title: No effects of acute hyperglycaemia and hyperinsulinaemia on skin microcirculation and endothelial markers in Type II diabetes mellitus.
abstract: BACKGROUND
  Increased microvascular permeability is a hallmark of microangiopathy in Type I diabetes mellitus and is associated with endothelial dysfunction and haemodynamic alterations. Type II diabetes mellitus is characterized by insulin resistance and hyperinsulinaemia. The purpose of this study was to determine whether acute hyperinsulinaemia, under both normoglycaemic and hyperglycaemic conditions, increases skin capillary permeability through its effect on skin haemodynamics, capillary recruitment or circulating markers of endothelial dysfunction in Type II diabetes.
  
  
  METHODS
  Nine Type II diabetic patients without microalbuminuria, (pre-) proliferative retinopathy or clinical neuropathy underwent three glucose clamps of 210 min., in random order, on separate days. A "standard" clamp (insulin-infusion rate 30 mU kg(-1) h(-1), glucose-target 5.0 mmol/L) was compared with a hyperinsulinaemic (insulin-infusion rate 150 mU kg(-1) h(-1), glucose-target 5.0 mmol/L) and a hyperinsulinaemic, hyperglycaemic (insulin-infusion rate 150 mU kg(-1) h(-1), glucose-target 12.0 mmol/L) clamp. Skin capillary permeability and density were measured using large-window sodium fluorescein videodensitometry, and skin blood flow by laser Doppler flowmetry. Endothelial dysfunction was estimated from increases in soluble intercellular adhesion molecule-1 (sICAM-1) and von Willebrand factor antigen (vWF).
  
  
  RESULTS
  No differences were found in skin capillary permeability, skin haemodynamics and capillary density at the end of the three glucose clamp periods. sICAM-1 and vWF did not increase as compared to the standard glucose clamp. sICAM-1 (r=-0.76, p<0.05) and vWF (r=-0.71, p<0.05) correlated negatively with insulin sensitivity, but not with skin microcirculatory parameters.
  
  
  CONCLUSIONS
  Acute hyperinsulinaemia, both with and without concomitant hyperglycaemia, does not increase skin microvascular permeability, haemodynamics or parameters of endothelial dysfunction in Type II diabetic patients. Furthermore, these data suggest that the coexistence of hyperinsulinaemia and endothelial dysfunction in Type II diabetes does not indicate a causal relationship, but may rather indicate decreased insulin sensitivity as a common underlying cause.
authors.affiliation: Department of Internal Medicine, Division of General Internal Medicine, University Hospital, Groningen, The Netherlands. p.h.n.oomen@int.azg.nl
authors.forename: P H N
authors.initials: PH
authors.lastname: Oomen
authors.forename: G D
authors.initials: GD
authors.lastname: Kant
authors.forename: R P F
authors.initials: RP
authors.lastname: Dullaart
authors.forename: J W Cohen
authors.initials: JW
authors.lastname: Tervaert
authors.forename: W D
authors.initials: WD
authors.lastname: Reitsma
authors.forename: A J
authors.initials: AJ
authors.lastname: Smit
mesh_terms: D000941:Antigens / Q000378:metabolism; D015415:Biomarkers / Q000032:analysis; D002199:Capillary Permeability; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism* / Q000502:physiology; D005453:Fluorescence; D005947:Glucose / Q000378:metabolism; D015309:Glucose Clamp Technique; D006439:Hemodynamics; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism*; D006946:Hyperinsulinism / Q000097:blood / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D008833:Microcirculation; D008875:Middle Aged; D009566:Nitrates / Q000652:urine; D009573:Nitrites / Q000652:urine; D012867:Skin / Q000098:blood supply*; D012964:Sodium / Q000652:urine; D014841:von Willebrand Factor / Q000276:immunology
chemical_list: D000941:Antigens; D015415:Biomarkers; D007328:Insulin; D009566:Nitrates; D009573:Nitrites; C029417:Von Willebrand antigen; D014841:von Willebrand Factor; D018799:Intercellular Adhesion Molecule-1; D012964:Sodium; D005947:Glucose