Risk stratification for thrombosis in type 2 diabetic patients

UoM administered thesis: Phd

Abstract

The leading cause of mortality in type 2 diabetes mellitus patients is
cardiovascular disease, with patients exhibiting platelet hyperreactivity and
prothrombotic propensity. The mechanisms that underpin these effects however
are unclear. The aim of this study was to determine which of the biochemical
features associated with type 2 diabetes are responsible for increased platelet
reactivity.
Whole blood from fasted healthy participants supplemented with increasing
concentrations of glucose, exhibited a significant elevation in mean platelet
volume (MPV) and basal αIIbβ3 receptor activation. Platelet aggregation in
response to ADP and collagen was not increased by acute hyperglycaemia in
platelet rich plasma or whole blood, and there was no significant increase in α–
granule secretion or αIIbβ3 activation following ADP stimulation. Furthermore, in
type 2 diabetic patients, HbA1c and fasting blood glucose correlated with MPV,
but not platelet activation or aggregation. This suggests that hyperglycaemia
elevates MPV and increases αIIbβ3 activation in circulating platelets, but does not
increase platelet reactivity as previously reported.
The key finding from this study was the strong positive correlation for low-density
lipoprotein cholesterol (LDL-C) and both ADP and collagen-activated platelet
aggregation, and this was independent of diabetes. More importantly, patients
with LDL-C over 2.0 mmol/L had significantly increased platelet aggregation.
Furthermore, LDL-C was associated with elevated platelet production, and
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participants with LDL-C over 3.0 mmol/L had significantly increased immature
platelet fraction.
This study demonstrates that LDL-C may act as a biomarker to identify type 2
diabetes patients who would benefit from antiplatelet prophylaxis. Additionally,
lipid-lowering medication could indirectly provide antithrombotic benefit by
reducing LDL-C levels. Moreover, enhanced platelet production mediated by
elevated LDL-C is likely responsible for both enhanced platelet reactivity and
reduced antiplatelet efficacy in type 2 diabetic patients.

Details

Original languageEnglish
Awarding Institution
  • Manchester Metropolitan University (MMU)
Supervisors/Advisors
  • Sarah Jones (External person) (Supervisor)
Award date31 Jan 2019