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Serum Level of Fibroblast Growth Factor 21 in Type 2 Diabetic Patients with and without Metabolic Syndrome



Azam Shafaei, Masoud Khoshnia and Abdoljalal Marjani
 
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ABSTRACT

Effect of FGF21 on metabolic syndrome patients is not exactly clear. In the present study, we assessed serum level of fibroblast growth factor 21 in type 2 diabetic patients with and without metabolic syndrome in Gorgan. The study groups consisted of 120 patients with type 2 diabetes and 60 healthy subjects. Diabetic patients divided into two groups. All subjects were matched according to age and sex. The mean waist circumference, systolic and diastolic blood pressure, triglyceride and fasting blood glucose levels and body mass index were significantly higher in the subjects with metabolic syndrome than control group, but the mean HDL-cholesterol was significantly lower (p = 0.0001). Mean serum level of FGF21 was higher in type 2 diabetic subjects with and without metabolic syndrome than that of control subject (p = 0.0001). There were significant negative correlation between FGF21 and BMI, diastolic blood pressure and HDL-cholesterol in subjects with metabolic syndrome (p<0.05). There were also significant negative correlation between FGF21 and cholesterol and HDL-cholesterol in control group (p<0.05). The findings of this study suggest that serum FGF21 are higher in patients with type 2 diabetes with and without metabolic syndrome than in age and sex matched control group. Our study shows that some of metabolic syndrome components (especially HDL-cholesterol) are associated with high serum FGF21 levels. Because of different effects of FGF21 in rodents, primates and in humans, it may require more investigating on metabolic effects of FGF21 in human’s samples.

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Azam Shafaei, Masoud Khoshnia and Abdoljalal Marjani, 2015. Serum Level of Fibroblast Growth Factor 21 in Type 2 Diabetic Patients with and without Metabolic Syndrome. Journal of Medical Sciences, 15: 80-86.

DOI: 10.3923/jms.2015.80.86

URL: https://scialert.net/abstract/?doi=jms.2015.80.86
 
Received: May 27, 2015; Accepted: July 16, 2015; Published: July 29, 2015



INTRODUCTION

The metabolic syndrome consisted of some metabolic abnormalities such as hypertension, dyslipidaemia, obesity, insulin resistance and high fasting plasma glucose (Miranda et al., 2005). It has been reported that genetic differences, diet, physical activity, age and sex affect the prevalence of metabolic syndrome and its components (Cameron et al., 2004). Many studies showed that metabolic syndrome changes in different ethnic and age groups and postmenopausal women (Marjani, 2005a, b, 2006a, b; Marjani et al., 2007a, b, c, 2008, 2010). The role of Fibroblast Growth Factor 21 (FGF21) was first reported in 2005. Glucose uptake was stimulated by FGF 21 in human and mouse adipocytes (Chen et al., 2011). The FGF 21 is encoded by chromosome 19. Production of this factor takes place in the liver, white adipose tissue, skeletal muscle and pancreas. Glucose and lipid metabolism regulation may depend on FGF21 (Iglesias et al., 2012). Some studies have shown that fasting and feeding may regulate FGF21 expression (Uebanso et al., 2011). This factor may be a risk factor for some diseases like insulin resistance, type 2 diabetes mellitus and metabolic syndrome (Mraz et al., 2009; Bobbert et al., 2013). Some studies have revealed that serum FGF21 influenced by high blood glucose, increased body mass index, uric acid level and low physical activity (Cuevas-Ramos et al., 2010). It has shown that FGF21 may effects endocrine pancreas function. Short-term treatment with FGF21 can reduce plasma insulin levels (Kharitonenkov et al., 2008). Some studies on rodents and primates have shown that FGF21 could have effect on carbohydrate and lipid metabolism (Badman et al., 2007; Inagaki et al., 2007; Lundasen et al., 2007). Studies on mice were indicated that FGF21 prevents hepatic glucose production, liver glycogen reduction and decrease glucagon level (Berglund et al., 2009). Several investigations on diabetic and obese rodents revealed that FGF21 reduces plasma triglyceride, free fatty acids and cholesterol levels (Kharitonenkov et al., 2005; Xu et al., 2009). Chronic therapy with FGF21 on diabetic rhesus monkeys showed that this factor causes a decrease in triglyceride and LDL-cholesterol levels and an increase in HDL-cholesterol level (Kharitonenkov et al., 2007). In studies on human have shown that lipolysis inhibition in adipocytes takes place by FGF21 (Arner et al., 2008), while other findings have indicated that high level of serum FGF21 associated with abdominal adiposity, insulin resistance, high level of triglyceride and type 2 diabetes (Jian et al., 2012; Chavez et al., 2009; Dushay et al., 2010; Galman et al., 2008; Li et al., 2012; Zhang et al., 2008). It is reported that FGF21 are associated with metabolic syndrome patients (Chen et al., 2008), type 2 diabetes (Li et al., 2010), impaired glucose tolerance (Chavez et al., 2009), nonalcoholic fatty liver disease (Dushay et al., 2010; Li et al., 2011; Yilmaz et al., 2010; An et al., 2012) and carotid artery disease (Yang et al., 2011; Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, 2001). Effect of FGF21 in human on metabolic syndrome patients is not exactly clear. In the present study, we assessed serum level of fibroblast growth factor 21 in type 2 diabetic patients with and without metabolic syndrome in Gorgan.

MATERIALS AND METHODS

The study groups consisted of 120 patients with type 2 diabetes and 60 healthy subjects. Diabetic patients divided into two groups. The control group had no hepatic, renal or any other diseases. All subjects were matched according to age and sex. All subjects gave informed consent to take part in the study. Blood samples were provided from all subjects after a 12 h fasting. Serum glucose, Total Cholesterol (TC) and High Density Lipoprotein Cholesterol (HDL-C), Low Density Lipoprotein Cholesterol (LDL-C), triglycerides (TG), were determined using commercial kits and spectrophotometer technique in the Metabolic Disorders Research Center, Gorgan Faculty of Medicine. Serum FGF21 was determined by ELISA kit. It provided from Bioassay Technology Laboratory (Shanghai Crystal Day Biotech Co., LTD, China). The metabolic syndrome diagnostic criteria were used as suggested by ATP III (Adult Treatment Panel III) (Altekin et al., 2005), including: (1) Waist circumference >102 cm in men and >88 cm in women, (2) Serum triglycerides level ≥150 mg dL–1, (3) Low HDL-cholesterol: < 40 mg dL–1 in men and <50 mg dL–1 in women, (4) Systolic Blood Pressure (SBP) ≥130 mmHg and/or Diastolic Blood Pressure (DBP) ≥85 mmHg or on treatment for hypertension and (5) Serum glucose level ≥110 mg dL–1 or on treatment for diabetes. Subjects with any 3 or more of the above mentioned criteria specified as a metabolic syndrome subject. A digital scale was used to determine weight in all subjects, while they were minimally clothed without shoes. Height was measured in standing position using tape meter while the shoulder was in a normal position. Body Mass Index (BMI) was determined as weight in kilograms divided by height in meters squared. Overweight and obese were specified as BMI = 25.0-29.9 and ≥30 kg m‾2, respectively (WHO., 1998). Waist circumferences were measured at the point halfway between the lower border of ribs and the iliac crest in a horizontal plane (Ryden, 2009). Systolic and diastolic blood pressure was measured by using a standard mercury manometer with study groups in sitting position, from their right hands. SPSS- 18 version software was used to calculate statistical analysis (as means and standard deviations). The association of serum FGF21 level and components of metabolic syndrome and other parameters was done by using Pearson’s correlation test. One way analysis of variance (ANOVA) followed by Post Hoc Tukey’s test was used to test the differences between groups. p-value lower than 0.05 was considered statistically significant.

RESULTS

Table 1 shows the clinical and biochemical data of type 2 diabetic subjects with metabolic syndrome and control group. The mean waist circumference, systolic and diastolic blood pressure, triglyceride and fasting blood glucose levels and BMI were significantly higher in the subjects with metabolic syndrome than control group, but the mean HDL-cholesterol was significantly lower (p = 0.0001). Mean serum level of FGF21 were higher in type 2 diabetic subjects with and without metabolic syndrome than that of control subject (p = 0.0001). Correlation between metabolic syndrome components and serum FGF21 in control group and subjects with and without metabolic syndrome are summarized in Table 2. There were significant negative correlation between FGF21 and BMI, diastolic blood pressure and HDL-cholesterol in subjects with metabolic syndrome (p<0.05). There were also significant negative correlation between FGF21 and cholesterol and HDL-cholesterol in control group (p<0.05).

Table 1:Clinical and biochemical data of type 2 diabetic subjects with and without metabolic syndrome and control group
Image for - Serum Level of Fibroblast Growth Factor 21 in Type 2 Diabetic Patients with and without Metabolic Syndrome
P1: Comparison between control group and diabetic subjects with metabolic syndrome, P2: Comparison control group and diabetic subjects, without metabolic syndrome and P3: Comparison of diabetic subjects with and without metabolic syndrome, BMI: Body mass index

Table 2:Fibroblast growth factor 21 correlated with metabolic syndrome components of control group, type 2 diabetic subjects with and without metabolic syndrome
Image for - Serum Level of Fibroblast Growth Factor 21 in Type 2 Diabetic Patients with and without Metabolic Syndrome

DISCUSSION

Fibroblast Growth Factors (FGFs), as new proteins, include FGF19, FGF21 and FGF23. Endocrine FGFs can bind weakly to heparin/heparin sulfate, which allows them to function as endocrine factors (Coskun et al., 2008). It is not clear that the elevations of FGF21 levels are related to FGF21 resistance or to the metabolic disorders. Many studies reported that FGF21 shows functions such as metabolic regulator or as a biomarker of metabolic diseases. The metabolic effects of FGF21 were first recognized in murine studies (Li et al., 2008). The FGF21 causes stimulation of insulin-independent glucose uptake by increasing GLUT-1 expression, reduce blood glucose and triglyceride levels in obese mice and reduce body weight (Kharitonenkov et al., 2005). Serum FGF21 shows metabolic effects in different animal models of obesity and diabetes mellitus. It has reported that expression and regulation of FGF21 in human seems to be different when compare to animal models. This may open an idea for discussions about the possible clinical roles of FGF21. In our study, no significant differences in age, BMI and systolic and diastolic blood pressures, cholesterol and HDL-cholesterol were seen between the patients without metabolic syndrome and control group. The mean Body Mass Index (BMI) was lower in the control group than the patient groups. The FGF21levels of the patients were significantly higher than those of the control group (p = 0.0001 for all). There was a significant negative correlation between serum FGF21 and BMI, diastolic blood pressure and HDL-cholesterol in the group of patients with metabolic syndrome (r = 0.266 p = 0.040, r = 0.284 p = 0.028 and r = 0.259 p = 0.046 r = 0.498, resp).

In the present study, we showed that serum FGF-21 levels in humans are increased in diabetic subjects and are negatively correlated with some components of metabolic syndrome. This is in agreement with the results of other findings (Chen et al., 2011; Zhang et al., 2008) that indicated increased plasma FGF-21 level in obesity and type 2 diabetes mellitus. Our study is also in agreement with previous findings in Asian populations, in which elevated plasma FGF-21 levels were observed in treated type 2 diabetic subjects (Li et al., 2008, 2009; Zhang et al., 2008; Chavez et al., 2009). Study of FGF-21 level in rodent models showed that FGF-21 increases GLUT4 expression in adipocytes. Findings of Arner et al. (2008) indicated that FGF-21 inhibits lipolysis in human adipocytes. They mentioned that this may help to cause the protein’s insulin-sensitizing effect in humans. Study in animal models of FGF-21 has been indicated that FGF-21 has glucose-lowering effects which are mediated by its actions on liver (Eto et al., 2010; Kharitonenkov et al., 2005). The different findings of many studies in humans and in animal models may express difference in the metabolic influences of FGF-21 in humans and animals studies. No significant correlation was found between serum FGF-21 levels and age, waist circumference, fasting glucose, triglyceride, cholesterol, LDL-cholesterol levels in subjects with metabolic syndrome. In our study, we did not also find any correlation between serum FGF-21 and serum fasting glucose levels in all groups, which is in accordance with the results of the Galman et al. (2008). This means that FGF21 may has no effect on glucose metabolism which is especially important in type 2 diabetic subjects. The serum FGF21 levels were significantly higher in diabetic subjects with metabolic syndrome and correlated negatively with HDL cholesterol (Zhang et al., 2008; Li et al., 2009), while some other studies showed that serum FGF21 level was associated with triglycerides (Eto et al., 2010; Stein et al., 2010). Study of Chen et al. (2008) showed a negative correlation between serum FGF21 levels and fasting plasma glucose levels. Our results are not in agreement with the findings of other studies (Eto et al., 2010; Stein et al., 2010; Chen et al., 2008). The elevation of FGF21 levels in type 2 diabetic patients may be associated with a compensatory response, FGF21 resistance (Chavez et al., 2009; Chen et al., 2011).Studies on animal models have indicated that FGF21 is expressed in the pancreas (Tacer et al., 2010) to protect the mass and function of pancreatic beta-cells (Wente et al., 2006). The increased serum FGF-21 level in diabetic patients may prevent the abnormal metabolic process by causing to improve lipid profile. (Titan et al., 2011). Studies in human subjects suggested that FGF-21 may be a metabolic regulator that plays an important role in metabolic process such as lipid and energy metabolism. Some studies showed increased FGF-21 levels in patients with obesity and T2DM (Zhang et al., 2008; Chen et al., 2008). The FGF-21 level was indicated to be associated with several symptoms of metabolic syndrome (Zhang et al., 2008). However, other studies revealed that FGF-21 was positively associated with metabolic disorders, including dyslipidemia, obesity, high plasma glucose level and insulin resistance (Dostalova et al., 2008; Mai et al., 2011; Chavez et al., 2009). The cause of these discrepancies is still unclear. There are different findings about FGF-21 in human and other mammals. The results of our study differed considerably from those obtained in mice, suggesting that the physiologic role of FGF-21 in humans may differ from that in animals. In this study, we found that FGF-21 level negatively correlated with HDL-C level, which was inconsistent with the beneficial metabolic function of FGF-21 in rodents (Coskun et al., 2008).

CONCLUSION

The findings of this study suggest that serum FGF21 are higher in patients with type 2 diabetes with and without metabolic syndrome than in age and sex matched control group. Our study shows that some of metabolic syndrome components (especially HDL-cholesterol) are associated with high serum FGF21 levels. Because of different effects of FGF21 in rodents, primates and in humans, it may require more investigating on metabolic effects of FGF21 in human's samples.

REFERENCES

  1. An, S.Y., M.S. Lee, S.A. Yi, E.S. Ha and S.J. Han et al., 2012. Serum fibroblast growth factor 21 was elevated in subjects with type 2 diabetes mellitus and was associated with the presence of carotid artery plaques. Diabetes Res. Clin. Pract., 96: 196-203.
    CrossRef  |  Direct Link  |  


  2. Altekin, E., C. Coker, A.R. Sisman, B. Onvural, F. Kuralay and O. Kirımli, 2005. The relationship between trace elements and cardiac markers in acute coronary syndromes. J. Trace Elements Med. Biol., 18: 235-242.
    CrossRef  |  Direct Link  |  


  3. Arner, P., A. Pettersson, P.J. Mitchell, J.D. Dunbar, A. Kharitonenkov and M. Ryden, 2008. FGF21 attenuates lipolysis in human adipocytes-a possible link to improved insulin sensitivity. FEBS Lett., 582: 1725-1730.
    CrossRef  |  Direct Link  |  


  4. Bobbert, T., F. Schwarz, A. Fischer-Rosinsky, A.F. Pfeiffer, M. Mohlig, K. Mai and J. Spranger, 2013. Fibroblast growth factor 21 predicts the metabolic syndrome and type 2 diabetes in Caucasians. Diabetes Care, 36: 145-149.
    CrossRef  |  PubMed  |  Direct Link  |  


  5. Badman, M.K., P. Pissios, A.R. Kennedy, G. Koukos, J.S. Flier and E. Maratos-Flier, 2007. Hepatic fibroblast growth factor 21 is regulated by PPARα and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab., 5: 426-437.
    CrossRef  |  Direct Link  |  


  6. Berglund, E.D., C.Y. Li, H.A. Bina, S.E. Lynes and M.D. Michael et al., 2009. Fibroblast growth factor 21 controls glycemia via regulation of hepatic glucose flux and insulin sensitivity. Endocrinology, 150: 4084-4093.
    CrossRef  |  Direct Link  |  


  7. Cameron, A.J., J.E. Shaw and P.Z. Zimmet, 2004. The metabolic syndrome: Prevalence in worldwide populations. Endocrinol. Metab. Clin. North Am., 33: 351-375.
    CrossRef  |  PubMed  |  Direct Link  |  


  8. Chen, C., B.M. Cheung, A.W. Tso, Y. Wang and L.S. Law et al., 2011. High plasma level of fibroblast growth factor 21 is an Independent predictor of type 2 diabetes: A 5.4-year population-based prospective study in Chinese subjects. Diabetes Care, 34: 2113-2115.
    PubMed  |  Direct Link  |  


  9. Cuevas-Ramos, D., P. Almeda-Valdes, F.J. Gomez-Perez, C.E. Meza-Arana and I. Cruz-Bautista et al., 2010. Daily physical activity, fasting glucose, uric acid, and body mass index are independent factors associated with serum fibroblast growth factor 21 levels. Eur. J. Endocrinol., 163: 469-477.
    PubMed  |  Direct Link  |  


  10. Chavez, A.O., M. Molina-Carrion, M.A. Abdul-Ghani, F. Folli, R.A. DeFronzo and D. Tripathy, 2009. Circulating fibroblast growth factor-21 is elevated in impaired glucose tolerance and type 2 diabetes and correlates with muscle and hepatic insulin resistance. Diabetes Care, 32: 1542-1546.
    PubMed  |  Direct Link  |  


  11. Chen, W.W., L. Li, G.Y. Yang, K. Li and X.Y. Qi et al., 2008. Circulating FGF-21 levels in normal subjects and in newly diagnose patients with type 2 diabetes mellitus. Exp. Clin. Endocrinol. Diabetes., 116: 65-68.
    CrossRef  |  PubMed  |  Direct Link  |  


  12. Coskun, T., H.A. Bina, M.A. Schneider, J.D. Dunbar and C.C. Hu et al., 2008. Fibroblast growth factor 21 corrects obesity in mice. Endocrinology, 149: 6018-6027.
    CrossRef  |  Direct Link  |  


  13. Dushay, J., P.C. Chui, G.S. Gopalakrishnan, M. Varela-Rey and M. Crawley et al., 2010. Increased fibroblast growth factor 21 in obesity and nonalcoholic fatty liver disease. Gastroenterology, 139: 456-463.
    CrossRef  |  Direct Link  |  


  14. Dostalova, I., P. Kavalkova, D. Haluzikova, Z. Lacinova, M. Mraz, H. Papezova and M. Haluzik, 2008. Plasma concentrations of fibroblast growth factors 19 and 21 in patients with anorexia nervosa. J. Clin. Endocrinol. Metab., 93: 3627-3632.
    CrossRef  |  Direct Link  |  


  15. Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults, 2001. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III). J. Am. Med. Assoc., 285: 2486-2497.
    CrossRef  |  PubMed  |  Direct Link  |  


  16. Eto, K., B. Tumenbayar, S.I. Nagashima, F. Tazoe and M. Miyamoto et al., 2010. Distinct association of serum FGF21 or adiponectin levels with clinical parameters in patients with type 2 diabetes. Diabetes Res. Clin. Pract., 89: 52-57.
    CrossRef  |  Direct Link  |  


  17. Tacer, K.F., A.L. Bookout, X. Ding, H. Kurosu and G.B. John et al., 2010. Research resource: Comprehensive expression atlas of the fibroblast growth factor system in adult mouse. Mol. Endocrinol., 24: 2050-2064.
    CrossRef  |  Direct Link  |  


  18. Galman, C., T. Lundasen, A. Kharitonenkov, H.A. Bin and M. Eriksson et al., 2008. The circulating metabolic regulator FGF21 is induced by prolonged fasting and PPARα activation in man. Cell Metab., 8: 169-174.
    CrossRef  |  Direct Link  |  


  19. Iglesias, P., R. Selgas, S. Romero and J.J. Diez, 2012. Biological role, clinical significance and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21. Eur. J. Endocrinol., 167: 301-309.
    PubMed  |  Direct Link  |  


  20. Inagaki, T., P. Dutchak, G. Zhao, X. Ding and L. Gautron et al., 2007. Endocrine regulation of the fasting response by PPARα-mediated induction of fibroblast growth factor 21. Cell Metab., 5: 415-425.
    CrossRef  |  Direct Link  |  


  21. Jian, W.X., W.H. Peng, J. Jin, X.R. Chen and W.J. Fang et al., 2012. Association between serum fibroblast growth factor 21 and diabetic nephropathy. Metabolism, 61: 853-859.
    CrossRef  |  Direct Link  |  


  22. Kharitonenkov, A., J.D. Dunbar, H.A. Bina, S. Bright and J.S. Moyers et al., 2008. FGF-21/FGF-21 receptor interaction and activation is determined by βKlotho. J. Cell. Physiol., 215: 1-7.
    CrossRef  |  Direct Link  |  


  23. Kharitonenkov, A., T.L. Shiyanova, A. Koester, A.M. Ford and R. Micanovic et al., 2005. FGF-21 as a novel metabolic regulator. J. Clin. Invest., 115: 1627-1635.
    CrossRef  |  Direct Link  |  


  24. Kharitonenkov, A., V.J. Wroblewski, A. Koester, Y.F. Chen and C.K. Clutinger et al., 2007. The metabolic state of diabetic monkeys is regulated by fibroblast growth factor-21. Endocrinology, 148: 774-781.
    CrossRef  |  Direct Link  |  


  25. Li, H., Z. Gao, J. Zhang, X. Ye, A. Xu, J. Ye and W. Jia, 2012. Sodium butyrate stimulates expression of fibroblast growth factor 21 in liver by inhibition of histone deacetylase 3. Diabetes, 61: 797-806.
    CrossRef  |  Direct Link  |  


  26. Li, H., Q. Fang, F. Gao, J. Fan and J. Zhou et al., 2010. Fibroblast growth factor 21 levels are increased in nonalcoholic fatty liver disease patients and are correlated with hepatic triglyceride. J. Hepatol., 53: 934-940.
    CrossRef  |  Direct Link  |  


  27. Li, X., X. Fan, F. Ren, Y. Zhang and C. Shen et al., 2011. Serum FGF21 levels are increased in newly diagnosed type 2 diabetes with nonalcoholic fatty liver disease and associated with hsCRP levels independently. Diabetes Res. Clin. Pract., 93: 10-16.
    CrossRef  |  Direct Link  |  


  28. Li, L., G. Yang, H. Ning, M. Yang, H. Liu and W. Chen, 2008. Plasma FGF-21 levels in type 2 diabetic patients with ketosis. Diabetes Res. Clin. Pract., 82: 209-213.
    CrossRef  |  Direct Link  |  


  29. Li, H., Y. Bao, A. Xu, X. Pan and J. Lu et al., 2009. Serum fibroblast growth factor 21 is associated with adverse lipid profiles and γ-glutamyltransferase but not insulin sensitivity in Chinese subjects. J. Clin. Endocrinol. Metab., 94: 2151-2156.
    CrossRef  |  Direct Link  |  


  30. Lundasen, T., M.C. Hunt, L.M. Nilsson, S. Sanyal, B. Angelin, S.E.H. Alexson and M. Rudling, 2007. PPARα is a key regulator of hepatic FGF21. Biochem. Biophys. Res. Commun., 360: 437-440.
    CrossRef  |  Direct Link  |  


  31. Miranda, P.J., R.A. DeFronzo, R.M. Califf and J.R. Guyton, 2005. Metabolic syndrome: Definition, pathophysiology and mechanisms. Am. Heart J., 149: 33-45.
    CrossRef  |  PubMed  |  Direct Link  |  


  32. Marjani, A., A. Moradi and M. Saeedi, 2007. Plasma lipid peroxidation zinc and erythrocyte Cu-Zn superoxide dismutase enzyme activity in patients with type 2 diabetes mellitus in Gorgan city (South East of the Caspian Sea). J. Med. Sci., 7: 585-590.
    CrossRef  |  Direct Link  |  


  33. Marjani, A., A.R. Mansoorian, H.R. Joshaghani, K. Heydari and A. Sarikhani, 2007. The alterations of plasma lipid peroxidation and erythrocyte superoxide dismutase and glutathione peroxidase enzyme activities during storage of blood. J. Gorgan Univ. Med. Sci., Vol. 1, No. 1.
    Direct Link  |  


  34. Marjani, A., 2006. Effect of haemodialysis on plasma lipid peroxidation and endogenous non-enzymic antioxidants in Gorgan (South East of Caspian Sea). J. Medical Sci., 6: 681-685.
    CrossRef  |  Direct Link  |  


  35. Marjani, A., 2006. Alterations in plasma lipid peroxidation and total antioxidant status during storage of blood. Pak. J. Biol. Sci., 9: 2520-2523.
    CrossRef  |  Direct Link  |  


  36. Marjani, A., A.R. Mansourian, G.R. Veghari and M.R. Rabiee, 2007. Age-related alterations of plasma lipid peroxidation and erythrocyte superoxide dismutase activity in different ethnic groups of gorgan. J. Applied Sci., 7: 1795-1799.
    CrossRef  |  Direct Link  |  


  37. Marjani, A., 2005. Clinical Effect of haemodialysis on plasma lipid peroxidation and erythrocyte antioxidant enzyme activities in Gorgan (South East of Caspian sea). Indian J. Nephrol., 15: 214-217.
    Direct Link  |  


  38. Marjani, A., 2005. Age-related alterations of plasma lipid peroxidation and erythrocyte superoxide dismutase activity in different age groups of Gorgan City, Iran. Saudi Med. J., 26: 1647-1648.
    PubMed  |  Direct Link  |  


  39. Marjani, A., A.R. Mansourian, E.O. Ghaemi, A. Ahmadi and V. Khori, 2008. Lipid peroxidation in the serum of hypothyroid patients (In Gorgan-South East of Caspian Sea). Asian J. Cell Biol., 3: 47-50.
    CrossRef  |  Direct Link  |  


  40. Marjani, A., G. Veghari and M.T. Badeleh, 2010. Serum lipid peroxidation and leptin levels in male and female type 2 diabetic patients in Gorgan (South East of Caspian Sea), Iran. J. Chin. Clin. Med., 5: 26-35.
    Direct Link  |  


  41. Mraz, M., M. Bartlova, Z. Lacinova, D. Michalsky and M. Kasalicky et al., 2009. Serum concentrations and tissue expression of a novel endocrine regulator fibroblast growth factor-21 in patients with type 2 diabetes and obesity. Clin. Endocrinol., 71: 369-375.
    CrossRef  |  Direct Link  |  


  42. Mai, K., F. Schwarz, T. Bobbert, J. Andres, A. Assmann, A.F. Pfeiffer and J. Spranger, 2011. Relation between fibroblast growth factor-21, adiposity, metabolism and weight reduction. Metabolism, 60: 306-311.
    CrossRef  |  Direct Link  |  


  43. Ryden, M., 2009. Fibroblast growth factor 21: An overview from a clinical perspective. Cell. Mol. Life Sci., 66: 2067-2073.
    CrossRef  |  Direct Link  |  


  44. Stein, S., H. Stepan, J. Kratzsch, M. Verlohren and H.J. Verlohren et al., 2010. Serum fibroblast growth factor 21 levels in gestational diabetes mellitus in relation to insulin resistance and dyslipidemia. Metabolism, 59: 33-37.
    CrossRef  |  Direct Link  |  


  45. Titan, S.M., R. Zatz, F.G. Graciolli, L.M. dos Reis, R.T. Barros, V. Jorgetti and R.M. Moyses, 2011. FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin. J. Am. Soc. Nephrol., 6: 241-247.
    PubMed  |  Direct Link  |  


  46. Uebanso, T., Y. Taketani, H. Yamamoto, K. Amo and H. Ominami et al., 2011. Paradoxical regulation of human FGF21 by both fasting and feeding signals: Is FGF21 a nutritional adaptation factor? PLoS ONE, Vol. 6.
    CrossRef  |  Direct Link  |  


  47. WHO., 1998. Prevention and management of the global epidemic of obesity. Report of the WHO Consultation on Obesity, Technical Report Series, No. 894, WHO, Geneva.


  48. Wente, W., A.M. Efanov, M. Brenner, A. Kharitonenkov and A. Koster et al., 2006. Fibroblast growth factor-21 improves pancreatic β-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Diabetes, 55: 2470-2478.
    CrossRef  |  Direct Link  |  


  49. Xu, J., D.J. Lloyd, C. Hale, S. Stanislaus and M. Chen et al., 2009. Fibroblast growth factor 21 reverses hepatic steatosis, increases energy expenditure and improves insulin sensitivity in diet-induced obese mice. Diabetes, 58: 250-259.
    CrossRef  |  Direct Link  |  


  50. Yilmaz, Y., F. Eren, O. Yonal, R. Kurt and B. Aktas et al., 2010. Increased serum FGF21 levels in patients with nonalcoholic fatty liver disease. Eur. J. Clin. Invest., 40: 887-892.
    CrossRef  |  Direct Link  |  


  51. Yang, S.J., H.C. Hong, H.Y. Choi, H.J. Yoo and G.J. Cho et al., 2011. Effects of a three-month combined exercise programme on fibroblast growth factor 21 and fetuin-A levels and arterial stiffness in obese women. Clin. Endocrinol., 75: 464-469.
    CrossRef  |  Direct Link  |  


  52. Zhang, X., D.C.Y. Yeung, M. Karpisek, D. Stejskal and Z.G. Zhou et al., 2008. Serum FGF21 levels are increased in obesity and are independently associated with the metabolic syndrome in humans. Diabetes, 57: 1246-1253.
    CrossRef  |  Direct Link  |  


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