Elevated numbers of tissue-factor exposing microparticles correlate with components of the metabolic syndrome in uncomplicated type 2 diabetes mellitus.
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.


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-alpha 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 F(1+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.
Diamant
Michaela
M
Department of Endocrinology/Diabetes Center, VU University Medical Center, Amsterdam, The Netherlands. m.diamant@vumc.nl
Nieuwland
Rienk
R
Pablo
Renée F
RF
Sturk
Augueste
A
Smit
Jan W A
JW
Radder
Jasper K
JK
D000328:Adult; D000368:Aged; D000954:Antigens, Surface / Q000032:analysis / Q000096:biosynthesis; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism; D015992:Body Mass Index; D021961:Cell Membrane Structures / Q000737:chemistry / Q000378:metabolism*; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005260:Female; D006098:Granulocytes / Q000276:immunology; D006801:Humans; D046911:Macromolecular Substances; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis*; D008875:Middle Aged; D012016:Reference Values; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism; D013917:Thrombin / Q000096:biosynthesis; D013925:Thromboplastin / Q000032:analysis / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000378:metabolism
D000954:Antigens, Surface; D015415:Biomarkers; D008076:Cholesterol, HDL; D046911:Macromolecular Substances; D014409:Tumor Necrosis Factor-alpha; D013925:Thromboplastin; D013917:Thrombin