Abstract
Beta2-adrenergic receptor (β2AR) agonists can have protective effects targeting macrophage activation, but research on human subjects has not been done. This study was designed to assess the relationship between the use of β2AR agonists and diabetic vascular complications. Using data from the Korean National Health Insurance Service, adults first diagnosed with diabetes in 2004 (n = 249,222) were followed up until 31 December 2015. Propensity score matching was performed between case and control groups (n = 5179 in each), and multivariate analysis was conducted. The β2AR agonist group was divided into quartiles according to the duration of β2AR agonist use. During the follow-up, the incidence of vascular complications gradually decreased as the duration of β2AR agonist administration increased. Multivariate analysis revealed that the hazard ratio for all composite vascular complications was 0.80 (95% CI, 0.75–0.86, p < 0.001) in the longest quartile of β2AR agonist use as compared with the control group after adjusting for confounding variables. The association between the duration of β2AR agonist use and the risk of each vascular complication including cerebrovascular, peripheral vascular, peripheral neural, renal, and ophthalmic complications was consistent, and the risks were significantly lower in the longest users than the control group. Long-term use of β2AR agonists may exert a protective effect against diabetic vascular complications.
Highlights
Diabetes is associated with multiple vascular diseases that affect almost every arterial vascular bed [1]
We found the occurrence of vascular complications of diabetic patients significantly decreased with an increased duration of beta2-adrenergic receptor (β2AR) agonist administration, and eventually the risks were significantly lower than those in the non-β2AR agonist group for the longest users
We conducted this study to examine the association between β2AR agonists and the outcomes of diabetic macro- and microvascular complications, and to investigate whether β2AR agonists exert protective effects against these complications clinically, as observed in animal studies
Summary
Diabetes is associated with multiple vascular diseases that affect almost every arterial vascular bed [1]. Proatherogenic changes in diabetic patients include increases in vascular inflammation and derangements in the cellular components of the vasculature, most notably, endothelial cells and vascular smooth muscle cells [1]. Previous studies have reported an association between macrophage differentiation and diabetic retinopathy [4], nephropathy [5], and coronary vascular diseases [2]. Adults with diabetes have a two- to three-fold increased risk of a wide range of vascular diseases, including coronary heart disease and stroke [6]. The odds ratios for diabetic patients with chronic kidney disease (CKD) vary by region between 1.3 and 4.6 [7]
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