Effects of acute hypoglycemia on inflammatory and pro-atherothrombotic biomarkers in individuals with type 1 diabetes and healthy individuals.
OBJECTIVE
Recent large randomized trials have linked adverse cardiovascular and cerebrovascular events with hypoglycemia. However, the integrated physiological and vascular biological mechanisms occurring during hypoglycemia have not been extensively examined. Therefore, the aim of this study was to determine whether 2 h of moderate clamped hypoglycemia could decrease fibrinolytic balance and activate pro-atherothrombotic mechanisms in individuals with type 1 diabetes and healthy individuals.


METHODS
Thirty-five healthy volunteers (19 male and 16 female subjects age 32 +/- 2 years, BMI 26 +/- 2 kg/m(2), A1C 5.1 +/- 0.1%) and twenty-four with type 1 diabetes (12 male and 12 female subjects age 33 +/- 3 years, BMI 24 +/- 2 kg/m(2), A1C 7.7 +/- 0.2%) were studied during either a 2-h hyperinsulinemic (9 pmol x kg(-1) x min(-1)) euglycemic or hypoglycemic (2.9 +/- 0.1 mmol/l) clamp or both protocols. Plasma glucose levels were normalized overnight in type 1 diabetic subjects prior to each study.


RESULTS
Insulin levels were similar (602 +/- 44 pmol/l) in all four protocols. Glycemia was equivalent in both euglycemic protocols (5.2 +/- 0.1 mmol/l), and the level of hypoglycemia was also equivalent in both type 1 diabetic subjects and healthy control subjects (2.9 +/- 0.1 mmol/l). Using repeated ANOVA, it was determined that plasminogen activator inhibitor (PAI-1), vascular cell adhesion molecule (VCAM), intercellular adhesion molecule (ICAM), E-selectin, P-selectin, interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and adiponectin responses were all significantly increased (P < 0.05) during the 2 h of hyperinsulinemic hypoglycemia as compared with euglycemia in healthy control subjects. All measures except PAI-1 were also found to be increased during hypoglycemia compared with euglycemia in type 1 diabetes.


CONCLUSIONS
In summary, moderate hypoglycemia acutely increases circulating levels of PAI-1, VEGF, vascular adhesion molecules (VCAM, ICAM, E-selectin), IL-6, and markers of platelet activation (P-selectin) in individuals with type 1 diabetes and healthy individuals. We conclude that acute hypoglycemia can result in complex vascular effects including activation of prothrombotic, proinflammatory, and pro-atherogenic mechanisms in individuals with type 1 diabetes and healthy individuals.
Gogitidze Joy
Nino
N
University of Maryland School of Medicine, Baltimore, Maryland, USA. sdavis@medicine.umaryland.edu.
Hedrington
Maka S
MS
Briscoe
Vanessa J
VJ
Tate
Donna B
DB
Ertl
Andrew C
AC
Davis
Stephen N
SN
D000208:Acute Disease; D052242:Adiponectin / Q000097:blood; D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism*; D019040:E-Selectin / Q000097:blood; D005260:Female; D005342:Fibrinolysis / Q000502:physiology; D015309:Glucose Clamp Technique / Q000379:methods; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism*; D007003:Hypoglycemia / Q000378:metabolism*; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D019007:P-Selectin / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D015539:Platelet Activation / Q000502:physiology; D013927:Thrombosis / Q000378:metabolism*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D019040:E-Selectin; D007004:Hypoglycemic Agents; C508600:IL6 protein, human; D007328:Insulin; D015850:Interleukin-6; D019007:P-Selectin; D017395:Plasminogen Activator Inhibitor 1; C467484:VEGFA protein, human; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D018799:Intercellular Adhesion Molecule-1