Search

Introduction : Osteoprotegerin (OPG) inhibits vascular calcification which is central to pathogenesis of arterial stiffness. However, it promotes inflammation by upregulating expression of vascular cell adhesion molecule-1(VCAM-1), thereby contributing to arterial stiffness. We investigated longitudinal association between OPG and arterial stiffness in type 2 diabetes (T2D), causality of the association and mediation by VCAM-1. Methods : This was a prospective cohort study of T2D patients (N = 1877, mean age 57.0 ± 10.8) with 10 years' follow-up. Baseline plasma OPG was measured using immunoassay. Pulse wave velocity (PWV) was assessed using applanation tonometry. We examined association between OPG and follow-up PWV using linear mixed model. One-sample Mendelian Randomization (MR) was conducted with rs1385492 as OPG-associated single nucleotide polymorphism (SNP). Results : Baseline natural log (Ln)-transformed OPG was positively associated with baseline and follow-up PWV with adjusted coefficients 0.43 (95%CI 0.05, 0.80; p =.026) and 0.51 (95%CI 0.06 to 0.97; p =.028) respectively. Genetically-predicted higher levels of plasma OPG was associated with higher last follow-up PWV with coefficient 10.81 (95%CI 2.97, 18.65; p =.007) per unit increase in LnOPG. Higher VCAM-1 accounted for 10.2% of association between LnOPG and follow-up PWV. Discussion : Baseline plasma OPG was associated with higher follow-up PWV in patients with T2D, with genetic evidence from MR. This association may be mediated, at least in part, by VCAM-1. [ABSTRACT FROM AUTHOR]

Context Leucine-rich α-2-glycoprotein 1 (LRG1) has been implicated in the pathogenesis of diabetic complications, but its association with cognitive function remains unclear. Objective Our primary objective is to investigate the longitudinal association between LRG1 and cognitive function in patients with type 2 diabetes mellitus (T2DM). Secondarily, we determine the causal relationship using Mendelian randomization (MR) and the role of arterial stiffness as a potential mediator. Methods T2DM patients (n = 1039; age = 64.1 ± 6.4 years) were followed-up for 5.3 ± 1.2 years. Plasma LRG1 was measured at baseline using enzyme-linked immunosorbent assay. Baseline and follow-up cognitive function was assessed using Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). One-sample MR was performed with rs4806985 as plasma LRG1-associated single-nucleotide polymorphism. Mediation analysis was performed to examine if pulse wave velocity (PWV), an arterial stiffness index, mediated the association between plasma LRG1 and follow-up cognitive function. Results Elevated baseline natural log (Ln)-transformed LRG1 was inversely associated with baseline and follow-up RBANS total score with adjusted coefficients −1.38 (95% CI −2.55 to −.21; P =.021) and −1.38 (95% CI −2.70 to −.07; P =.039), respectively. Genetically predicted higher levels of plasma LRG1 was associated with lower follow-up RBANS total score with coefficient −7.44 (95% CI −14.14 to −.74; P =.030) per unit increase in LnLRG1. Higher PWV accounted for 27.7% of the association between LnLRG1 and follow-up RBANS total score. Conclusion Baseline plasma LRG1 was associated with lower cognitive function at follow-up in patients with T2DM, mediated by PWV. MR analysis provided evidence of an association between genetically influenced plasma LRG1 and lower cognitive function at follow-up. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

As the COVID-19 pandemic worsens, early case detection is vital to limiting community spread. We describe our experiences with four COVID-19 cases at the polyclinics in January and February 2020. This retrospective case series highlights the challenges primary care clinicians face in the early identification of suspect cases based on clinical criteria only. To improve case detection, clinicians can sharpen their clinical acumen by keeping abreast with the latest COVID-19 developments and by maintaining a high state of vigilance. [ABSTRACT FROM AUTHOR]

As the COVID-19 pandemic worsens, early case detection is vital to limiting community spread. We describe our experiences with four COVID-19 cases at the polyclinics in January and February 2020. This retrospective case series highlights the challenges primary care clinicians face in the early identification of suspect cases based on clinical criteria only. To improve case detection, clinicians can sharpen their clinical acumen by keeping abreast with the latest COVID-19 developments and by maintaining a high state of vigilance., (Copyright: © Singapore Medical Association.)