IR may be important risk factors to target to prevent lacunar disease.
authors.affiliation: From the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.D.); Department of Epidemiology, Bloomberg School of Public Health (A.L.C.S., A.R.S., E.S.), Department of Neurology, School of Medicine (A.L.C.S., R.F.G.), and Welch Center for Prevention, Epidemiology and Clinical Research (E.S., R.F.G.), Johns Hopkins University, Baltimore, MD; Division of Geriatrics, Department of Medicine, The University of Mississippi School of Medicine, Jackson (T.H.M., B.G.W.); Department of Neurology, Pro Cardiaco Hospital, Rio de Janeiro, Brazil (D.C.B.); Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Division of Public Health Sciences, The Wake Forest University School of Medicine, Winston-Salem, NC (L.H.C., L.E.W.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.).
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Dearborn
authors.affiliation: From the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.D.); Department of Epidemiology, Bloomberg School of Public Health (A.L.C.S., A.R.S., E.S.), Department of Neurology, School of Medicine (A.L.C.S., R.F.G.), and Welch Center for Prevention, Epidemiology and Clinical Research (E.S., R.F.G.), Johns Hopkins University, Baltimore, MD; Division of Geriatrics, Department of Medicine, The University of Mississippi School of Medicine, Jackson (T.H.M., B.G.W.); Department of Neurology, Pro Cardiaco Hospital, Rio de Janeiro, Brazil (D.C.B.); Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Division of Public Health Sciences, The Wake Forest University School of Medicine, Winston-Salem, NC (L.H.C., L.E.W.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.).
authors.forename: Andrea L C
authors.initials: AL
authors.lastname: Schneider
authors.affiliation: From the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.D.); Department of Epidemiology, Bloomberg School of Public Health (A.L.C.S., A.R.S., E.S.), Department of Neurology, School of Medicine (A.L.C.S., R.F.G.), and Welch Center for Prevention, Epidemiology and Clinical Research (E.S., R.F.G.), Johns Hopkins University, Baltimore, MD; Division of Geriatrics, Department of Medicine, The University of Mississippi School of Medicine, Jackson (T.H.M., B.G.W.); Department of Neurology, Pro Cardiaco Hospital, Rio de Janeiro, Brazil (D.C.B.); Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Division of Public Health Sciences, The Wake Forest University School of Medicine, Winston-Salem, NC (L.H.C., L.E.W.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.).
authors.forename: A Richey
authors.initials: AR
authors.lastname: Sharrett
authors.affiliation: From the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.D.); Department of Epidemiology, Bloomberg School of Public Health (A.L.C.S., A.R.S., E.S.), Department of Neurology, School of Medicine (A.L.C.S., R.F.G.), and Welch Center for Prevention, Epidemiology and Clinical Research (E.S., R.F.G.), Johns Hopkins University, Baltimore, MD; Division of Geriatrics, Department of Medicine, The University of Mississippi School of Medicine, Jackson (T.H.M., B.G.W.); Department of Neurology, Pro Cardiaco Hospital, Rio de Janeiro, Brazil (D.C.B.); Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Division of Public Health Sciences, The Wake Forest University School of Medicine, Winston-Salem, NC (L.H.C., L.E.W.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.).
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
authors.affiliation: From the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.D.); Department of Epidemiology, Bloomberg School of Public Health (A.L.C.S., A.R.S., E.S.), Department of Neurology, School of Medicine (A.L.C.S., R.F.G.), and Welch Center for Prevention, Epidemiology and Clinical Research (E.S., R.F.G.), Johns Hopkins University, Baltimore, MD; Division of Geriatrics, Department of Medicine, The University of Mississippi School of Medicine, Jackson (T.H.M., B.G.W.); Department of Neurology, Pro Cardiaco Hospital, Rio de Janeiro, Brazil (D.C.B.); Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Division of Public Health Sciences, The Wake Forest University School of Medicine, Winston-Salem, NC (L.H.C., L.E.W.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.).
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Bezerra
authors.affiliation: From the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.D.); Department of Epidemiology, Bloomberg School of Public Health (A.L.C.S., A.R.S., E.S.), Department of Neurology, School of Medicine (A.L.C.S., R.F.G.), and Welch Center for Prevention, Epidemiology and Clinical Research (E.S., R.F.G.), Johns Hopkins University, Baltimore, MD; Division of Geriatrics, Department of Medicine, The University of Mississippi School of Medicine, Jackson (T.H.M., B.G.W.); Department of Neurology, Pro Cardiaco Hospital, Rio de Janeiro, Brazil (D.C.B.); Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Division of Public Health Sciences, The Wake Forest University School of Medicine, Winston-Salem, NC (L.H.C., L.E.W.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.).
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.affiliation: From the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.D.); Department of Epidemiology, Bloomberg School of Public Health (A.L.C.S., A.R.S., E.S.), Department of Neurology, School of Medicine (A.L.C.S., R.F.G.), and Welch Center for Prevention, Epidemiology and Clinical Research (E.S., R.F.G.), Johns Hopkins University, Baltimore, MD; Division of Geriatrics, Department of Medicine, The University of Mississippi School of Medicine, Jackson (T.H.M., B.G.W.); Department of Neurology, Pro Cardiaco Hospital, Rio de Janeiro, Brazil (D.C.B.); Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Division of Public Health Sciences, The Wake Forest University School of Medicine, Winston-Salem, NC (L.H.C., L.E.W.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.).
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Selvin
authors.affiliation: From the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.D.); Department of Epidemiology, Bloomberg School of Public Health (A.L.C.S., A.R.S., E.S.), Department of Neurology, School of Medicine (A.L.C.S., R.F.G.), and Welch Center for Prevention, Epidemiology and Clinical Research (E.S., R.F.G.), Johns Hopkins University, Baltimore, MD; Division of Geriatrics, Department of Medicine, The University of Mississippi School of Medicine, Jackson (T.H.M., B.G.W.); Department of Neurology, Pro Cardiaco Hospital, Rio de Janeiro, Brazil (D.C.B.); Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Division of Public Health Sciences, The Wake Forest University School of Medicine, Winston-Salem, NC (L.H.C., L.E.W.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.).
authors.forename: Clifford R
authors.initials: CR
authors.lastname: Jack
authors.affiliation: From the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.D.); Department of Epidemiology, Bloomberg School of Public Health (A.L.C.S., A.R.S., E.S.), Department of Neurology, School of Medicine (A.L.C.S., R.F.G.), and Welch Center for Prevention, Epidemiology and Clinical Research (E.S., R.F.G.), Johns Hopkins University, Baltimore, MD; Division of Geriatrics, Department of Medicine, The University of Mississippi School of Medicine, Jackson (T.H.M., B.G.W.); Department of Neurology, Pro Cardiaco Hospital, Rio de Janeiro, Brazil (D.C.B.); Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Division of Public Health Sciences, The Wake Forest University School of Medicine, Winston-Salem, NC (L.H.C., L.E.W.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.).
authors.forename: Laura H
authors.initials: LH
authors.lastname: Coker
authors.affiliation: From the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.D.); Department of Epidemiology, Bloomberg School of Public Health (A.L.C.S., A.R.S., E.S.), Department of Neurology, School of Medicine (A.L.C.S., R.F.G.), and Welch Center for Prevention, Epidemiology and Clinical Research (E.S., R.F.G.), Johns Hopkins University, Baltimore, MD; Division of Geriatrics, Department of Medicine, The University of Mississippi School of Medicine, Jackson (T.H.M., B.G.W.); Department of Neurology, Pro Cardiaco Hospital, Rio de Janeiro, Brazil (D.C.B.); Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Division of Public Health Sciences, The Wake Forest University School of Medicine, Winston-Salem, NC (L.H.C., L.E.W.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.).
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alonso
authors.affiliation: From the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.D.); Department of Epidemiology, Bloomberg School of Public Health (A.L.C.S., A.R.S., E.S.), Department of Neurology, School of Medicine (A.L.C.S., R.F.G.), and Welch Center for Prevention, Epidemiology and Clinical Research (E.S., R.F.G.), Johns Hopkins University, Baltimore, MD; Division of Geriatrics, Department of Medicine, The University of Mississippi School of Medicine, Jackson (T.H.M., B.G.W.); Department of Neurology, Pro Cardiaco Hospital, Rio de Janeiro, Brazil (D.C.B.); Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Division of Public Health Sciences, The Wake Forest University School of Medicine, Winston-Salem, NC (L.H.C., L.E.W.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.).
authors.forename: Lynne E
authors.initials: LE
authors.lastname: Wagenknecht
authors.affiliation: From the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.D.); Department of Epidemiology, Bloomberg School of Public Health (A.L.C.S., A.R.S., E.S.), Department of Neurology, School of Medicine (A.L.C.S., R.F.G.), and Welch Center for Prevention, Epidemiology and Clinical Research (E.S., R.F.G.), Johns Hopkins University, Baltimore, MD; Division of Geriatrics, Department of Medicine, The University of Mississippi School of Medicine, Jackson (T.H.M., B.G.W.); Department of Neurology, Pro Cardiaco Hospital, Rio de Janeiro, Brazil (D.C.B.); Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Division of Public Health Sciences, The Wake Forest University School of Medicine, Winston-Salem, NC (L.H.C., L.E.W.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.).
authors.forename: Beverly G
authors.initials: BG
authors.lastname: Windham
authors.affiliation: From the Department of Neurology, Yale University School of Medicine, New Haven, CT (J.L.D.); Department of Epidemiology, Bloomberg School of Public Health (A.L.C.S., A.R.S., E.S.), Department of Neurology, School of Medicine (A.L.C.S., R.F.G.), and Welch Center for Prevention, Epidemiology and Clinical Research (E.S., R.F.G.), Johns Hopkins University, Baltimore, MD; Division of Geriatrics, Department of Medicine, The University of Mississippi School of Medicine, Jackson (T.H.M., B.G.W.); Department of Neurology, Pro Cardiaco Hospital, Rio de Janeiro, Brazil (D.C.B.); Departments of Neurology (D.S.K.) and Radiology (C.R.J.), Mayo Clinic, Rochester, MN; Division of Public Health Sciences, The Wake Forest University School of Medicine, Winston-Salem, NC (L.H.C., L.E.W.); and Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis (A.A.). rgottesm@jhmi.edu.
authors.forename: Rebecca F
authors.initials: RF
authors.lastname: Gottesman
mesh_terms: D050197:Atherosclerosis / Q000175:diagnosis* / Q000453:epidemiology; D005260:Female; D006801:Humans; D015994:Incidence; D007333:Insulin Resistance; D008279:Magnetic Resonance Imaging; D008297:Male; D024821:Metabolic Syndrome / Q000175:diagnosis / Q000453:epidemiology; D055806:Microvessels / Q000473:pathology; D008875:Middle Aged; D009765:Obesity / Q000175:diagnosis* / Q000453:epidemiology; D011446:Prospective Studies; D012111:Residence Characteristics; D012307:Risk Factors; D059409:Stroke, Lacunar / Q000175:diagnosis* / Q000453:epidemiology
keywords: atherosclerosis; body mass index; obesity; risk factors; white matter