Younger age, higher body mass index and lower adiponectin concentration predict higher serum thromboxane B2 level in aspirin-treated patients with type 2 diabetes: an observational study

Abstract

BackgroundEvidence from the literature suggests diminished acetylsalicylic acid (ASA) treatment efficacy in type 2 diabetes (DM2). High on-aspirin platelet reactivity (HAPR) in DM2 has been linked to poor glycemic and lipid control. However, there are no consistent data on the association between HAPR and insulin resistance or adipose tissue metabolic activity. The aim of this study was to assess the relationship between laboratory response to ASA and metabolic control, insulin resistance and adipokines in DM2.MethodsA total of 186 DM2 patients treated with oral antidiabetic drugs and receiving 75 mg ASA daily were included in the analysis. Response to ASA was assessed by measuring serum thromboxane B2 (TXB2) concentration and expressed as quartiles of TXB2 level. The achievement of treatment targets in terms of glycemic and lipid control, insulin resistance parameters (including Homeostatic Model Assessment-Insulin Resistance, HOMA-IR, index), and serum concentrations of high-molecular weight (HMW) adiponectin, leptin and resistin, were evaluated in all patients. Univariate and multivariate logistic regression analyses were performed to determine the predictive factors of serum TXB2 concentration above the upper quartile and above the median.ResultsSignificant trends in age, body mass index (BMI), HOMA-IR, HMW adiponectin concentration, C-reactive protein concentration and the frequency of achieving target triglyceride levels were observed across increasing quartiles of TXB2. In a multivariate analysis, only younger age and higher BMI were independent predictors of TXB2 concentration above the upper quartile, while younger age and lower HMW adiponectin concentration were predictors of TXB2 concentration above the median.ConclusionsThese results suggest that in DM2, the most important predictor of HAPR is younger age. Younger DM2 patients may therefore require total daily ASA doses higher than 75 mg, preferably as a twice-daily regimen, to achieve full therapeutic effect. Higher BMI and lower HMW adiponectin concentration were also associated with less potent ASA effect. This is the first study to demonstrate an association of lower adiponectin concentration with higher serum TXB2 level in patients treated with ASA.

Resistin is a prognostic factor for death in type 2 diabetes

“…More recently, adipose tissue has been discovered to be a source of a wide variety of cytokines, hormones, and growth factors, collectively termed adipokines . They exert multiple endocrine and paracrine actions, including influence on glucose and lipid metabolism, insulin responsiveness, inflammatory processes, and endothelial function, and their dysregulation in obesity was implicated in the development of T2D, as well as its complications …”

“…Adipokines are not a homogeneous group but differ in structure and origin. Some, such as leptin, are produced exclusively or mainly by white adipocytes, while others, such as resistin or tumour necrosis factor‐alpha (TNF‐α), are released predominantly from peripheral‐blood mononuclear cells and macrophages . They also vary distinctively with respect to their mode of action and mediated effects: some were proven to promote insulin resistance, inflammation, and endothelial dysfunction, while others act in an insulin sensitizing, anti‐inflammatory, and antiatherosclerotic fashion.…”

“…They also vary distinctively with respect to their mode of action and mediated effects: some were proven to promote insulin resistance, inflammation, and endothelial dysfunction, while others act in an insulin sensitizing, anti‐inflammatory, and antiatherosclerotic fashion. Finally, some adipokines, such as leptin, are relatively well‐characterized and studied, while others, including resistin, are still a subject of debate and controversies regarding their effect in humans …”

“…Some, such as leptin, are produced exclusively or mainly by white adipocytes, while others, such as resistin or tumour necrosis factor-alpha (TNF-α), are released predominantly from peripheralblood mononuclear cells and macrophages. [4][5][6] They also vary distinctively with respect to their mode of action and mediated effects: some were proven to promote insulin resistance, inflammation, and endothelial dysfunction, while others act in an insulin sensitizing, anti-inflammatory, and antiatherosclerotic fashion. Finally, some adipokines, such as leptin, are relatively well-characterized and studied, while others, including resistin, are still a subject of debate and controversies regarding their effect in humans.…”

The Prevalence and Clinical Relevance of ASA Nonresponse After Cardiac Surgery: A Prospective Bicentric Study

“…2 The influences by genetic predisposition and risk factors, such as diabetes, obesity, or a metabolic syndrome, are under discussion but have not yet been fully clarified. 3,4 Individuals with a reduced response to ASA treatment had an increased risk of cardiovascular or cerebrovascular events such as myocardial infarction or stroke. 2,5,6 A problem addressed by most meta-analyses was the heterogenous definition of ASA nonresponse in the included studies with different technical devices and laboratory analyses used for the detection of ASA nonresponse.…”