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Meal intake increases circulating procoagulant microparticles in patients with type 1 and type 2 diabetes mellitus |
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| Authors: | Galia Spectre Fariborz Mobarrez Ragnhild Stålesen Claes-Göran Östenson David Varon Håkan Wallen |
| Affiliation: | 1. Department of Medicine Solna, Clinical Pharmacology Unit, Karolinska Institutet and Karolinska University Hospital/Solna, Stockholm, Sweden;2. Hematology Institute, Thrombosis and Heamostasis Unit, Rabin Medical Center, Beilinson Hospital, Petach Tikva, Israel;3. The Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv, Israel;4. Department of Clinical Sciences, Danderyds Hospital, Division of Cardiovascular Medicine, Karolinska Institutet, Stockholm, Sweden;5. Karolinska Institutet, Department of Medicine Solna, Unit of Rheumatology, Karolinska University Hospital, Stockholm, Sweden;6. Department of Molecular Medicine and Surgery, Endocrinology and Diabetology Unit, Karolinska Institutet, Karolinska University Hospital/Solna, Stockholm,Sweden;7. Department of Hematology, Coagulation Unit, Hadassah –Hebrew University Medical Center, Jerusalem, Israel |
| Abstract: | Diabetes mellitus (DM) is associated with prothrombotic alterations, and postprandial hyperglycemia is an independent risk factor for cardiovascular complications. We therefore investigated whether a standardized mixed meal alters circulating microparticles (MPs) and their procoagulant activity in DM patients. Patients with DM type 1 (T1DM, n = 11) and type 2 (T2DM; n = 9) were studied before and 90 min after a standardized meal (without premeal insulin). MPs in plasma derived from platelets (PMPs), endothelial cells (EMPs), or monocytes (MMPs) were measured by flow cytometry. MP-induced thrombin generation in plasma was assessed by a calibrated automated thrombogram. In the fasting state, MPs did not differ significantly between T1DM and T2DM. Meal intake increased the following microparticles: PMPs expressing phosphatidylserine (by 55%, on average), P-selectin (by 86%), and tissue factor (TF; by 112%); EMPs expressing E-selectin (by 96%) and MMPs expressing TF (by 164%), with no significant group differences between T1DM and T2DM. There were no increments in EMPs expressing phosphatidylserine or TF. Meal intake increased MP-induced thrombin generation similarly in T1DM and T2DM with increased endogenous thrombin potential (p = 0.02) and peak thrombin (p = 0.03) and shortened time to peak (p = 0.02). Phosphatidylserine inhibition by lactadherin completely abolished MP-induced thrombin generation, while an anti-TF antibody had no effect. In conclusion, meal intake increased several types of circulating MPs in patients with diabetes mellitus. These MPs have a procoagulant potential, which is related to phosphatidylserine expression and negatively charged MP surfaces rather than to TF. |
| Keywords: | Diabetes mellitus microparticles postprandial thrombin generation |