Reduced platelet response to aspirin in patients with coronary artery disease and type 2 diabetes mellitus

Introduction

Diabetes mellitus is complicated by accelerated atherosclerosis, resulting in an increased risk of coronary artery disease (CAD) and thrombosis. Despite the proven benefits of aspirin, previous studies indicate a reduced cardiovascular protection from aspirin in diabetic patients. We aimed to investigate whether diabetes mellitus influenced the platelet response to aspirin in patients with CAD.

Materials and Methods

Platelet aggregation and activation were evaluated during aspirin treatment in 85 diabetic and 92 non-diabetic patients with CAD. Adherence to aspirin was carefully controlled. All patients had CAD verified by coronary angiography and were taking 75 mg non-enteric coated aspirin daily.

Results

Diabetic patients showed significantly higher levels of platelet aggregation compared to non-diabetic patients evaluated by VerifyNow^® Aspirin (p = 0.03) and Multiplate^® aggregometry using arachidonic acid (AA) 0.5 mM (p = 0.005) and 1.0 mM (p = 0.009). In addition, platelet activation determined by soluble P-selectin was significantly higher in diabetics compared to non-diabetics (p = 0.005). The higher AA-induced aggregation was associated with higher levels of HbA_1c. Compliance was confirmed by low levels of serum thromboxane B₂ (below 7.2 ng/mL). Diabetics had significantly higher levels of serum thromboxane B₂ (p < 0.0001).

Conclusions

Diabetic patients with CAD had significantly higher levels of both platelet aggregation and activation compared to non-diabetic patients with CAD despite treatment with the same dosage of aspirin. These findings may partly explain the reduced cardiovascular protection from aspirin in diabetic patients.     

Impaired glucose metabolism and type 2 diabetes are associated with hypercoagulability: potential role of central adiposity and low-grade inflammation--the Hoorn Study

Introduction

Type 2 diabetes (DM2) is associated with greater risk for cardiovascular disease (CVD), which may, at least partially, be explained by prothrombotic alterations. We therefore investigated; first, the extent to which individuals with impaired glucose metabolism (IGM) and/or DM2 had greater levels of thrombin generation than those with normal glucose metabolism (NGM); and second, whether any differences were independent of other cardiovascular risk factors, such as smoking, hypertension, dyslipidaemia, (micro)albuminuria, glycemic control and (central) adiposity, and/or were potentially ‘mediated’ by low-grade inflammation (high-sensitivity C-reactive protein (hsCRP)).

Materials and methods

We studied 744 individuals from the Hoorn Study (275 NGM, 176 IGM and 293 DM2, mean age 68.6 ± 7.1 years). Thrombin generation in platelet-poor plasma was measured using the Calibrated Automated Thrombogram and three parameters were derived: lag time, peak height and endogenous thrombin potential (ETP). Data were analyzed with multiple linear regression analyses.

Results

After adjustment for age, sex, prior CVD and smoking status, individuals with IGM or DM2 had a longer lag time [ß = 0.14 min (95% CI: 0.02; 0.26)], higher peak height [ß = 7.29 nM (− 1.33; 15.91)] and ETP [ß = 35.65nM*min (0.97; 70.34)] than those with NGM. These differences were attenuated to ß = 0.06 min (− 0.07; 0.19), 3.82 nM (− 5.46; 13.10) and 16.34 nM*min (− 20.92; 53.59), respectively, when further adjusted for waist circumference and hsCRP.

Conclusion

Individuals with IGM or DM2 had up to 4% higher thrombin generation compared with NGM, which may be explained, to a great extent, by the greater levels of central adiposity and related low-grade inflammation characterizing these individuals.     

Association between nighttime sleep duration,midday naps,and glycemic levels in Japanese patients with type 2 diabetes

ObjectivesTo clarify the relationship between nighttime sleep duration, midday naps, and glycemic control in Japanese patients diagnosed with type 2 diabetes (n = 355) or impaired glucose tolerance (n = 43).MethodsA total of 398 patients completed a self-administered questionnaire on sleep duration/quality and were divided into five groups according to their self-reported nighttime sleep duration: <5 h, 5–6 h, 6–7 h, 7–8 h, and >8 h. Each group was further divided into two subgroups each according to the presence or absence of midday naps. Poor glycemic control was defined as HbA1c ≥ 7.0%.ResultsShort nighttime sleep (<5 h), poor sleep induction, daytime sleepiness, and low sleep satisfaction were associated with high HbA1c levels. HbA1c was higher in the short nighttime sleep/no nap group than in non-nappers with different nighttime sleep duration, whereas the short nighttime sleep/nap group showed similar HbA1c levels to the other nap subgroups. In multivariate logistic regression models, after adjusting for a number of potential confounders, short (<5 h) nighttime sleep without nap was significantly associated with poor glycemic control compared with 6–7 h nighttime sleep without nap (OR [95% CI]: 7.14 [2.20–23.20]). However, taking naps reduced this risk for poor glycemic control in short sleepers. Other risk factors for poor glycemic control were low sleep satisfaction (1.73 [1.10–2.70]) and poor sleep induction (1.69 [1.14–2.50]).ConclusionsPoor sleep quality and quantity could aggravate glycemic control in type 2 diabetes. Midday naps could mitigate the deleterious effects of short nighttime sleep on glycemic control.Clinical trials registrationUMIN 000017887.