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(Circulation. 2002;106:2442.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

Elevated Numbers of Tissue-Factor Exposing Microparticles Correlate With Components of the Metabolic Syndrome in Uncomplicated Type 2 Diabetes Mellitus

Michaela Diamant, MD; Rienk Nieuwland, PhD; Renée F. Pablo; Augueste Sturk, PhD; Jan W.A. Smit, MD; Jasper K. Radder, MD

From the Department of Endocrinology/Diabetes Center (M.D.), VU University Medical Center, Amsterdam, the Netherlands; the Departments of Endocrinology (M.D., J.W.A.S., J.K.R.) and Clinical Chemistry (R.N., R.F.P., A.S.), Leiden University Medical Center, Leiden, the Netherlands; and the Department of Clinical Chemistry (R.N., A.S.), Academic Medical Center, Amsterdam, the Netherlands.

Correspondence to Michaela Diamant, MD, PhD, Diabetes Center/Department of Endocrinology, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, The Netherlands. E-mail m.diamant{at}vumc.nl

Background— Type 2 diabetes is associated with accelerated atherosclerosis. Because cell-derived microparticles support coagulation and inflammation, they may be involved in atherogenesis. We characterized circulating microparticles both in patients with uncomplicated, well-regulated type 2 diabetes and in healthy subjects, as well as their relationship with coagulation and metabolic control.

Methods and Results— Microparticles were isolated from plasma, stained with annexin V, cell-specific monoclonal antibodies (MoAbs) and a MoAb directed against tissue factor (TF), and analyzed by flow cytometry. Microparticle numbers and origin were comparable in the two groups, but the median number of TF-positive microparticles was twice as high in patients than in controls (P=0.018). Patients had higher percentages of TF-positive microparticles from T-helper cells (P=0.045), granulocytes (P=0.004), and platelets (P=0.002). Subpopulations of TF-positive microparticles from platelets and T-helper cells exposed granulocytic markers. Correlations were found between the numbers of various TF-positive microparticle subpopulations and body mass index, fasting plasma glucose and insulin, or tumor necrosis factor- and serum HDL cholesterol. Microparticles from patients generated less thrombin in vitro (P=0.007). Microparticle numbers did not correlate with in vivo coagulation markers prothrombin fragment F₁₊₂ and thrombin-antithrombin complexes.

Conclusions— TF, possibly of granulocytic origin, is exposed on microparticle subpopulations in asymptomatic patients with well-regulated type 2 diabetes. TF-positive microparticles are associated with components of the metabolic syndrome but not with coagulation. Thus, TF on microparticles may be involved in processes other than coagulation, including transcellular signaling or angiogenesis.

Key Words: diabetes mellitus • microparticles • tissue factor • atherosclerosis • coagulation

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