High-risk type-2 diabetes mellitus patients, without prior ischemic events, have normal blood platelet functionality profiles: a cross-sectional study

Abstract

BackgroundPatients with type 2 diabetes mellitus (DM) display a predisposition for vascular disease. Platelets taken from vasculopathic diabetic patients, show enhanced stimuli-induced activation and aggregation responses. Aspirin remains the cornerstone antiplatelet agent for secondary prevention of vascular complications among diabetic patients, yet evidence of its efficacy and safety in primary prevention are conflicting. Our aim was to assess whether high risk diabetic patients, without previous ischemic events, have abnormal platelet functionality profiles.MethodsThe study included 82 diabetic patients and 86 matched non-diabetic patients without prior ischemic events nor treatment with anti-platelet medications. Blood samples were analyzed for platelet markers of activation, turnover and leukocyte-platelet interactions.ResultsOur final analysis included 122 males (74 %), with a mean age of 61 years. Mean platelet volume (MPV) was similar between the diabetic patients and controls (9.2 fL for both). Following activation, PAC-1 binding and P-selectin expression were found comparable between the diabetic patients and controls (83 % versus 81 % and 76 % versus 74 %, respectively). Leukocyte-platelet aggregates (LPAs) were similar between the diabetic patients and controls (18 % versus 17 %, respectively). Neutrophil-platelet aggregates (NPAs) and monocyte-platelet aggregates (MPAs) were also found similar in the diabetic patients and controls. Elevated fasting plasma glucose was associated with increased LPAs rates.ConclusionsHigh risk type-2 diabetes mellitus patients, without prior ischemic events, have normal blood platelet functionality profiles.

Platelet, monocyte and neutrophil activation and glucose tolerance in South African Mixed Ancestry individuals

“…In agreement with our findings, several studies however, have failed to show an association between elevated PMAs and markers of glucose control1939. Platelet leucocyte aggregates while increased in the prediabetic and known diabetic groups were lower in patients who had been newly diagnosed.…”

“…Platelet leucocyte aggregates while increased in the prediabetic and known diabetic groups were lower in patients who had been newly diagnosed. This phenomenon seems to support the theory that the activation of platelets is not linked to glucose metabolism but rather the progression of the disease and the onset of vascular complications1940. This theory remains controversial however, and a study by Patkό et al ., reported a direct association between elevated levels of PMAs and fasting plasma glucose levels.…”

“…This pattern could suggest that the persistently elevated levels of activation within the innate immune system eventually leads to immune exhaustion and dysfunction, a common finding in patients with newly diagnosed but untreated diabetes363738. Treatment with drugs such as metformin restore immune function, however as the disease progresses the activation of monocytes and neutrophils increases leading to the formation of platelet leucocyte aggregates (PLAs) which are associated with the development of cardiovascular complications and thrombotic plaques1819.…”

“…Importantly both PMA’s and PLA’s have been associated with vascular damage18. Although platelet activation has been described in patients with chronic inflammation, the presence of increased PMA’s in T2D remains controversial and recent research has shown that high risk T2D patients have normal functioning platelets with no increase in PMA’s or PLA’s19.…”

Platelets, diabetes and myocardial ischemia/reperfusion injury

“…Of note, elevated fasting plasma glucose is associated with increased leukocyte-platelet aggregate rates, but high risk T2DM patients, without prior ischemic events, may have normal blood platelet functionality profiles [41]. These observations can explain why aspirin has no benefit in primary prevention of well-controlled diabetes, but is in some way only effective in secondary prevention (i.e.…”