title: Arterial norepinephrine concentration is inversely and independently associated with insulin clearance in obese individuals with metabolic syndrome.
abstract: BACKGROUND
  Impaired insulin clearance contributes to the hyperinsulinemia of obesity, yet relatively little is known concerning the pathophysiological determinants of insulin clearance in obese populations.
  
  
  OBJECTIVE
  To examine the cross-sectional relationship between insulin clearance and resting sympathetic nervous system activity in a cohort of obese subjects with metabolic syndrome.
  
  
  METHODS
  Unmedicated, nonsmoking subjects (31 male, 27 female; aged 56 ± 1 year; body mass index 33.7 ± 0.6 kg/m(2)) underwent euglycemic hyperinsulinemic clamp to determine insulin sensitivity (M) and insulin clearance, assessment of norepinephrine kinetics, peripheral arterial tonometry, Doppler echocardiography, and oral glucose tolerance test.
  
  
  RESULTS
  Univariate correlation analyses showed inverse associations between insulin clearance and arterial norepinephrine concentration (r = -0.44, P = .0006), calculated norepinephrine spillover rate (r = -0.33, P = .01), augmentation index (AI, r = -0.37, P = .005), and positive associations with M (r = 0.30, P = .02), Matsuda insulin sensitivity index (r = 0.27, P = .04), and cardiac output (r = 0.27, P = .04). Insulin clearance and sensitivity did not differ between genders, however females had higher AI compared to males (35 ± 3% versus 14 ± 2%, P < .001). In age and gender adjusted stepwise regression analyses, arterial norepinephrine concentration alone explained 19% of the variance in insulin clearance. When all significant variables were entered into the regression model, arterial norepinephrine, AI, gender, and M were independent predictors of insulin clearance, together explaining 41% of the variance.
  
  
  CONCLUSIONS
  Arterial norepinephrine concentration is inversely and independently associated with whole-body insulin clearance rate in obese individuals with metabolic syndrome. Prospective studies are needed to determine the direction of causality and the chronology of interactions between insulin clearance and sympathetic neural activity.
authors.affiliation: Laboratories of Human Neurotransmitters (N.E.S., M.T.G., E.A.L., C.I.A., N.E., S.E.P., J.B.D., G.W.L.), Cardiovascular Nutrition (P.J.N.) and Neurovascular Hypertension and Kidney Disease (D.H., M.P.S.), and Alfred Baker Medical Unit (S.K.), Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia.
authors.forename: Nora E
authors.initials: NE
authors.lastname: Straznicky
authors.forename: Mariee T
authors.initials: MT
authors.lastname: Grima
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Lambert
authors.forename: Carolina I
authors.initials: CI
authors.lastname: Sari
authors.forename: Nina
authors.initials: N
authors.lastname: Eikelis
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Nestel
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Phillips
authors.forename: Dagmara
authors.initials: D
authors.lastname: Hering
authors.forename: Sofie
authors.initials: S
authors.lastname: Karapanagiotidis
authors.forename: John B
authors.initials: JB
authors.lastname: Dixon
authors.forename: Markus P
authors.initials: MP
authors.lastname: Schlaich
authors.forename: Gavin W
authors.initials: GW
authors.lastname: Lambert
mesh_terms: D001158:Arteries; D001786:Blood Glucose / Q000378:metabolism; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism*; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood*; D009765:Obesity / Q000150:complications / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D007328:Insulin; D009638:Norepinephrine