Meal intake increases circulating procoagulant microparticles in patients with type 1 and type 2 diabetes mellitus

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.

<p>Circulating Tissue Factor-Positive Procoagulant Microparticles in Patients with Type 1 Diabetes</p>

“…26,[35][36][37] A recent study suggested that the TF + and PS + MPs were associated with meal intake, and lipid-lowering agents in T1DM patients. 38 In our study, the elevated counts of TF + MPs in patients with T1DM, mostly derived from platelet, lymphocytes and endothelial cells, suggested a hypercoagulable state of T1DM patients. 39 TF + PS + MP count was higher in patients with established microvascular complications without an obvious signal of its subgroup.…”

Dietary modulation of large extracellular vesicles: the good and the bad for human health

“…One study did not observe a variation of L-EV levels after a high fat meal while they used CD31-CD42b-CD62 markers to identify the endothelial L-EVs 55 . An acute increase of L-EV levels during the postprandial period was also observed in diabetic patients 58 , in individuals with cardiovascular risk 61 and in atherosclerotic patients 56 , all of them presenting already a higher fasting level of L-EVs when compared to healthy volunteers. It is noteworthy that the postprandial increase of L-EV levels had similar magnitude in individuals at CVD risk than in healthy volunteers 56 .…”

“…Several subtypes of circulating L-EVs increased in response to fat intake: the endothelial L-EVs identified as CD31 + -CD42b -(+50-160 %) 53,54,59 , annexin V + -CD31 + -CD42b -(+30%) 51 , CD144 + (+ 20 %) 60 and CD144 + -CD62b -(+ 100-130 %) 47,48 EVs, and the platelet-derived L-EVs characterized as annexin V + -CD31 + -CD42b + 51 and CD41 + -CD61 + 56 EVs. Studies from Tushuizen et al 62 , Sustar et al 46 and Spectre et al 58 also showed that all annexin V + L-EVs increased postprandially after a high fat meal. One study did not observe a variation of L-EV levels after a high fat meal while they used CD31-CD42b-CD62 markers to identify the endothelial L-EVs 55 .…”

“…The response of L-EVs to the acute intake of different test meals (providing high dose of glucose, of saturated fat or enriched in polyunsaturated fatty acids) has been investigated during the postprandial period (Table 2) [46][47][48][51][52][53][54][55][56][57][58][59][60][61][62] . The studies reported on the level of L-EVs assessed mainly 2-3 hours after the intake of the test meal in comparison to fasting conditions or to the consumption of a control meal.…”

Primary prevention of cardiovascular diseases in diabetes mellitus: 2020 strategy

“…Известно, что активированные тромбоциты способствуют развитию атеросклероза и его тромботических осложнений [22]. Различные механизмы могут способствовать активации тромбоцитов при СД: гипергликемии после приема пищи, гиперинсулинемии, воспалению, сопутствующим заболеваниям, таким как ожирение, а также усилению перекисного окисления липидов, приводящему к неферментативному образованию F2-изопростанов, которые обладают способностью действовать как агонисты рецептора TXA2 [22,[24][25][26]. Следует отметить, что описанные изменения тромбоцитов у пациентов с СД сохраняются и на фоне хорошего гликемического контроля [19,20].…”