IBN AL- HAITHAM J. FO R PURE & APPL. SC I VO L.22 (3) 2009 The Effect of Leptin Hormone Levels In Type( II) Diabetic Nephropathy Patients N. T. Taher National diabete s center (NDS), Unive rsity of AL-Mustansriya. Abstract Ty p e 2 diabetes Nep hrop athy comp lication is one of the most commonest metabolic disorders that becomes an advanced serum level of hormone altered. The objective is to st udy the effect of lep tin levels in Ty p e 2 diabetes nephrop athy (D.N) comp lication and healthy subject. This st udy was done in National Diabetes Center (NDC), AL-M ust ansriya University ;on a total (64) individuals whase age were ranged from(45-60) y ears,of which (38) p atients of ty p e 2 diabetes nephrop athy , and (26) healthy ( controls). The collected data ,information concerning the individuals used in the p resent st udy were: age, sex , body mass index (BM I) and blood samp les to estimate serum leptin levels , fasting p lasma glugcose (FPG) , glycated hemoglobin (HbA1c), serum creatinine, blood urea , and micral tests (urinary to microalbumine to creatinine ratio). The mean FPG, HbA1c and M icral tests of ty p e 2 diabetes nephrop athy (D.N) showed st atist ical significant with healthy control ;on the other hard the data shows significant increases in lep tin level in ty p e 2 diabetes nephrop athy (D.N) ( urinary microalbumin to creatnin ratio ranged 30-300 mg/g) comp ared with healthy control. No significant correlation was p resent between serum lep tin and both serum creatinine and blood urea ,so there wasn’t any correlation between BM I and serum lep tin levels .In conclusion the results showed that serum lep tin level was elevated in ty p e 2 diabetes nephrop athy (D.N) because imp aired increase with p rogression of renal disease in diabetic nephrop athy . Introduction Ty p e 2 diabetes mellitus: called non insulin depended diabetes mellitus (NIDDM ) accounts for 90% of the p op ulation with diabetes in this ty p e. There are varying degrees of insulin resistance or insulin secretary defects (1). Complication of diabetes occurs after many y ears of uncontrolled hy p erglycemia (2).The consequences of diabetes are nephrop athic disease ,which lead to chronic renal failure (CRF)(3). Diabetic Nep hrop athy (D.N) is a p rogressive kidney disease caused by angiopathy of cap illaries in the kidney glomeruli .It is characterized by nephrotic sy ndrome and long st anding diabetes mellitus and is a p rimary cause for dialysis in many west ern countries(4). In diabetic nephrop athy measurement microalbuminuria test results may aid clinicians in the detection of p atient at risk of developing kidney damage (5,6) . Lep tin is a 16KD p rotein hormone of 167 amino acids which p lay s a key role in regulation food intake and energy exp enditure , including the regulation of app etite and increase of metabolism (7,8). Human kidney p lay s a substantial role in lep tin removal from p lasma by taking up and degrading the p eptide . Renal lep tin net balance and urinary lep tin execretion were detected by Lineweaver-Burk analysis . This analysis indicated that renal lep tin up take followed saturation kinetics with an app arent M ichaelis-M enten constant of 10.9 ng/ml . Renal lep tin up take could be 80% of all lep tin removal from p lasma , generally lep tin was undetectable in urine(9) about 20-30% of p atients with ty p e1 or ty p e2 diabetes develop evidence of nephrop athy , and such p atients currently st arting of dialysis (10). Furt hermore, Hy p erglycemia also activate p rotein kinase c, may contribute to renal diseases and vascular comp lications of diabetes (9), and also familiar or genetic factor p lay s a role in diabetic IBN AL- HAITHAM J. FO R PURE & APPL. SC I VO L.22 (3) 2009 nephrop athy (3) .In addition p reviously described direct and indirect effects of lep tin on the kidney include natriuretic effects ,an increase in sy mpathetic nervous activity , and st imulation of reactive oxy gen sp ecies . These findings collectively suggest that the kidney is a target organ for lep tin and that this hormone might p lay an imp ortant role in renal p athop hy siology (11). Materials and Method This st udy was carried out in National Diabetes Center (NDC), AL- M ust ansiriy a University ; on a total (64) individuals ,(30 females and 34 males) aged (45-60) y ears .Thirty eight p atients Ty p e 2 diabetes nephrop athic (urinary microalbumin to creatinine ratio was range 30-300 mg/g) , (26) healthy controls . Data collection about age , sex and body mass index(BM I). Blood samples from the individuals were taken for laboratory invest igation: which included , Fast ing Plasma Glucose (FPG) , Gly cated Hemoglobin (HbA1c) , blood urea , serum creatinine and determination lep tin level in serum ; (DGR instruments GmbH , Germany ,ELISA KIT)(12), and M icral tests ; sup p lied by Bayer Healthy Care, V.S.A(13). Analysis of data was carried out by using SPSS(st atist ical p ackage for social sciences). Re sults and Discussion A total of 64 individuals(38 p atients and 26 control) were examined successfully without any healthy p roblems . Diabetes is the most common cause of renal failure, and there is an account for more than 40 p ercent of new cases who have develop ment of kidney p roblems in people with diabetes (14). Lep tin hormone ,which is secreted from adipocytes has a role in the regulation of ap p etite and energy exp enditure.This p rotein is p roduced by adip ocrine , p ancreas and other organs by activating the transmembranc receptor and is cleared from p lasma mainly by the kidney (15).The results showed that the serum lep tin levels in the Ty p e 2 diabetes nephrop athy (urinary microalbumin to creatinin ratio 30-300 mg/g) significantly were higher p < 0.05 (Table-1) compared with healthy controls and this result agrees with Chan- Wb et al.(17)and Fruehwared-Schultes et al.(16) ,they found significant elevated levels of serum lep tin in Ty p e 2 diabetes nep hrop athy (D.N) comp ared with non diabetic controls .The human kidney p lay s a substantial role in lep tin removal from the p lasma by absorp ing and degrading the p eptide (18). Increasing albumin level in urin (microalbuminuria) is considered as key characterist ics of diabetic nep hrop athy (16).Table(2) showed that there was a significant p ositive correlation of FPG , HbA1c p <0.05 in Ty p e 2 diabetes nephrop athy (D.N) comp ared with healthy control subjects, serum lep tin level did not correlate with FPG and HbA1c (r =0.343, r=0.315) resp ectively (table-3),these results agreed with Fu-M e chung et al. (19) . He found that t here was no correlation between lep tin level and FPG, HbA1c, which indicate that lep tin is not affected by the degree of glycemic control ,while Pist rosh et al. (20) found that p atients with Ty p e 2 diabetes had high levels of FBG and HbA1c, comp ared with healthy control .Such increase may be due to insulin resistance in Ty p e 2 diabetic nephrop athy p atients in which lep tin reduces insulin secretion and enhances hematop iesis (21).There was a significant p ositive correlation of BM I in Ty p e 2 diabetic nephrop athy comp ared with control p <0.05 (T able-2) but there wasn’t any significant correlation between BM I and lep tin level in Ty p e 2 diabetic nephrop athy as shown in(table-3) . This correlation may be exp lained by the p resence of additional factor which would increase the imp aired degradation by the affected kidney (22) . Hy p erliptenimia may p lay a role in the decreased BM I (anorexia and malnutrition) that usually accomp anied chronic renal failure. Furt hermore , there were no significant correlation between serum creatinine and blood urea levels with serum leptin levels in Ty p e 2 diabetic nephrop athy (19) , but both creatinine and urea levels increase in Ty p e 2 diabetes; this may be due to renal imp airment in Ty p e 2 diabetic nephrop athy (23) . In conclusion the results showed that serum leptin level was elevated in IBN AL- HAITHAM J. FO R PURE & APPL. SC I VO L.22 (3) 2009 ty p e 2 diabetes nephrop athy (D.N) because imp aired would increase with the p rogression of renal disease in diabetic nephrop athy . Re ferences 1. Bishop , M . L .; Duben, E. J. and Fody , E. P. ( 2000),clinical chemist ry , forth eddition.,p.220. 2. Shichiri, M .; Kishikawa, H.; Oct kutooy ,Nake ,N. ( 2000), diabetes.Diabetes Care ., 23(2):.21-29 . 3. Sandeep ,S .; Soman ,M .D.; M BBS.;Anjana,S. DNB. ( 2006), Diabetes Nep hrop athy M edicin . August ., 509(4):521-542. 4. Diabetic Nep hrop athy -Wikipedia, the free ency clop edia,1. ( 2007): [Internet article]. 5. M ogensen ,C. E. (1984,). N. Eng . J. M ed ., 310: 356-360. 6. M ogensen, C.E.;Keane,W.F.;Bennett ,P.H.;Jerums,G.and Parving,H.H (1995),.Lancet., 346:1080-1085 . 7. Jeffrey, M .F. and Jeffrey,L.H. (1998), Nature, 395:763-770. 8. Yang ,J.; Zhao, X.Q.; Guo,S.C.; Wang, D.P.; Cao,J.H.; Li,H.G. and Qi, D.L. ( 2006).J. Biochemical and biop hy sical Research Communication, 345(4):1405-1413 . 9. Christian ,M .; Dare, R.; Smonsen,E.;Amtssvgehuset,F.;Frommann,N.; Streit,M . Haghigh at,R. ( 1997),. Am . J. Phy siol Endocrinol M etab., 273(5):903-907 . 10. Lewis, E.J; Hunsiker, L.G.; Clarke, W.R.; Berl, T.P. Ohi, M .A. (2001).N . Eng . J. M ed., 345:860-891. 11.Wolf ,G.and Ziyadeh,F.N. (2006). Lep tin and renal fibrosis .Contrib Nep hrol- p ubmed result, schuilly University .,151:83-175. 12. Guillaume, M . Bjorntop , P. ( 1996) .Horm. M etab. Res , 28(573):581 . 13. Pugia, M .J.; Lott ,J.A.;Clark,L.W.;Parker,D.R,Wallace,J.F.and Willis,T.W.( 1997) ,. Eur . J .Clin . Chem . Biochem., 35(9):693-700 . 14. Jwatt kin, P.; Tay istock,S.;Hansonn ,L.;Zanchett i, A.and Garruthers,G.S . ( 1998), ABC of diabetes Forth edition . BM J Publishing group . 15. Chabava,V.; Tesar, V.; Persuicova, J.; Zima,T.and Zabka, J. (1999). Caas Lek Cest , 128(15): 80-465 . 16. Fried Wald ,W.T.; Levy , R. J.; Fredrickson , D .S .;Furnkawa,S.; Fujita,T.; Shimabukuro,M .; Pitrobelli,A.; Lee,R.C.;Capristo,E.and Deckelbaum,R.J (1972) .Clin.Chem,18:499 . 17. Chan,W.B.; M a, R.C.W.; Chan, N.N.; Ng, M .C; Lee, Z.S.K.;Lai, C.W.K.; Tong, P.C.Y.;So,W.Y.and Chan, J.C.N. ( 2004), Diabetes Rec Clin,64(2) :93-8. 18. M eyer, C.; Robson, D.and Racksky ,N.(1997), Am . J . Phy siol ., 263: 903-907 . 19. Fu-M ei Chung, M .S.; Jack, C.;Tsai,R.;M D.;Dao-M ing Chang.M .D.; Shy i-Jang Shin,M .D.and Yan-Jiunn Lee.( 2005). Diabetes Care , 28:1710-1717 . 20. Frank Pist rosch .; Kay Herbring .; Beate Kindel.,Jens Passauer.and Peter Gross. (2005),. Diabetes , 54: 2206-2211 . 21. Dafni –Kalliop.; Pap afrakaki.; George To Llis.;( 2005), Obesity and renal disease : A p ossible role of Leptin Hormone, 4(2):90-95 . 22. Ostland , J.R.; Yang, J. W.; Klin, S. and Gingerich ,R.(1996). M etab, 81: 3909-3913 . 23. Philp, M .H ;( 2006).Diabetes Sp ectrum , 19:18-24 . IBN AL- HAITHAM J. FO R PURE & APPL. SC I VO L.22 (3) 2009 Table(1) :Se rum leptin levels in Type 2 Di abetic Nephropathy and control Table(2) :The mean of BMI, FBG, and HbAIc in Type 2 Diabetes Ne phropathy (D.N)and controls Type 2 (D .N) n=38 Control n=26 28.99+6.69 25.01+3.40 BMI (Kg/m) 177.62+50.20 77.19+2.25 FPG mg/dl)( 9.23+2.48 4.18+0.12 HbAIc (%) Table(3) :The correl ation coefficient (r) between BMI ,FPG, and HbA1c with serum leptin levels (control & diabetic nephropathy) Type 2 (D.N ) Control 20.18+4.40 10.60+3.17 Leptin (ng\ml) Type 2 (D.N) Control Leptin (ng/ml) Leptin (ng/ml) 0.392 0.380 r BMI 0.120 0.055 P 0.343 0.259 r FBG 0.101 0.201 p 0.315 0.256 r HbA1c 0.164 0.207 p 2009) 3( 22والتطبیقیة المجلدمجلة ابن الهیثم للعلوم الصرفة تأثیر مستوى هرمون اللبتین لدى مرضى السكري النوع الثاني والمصاحب باعتالل الكلى نور ثائر طاھر المركز الوطني السكري ، الجامعة المستنصریة الخالصة غیـر ةالذي یعـزى الـى عملیـات ایضـی ةداء السكري النوع الثاني والمصاحب باعتالل الكلى من االمراض الشائع دیع النـوع (تـم درس تـاثیر مسـتوى هرمـون اللبتـین عنـد مرضـى السـكري .محدث تغیرات في مستویات معظـم الهرمونـات ةطبیعی تراوحــت ، فــردا) 64(علــى ةریـت الدراســاذ اج، االخــرى ةكریوالمصــاحب بــاعتالل الكلــى ومـدى عالقتــه بالمعاییرالســ) الثـاني ) 26(و ،یعـانون مــن مـرض الســكري النـوع الثــاني والمصـاحب بــاعتالل الكلــى "امریضــ) 38(، ةسـن) 60-45(اعمـارهم بــین ،والجـنس ،بـالعمر ةالمعلومـات الخاصـ تجمعـ و. ةالمستنصـری ةالجامع -من االصحاء في المركز الوطني السكري "اشخص والیوریـا ،والهیموغلـوبین المتسـكر، واخـذت العینـات لغـرض قیـاس مسـتوى هرمـون اللبتـین وقیـاس الكلوكـوز ،الجسـم ةومعدل كتل فـي ةاحصـائی ةبینـت النتـائج وجـود قیمـ) . االلبـومین الـى الكریـاتنین فـي البـول ةنسب(س فحص مكرل ین وكذلك قیوالكریاتن، وفحص مكرل عند مرضى السكري،سكروالهیموغلوبین المت،فحص السكر الصائم ارتفـاع مســتوى اللبتــین عنــد ةوكـذلك بینــت الدراســ، االصــحاء ةمـع مجموعــ ةالنـوع الثــاني والمصــاحب بـاعتالل الكلــى مقارنــ -30االلبومین الى الكریـاتنین فـي البـول تتـراوح بـین ةنسب(مرضى السكري النوع الثاني المصاحب باعتالل الكلى التي كانت مــع االصــحاء كـذلك عــدم وجــود عالقـه ترابطیــه بــین مسـتوى اللبتــین وكــل مـن مســتوى الكریــاتنین ةمقارنـ) غــم/ملغـم 300 .بین معدل كتله الجسم ومستوى اللبتین ةترابطی ةولم یالحظ وجود عالق،والیوریا في مصل الدم اني والمصـاحب بـاعتالل الكلـى نتیجـه ان مستوى هرمون اللبتـین یرتفـع عنـد مرضـى السـكري النـوع الثـ ةنستنتج من هذه الدراس .والتحلیل عند مرضى السكري ةضعف الكلى تدریجیا على التجزئل