| Background:Macrovascular complications are the most important cause of death and disability to the type2diabetes mellitus (T2DM) patients, which have been existent in patients with impaired glucose regulation (IGR). However, its mechanism has not been fully defined, and chronic low-grade inflammation and disordered endocrine of adipocyte may be closely involved in the pathogenesis of T2DM and atherosclerosis. Several studies showed that protein growth arrest-specific6(Gas6) was associated with atherosclerosis, inflammation and adipocyte differentiation. Gas6is one member of the family of plasma vitamin K-dependent proteins, and it interacts with the family of Axl receptor tyrosine kinase. Recently, studies revealed that the Gas6/TAM system was involved in the pathogenesis of new onset of T2DM and diabetic renal, but the reports about Gas6in the occurrence and development of T2DM and macrovascular complication were rare. We have addressed this issue by investigating the levels of plasma Gas6and the relationships between plasma Gas6and high sensitivity C-reactive protein (hs-CRP), visfatin, the pulse wave velocity (PWV) and the ankle brachial index(ABI) in patients with different glucose tolerance, and provide a new idea for the intervention treatment of T2DM and macrovascular complication.Objective:To study the levels of plasma Gas6and the relationships between plasma Gas6 and hs-CRP, visfatin, PWV, and ABI in patients with different glucose tolerance.Methods:71subjects with T2DM,24with IGR and25with normal glucose tolerance (NGT) were recruited in our study. According to the results of double-lower extremity arterial color Doppler flow imaging, diabetes mellitus patients were divided into T2DM group and T2DM with lower extremity artery diseases (T2DM-LEAD) group. Plasma Gas6and visfatin level were assayed by enzyme-linked immunosorbent assay, and PWV and ABI were tested by the non-invasive vascular screening device in the four groups. Other results of all patients included clinical and biochemical parameters and hs-CRP were collectded.Results:(1)Plasma Gas6level in T2DM-LEAD group was lower than that in T2DM group (p<0.05), and it was significantly reduced in T2DM group compared with NGT group (p<0.01). The level of plasma Gas6in IGR group was lower than that in T2DM group and higher than that in NGT group, but the differences with the two groups were not significant.(2) In T2DM-LEAD group and T2DM group, Hs-CRP, visfatin and PWV were significantly higher than that in NGT group (P<0.05or P<0.01), and ABI was lower than that in NGT group (P<0.01). Compared with that in subjects of T2DM, hs-CRP, visfatin and PWV were increased and ABI was reduced in patients with T2DM-LEAD (P<0.05or P<0.01). PWV was higher in IGR group than that in NGT group (P<0.01).(3) Fasting plasma glucose (FPG)、2h plasma glucose after glucose loading (2hPG) and HbA1c were higher in T2DM-LEAD and T2DM groups than that in IGR and NGT groups (P<0.05or P<0.01). The duration of diabetes was longest in T2DM-LEAD group (P<0.01).(4)Pearson’s correlation analysis showed that plasma Gas6level kept negative with age, duration of diabetes, FPG,2hPG, HbA1c, waist to hip ratio, visfatin, hs-CRP and PWV (P<0.01or p<0.05), and positive with ABI(P<0.01).(5)In multiple stepwise regression analysis, waist to hip ratio, HbA1c and hs-CRP were independently related with plasma Gas6level.Conclusions: The plasma Gas6level is significantly reduced in patients with T2DM and T2DM-LEAD, and lower in patients with IGR.The change of Gas6level is associated with inflammation, peripheral vessels atherosclerosis and visceral fat, which may play a role in the occurrence and development of T2DM and macrovascular complications. Gas6and its receptors stand for new therapeutic targets, and provide a new idea for the intervention treatment of T2DM and macrovascular complications. |
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