title: Muscle microvascular recruitment predicts insulin sensitivity in middle-aged patients with type 1 diabetes mellitus.
abstract: OBJECTIVE
  Insulin delivery to muscle is rate-limiting for insulin's metabolic action and is regulated by insulin's own action to increase skeletal muscle blood flow and to recruit microvasculature. Microvascular dysfunction has been observed in insulin resistant states. We investigated the relation between insulin's action to recruit microvasculature and its metabolic action in type 1 diabetes.
  
  
  METHODS
  Near euglycaemia was obtained by an overnight insulin infusion during 17 inpatient admissions of participants with type 1 diabetes. This was followed by a 2 h 1 mU kg⁻¹ min⁻¹ euglycaemic-hyperinsulinaemic clamp. Microvascular blood volume (MBV) was assessed using contrast-enhanced ultrasound 10 min before and 30 min after starting the clamp.
  
  
  RESULTS
  We observed that, after overnight modest hyperinsulinaemia (average ≈ 286 pmol/l), MBV was positively related to the steady-state insulin sensitivity measured during the subsequent clamp (r = 0.62, p = 0.008). The more marked hyperinsulinaemia during the clamp (average steady-state insulin ≈ 900 pmol/l) increased MBV in the more insulin resistant participants within 30 min but not in the insulin sensitive participants. The change in MBV during the clamp was negatively correlated to the insulin sensitivity (r = -0.55, p = 0.022). As a result, MBV after 30 min of marked hyperinsulinaemia was comparable between the insulin sensitive and resistant participants.
  
  
  CONCLUSIONS
  We conclude that moderate overnight hyperinsulinaemia recruited microvasculature in the more sensitive participants, while higher levels of plasma insulin were needed for more insulin resistant participants. This suggests that microvascular responsiveness to insulin is one determinant of metabolic insulin sensitivity in type 1 diabetes.
authors.affiliation: Center for Diabetes Technology, University of Virginia, PO 400 888, Charlottesville, VA 22908-4888, USA. ac8dk@virginia.edu
authors.forename: A
authors.initials: A
authors.lastname: Chan
authors.forename: E J
authors.initials: EJ
authors.lastname: Barrett
authors.forename: S M
authors.initials: SM
authors.lastname: Anderson
authors.forename: B P
authors.initials: BP
authors.lastname: Kovatchev
authors.forename: M D
authors.initials: MD
authors.lastname: Breton
mesh_terms: D000328:Adult; D016000:Cluster Analysis; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D005542:Forearm; D015309:Glucose Clamp Technique; D006801:Humans; D006946:Hyperinsulinism / Q000097:blood / Q000378:metabolism / Q000503:physiopathology; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D007333:Insulin Resistance; D007700:Kinetics; D008297:Male; D055806:Microvessels / Q000503:physiopathology*; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D012039:Regional Blood Flow
chemical_list: D007328:Insulin