دراسة مؤشرات مناعية وبايوكيميائية مختارة لمرضى السكري النوع الثاني المصحوب وغير المصحوب باعتلال الكلى ذات الادرار قليل الزلال == Study Of Selected Immunological And Biochemical Markers In Type 2 Diabetes With And Without Microalbuminuric Nephropathy
Author name:
علي ناصر محمد علي
Supervisor name:
عبد العظيم ياسين عبود البراك | حازم عبد الرزاق عبد الوهاب
General topic:
Medicine
Specific topic:
Microbiology
Degree:
Doctorate
University:
Mustansiriyah University
Language:
English
University location:
Baghdad
First pages:
19T1144 - p.pdf
Abstract:
Diabetic Nephropathy (DN) is a common complication of diabetic diseases occuring all over the world including Iraq. This type of microvascular complication of diabetes mellitus represents the most common reason of end stage renal disease (ESRD) in the world which considers the main reason for hemodialysis, kidney transplantation and death in developed countries. For this reason the assessment of some biomarkers as an early predicator before onset of microalbuminuria stage of diabetic nephropathy and the correlations between these biomarkers with microalbuminuria were carried out.This study was achieved at AL - Yarmouk Teaching Hospital and the Diabetes National Center /AL - Mustansiriyah University/Baghdad from January 2013 to September 2014. The study involved ninety individuals, twenty volunteers selected from the local community; apparently healthy (group I), 40 type 2 diabetics with normal urinary albumin to creatinine ratio (UACR) (<30 mg/g) (group II), and 30 type 2 diabetic patients with abnormal UACR (? 30 - 300 mg/g) (group III). Mean of diabetes duration (D.D.) in group II is about 4 years and in group III is about 8 years. The mean age for group I, II and III were 53, 55 and 58 years respectively. The concentration was measured of each microalbuminuria by turbidmeteric method, estimated glomerular filtration rate (eGFR) by using chronic kidney diseases - epidemiology equation, glycated heamoglobin (HbA1c) by using high performance liquid chromatography (HPLC), both fasting blood sugar (FBS) and creatinine (serum and urine) by using colorimeteric method, body weight by using body mass index (BMI) and all of IL - 18, IL - 12 IL - 4, IFN - ? and urinary vitamin binding protein (VDBP) by using ELISA method in three groups.The present study showed that there is inverse correlation between UACR and eGFR. The cause of this inverse correlation is that the decline in renal function of diabetics can be predicted accurately by using both UACR to show the increase in microalbuminuria while eGFR show a measure of the decrease in the ability of kidney for filtration.The difference of FBS mean between group I and II and group I and III was significant (P= 0.000 for both). The P - value between II and III groups was significant (P= 0.024). The difference of HbA1c mean between group I and II, group I and III and group II and III was significant (P=0. 000 for all). These results were expected as high HbA1c level is in consequence of high FBS. The difference of BMI mean between group I and II, group I and III and group II and III was not significant (P= 0.870, 0.885 and 0.968 respectively). Because the BMI levels were approximately constant in three groups. The difference of D.D. between group II and III was significant (P= 0.000).There was no significant correlation in group II between urinary albumin to creatinine ratio with each of diabetic duration, glycated haemoglobin, fasting blood sugar and body mass index (r=0.219 with P=0.244, r=0.039 with P=0.840, r=0.080 with P=0.673 and r= - 0.126 with P= 0.506 respectively); but there was positively significant correlation between urinary albumin to creatinine ratio with each diabetic duration, HbA1c and fasting blood sugar in group III (r=0.298 with P=0.043, r=0.869 with P=0.000 and r=0.518 with P=0.003 respectively) which may be due to the chronic nature of the disease in this group that require these risk factors to initiation; however, the correlation was non significant between UACR and BMI (r= - 0.127 with P=0.228) in group III.The difference of S.Cr. among I and II groups, I and III groups and II and III groups were not significant (P= 0.998, P= 0.331 and P= 0.145 respectively).The correlation was not significant in group II between serum creatinine with each of diabetic duration, glycated haemoglobin, fasting blood sugar and body mass index (r= - 0.140 with P=0.462, r= - 0.124 with P=0.515, r=0.168 with P=0.374 and r=0.007 with P= 0.969 respectively). Also, there was no significant correlation in group III between S. Cr. with each D.D., HbA1c, FBS and BMI (r=0.187 with P=0.077, r=0.109 with P=0.220 and r=0.175 with P=0.124 respectively). The reason of these results backs to that S. Cr. level is not increased as the podocytes remain intact in the diabetics with and without microalbuminuria.The difference of eGFR between group I and II was not significant (P= 0.303). The difference between group I and III and group II and III was significant (P= 0.001 and 0.010 respectively). The correlation was not significant in group II between eGFR with each of diabetic duration, glycated haemoglobin, fasting blood sugar and body mass index (r=0.121 with P=0.524, r= - 0.180 with P=0.341, r= - 0.310 with P=0.096 and r=0.021 with P= 0.911 respectively). Also, there was no a significant correlation in group III between eGFR with each diabetic duration, HbA1c, FBS and BMI (r= - 0.179 with P=0.07, r= - 0.188 with P=0.061, r= - 0.123 with P=0.388 and r= - 0.112 with P=0.557 respectively). The reason of these results back to that eGFR level is at the normal range in group II and slightly beneath the normal range in group III in consequence of the podocytes remain intact in the diabetics with and without microalbuminuria.The difference of urinary VDBP level between group I and II, group I and III and group II and III was significant (P= 0.000 for all). The correlation between urinary albumin to creatinine ratio levels and VDBP level (r=0.963) with P - value 0.000 which was positively significant in group III. The correlationbetween eGFR and VDBP was - 0.524 with P - value 0.003 which is inversely significant in group III. The reason of this inverse correlation may be similar to the reason of inverse correlation between eGFR and UACR, as the cubilin - megalin receptors are common receptors for albumin and vitamin D binding protein. Otherwise, the correlation between urinary VDBP and eGFR in the group I was a weak negative with non significant P - value (r= - 0.188, P=0. 428). The reason of this non significant correlation is that the cubilin - megalin receptors are not damaged by inflammatory process to elevate VDBP in urine; also the podocytes in glomeruli are intact from the damage by inflammatory process, so the eGFR was at the normal range in the control group.The correlation was a positive between HbA1c and VDBP levels in group II and group III (r=0.579, P=0. 001 and r=0.686, P=0.000 respectively). This positive correlation was explained on the basis that deterioration of sugar level control lead to increase the proinflammatory cytokines that damage cubilin - megalin receptors then VDBP increase in urine.The difference of serum IL - 18 level between group I and II, group I and III and group II and III was significant (P=0.000 for all).The correlation between urinary albumin to creatinine ratio and IL - 18 was 0.983 with P - value 0.000 which was positively significant in group III. This may back to damage the cubilin - megalin receptors by IL - 18 action that lead to increase of UACR in urine. In other words, the correlation between serum creatinine and serum IL - 18 in group III was not significant (r=0.041 with P= 0.830). This may back to that podocytes remain intact in this early stage of diabetic nephropathy. There is a significant positive correlation between serum IL - 18 levels and HbA1c levels in group II and group III (r=0.641, P=0.000 and r=0.721, P=0.000 respectively). These two positive correlations support the suggestion of choosing serum IL - 18 as an excellent biomarker for avoidance an early stage of the disease.The difference of IFN - ? levels between group I and group II, between group I and group III and between group II and group III were not significant as follows : (P=0.640, P=0.292 and P=0.522 respectively). The correlation between UACR and IFN - ? (r=0.047) with P - value 0.830 which was not significant in group III which means that IFN - ? is not a good biomarker for prediction of the microalbuminuria as an early stage of DN.The difference of IL - 12 level between group I and group II, between group I and group III and between group II and group III were not significant (0.884, 0.431 and 0.439) respectively. The correlation between UACR and IL - 12 (r=0.190) with P - value 0.314 which was not significant in group III.The difference of IL - 4 levels between group I and group II, between group I and group III and between group II and group III were not significant (0.943, 0.704 and 0.648 respectively). The correlation between UACR and IL - 4 (r=0.169) with P - value 0.371 which was not significant in group III.These results of IFN - ?, IL - 12 and IL - 4 might lead to conclude that both cytokines can’t be selected as a biomarker for an early detection of DN. Finally from the all presented data it can be concluded that IL - 18 and VDBP are considered more sensitive and more efficient than a classic diagnostic method (UACR and eGFR) for avoidance and detection the early stage of DN.
