Relationship between serum irisin, glycemic indices, and renal function in type 2 diabetic patients

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1 J Renl Inj Prev. 2017; 6(2): Journl of Renl Injury Prevention DOI: /jrip Reltionship between serum irisin, glycemic indices, nd renl function in type 2 dibetic ptients Leil Mhmoodni 1, Mrym Sdoughi 1, Ali Ahmdi 2, Mrzieh Kfeshni 3* 1 Deprtment of Internl Medicine, Shhrekord University of Medicl Sciences, Shhrekord, Irn 2 Deprtment of Epidemiology nd Biosttistics, Shhrekord University of Medicl Sciences, Shhrekord, Irn 3 School of Nutrition & Food Science, Isfhn University of Medicl Sciences, Isfhn, Irn A R T I C L E I N F O Article Type: Originl Article History: Received: 23 August 2016 Accepted: 28 October 2016 Published online: 20 November 2016 Keywords: Irisin Type 2 dibetic ptients Body mss index A B S T R A C T Introduction: Irisin is novel peptide tht plys notble role in humn nd niml biology nd physiology. It hs been reported tht irisin my improve insulin resistnce nd relted disturbnces. Objectives: The im of this investigtion ws to ssess the reltionship between serum irisin, glycemic indices, nd renl function in dibetic subjects. Ptients nd Methods: In this cross-sectionl study, totl of 102 type 2 dibetes mellitus (T2DM) ptients were recruited. Blood biochemicl prmeters, including fsting plsm sugr (FBS), glycosylted hemoglobin (HbA 1C ), serum uric cid (sua), cretinine concentrtion nd glomerulr filtrtion rte (GFR) were mesured. All sttisticl nlysis ws performed with SPSS Results: There ws positive correltion between irisin nd ge (P = 0.05, r= 0.19) nd negtive correltion between irisin nd body mss index (BMI) (P = 0.01, r= -0.25) ws detected. There ws significnt difference of serum irisin level between ptients with norml nd bnorml FBS too. Conclusion: In this study we found, irisin concentrtion ws incresed with ge, decresed with BMI, nd it ws higher in subject with bnorml FBS. Thus further reserch is needed to provide inclusive understnding of irisin ssocited physiologicl effects nd possible implictions in clinicl conditions. Originl Impliction for helth policy/prctice/reserch/medicl eduction: In study on 102 type 2 dibetic ptients, we found, irisin concentrtion ws incresed with ge, decresed with BMI, nd it ws higher in subject with bnorml FBS. Plese cite this pper s: Mhmoodni L, Sdoughi M, Ahmdi A, Kfeshni M. Reltionship between serum irisin, glycemic indices, nd renl function in type 2 dibetic ptients. J Renl Inj Prev. 2017;6(2): DOI: /jrip Introduction The worldwide prevlence of dibetes ws estimted 382 million people by the Interntionl Dibetes Federtion in Dibetes mellitus is complex public helth concern tht is relted with vrious micro-vsculr (neuropthy, nephropthy, nd retinopthy) nd mcro-vsculr (peripherl rteril disese, coronry rtery disese, nd stroke) complictions. These complictions cuse vst disbility, morbidity, nd mortlity, nd even low qulity of life. There re different fctors tht influence on the risk of developing dibetes nd its compliction (1). Recently, reserchers hve shown n incresed interest in ssocition between irisin level nd diseses. Irisin is novel peptide tht plys notble role in humn nd niml biology nd physiology. It hs been reported tht irisin my improve body weight sttes nd insulin resistnce. Irisin ws first introduced s exercise-induced myokines by Boström et l in 2012, but other studies showed it lso is n dipokine tht secreted by subcutneous dipocytes nd ffected by exercise nd nutritionl fctors (2). In brief, Boström et l demonstrted tht exercise enhnces levels of peroxisome prolifertor-ctivted receptor-γ coctivtor-1α (PGC-1α) in the muscle thus the expression of the type I membrne precursor protein fibronectin-type *Corresponding uthor: Mrzieh Kfeshni, Emil: mrzikfeshni@hlth.mui.c.ir

2 Serum irisin in dibetic ptients III domin-contining 5 (FNDC5) ws induced. Then irisin ws produced by ttching N-terminl fibronectin III (FNIII)-like domin to flexible C-terminl. Irisin stimulted the expression of brown dipose tissue (BAT) relted genes such s uncoupling protein 1 (UCP1, highly expressed in BAT nd mrker of browning), prtilly through incresed PPAR α nd other incompletely understood method (3). Lesser circulting irisin ws relted with the insulin resistnce, dibetes (4,5), chronic kidney disese (6,7) nd other disese (8). The results of studies on irisin nd glucose homeostsis hve been controversil. Some studies estblished tht serum irisin ws significntly negtively correlted with hemoglobin A 1C, fsting blood glucose, 2 hours plsm glucose nd homeostsis model ssessment of insulin resistnce (HOMA-IR) nd other studies found positive correltion (9). Studies regrding reltionship between serum irisin nd renl functionl mrkers re scres however these reserches suggested tht irisin level might be ssocited with renl function in humns. Objectives According to the limited studies nd the controversy bout scientific evidence, there is need for further reserch to identify the reltionship between irisin, nd clinicl nd biochemicl mrkers of vrious chronic diseses. The min im of this investigtion ws to ssess the reltionship between serum irisin, glycemic indices, nd renl function in dibetic individuls. Ptients nd Methods Ptients In this cross-sectionl study, totl of 102 type 2 dibetes mellitus (T2DM) ptients were recruited from Imm- Ali clinic, Shhrekord, Irn. In the present study, T2DM ws defined using the Americn Dibetes Assocition (ADA) criteri. Stndrd questionnire ws used for ssessing informtion, including ge, sex, disese history, nti-dibetic nd nti-hypertensive drugs. Dibetic ptients on dilysis, ptients with kidney trnsplnts, nd mentlly retrded ptients who were not ble to give informed consent were excluded. Additionlly ptients with mlignncy nd ctive or chronic infections were excluded. Ethicl issues The reserch dhered to the principles of the Declrtion of Helsinki; the purpose nd design of study were explined for ll subjects nd they completed n informed consent form. Ethicl Committee of Shhrekord University of Medicl Science pproved the protocol (#IR.SKUMS.REC ). Biochemicl ssessments Blood biochemicl prmeters, including fsting plsm sugr (FBS), serum uric cid (sua) nd cretinine (Cr) concentrtion were mesured by commercilly vilble enzyme ssy kits (Prs Azmon kit, Irn). HbA 1C ws mesured with chromtogrphy using Biosystem kit (Spin). Glomerulr filtrtion rte (GFR) ws estimted from the results of blood Cr test nd by the Modifiction of Diet in Renl Disese (MDRD) eqution. Circulting irisin ws quntified using commercil ELISA kit (BioVendor Lbortorni Medicin, Czech Republic). Clinicl mesurements Blood pressure (BP) ws determined in seted position where their rm sustined t hert level, fter 5 minute rest. BP ws noted s three sequentil mounts t intervls of 30 seconds. The men of the three BP mesurements ws utilized in the nlysis. Sttisticl nlysis The normlity of dt ws tested by using Kolmogorov- Smirnov test. The nonprmetric sttisticl methods were used to nlyses the numericl dt becuse the dt hd no norml distribution. Prmetric vribles were extrcted s men ± stndrd devition (SD). Ctegoricl dt were stted s percent nd compred by χ 2 test. Medin nd qurtile were used to describe nonprmetric dt. Mnn Whitney U rnk test ws used to compre differences between groups. Kruskl Wllis one-wy nlysis of vrince test ws used to compre irisin between different levels of body mss index (BMI). Spermn s correltion coefficient nd prtil correltion tests were pplied to evlute the correltion between nonprmetric vribles. The dt were nlyzed by SPSS version 16. In this study, P vlue below 0.05 ws respected s sttisticlly significnt for ll tests. Results Tble 1 illustrtes some of the min chrcteristics of the subjects. The men ge ws ± 11.7 yers. The mjority of subjects were women (68% of totl), nd durtion of dibetes ws 7.64 yers. The results of the correltionl nlysis re presented in Tble 2. In this study positive correltion between serum irisin nd ge (P = 0.05, r = 0.19) nd negtive correltion between irisin nd BMI ws detected (P = 0.01, r = -0.25). Accordingly positive correltion between ge nd serum Cr (P = 0.02, r = 0.23) ws detected. Spermn s correltion nlysis ws performed to study the correltion between vribles. The ssocition between circulting irisin nd biochemicl nd demogrphic prmeters ws shown in Tbles 3 nd 4. Dt from both tbles shows tht, the mjority of individuls hd norml FBS (mg/dl), HbA 1C (%), nd GFR, however sua (mg/ dl) nd scr (mg/dl) in the most of them were bnorml. There ws significnt difference in serum irisin level between ptients with norml nd bnorml FBS (mg/ dl), but there ws no significnt differences in irisin level between subjects with norml nd bnorml other biochemicl prmeters. Also there ws no significnt difference between men nd women nd ptients who tking insulin or orl hypoglycemic gents. Journl of Renl Injury Prevention, Volume 6, Issue 2, June

3 Mhmoodni L et l Discussion The present study ws designed to determine reltionship between serum irisin, glycemic indices, nd renl function in dibetic ptients. The results of this study indicted positive correltion between irisin nd ge nd negtive correltion between irisin nd BMI. We lso found mrginlly negtive correltion between irisin nd FBS. However no significnt correltion between circulting irisin nd ws detected. There ws significnt difference in serum irisin level between the subject with norml nd bnorml FBS, so it cn be concluded tht circulting irisin ws higher in dibetic subjects with uncontrolled FBS. These results re consistent with other studies. Huh et l found circulting irisin concentrtions were positively correlted with FBS (5) nd Mehrbin et l determined serum irisin level correlted positively with insulin levels nd FBS in norml weight obese subjects (10). Also Liu et l demonstrted the positive correltion between circulting irisin nd FBS in nonobese, non-dibetic individuls. These results differ from some published studies (7). Zhng et l nd Du et l in two different met-nlysis estblished tht circulting irisin concentrtions were significntly lower in ptients with T2DM (4,11). Snchis-Gomr et l reported positive correltion between irisin level nd in T2DM ptients with nd without obesity (12). While, the mjority of subjects were obese or over weight hence one explntion Tble 1. Bsic chrcteristics of dibetic subjects (n = 103) Men or medin c SD or rnge Age (yers) BMI (kg/m 2 ) Mle (%) 32 Types of drug (%) Insulin Orl hypoglycemic gents Durtion of dibetes (yers) FBS (mg/dl) (%) sua (mg/dl) Cr (mg/dl) egfr (ml/min/1.73 m 2 ) GFR (MDRD) b (cc/min) Irisin (ng/dl) Abbrevitions: BMI, body mss index; FBS, fsting blood sugr;, glycosylted hemoglobin; sua, serum uric cid; Cr, cretinine. egfr (estimted glomerulr filtrtion rte) clculted from the results of blood cretinine, ge, body size nd gender. b GFR (MDRD), clculted from the Modifiction of Diet in Renl Disese (MDRD) eqution. Dt for ctegoricl vribles re presented s percentges. c Prmetric nd non-prmetric vribles were extrcted s men ± SD nd medin, qurtile respectively. Tble 2. Correltion between serum irisin, glycemic indices, nd renl function in dibetic ptients Irisin Age sua scr egfr GFR FBS HTN BMI Irisin b Age sua Cr GFR (ml/min/1.73 m 2 ) GFR (MDRD) (cc/min) FBS Abbrevitions: BMI, body mss index; FBS, fsting blood sugr;, glycosylted hemoglobin; sua, serum uric cid; scr, serum cretinine. egfr, estimted glomerulr filtrtion rte; HTN, hypertension; MDRD, Modifiction of Diet in Renl Disese. P < 0.05 is significnt; b is mrginlly significnt. Tble 3. Compre circulting irisin between dibetic subjects with norml nd bnorml biochemicl chrcteristics Norml Abnorml Percent Men (ng/dl) SD Percent Men (ng/dl) SD sua (mg/dl) Cr (mg/dl) egfr (ml/min/1.73 m 2 ) GFR (MDRD) FBS (mg/dl) (%) Abbrevitions: FBS, fsting blood sugr;, glycosylted hemoglobin; sua, serum uric cid; Cr, cretinine; egfr, estimted glomerulr filtrtion rte; MDRD, Modifiction of Diet in Renl Disese. P vlue 90 Journl of Renl Injury Prevention, Volume 6, Issue 2, June

4 Serum irisin in dibetic ptients Tble 4. Assocition of circulting irisin with demogrphic prmeters nd BMI levels in dibetic subjects Men (ng/dl) SD P vlue Sex 0.58 Femle Mle Age > BMI (kg/m 2 ) > Types of drug 0.48 Insulin OHA Abbrevitions: BMI, body mss index; OHA, orl hypoglycemic gents. P < 0.5 is significnt. for our result is irisin resistnce in obese people s sme s leptin nd insulin resistnce (13). Our findings reveled tht no correltion between irisin nd renl function tests nd indices such s sua, Cr, nd GFR ws detected. Also no significnt difference between the subjects with norml nd bnorml renl function mrkers ws seen. The findings of the current study do not support the previous reserch (6,7), while, Wen et l estblished tht plsm irisin levels were significntly decresed in chronic kidney disese (CKD) ptients (6,7). Accordingly, Liu et l found tht circulting irisin ws significntly decresed in dibetic ptients with renl insufficiency compred to T2DM ptients with norml renl function. They found tht circulting irisin ws independently ssocited with GFR (7). Yng et l determined tht high serum irisin level ws ssocited with reduced risk of chronic kidney disese (CKD) (14). A possible explntion for this inconsistency my be due to studied different popultions. Conclusion This study presented the reltionship between serum irisin, glycemic indices, nd renl function in dibetic subjects. This reserch hs shown positive correltion between irisin nd ge nd negtive correltion between irisin nd BMI (P = 0.01, r = -0.25). We lso showed significnt difference in serum irisin level between the subjects with norml nd bnorml FBS. In generl, it seems tht serum irisin concentrtion ws incresed with ge nd decresed with BMI nd it ws higher in subject with bnorml FBS. However, further reserch is suggested to provide inclusive understnding of irisin ssocited physiologicl effects nd possible implictions in clinicl conditions. Limittions of the study Low proportion of ptients is limittion of our study. Authors contribution All uthors prticipted to design of the study. LM mnged the reserch. MS performed the investigtion. AA nd MK nlyzed the dt. MK prepred the mnuscript. All uthors red, revised nd pproved the mnuscript. Conflicts of interest The uthors declre tht they hve no competing interests. Ethicl considertions Ethicl issues (including plgirism, dt fbriction, double publiction) hve been completely observed by the uthors. Funding/ Support This study ws extrcted from MD thesis of Mrym Sdoughi (# 1252) nd supported by the Vice-Chncellery for Reserch nd Technology of Shhrekord University of Medicl Sciences. References 1. Gurigut L, Whiting D, Hmbleton I, Begley J, Linnenkmp U, Shw J. Globl estimtes of dibetes prevlence for 2013 nd projections for Dibetes Res Clin Prct. 2014;103: doi: /j. dibres Boström P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et l. A PGC1-lph-dependent myokine tht drives brown-ft-like development of white ft nd thermogenesis. Nture. 2012;481: doi: / nture Crujeirs AB, Prdo M, Arturo RR, Sntigo NC, Zulet M, Mrtínez JA, et l. Longitudinl vrition of circulting irisin fter n energy restriction induced weight loss nd following weight regin in obese men nd women. Am J Hum Biol. 2014;26: doi: /jhb Du XL, Jing WX, Lv ZT. Lower circulting irisin level in ptients with dibetes mellitus: systemtic review nd met-nlysis. Horm Metb Res. 2016;48: doi: /s Huh JH, Ahn SV, Choi JH, Koh SB, Chung CH. High Serum irisin level s n independent predictor of dibetes mellitus: longitudinl popultionbsed study. Medicine. 2016;95:e3742. doi: / MD Wen MS, Wng CY, Lin SL, Hung KC. Decrese in irisin in ptients with chronic kidney disese. PLoS One. 2013;8:e doi: /journl. pone Liu JJ, Wong MD, Toy WC, Tn CS, Liu S, Ng XW, et l. Lower circulting irisin is ssocited with type 2 dibetes mellitus. J Dibetes Complictions. 2013;27: doi: /j.jdicomp Zhng HJ, Zhng XF, M ZM, Pn LL, Chen Z, Hn HW, et l. Irisin is inversely ssocited with intrheptic triglyceride contents in obese Journl of Renl Injury Prevention, Volume 6, Issue 2, June

5 Mhmoodni L et l dults. J Heptol. 2013;59: doi: /j. jhep Hojlund K, Boström P. Irisin in obesity nd type 2 dibetes. J Dibetes Complictions. 2013;27: doi: /j.jdicomp Mehrbin S, Theri E, Krkhneh M, Qorbni M, Hosseini S. Assocition of circulting irisin levels with norml weight obesity, glycemic nd lipid profile. J Dibetes Metb Disord. 2015;15:17. doi: / s Zhng C, Ding Z, Lv G, Li J, Zhou P, Zhng J. Lower irisin level in ptients with type 2 dibetes mellitus: A cse-control study nd met-nlysis. J Ddibetes. 2016;8: doi: / Snchis-Gomr F, Lippi G, Myero S, Perez-Quilis C, Grci-Gimenez JL. Irisin: new potentil hormonl trget for the tretment of obesity nd type 2 dibetes. J Dibetes. 2012;4:196. doi: /j x. 13. Choi YK, Kim MK, Be KH, Seo HA, Jeong JY, Lee WK, et l. Serum irisin levels in new-onset type 2 dibetes. Dibetes Res Clin Prct. 2013;100: doi: /j.dibres Yng S, Xio F, Pn L, Zhng H, M Z, Liu S, et l. Assocition of serum irisin nd body composition with chronic kidney disese in obese Chinese dults: cross-sectionl study. BMC Nephrol. 2015;16:16. doi: /s Copyright 2017 The Author(s); Published by Nickn Reserch Institute. This is n open-ccess rticle distributed under the terms of the Cretive Commons Attribution License ( which permits unrestricted use, distribution, nd reproduction in ny medium, provided the originl work is properly cited. 92 Journl of Renl Injury Prevention, Volume 6, Issue 2, June