Abstract

Diabetic nephropathy (DN) is the leading cause of end stage renal disease (ESRD) in type 2 diabetes patients. Osteopontin (OPN) is a 44 kDa protein identified as a key regulatory molecule of metabolic and inflammatory disease including diabetes and DN. Recently, studies have shown OPN upregulation in DN enhances glomerular damage. The aim of the present study is to assess a possible association between OPN and risk factors of DN in patients with type 2 diabetes. This cross-sectional study was performed in 384 type 2 diabetes patients aged between 35-70 years with the duration of diabetes for more than 10 years. The patients were diagnosed according to American Diabetes Association criteria and categorized into 2 groups according to urinary albumin-to-creatinine ratio (ACR). Lipid profile, glucose, HbA1c, ACR was measured. Osteopontin was measured by a commercially available ELISA kit. HOMA-IR and eGFR was calculated in all the subjects. A total of 384 patients were evaluated as shown in table 1. There were 200 control T2D patients and 184 DN patients. OPN level were significantly increased in DN group (169.56 pg/ml). OPN level was significantly varied according to low eGFR and high ACR in DN group as shown in table 2. OPN level were significantly correlated positively with risk factors of DN such as FBS, HbA1c, CRP, HOMA-IR, and ACR as shown in table 3.Table 1Clinical characteristics and biochemical assessment of study subjectParametersType 2 diabetes subjects (n= 384)Age (years)55.6±5.9Diabetes Duration (years)17.9±5.4BMI (kg/m2)32.5±5.7SBP (mmHg)134.9±18.8DBP (mmHg)73.4±10.6FBS (mg/dL)208.4±86.9HbA1c (%)10.2±1.52Insulin (μIU/mL)16.7 (9.8-27.7)C-Peptide (ng/mL)0.53 (0.33-1.15)HOMA-IR2.9 (1.7-4.5)Cholesterol (mg/dL)181.4±44.8Triglyceride (mg/dL)171.8±78.6HDL Cholesterol (mg/dL)46.3±12.8LDL Cholesterol (mg/dL)133.2±43.7C -reactive protein (ng/mL)1994 .0(1148.5-3872.0)eGFR (ml/min/m2)74.0 (59.0-89.0)ACR (mg/g creatinine)25.5(7.0-88.0)Osteopontin (pg/mL)134.5 (72.7-302.5)Data are given as either the number of patients (n), mean±SD, Median (Interquartile range). Open table in a new tab Table 2Comparison of Osteopontin level in control T2D and DN subjectsParameterControl T2D (n=200)DN (n=184)P valueACR (mg/g creatinine)7.5 (4.4-15.0)91.6 (46.3-158.0)<0.001eGFR (ml/min/m2)80.0 (67.0-94.0)64.0 (52.0-79.5)<0.001Osteopontin (pg/mL)96.57 (31.19-260.39)169.56 (123.45-349.35)<0.001Data are given as either the number of patients (n), Median (Interquartile range). eGFR: estimated golmerular filtration rate; ACR: Albumin creatinine ratio. Open table in a new tab Table 3Correlation of Osteopontin with different risk factors of DN in total T2D subjectsParametersOsteopontin (pg/ml), (n=384)rhoP valueAge (years)0.0570.279BMI (kg/m2)0.0640.226SBP (mmHg)0.1000.057DBS (mmHg)0.0300.557C-reactive protein (ng/mL)0.1100.047FBS (mg/dL)0.1060.046HbA1c (%)0.1220.021HOMA-IR0.1550.011ACR (mg/g creatinine)0.3000.001 Open table in a new tab Data are given as either the number of patients (n), mean±SD, Median (Interquartile range). Data are given as either the number of patients (n), Median (Interquartile range). eGFR: estimated golmerular filtration rate; ACR: Albumin creatinine ratio. In type 2 DN patients, increased OPN is independently associated with increased hyperglycemia, inflammation, insulin resistance, and proteinuria.

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