Postprandial platelet activation is related to postprandial plasma insulin rather than glucose in patients with type 2 diabetes

Abstract

Postprandial hyperglycemia is associated with platelet activation. We thus investigated if meal-induced platelet activation could be attenuated by meal insulin. A randomized, double-blind, cross-over study was performed to compare postprandial platelet activation after premeal injections of placebo or insulin aspart (0.1 and 0.2 units/kg) in 18 patients with type 2 diabetes mellitus (T2DM). Platelet activation was assessed by flow cytometry, without and with stimulation by the thromboxane analog U46619 or ADP. Measurements were before and after premeal blood glucose standardization (to 6-7 mmol/L by insulin infusion, if needed) and at 90 min after the meal. Premeal insulin reduced postprandial hyperglycemia by 2-3 mmol/L compared with placebo. Postmeal insulin levels were doubled with placebo and further elevated with insulin injections. The standardized meal enhanced U46619-induced platelet P-selectin expression by 23% after placebo; this response was more than doubled after premeal insulin. U46619-induced fibrinogen binding was unchanged after meal intake with placebo but was markedly enhanced (by ~50-60%) after premeal insulin. Postprandial platelet activation correlated positively to postprandial insulin levels and inversely to glucose levels. Premeal insulin infusion was also associated with platelet activation. Our results suggest that postprandial insulin rather than glucose accounts for postprandial platelet activation in T2DM patients.

Trial registration: ClinicalTrials.gov NCT00771693.

Figures

FIG. 1.

Concentrations for plasma (P) glucose (A), insulin (B), and C-peptide (C) are shown on the three experimental occasions. Measurements were performed before (B1) and after (B2) blood glucose standardization (by insulin infusion, if needed) to 6–7 mmol/L before the experimental treatment and meal intake. Measurements after the meal were as indicated, with the last measurement after 90 min (PP). Premeal treatments were placebo (solid lines) and insulin aspart at 0.1 units/kg (dashed lines) and at 0.2 units/kg (dotted lines). For statistics, see Table 2 and results. Mean values and SEM are shown from 18 patients.

FIG. 2.

Platelet P-selectin expression (A) and fibrinogen binding (B) expressed as the percentage of positive cells without (Rest) and with thromboxane A2 receptor stimulation by U46619 (0.3 µmol/L) on the three experimental occasions (i.e., with premeal injections of placebo or 0.1 or 0.2 units/kg insulin). Measurements were performed before (B1; □) and after (B2; ▨) glucose standardization, and 90 min after the meal (PP; ■). Mean values and SEM. *P < 0.05, **P < 0.01. The postprandial platelet activation responses to U46619 were significantly enhanced by meal insulin treatment in the ANOVA. Correlations are shown between postprandial glucose (C) and insulin responses (D) and platelet P-selectin responses to U46619 (PS-U) stimulation. The postprandial responses were calculated as PP-to-B2 ratios and are shown for all 18 patients on all occasions. The postprandial platelet activation correlated inversely with the postprandial glucose response and positively with the increase in plasma insulin 90 min after the meal. (A high-quality color representation of this figure is available in the online issue.)