Arina Miyoshi1, Mai Yamada2, Haruki Shida1, Daigo Nakazawa1, Yoshihiro Kusunoki1, Akinobu Nakamura1, Hideaki Miyoshi1, Utano Tomaru3, Tatsuya Atsumi1, Akihiro Ishizu4
1Division of Rheumatology, Endocrinology and Nephrology and
2Graduate School of Health Sciences and
3Department of Pathology, Hokkaido University Graduate School of Medicine, and
4Faculty of Health Sciences, Hokkaido University, Sapporo, Japan
Tóm tắt
<b><i>Objectives:</i></b> Although intensive therapy for type 2 diabetes (T2D) prevents microvascular complications, 10% of well-controlled T2D patients develop microangiopathy. Therefore, the identification of risk markers for microvascular complications in well-controlled T2D patients is important. Recent studies have demonstrated that high-dose glucose induces neutrophil extracellular trap (NET) formation, which can be a risk for microvascular disorders. Thus, we attempted to determine the correlation of circulating NET levels with clinical/laboratory parameters in well-controlled T2D patients and to reveal the mechanism of NET formation induced by high-dose glucose. <b><i>Methods:</i></b> Circulating NET levels represented by myeloperoxidase (MPO)-DNA complexes in the serum of 11 well-controlled T2D patients and 13 healthy volunteers were determined by enzyme-linked immunosorbent assay. The pathway involved in the NET formation induced by high-dose glucose was determined using specific inhibitors. <b><i>Results:</i></b> Serum MPO-DNA complex levels were<b> </b>significantly higher in some well-controlled T2D patients in correlation with the clinical/laboratory parameters which have been regarded as risk markers for microvascular complications. The aldose reductase inhibitor, ranirestat, could inhibit the NET formation induced by high-dose glucose. <b><i>Conclusions:</i></b> Elevated levels of circulating NETs can be a risk marker for microvascular complications in well-controlled T2D patients. The polyol pathway is involved in the NET formation induced by high-dose glucose.
