The changes of serum sKlotho and NGAL levels and their correlation in type 2 diabetes mellitus patients with different stages of urinary albumin.
To investigate the changes of serum anti-aging protein Klotho and neutrophil gelatinase-associated lipocalin (NGAL) levels and their correlation in type 2 diabetes mellitus (T2DM) patients at different stages of diabetic kidney disease (DKD) determined by urinary albuminuria.
462 cases with T2DM were divided into three groups: normoalbuminuric [N-UAlb; urinary albumin to creatinine ratio (UACR) < 30 mg/g, n=180], microalbuminuric [M-UAlb; UACR 30-300 mg/g, n = 158], macroalbuminuric [L-UAlb; UACR > 300 mg/g, n = 124]. The levels of serum soluble-Klotho (sKlotho), NGAL, 8-isoprostane prostaglandin F2α (8-iso-PGF2α), monocyte chemotactic protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1) were determined by enzyme-linked immunosorbent assay (ELISA) in all cases and 160 control subjects.
Compared with control, serum sKlotho levels were significantly decreased (P < 0.001), and serum NGAL levels increased significantly (P < 0.001) in T2DM patients. Furthermore, serum sKlotho and NGAL levels were significantly negatively correlated (P < 0.001). Serum sKlotho levels negatively correlated with UACR, TG, CHO, LDL, 8-Iso-PGF2α, MCP-1, TNF-α, TGF-β1 (P < 0.001), but positively correlated with LDL (P < 0.001). Serum NGAL levels positively correlated with UACR, 8-Iso-PGF2α, MCP-1, TNF-α, TGF-β1 (P < 0.001). In addition, serum NGAL levels and LDL were significantly positively correlated (P = 0.005), and HDL was significantly negatively correlated (P < 0.001).
Serum Klotho and NGAL levels may become new biomarkers of the early diagnosis of DKD in T2DM. Klotho may participate in the development of DKD pathological mechanism such as oxidative stress related to inflammation, renal fibrosis, lipid metabolic disorders, modulating the pathological process of diabetic kidney tissue. NGAL may play a part in these mechanisms.
Wu C
，Wang Q
，Lv C
，Qin N
，Lei S
，Yuan Q
，Wang G
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The changes in miR-130b levels in human serum and the correlation with the severity of diabetic nephropathy.
Circulating microRNA 130b has been closely associated with multiple diseases in humans such as cancer, obesity and diabetes mellitus. This study evaluates the correlation between serum miR-130b and the severity of diabetic nephropathy evaluated by measurement of albuminuria.
Three hundred twenty-seven patients with type 2 diabetes mellitus (T2DM) were divided into three groups: normoalbuminuria group [diabetes mellitus, urinary albumin to creatinine ratio (UACR) < 30 mg/g, n = 137], microalbuminuria group (DN1, UACR 30-300 mg/g, n = 122) and macroalbuminuria group (DN2, UACR > 300 mg/g, n = 68). The levels of serum miR-130b were validated by real-time polymerase chain reaction. Serum transforming growth factor β1 (TGF-β1), hypoxia inducible factor 1α (HIF-1α) and fibronectin were determined by enzyme-linked immunosorbent assay.
Compared with control, serum miR-130b levels were significantly decreased in T2DM patients and further decreased in the patients of diabetes mellitus, DN1 and DN2 groups (p < 0.001). Furthermore, age-adjusted and sex-adjusted regression analyses showed that decreased level of serum miR-130b, increased levels of glycated haemoglobin (HbA1c ), homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride (TG), low-density lipoprotein (LDL), serum creatinine, blood urea nitrogen (BUN), TGF-β1, HIF-1α and fibronectin were significantly correlated with UACR (p < 0.05). In addition, serum miR-130b levels were inversely correlated with HbA1c , HOMA-IR, TG, LDL, BUN, TGF-β1, HIF-1α and FN (p < 0.05).
Our findings suggest that serum miR-130b may be a new biomarker for the early diagnosis of DN in T2DM. Circulating miR-130b may possibly be involved in the pathological mechanism of DN, such as lipid metabolic disorders, oxidative stress, extracellular matrix deposition and renal fibrosis.
Lv C
，Zhou YH
，Wu C
，Shao Y
，Lu CL
，Wang QY
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Expression levels of serum vasohibin-1 and other biomarkers in type 2 diabetes mellitus patients with different urinary albumin to creatinine ratios.
To determine the serum levels of vasohibin (VASH)-1 and other biomarkers in type 2 diabetes mellitus (T2DM) patients with different urinary albumin to creatinine ratios (UACR), and correlate VASH-1 expression with the inflammation and fibrosis in diabetic kidney disease (DKD).
A total of 697 T2DM patients were stratified into four groups: N-UAlb (UACR <30 mg/g with normal blood pressure, n = 144), M-UAlb (UACR 30-300 mg/g with normal blood pressure, n = 143), L-UAlb (UACR >300 mg/g with normal blood pressure, n = 126), and L-UAlb+HP (UACR >300 mg/g with hypertension, n = 134). In addition, 150 healthy subjects were included as normal controls (NC). In addition to recording the age and duration of diabetes, the serum levels of VASH-1, silent information regulator factor 2-related enzyme 1 (sirtuin-1, SIRT1), hypoxia inducible factor 1α (HIF1α), vascular endothelial growth factor (VEGF), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), and the erythrocyte sedimentation rate (ESR) were measured. Clinical parameters related to UACR and VASH-1 were analyzed by one-way ANOVA, Pearson correlation and ridge regression analysis.
The UACR, VASH-1, glycosylated hemoglobin (HbA1c), ESR, CRP, VEGF, HIF1α, TNF-α and TGF-β1 levels in all patient groups were significantly higher, and SIRT1 levels were lower compared to the NC group. Pearson correlation analysis showed that UACR and VASH-1 levels were positively correlated with HbA1c, ESR, CRP, VEGF, HIF1α, TNF-α and TGF-β1, and negatively with SIRT1. Ridge regression analysis showed that every serological marker was an independent factor affecting UACR.
Serum VASH-1 may be associated with the expression of renal inflammation and fibrosis-related factors, and have a potential connection with DKD.
Ren H
，Shao Y
，Ma X
，Yang M
，Liu Y
，Wang Q
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