الفهرس 
Review of literatureOnly 14 pages are availabe for public view
 |  | from | 201 |  |  |
| | | from | 201 | | |
Abstract
Diabetes is a growing public health problem. The incidence of chronic kidney disease (CKD) in diabetes continues to rise. Early detection of a risk leading to intervention before advanced renal damage has occurred is an obviously important goal. Hyperfiltration is the earliest measurable biomarker for diabetic nephropathy, microalbumin has emerged as a very powerful clinical predictor of overt renal and cardiovascular disease.
Fibroblast growth factor 21 (FGF21), a metabolic hormone predominantly produced by the liver, is also expressed in adipocytes and pancreas. It regulates glucose and lipid metabolism through pleiotropic actions in these tissues.
In human studies, individuals with obesity and its related cardiometabolic disorders including metabolic syndrome, Type 2 diabetes, NALFD and coronary artery disease are associated with high serum FGF21 levels, which may be due to a compensatory response to protect the body from adverse metabolic conditions. The findings in human studies suggest that serum FGF 21 level has the potential to be an important biomarker for the early diagnosis of metabolic diseases or its complications.
The present study aimed to evaluate Fibroblast growth factor 21 (FGF21) as a biomarker of progressive nephropathy. To accomplish the aim of this study, FGF21 levels, diabetic biomarkers, lipid profile, serum cystatin C kidney function tests, microalbumin and creatinine in urine, A/C ratio and s.albumin were determined in normal volunteers and Type 2 diabetic patients with different degree of albuminuria. In addition, correlation studies were done between FGF 21 and the different examined parameters in all groups.
This study included eighty volunteers of both sexes (sex-matched by ratio in each subject group) classified as 20 normal healthy subjects and 6o Type 2 diabetic patients (The diabetic onset from 5 to 10 years). Diabetic patients were diagnosed according to Report of the Expert Committee on the Diagnosis and classification of Diabetes Mellitus 2006 and aged from (40 – 60 years). They were selected from the outpatient’s clinic of National Institute of Diabetes and Endocrinology (NIDE), Cairo, Egypt.
The participants in the diabetic groups were treated with oral hypoglycemic agents only. Hypoglycemic medications were withheld on the morning of the study. Demographic data were recorded for each subject using self-made questionnaire. The purpose, nature, and potential risks of the study were explained to all subjects and written voluntary consents were obtained before their participation.
The results can be summarized as follows:
Diabetes biomarkers:
1. Fasting plasma glucose and glycated hemoglobin (HbA1c) levels showed a highly significant increase (P<0.001) in all groups of diabetic patients compared to normal controls.
2. Insulin and Homeostasis model assessment for insulin resistance (HOMA-IR) levels showed a highly significant increase (P<0.001) in all groups of diabetic patients compared to normal control.
Fibroblast growth factor biomarker:
Serum fibroblast growth factor 21 levels showed significant increase (P<0.05) in diabetic normo-albuminuria, and a highly significant increase (P<0.001) in diabetic microalbuminuria and macroalbuminuria patients compared to normal controls.
Lipids profile:
1. Total cholesterol, TAG, LDL-C, VLDL-C, atherogenic index 1 and 2 levels showed a highly significant increase (P<0.001) in all diabetic patients compared to normal controls.
2. High density lipoprotein cholesterol HDL-C showed a highly significant decrease (P<0.001) in all diabetic patients compared to normal controls.
Kidney Function biomarkers:
1. Serum cystatin C levels showed a highly significant increase (P <0.001) in all diabetic patients compared to normal controls.
2. Serum creatinine, urea and BUN levels showed a significant increase (P<0.05) in diabetic normo-albuminuria patients, and a highly significant increase (P<0.001) in diabetic micoalbuminuria and macro-albuminuria patients compared to normal controls.
3. Microalbumin in urine and albumin/creatinine ratio showed a highly significant increase (P<0.001) in diabetic micoalbuminuria and macroalbuminuria patients compared to normal controls, while they showed a non-significant change in diabetic normoalbuminuria compared to normal controls.
4. Creatinine levels in urine showed a highly significant decrease (P<0.001) in diabetic micoalbuminuria and macroalbuminuria patients compared to normal controls, while they showed a non-significant change in diabetic normoalbuminuria compared to normal controls.
5. Estimated glomerular filtration rate (eGFR) levels showed a highly significant decrease (P<0.001) in diabetic micoalbuminuria and macroalbuminuria patients compared to normal controls, while it showed a non-significant change in diabetic normoalbuminuria compared to normal controls.
6. Serum albumin levels showed a significant decrease (P<0.05) in diabetic macroalbuminuria patients compared to normal controls, while it showed a non-significant change in diabetic normoalbuminuria and microa- lbuminuria compared to normal controls.
Correlations results:
In group II significant positive correlations were recorded between serum fibroblast growth factor 21 and FPG (r = 0.612, P < 0.01) and cystatin C (r = 0.913, P < 0.001). Moreover, significant negative correlations were recorded between FGF 21 and eGFR (r = - 0.831, P < 0.001). However, a non-significant correlations were recorded between FGF21 and age (r = -0.378 P > 0.05), BMI (r = - 0.433, P > 0.05), HbA1c (r = 0.037, P > 0.05), insulin (r = -0.173, P > 0.05), HOMA-IR (r = 0.118, P > 0.05), TC (r = 0.244, P < 0.05), HDL-C (r = - 0.075, P > 0.05), LDL-C (r = 0.059, P >0.05), VLDL-C (r = 0.437, P >0.05), TAG (r = 0.437, P > 0.05), atherogenic index 1 (r = 0.129, P > 0.05), atherogenic index 2 (r = 0.009, P > 0.05), s. creatinine (r = 0.281, P >0.05), urea (r = 0.075, P > 0.05), BUN (r = 0.075, P > 0.05), microalbumin (r = 0.095, P >0.05), creatinine in urine (r = 0.214, P > 0.05), A/C ratio (r = - 0.189, P > 0.05) and s. albumin (r = 0.064, P > 0.05).
In group III significant positive correlations were recorded between serum fibroblast growth factor 21 and FPG (r = 0.723, P < 0.001), cystatin C (r = 0.460, P < 0.05), serum creatinine (r = 0.660, P < 0.01), urea (r = 0.763, P < 0.001) and BUN (r = 0.763, P < 0.001). Moreover, significant negative correlations were found between FGF21 and eGFR (r = - 0.823, P < 0.001) and serum albumin (r = - 0.552, P < 0.05). However, a non-significant correlations were recorded between FGF21 and age (r = 0.175, P > 0.05), BMI (r = 0.290, P > 0.05), HbA1c (r = 0.173, P > 0.05), insulin (r = - 0.054, P > 0.05), HOMA-IR (r = 0.335, P > 0.05), TC (r = - 0.320, P < 0.05), HDL-C (r = - 0.342, P > 0.05), LDL-C (r = - 0.292, P >0.05), VLDL-C (r = - 0.107, P >0.05), TAG (r = - 0.107, P > 0.05), atherogenic index 1 (r = 0.032, P > 0.05), atherogenic index 2 (r = 0.016, P > 0.05), microalbumin (r = - 0.217, P >0.05), creatinine in urine (r = - 0.012, P > 0.05) and A/C ratio (r = - 0.164, P > 0.05).
In group IV significant positive correlations were recorded between serum fibroblast growth factor 21 and FPG (r = 0.535, P < 0.05), insulin (r = 0.571, P < 0.01), HOMA-IR (r = 0.598, P < 0.01), cystatin C (r = 0.507, P < 0.05), serum creatinine ((r = 0.735, P < 0.001), urea (r = 0.588, P < 0.01) and BUN (r = 0.588, P < 0.01). Moreover, significant negative correlations were found between FGF21 and eGFR (r = - 0.616, P < 0.01) and s. albumin (r = - 0.785, P < 0.001). However, a non-significant correlations were recorded between FGF21 and age (r = 0.216, P > 0.05) and BMI (r = -0.267, P > 0.05), HbA1c (r = - 0.282, P > 0.05), TC (r = 0.090, P < 0.05), HDL-C (r = 0.377, P > 0.05), LDL-C (r = 0.126, P >0.05), VLDL-C (r = - 0.258, P >0.05), TAG (r = - 0.258, P > 0.05), atherogenic index 1 (r = - 0.162, P > 0.05), atherogenic index 2 (r = - 0.075, P > 0.05), microalbumin (r = - 0.146, P >0.05), creatinine in urine (r = - 0.270, P > 0.05) and A/C ratio (r = 0.203, P > 0.05.
Conclusion:
FGF21 plays a role in the pathogenesis of type 2 diabetes. In the diabetic groups of patients, the progressive increase in serum FGF21 levels was associated with poor glycemic control, insulin resistance as well as with the decline in kidney functions.
Supporting the above findings that FGF21 was positively correlated to FPG and cystatin C, while it showed significant negative correlation with eGFR in all diabetic groups. Furthermore, FGF21 showed significant positive correlations with s. creatinine, urea and BUN, while it showed significant negative correlation with serum albumin in diabetic microalbuminuia and microalbumin- uria patients. However, FGF21 showed significant positive correlations with insulin and HOMA-IR in macroalbuminuria patients.
Accordingly, FGF21 can be used as a useful metabolic marker of diabetic nephropathy in Type 2 diabetic patients whom at risk of that disease.