title: Insulin is a key determinant of elevated retinal arteriolar flicker response in insulin-resistant individuals.
abstract: OBJECTIVE
  Insulin may link metabolic disorders to retinal microvascular pathology. The aim of the present study was to investigate the impact of early insulin resistance on retinal microcirculation.
  
  
  METHODS
  Retinal diameter responses to flicker-light stimulation were investigated in 81 clinically healthy participants (32 ± 6 years [mean ± SD], 59% women) who were recruited according to their BMI. All participants underwent an OGTT and euglycaemic-hyperinsulinaemic clamp (40 mU/m(2) · min(-1) insulin dose). After stratification by low and high insulin sensitivity based on a clamp-derived glucose disposal rate of ≤ or >4.9 mg/kg body mass, respectively, baseline retinal diameters and their relative changes to flicker stimulation were compared while controlling for mean arterial pressure, BMI and sex.
  
  
  RESULTS
  The arterial vasodilator response at the end of flicker stimulation (p = 0.044) and the area under the arterial reaction curve during flicker stimulation (p = 0.015) were significantly higher in individuals with low vs high insulin sensitivity. Vasodilatory responses of retinal veins to flicker stimulation and baseline retinal diameters did not differ between insulin-sensitive and insulin-resistant participants (p > 0.05). In a stepwise linear regression analysis, fasting insulin remained the only predictor of the arterial vasodilator response to flicker-light (p < 0.01). Waist circumference also contributed, although to a lesser extent, to the arterial vasodilator response (p = 0.023).
  
  
  CONCLUSIONS
  Insulin sensitivity is an important determinant of retinal microvascular function. We propose that the elevated arterial flicker response in insulin-resistant states is a result of higher circulating insulin levels.
authors.affiliation: Autonomic and Neuroendocrinological Laboratory Dresden, Department of Neurology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Fetscherstr. 74, 01307, Dresden, Germany, manja.reimann@uniklinikum-dresden.de.
authors.forename: Manja
authors.initials: M
authors.lastname: Reimann
authors.forename: Walthard
authors.initials: W
authors.lastname: Vilser
authors.forename: Matthias
authors.initials: M
authors.lastname: Gruber
authors.forename: Stefan R
authors.initials: SR
authors.lastname: Bornstein
authors.forename: Tjalf
authors.initials: T
authors.lastname: Ziemssen
mesh_terms: D000328:Adult; D000886:Anthropometry; D001160:Arterioles / Q000378:metabolism*; D001823:Body Composition; D015992:Body Mass Index; D005260:Female; D015309:Glucose Clamp Technique; D005951:Glucose Tolerance Test; D064368:Healthy Volunteers; D006439:Hemodynamics; D006801:Humans; D007328:Insulin / Q000097:blood / Q000378:metabolism; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012160:Retina / Q000502:physiology*; D012171:Retinal Vessels / Q000378:metabolism*; D014664:Vasodilation
chemical_list: D007328:Insulin