sotrastaurin and Diabetes-Mellitus--Type-2

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.. 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.. Serum MPO-DNA complex levels were 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.. 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.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Diabetes Mellitus, Type 2; Diabetic Angiopathies; DNA; Dose-Response Relationship, Drug; Extracellular Traps; Glucose; Humans; Hypoglycemic Agents; Middle Aged; Neutrophils; Peroxidase; Polymers; Pyrazines; Pyrroles; Quinazolines; Risk Factors; Spiro Compounds; Time Factors