The Investigation of Association between Fibroblast Growth Factor-21 and Related Disease: From Mitochondria to Diabetic Nephropathy

Autor: Shih-Li Su, 蘇矢立
Rok vydání: 2014
Druh dokumentu: 學位論文 ; thesis
Popis: 102
Background and purpose: Fibroblast growth factors play their roles in different diseases became noticed by many scholars gradually. In our previous studies found that fibroblast growth factor 21 can help clinicians to identify whether mitochondrial induced ataxia or not. At that same time, the high concentrations of fibroblast growth factor 21 in mitochondrial ataxia are associated with hyperglycemia. Fibroblast growth factor 21 (FGF21) is a novel peptide which participate the regulation of biological energy such as glucose and lipid metabolism. It will over-express in animal chronic inflammatory reaction experiments and doubling the concentration in the hypertensive population. FGF21 seems a suitable biomarker in clinical screening and tracking. Estimated glomerular filtration rate (eGFR) and measurable albuminuria has been widely used for screening and detection diabetic nephropathy in the early stage. Diabetes associated with nephropathies has become the major causes of adult dialysis in Taiwan and other developing countries. The risk factors of processing nephropathy include higher blood sugar, hypertension, older aging, diabetes duration, smoking, high lipid profiles and male gender. Therefore, clinical physics need to monitor many indicators for comprehensive observation. The aim of this study is try to find the association among the estimated glomerular filtration rate, albuminuria and FGF21,and for the more, to illustrate the role of FGF21 in the diabetes nephropathy. Materials and Methods: Two hundred and two diabetic subjects without clinical cardiovascular history and symptoms were enrolled into this study. All participants do not have acute hyperglycemic complications such as hyperosmolar syndrome, ketoacidosis and hypoglycemia in recent 6 months. Subjects with cancer, autoimmune disease, pregnancy, smoking and alcoholism were excluded. All are included after the signing the inform consent which is proved by the committee of institutional review board in Changhua Christian Hospital. They will be measured about personal basic height, weight, waist circumference, hip circumference and blood pressure. Blood sampling should be performed after 8 to 10 hours overnight fasting, for the check of kidney, liver function, lipid profiles, glucose, insulin, hemoglobin A1c, e-selectin, intercellular adhesion molecule (ICAM), vascular cell adhesion molecule (VCAM), vascular endothelial growth factor (VEGF), matrix metalloproteinase-9 (MMP-9) and FGF21. The morning awaking first voiding urine was also collected about 10 ml. According to the urinary albumin to creatinine ratio (A/C ratio), subjects were divided into three groups, normal, microalbuminuria and macroalbuminuria. An ANOVA test was done to find the differences between the three groups. Chronic kidney disease (CKD) was defined using the cut point of eGFR 60 ml /min/1.73 m2. . Despite the presence of albuminuria, we subdivided CKD into four groups and used ANOVA to detect the variances among the groups. Perform Pearson correlation and bivariate linear regression were used to confirm the correlation between the impacts. p-value less than 0.05 are defined as statistical significance standard. Results: The concentration of VCAM and FGF21 are increasing gradually in various normal, microalbuminuria and macroalbuminuria stages. FGF21 and A/C ratio showed a positive correlation and the correlation coefficient was 0.144 (p = 0.03). The correlation between the VCAM and A/C ratio has also been positively and the correlation coefficient is 0.366 (p
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