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CLINICAL STUDY: DIABETES AND CARDIOVASCULAR DISEASE

Acute, short-term hyperglycemia enhances shear stress-induced platelet activation in patients with type II diabetes mellitus

Paolo Gresele, MD, PhD^*,*, Giuseppe Guglielmini, BSc^*, Massimiliano De Angelis, MD, Silvia Ciferri, BSc^*, Marco Ciofetta, MD, Emanuela Falcinelli, BSc^*, Carlo Lalli, MD, Giovanni Ciabattoni, MD, Giovanni Davì, MD and Geremia B. Bolli, MD

^* Division of Internal and Cardiovascular Medicine, Department of Internal Medicine, University of Perugia, Perugia, Italy
Division of Internal Medicine, Endocrinology and Metabolism, Department of Internal Medicine, University of Perugia, Perugia, Italy
Departments of Medicine and Aging, Drug Sciences, University of Chieti, Chieti, Italy

Manuscript received July 10, 2002; revised manuscript received October 11, 2002, accepted November 19, 2002.

^* Reprint requests and correspondence: Dr. Paolo Gresele, Department of Internal Medicine, Section of Internal and Cardiovascular Medicine, University of Perugia, via E. Dal Pozzo, snc-06126, Perugia, Italy.
grespa{at}unipg.it

OBJECTIVES: The aim of our study was to assess whether acute, short-term hyperglycemia affects platelet reactivity in patients with Type II diabetes mellitus (T2DM).

BACKGROUND: Hyperglycemic spikes are thought to precipitate ischemic events in T2DM. Previous studies have shown in vivo platelet activation in diabetes; however, no studies have assessed whether acute in vivo hyperglycemia induces further activation of platelets.

METHODS: In a cross-over, randomized, double-blind study, 12 patients with T2DM underwent 4 h of either acute hyperglycemia (13.9 mmol/l, 250 mg/dl) or euglycemia (5.5 mmol/l, 100 mg/dl). Shear stress-induced platelet activation, P-selectin and lysosomal integral membrane protein (LIMP) expression on platelets in the bleeding-time blood, urinary 11-dehydro-thromboxane B₂ (TxB₂) excretion, von Willebrand factor:antigen (vWF:Ag), and von Willebrand factor:activity (vWF:activity) were measured before and after hyperglycemia or euglycemia.

RESULTS: Shear stress-induced platelet activation, P-selectin and LIMP expression on platelets in the bleeding-time blood, and urinary 11-dehydro-TxB₂ excretion increased significantly after hyperglycemic clamping, whereas no changes were observed after euglycemic clamping. Plasma vWF:Ag and vWF:activity increased strikingly in parallel fashion after hyperglycemic clamping, whereas no changes were observed after euglycemic clamping.

CONCLUSIONS: Our data demonstrate that acute, short-term hyperglycemia induces an increased activation of platelets exposed to high shear stress conditions in vitro (filtration method) or in vivo (bleeding time). In vivo platelet activation is reflected by an increased urinary excretion of 11-dehydro-TxB₂. The increased levels of vWF in the circulation correlate with the increase in platelet activation markers and may indicate some degree of causation. Acute, short-term hyperglycemia in T2DM may precipitate vascular occlusions by facilitating platelet activation.

Abbreviations and Acronyms   ADP   adenosine diphosphate   Ag   antigen   AUC   area under the curve   HbA1c   glycosylated hemoglobin   LIMP   lysosomal integral membrane protein   T2DM   Type II diabetes mellitus   TxB2   thromboxane B2   vWF   von Willebrand factor

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