Effect of T2DM progressing on renal glucose excretion till the T mG

In this study, an attempt has been made to measure the amount of glucose excreted in urine regarding the duration of T2DM. In order to achieve that 302 T2DM patients have been included and then classified into 3 groups according to duration of illness.T2DM patients have been tested for random blood glucose, urine glucose concentration and serum creatinine while glomerular filtration rate (GFR), tubular glucose load (TGL) and urine glucose excretion (UGE) have been calculated. Then an analytical tests were applied to analysis these parameters and comparing the results of different groups according to classification of this study. The maximum transport of glucose (T mG ) , and UGE till the T mG (splay region) are varied between T2DM patients. In order to evaluate the validity, ANOVA test for groups variance


‫للكلوك‬ ‫الكلوي‬ ‫الطرح‬ ‫على‬ ‫الثانً‬ ‫النمط‬ ‫السكري‬ ‫مرض‬ ‫مذة‬ ‫تأثٍر‬ ‫الحذ‬ ‫لغاٌت‬ ‫وز‬ ‫المتصاص‬ ‫االعلى‬ ‫الكلوكوز‬
SGLT2 is thought to be located exclusively on the luminal surface of the epithelial cells lining the S1 and S2 segments of the proximal tubule .Transport of sodium and glucose by SGLT2 occurs in a 1 : 1 ratio ( Kleta et al.,2004;Kim et al.,2010;Fujimori et al.,2009).The remaining 10% of glucose reabsorption is mediated by SGLT1, a high-affinity, low-capacity glucose/galactose transporter sodium/glucose coupling ratio = 2 : 1, located on the luminal surface of epithelial cells lining the S3 segment of the proximal tubule ( Pajor et al.,2008;Del Valle et al.,2002).Glucose reabsorbed from the proximal tubules by SGLTs is then released into the circulation through the action of facilitative glucose transporters (GLUTs) at the basolateral membrane of the epithelial cells lining the proximal tubules (GLUT2 in the S1/2 segments and GLUT1 in the S3 segment) .In contrast, GLUTs facilitate passive transport (equilibration) of glucose across membranes and do not require an energy source ( Uldery and Thorens, 2004).

Patients, Materials and Methods
Subjects involve in the current study are composed of 302 diabetes mellitus type 2 patients 40 years and above 186 male and 116 female attending to alwaffa diabetic center and Ibn sena teaching hospital.The patient selected are varied from newly to previously diagnosed as T2DM, with negative UTI test (Mavrakanas et al.,2009), normal blood pressure, not take aminoglycoside antibiotics at least two weeks before participate in this study (Takamoto et al.,2003), not on insulin treatment ( Chin et al., 1997) and if female she must be not pregnant ( Alto, 2005).Blood samples were obtained from all diabetic type 2 patient by antecubital venepuncture between 9-10 a.m. after taking breakfast at 7 o'clock.Urine samples were obtained from all patients by asking them to void and empty their bladders completely immediately after blood samples were taken.By this method we obtained the first sample which is discarded, the urine volume of the second sample which is obtained by voiding after an hour of time was measured in a graduated cylinder to calculate urine excretion per minute for each patient, this sample is used to measure urine glucose concentration.(Note: GUE was done first to exclude sample with UTI ).

Methods
We can illustrate the methodology in this study as follows:

2-Urine Glucose Excretion (UGE) a-Male with T2DM
It revealed that diabetic patients with (<2) years duration of disease had a significant difference regarding UGE mean value from diabetic patients with (2-<10) and 10 years and more duration of disease.and diabetic patients with (2-<10) years duration of disease had a non-significant difference regarding UGE mean value from diabetic patients with 10 years and more duration of disease as shown in the table (3).
b-Female with T2DM It revealed that diabetic patients with (<2) years duration of T2DM had a non-significant difference regarding UGE mean value from diabetic patients with (2-<10) duration of disease and had a significant difference regarding UGE mean value from diabetic patients with 10 years and more duration of disease.and diabetic patients with (2-<10) years duration of disease had a non significant difference regarding UGE mean value from diabetic patients with 10 years and more duration of disease as shown in the table (3).1990; whom demonstrated that high glucose in the proximal tubule directly stimulates sodium reabsorption via sodium-glucose cotransport and indirectly via increased expression of the sodium-glucose cotransporters, SGLT1 and SGLT2.In this study it was observed the urine glucose excretion till the transport maximum (splay region) for male and female are decreased as the duration of illness increase as shown in the tables (3,4) that mean the splay value for newly diagnosed Type 2 diabetic patient is more than that for patient with chronic illness this finding can supported by Freitas et al., 2008; who claimed that the Renal SGLT2 mRNA expression has also been reported to be elevated in chronic diabetic rats.Likewise Rahmoune et al., 2005; who demonstrated there are significantly elevated SGLT2 levels and glucose uptake are seen in human exfoliated proximal tubular epithelial cells isolated from the urine of type 2 diabetic individuals with disease progressing.

Conclusions
1-Duration of T2DM of both male and female can significantly affect UGE till the T mG ( Splay region ) inversively.
2-Duration of T2DM of both male and female can affect T mG ejectively.
Colored result was measured at 500 nm by using APEL spectrophotometer ( Jian et al., 2011; Ahmed et al., 2010; Iqbal, Kalsoom, and Jafri, 2011) .RANDOX kit made in united kingdom was used. in alkaline picrate solution forms a color complex ( Butller, 1975) detected at 520 nm by using APEL spectrophotometer.SYRBIO kit made in france was used.Calculated parameters 1-G lomerular Filtration Rate (GFR) ml/min.A commonly used surrogate marker for estimate of creatinine clearance is the Cockcroft-Gault formula ( Poggio et al., 2005), which in turn estimates GFR ( Melloni et al., 2008) 2-TGL mg/min.= 3-UGE mg/min = Results 1-Tubular Glucose Load (TGL) a. Male with T2DM It revealed that diabetic patients with (<2) years duration of disease had a non-significant difference regarding TGL mean value from diabetic patients with (2-<10) and 10 years and more duration of the disease.And diabetic patients with (2-<10) years duration of disease had a non-significant difference regarding TGL mean value from diabetic patients with 10 years and more duration of disease as shown in the table (4).b.Female with T2DM It revealed that diabetic patients with (<2) years duration of disease had a non-significant difference regarding TGL mean value from diabetic patients with (2-<10) and 10 years and more duration of disease.and diabetic patients with (2-<10) years duration of disease had a non-significant difference regarding TGL mean value from diabetic patients with 10 years and more duration of disease as shown in the table (4).