Relationship among the leptin-to-adiponectin ratio, systemic inflammation, and anisocytosis in well-controlled type 2 diabetic patients with atherosclerotic cardiovascular disease

Abstract

BACKGROUND Previous studies have shown that red blood cell distribution width (RDW) is an independent predictor of poor prognosis in type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). The mechanisms underlying increased anisocytosis in patients with T2D and confirmed ASCVD remain poorly understood. AIMS We sought to evaluate the relationship among the leptin-to-adiponectin ratio, systemic low-grade inflammation, and RDW in optimally treated patients with T2D and established ASCVD. METHODS A total of 68 patients, aged 47 to 85 years (mean [SD], 65.3 [6.8] years) and including 21 women (30.9%), were enrolled and grouped according to median RDW into those with RDW <13.5% (n = 33) and those with RDW ≥13.5% (n = 35). RESULTS Patients with RDW ≥13.5% had a significantly higher median (interquartile range [IQR]) serum leptin-to-adiponectin ratio (1.7 [0.49-2.3] ng/µg vs 0.66 [0.31-1.25] ng/µg; P = 0.04) and median (IQR) tumor necrosis factor α levels (1.58 [1.42-1.97] pg/ml vs 1.39 [1.18-1.57] pg/ml; P = 0.02). There were no significant differences in the concentrations of other inflammatory markers. The leptin-to-adiponectin ratio (r = 0.25; P = 0.04) and levels of tumor necrosis factor α (r = 0.32; P = 0.01) and soluble intercellular adhesion molecule 1 (r = 0.31; P = 0.01) were positively correlated with RDW, which was confirmed by univariate linear regression analysis. A multivariable regression model, which included demographic, clinical, and laboratory data, showed that white blood cell count (β = 0.25; 95% CI, 0.05-0.45; P = 0.01), soluble intercellular adhesion molecule 1 levels (β = 0.21; 95% CI, 0.02-0.41; P = 0.03), and mean corpuscular hemoglobin concentration (MCHC), (β =-0.48; 95% CI, 0.67 to-0.28; P <0.001) were independent predictors of RDW in our patients. CONCLUSIONS In well-controlled patients with T2D and ASCVD, the RDW values are associated with leptin-to-adiponectin imbalance and selected inflammatory markers.

The relationship between anisocytosis, quantitative and qualitative characteristics of coronary atherosclerosis, and major adverse cardiac events in patients with coronary artery disease: Rationale and study design

“…The increasing number of publications confirmed the prognostic value of RDW in patients with CAD; however, the substrate pathophysiology of this relationship is unknown. Some authors suggest that the presence of anisocytosis may reflect chronic subclinical inflammation, inflammatory biomarkers, oxidative stress, and abnormal erythropoiesis [9,10]. We showed, however, that this relationship does not depend on the level of hemoglobin [1].…”

Diabetes mellitus as a risk factor for aortic stenosis: from new mechanisms to clinical implications

“…The pathophysiology of diabetic vascular disease is complex. An impact of DM on vascular complications is linked with hyperglycemia-induced leptin-to-adiponectin imbalance inflammation leading to local hypoxia, vascular dysfunction, and hemodynamic changes, favoring a prothrombotic state [43,44]. The impact of high blood glucose levels on vasculature is mediated by the high sensitivity of endothelial cells to persistent hyperglycemia, which leads to reactive oxygen species overproduction [45].…”

The cardiometabolic predictive value of anthropometric parameters, vascular ultrasound indexes and fat depots among patients with high cardiovascular risk: an 8-year prospective cohort study

“…As has been shown repeatedly, adipose tissue is a metabolically active structure that, apart from adipocytes, consists of numerous cells representing its stromal fraction and various classes of inflammatory cells [24]. Through autocrine, paracrine, and endocrine interactions, the adipose tissue contributes to the induction of proinflammatory status and IR in obese patients [25][26][27]. Perivascular adipose tissue plays a vital role in modifying endothelial function and vascular activity, especially in patients with CCS [28].…”