title: Effects of acute insulin-induced hypoglycemia on indices of inflammation: putative mechanism for aggravating vascular disease in diabetes.
abstract: OBJECTIVE
  To examine the effects of acute insulin-induced hypoglycemia on inflammation, endothelial dysfunction, and platelet activation in adults with and without type 1 diabetes.
  
  
  METHODS
  We studied 16 nondiabetic adults and 16 subjects with type 1 diabetes during euglycemia (blood glucose 4.5 mmol/l) and hypoglycemia (blood glucose 2.5 mmol/l). Markers of inflammation, thrombosis, and endothelial dysfunction (soluble P-selectin, interleukin-6, von Willebrand factor [vWF], tissue plasminogen activator [tPA], high-sensitivity C-reactive protein [hsCRP], and soluble CD40 ligand [sCD40L]) were measured; platelet-monocyte aggregation and CD40 expression on monocytes were determined using flow cytometry.
  
  
  RESULTS
  In nondiabetic participants, platelet activation occurred after hypoglycemia, with increments in platelet-monocyte aggregation and P-selectin (P <or= 0.02). Inflammation was triggered with CD40 expression increasing maximally at 24 h (3.13 +/- 2.3% vs. 2.06 +/- 1.0%) after hypoglycemia (P = 0.009). Both sCD40L and hsCRP (P = 0.02) increased with a nonsignificant rise in vWF and tPA, indicating a possible endothelial effect. A reduction in sCD40L, tPA, and P-selectin occurred during euglycemia (P = 0.03, P <or= 0.006, and P = 0.006, respectively). In type 1 diabetes, both CD40 expression (5.54 +/- 4.4% vs. 3.65 +/- 1.8%; P = 0.006) and plasma sCD40L concentrations increased during hypoglycemia (peak 3.41 +/- 3.2 vs. 2.85 +/- 2.8 ng/ml; P = 0.03). Platelet-monocyte aggregation also increased significantly at 24 h after hypoglycemia (P = 0.03). A decline in vWF and P-selectin occurred during euglycemia (P <or= 0.04).
  
  
  CONCLUSIONS
  Acute hypoglycemia may provoke upregulation and release of vasoactive substances in adults with and without type 1 diabetes. This may be a putative mechanism for hypoglycemia-induced vascular injury.
authors.affiliation: Department of Diabetes, Royal Infirmary of Edinburgh, Edinburgh, UK.
authors.forename: Rohana J
authors.initials: RJ
authors.lastname: Wright
authors.forename: David E
authors.initials: DE
authors.lastname: Newby
authors.forename: David
authors.initials: D
authors.lastname: Stirling
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Ludlam
authors.forename: Ian A
authors.initials: IA
authors.lastname: Macdonald
authors.forename: Brian M
authors.initials: BM
authors.lastname: Frier
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D001792:Blood Platelets / Q000276:immunology; D002097:C-Reactive Protein / Q000378:metabolism; D019013:CD40 Antigens / Q000097:blood; D023201:CD40 Ligand / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage / Q000009:adverse effects*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009000:Monocytes / Q000276:immunology; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation / Q000187:drug effects / Q000276:immunology; D010959:Tissue Plasminogen Activator / Q000097:blood; D014657:Vasculitis / Q000276:immunology* / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D019013:CD40 Antigens; D007004:Hypoglycemic Agents; C508600:IL6 protein, human; D007328:Insulin; D015850:Interleukin-6; D019007:P-Selectin; D014841:von Willebrand Factor; D023201:CD40 Ligand; D002097:C-Reactive Protein; D010959:Tissue Plasminogen Activator