Nonalcoholic fatty liver disease and microvascular complications in type 2 diabetes

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1 Online Sumissions: doi:1.3748/wjg.v19.i.3134 World J Gstroenterol 13 My 28; 19(): ISSN (print) ISSN (online) 13 Bishideng. All rights reserved. BRIEF ARTICLE Nonlcoholic ftty liver disese nd microvsculr complictions in type 2 dietes Wen-Shn Lv, Rui-Xi Sun, Yn-Yn Go, Jun-Ping Wen, Rong-Fng Pn, Li Li, Jing Wng, Yu-Xin Xin, Ci-Xi Co, Ming Zheng Wen-Shn Lv, Rui-Xi Sun, Yn-Yn Go, Rong-Fng Pn, Li Li, Jing Wng, Yu-Xin Xin, Ci-Xi Co, the Deprtment of Internl Medicine, the Affilited Hospitl of Medicl College, Qingdo University, Qingdo 2661, Shndong Province, Chin Jun-Ping Wen, Ming Zheng, Fujin Provincil Hospitl, Fujin Provincil Geritric Hospitl, Fujin Medicl University, Fuzhou 351, Fujin Province, Chin Author contriutions: Lv WS nd Sun RX contriuted eqully to this work; Lv WS, Go YY nd Zheng M designed the reserch; Pn RF, Wen JP, Li L, Wng J, Xin YX nd Co CX performed the reserch; Lv WS nlyzed the dt nd wrote the mnuscript. Supported y Nturl Science Foundtion of Chin, No , No nd No ; nd Nturl Science Foundtion of Fujin Province, No. 11J1127 Correspondence to: Ming Zheng, MD, Fujin Provincil Hospitl, Fujin Provincil Geritric Hospitl, Fujin Medicl University, No. 88 Jiotong Rod, Fuzhou 351, Fujin Province, Chin. mingzhengcn@yeh.net Telephone: Fx: Received: Novemer 28, 12 Revised: Mrch 6, 13 Accepted: Mrch 23, 13 Pulished online: My 28, 13 Astrct AIM: To evlute the correltion etween nonlcoholic ftty liver disese (NAFLD) nd microvsculr complictions in type 2 dietes mellitus (T2DM). METHODS: Dt were otined from 1217 inptients with T2DM (757 femles, 4 mles; ged ± yers). NAFLD ws dignosed y heptic ultrsonogrphy. Dietic nephropthy (DN), dietic peripherl neuropthy (DPN), nd dietic retinopthy (DR) were dignosed ccording to their respective criteri. The prevlence of NAFLD nd the independent correltions of clinicl chrcteristics with NAFLD were determined y cross-tultion nd logistic regression, respectively. RESULTS: Approximtely 61% of inptients with T2DM in Qingdo, Chin hd NAFLD, which decresed significntly with increse in ge nd prolonged course of dietes. The prevlence of NAFLD in ptients presenting with DN, DPN nd DR ws 49.4%, 57.2% nd 54.9%, respectively. These rtes were significntly lower thn those of ptients without DN, DPN nd DR (65.9%, 65.6% nd 66.1%, respectively, P <.5). Prticipnts with NAFLD hd greter ody weight, wist circumference (WC), ody mss index (BMI), fsting lood glucose (FBG), hemogloin A1c, lnine minotrnsferse, sprtte minotrnsferse, γ-glutmyltrnsferse, lood pressure, s well s triglyceride (TG) levels nd lower high-density lipoprotein (HDL) concentrtion thn those without NAFLD (P <.5). NAFLD ws positively correlted with BMI, WC, TG, FBG, distolic lood pressure, nd systolic lood pressure ut negtively correlted with the durtion of dietes, DR, DPN, DN, nd HDL. CONCLUSION: Despite the enign nture of NAFLD, efforts should e directed towrd erly dignosis, intensive lood glucose nd lood pressure control, nd effective dyslipidemi correction. 13 Bishideng. All rights reserved. Key words: Nonlcoholic ftty liver disese; Type 2 dietes mellitus; Dietic nephropthy; Dietic retinopthy; Dietic neuropthy Core tip: Nonlcoholic ftty liver disese (NAFLD) nd dietic microngiopthy complictions represent importnt urdens for ptients with type 2 dietes mellitus (T2DM). However sed on the finding tht the prevlence of NAFLD ws negtively correlted with ge nd durtion of T2DM, we suggest tht NAFLD is enign process nd efforts should e directed t strengthening erly dignosis, intensive lood glucose 3134 My 28, 13 Volume 19 Issue

2 nd pressure control, nd effective dyslipidemi correction to prevent nd minimize occurrence of NAFLD. Lv WS, Sun RX, Go YY, Wen JP, Pn RF, Li L, Wng J, Xin YX, Co CX, Zheng M. Nonlcoholic ftty liver disese nd microvsculr complictions in type 2 dietes. World J Gstroenterol 13; 19(): Aville from: URL: DOI: INTRODUCTION Dietes is n independent risk fctor for the development of nonlcoholic ftty liver disese (NAFLD) nd progression to dvnced liver disese, including firosis, cirrhosis, nd heptocellulr crcinom [1]. Cross-sectionl studies hve reported tht the prevlence of NAFLD in ptients with type 2 dietes mellitus (T2DM) rnges from 42.1% to 75.2% in Chin [2,3]. With the rising incidence nd prevlence of T2DM in Chin [4], close estimte of the prevlence of NAFLD, s well s its clinicl risk fctors, is importnt for predicting the numer of ptients tht require monitoring for more dvnced liver diseses, or those who my enefit from future disesemodifying gents. Trgher et l [5] hve reported tht most individuls with NAFLD re older, more likely to e mle, nd hve longer durtion of dietes thn those without NAFLD. By contrst, Willimson et l [6] hve reported tht prticipnts with definite stetosis (grde 3) re significntly younger nd hve shorter durtion of dietes thn the comined norml/proly norml groups (grdes -2). Zhou et l [3] hve indicted tht the prevlence of NAFLD in men ged < 5 yers is higher thn tht in women. However, this finding is contrry for ptients > 5 yers; tht is, the prevlence of NAFLD is higher in women [3]. Thus, further studies must e conducted to scertin the differences in the prevlence of NAFLD etween the sexes nd the reltionship etween ge, durtion of dietes, nd prevlence of NAFLD. The present cross-sectionl study determined the prevlence nd some risk fctors for NAFLD nd evluted its correltions with microvsculr complictions in lrge cohort of inptients with T2DM in Qingdo, Chin. Differences in the prevlence of NAFLD etween men nd women, s well s the clinicl nd iochemicl chrcteristics of the condition, re discussed. MATERIALS AND METHODS A totl of 1217 T2DM ptients (757 women nd 4 men) prticipted in this study. All ptients were hospitlized etween Jnury 8 nd Jnury 12 t the Deprtment of Internl Medicine, Affilited Hospitl of Medicl College, Qingdo University, Chin. Most prticipnts stined from lcohol consumption (n = 117; 91%) or drnk minimlly (lcohol consumption < g/d; n = 11; 9%). Ptient informtion such s sex, irth dte, durtion of dietes, dily lcohol consumption, smoking sttus, nd medictions (including heptotoxic drugs such s glucocorticoids, miodrone, methotrexte, or ntineoplstic drugs) were otined y the questionnire method. The heights nd ody weights (BWs) of the ptients were mesured (i.e., without wering hevy cot nd shoes). Body mss index (BMI) ws clculted y dividing the BW (kg) y the squre of the height (m). Wist circumference (WC) ws mesured in stnding position t the level of the umilicus. Fsting plsm glucose (FPG), hemogloin A1c (HA1c), lnine minotrnsferse (ALT), sprtte minotrnsferse (AST), γ-glutmyltrnsferse (GGT), fsting serum triglyceride (TG), high-density lipoprotein (HDL) cholesterol, nd low-density lipoprotein (LDL) cholesterol were determined using stndrdized methods in our lortory. Serology for virl heptitis B nd C ws lso ssessed in ll prticipnts. Heptic ultrsonogrphy scnning ws performed on ptients fter n overnight fst y ssigned nd experienced rdiologists, who were linded to the helth conditions of the ptients. The liver ws grded for mrkers of heptic stetosis y using estlished criteri: right heptic echo pttern (compred with the echo response of the right kidney); incresed ttenution of the echo em; nd presence of focl ftty spring [6]. Prticipnts mnifesting symptoms of heptic stetosis or showing norml lood tests of liver function tests were further investigted for other prmeters such s ntinucler ntiody, ntismooth muscle ntiody, ntimitochondril ntiody, nd ferritin. This study ws pproved y the Ethics Committee of the Affilited Hospitl Medicl College, Qingdo University, nd ll prticipnts provided written informed consent. Definition of NAFLD NAFLD ws defined s the presence of definite heptic stetosis on ultrsound scn (i.e., grde 3) in the sence of secondry cuse for heptic stetosis. Secondry cuses were defined s: lcohol consumption 14 U/wk or prticipnt report of lcohol excess; use of heptotoxic mediction (glucocorticoids, isonizid, methotrexte, miodrone, nd tmoxifen) within 6 mo prior to the study; positive heptitis B or C serology; ferritin concentrtion 1 mg/l (milder hyperferritinemi cn e ssocited with oesity, insulin resistnce, nd NAFLD); cliniclly significnt positive immunology titers (ntismooth muscle ntiody titer 1:1 or ntimitochondril ntiody titer 1:); or previous dignosis of persistent secondry cuse for chronic liver disese ccording to their medicl records. Ptients were excluded from clcultions on the prevlence of NAFLD if their dt on the ove-mentioned mesures were missing, such tht secondry cuse could not e excluded. Dietic microvsculr complictions included di My 28, 13 Volume 19 Issue

3 Tle 1 Bseline chrcteristics of the study prticipnts, ccording to nonlcoholic ftty liver disese sttus Vriles Without NAFLD With NAFLD P vlue n Sex (femle/mle) 287/188 47/272 >.5 Age (yr) ± ± <.5 Dietes durtion (yr) ± ± 6.87 <.5 Height (cm) ± ± 8.24 >.5 BW (kg) ± ± <.5 WC (cm) ± ± 1.32 <.5 BMI (kg/m 2 ) ± ± 3.37 <.5 Current smokers (%) >.5 SBP (mmhg) ± ± <.5 DBP (mmhg) ± ± 9.57 <.5 FBG (mmol/l) 7.72 ± ± 3. <.5 HA1c (%) 8.45 ± ± 2.47 <.5 ALT (mmol/l) ± ± 13.1 <.5 AST (mmol/l) ± ± 9. <.5 GGT (mmol/l) ± ± <.5 TG (mmol/l) 1.45 ± ± 1.43 <.5 TC (mmol/l) 4.99 ± ± 1.22 >.5 LDL (mmol/l) 2.95 ± ±.82 >.5 HDL (mmol/l) 1.24 ± ±.28 <.5 Dt re expressed s men ± SD or proportions of the entire cohort of prticipnts. BW: Body weight; WC: Wist circumference; BMI: Body mss index; SBP: Systolic lood pressure; DBP: Distolic lood pressure; FBG: Fsting lood glucose; HA1c: Hemogloin A1c; ALT: Alnine minotrnsferse; AST: Asprtte minotrnsferse; GGT: γ-glutmyltrnsferse; TG: Triglyceride; TC: Totl cholesterol; LDL: Lowdensity lipoprotein; HDL: High-density lipoprotein. etic nephropthy (DN), dietic peripherl neuropthy (DPN), nd dietic retinopthy (DR). DN ws dignosed y positive persistent proteinuri for t lest three consecutive redings per yer, serum cretinine > 13 µmol/l, nd/or glomerulr filtrtion rte < ml/ min. DPN ws dignosed in the presence of persistent numness, presthesi, loss of hering of the tuning fork nd sense of virtion, nd filure to elicit knee nd/or nkle jerk. DR ws dignosed in the presence of retinl hemorrhge, exudtes, nd mculr edem [7]. Sttisticl nlysis Anlyses were conducted using SPSS version 17.. Dt re presented s mens ± SD or proportions, where pproprite. Skewed vriles (e.g., TG nd HDL) were logrithmiclly trnsformed, nd genomic mens re presented. Independent t nd χ 2 tests were used to compre the differences in mens or proportions etween different sugroups. The independent ssocitions of vriles with NAFLD were determined y inry logistic regression. A vlue of P <.5 ws considered sttisticlly significnt. RESULTS Clinicl nd iologicl chrcteristics of study popultion The men demogrphic nd clinicl chrcteristics of the ptients were s follows: ge, ± yers; durtion of dietes, 9.58 ± 7.9 yers; BW, 7.9 ± kg; WC, ± 1.48 cm; BMI, ± 3.54 kg/m 2 ; FBG, 8.48 ± 3.25 mmol/l; HA1c, 8.73% ± 2.47%; TG, 1.85 ± 1.33 mmol/l; totl cholesterol (TC), 5. ± 1.29 mmol/l; HDL, 1. ±.29 mmol/l; nd LDL, 2.95 ±.86 mmol/l. The seline chrcteristics of the study prticipnts ccording to their NAFLD sttus re presented in Tle 1. The prevlence of NAFLD in ptients with T2DM ws 61%, nd no sttisticl difference ws indicted etween men nd women (59.1% vs 62.1%, P >.5). Prticipnts with NAFLD hd higher BW, WC, BMI, FBG, HA1c, ALT, AST, GGT, lood pressure nd TG levels, nd lower HDL concentrtion thn those without NAFLD (P <.5). Menwhile, no sttisticl difference ws oserved in the smoking history, height, plsm TC, nd LDL levels etween the groups. However, prticipnts dignosed with NAFLD were younger nd hd shorter durtion of dietes thn those without NAFLD (P <.5). Prevlence of NAFLD in T2DM ptients y ge rnge nd durtion of dietes Ptients were divided into three groups ccording to ge: < 5, 5-, nd > yers. The prevlence rtes of NAFLD for the three ge groups were 73.4%, 61.6%, nd 57.8%, respectively, indicting tht the prevlence of NAFLD decresed significntly s ge incresed (Figure 1A, P <.5). This trend persisted even when ptients were clssified y sex (74.5%, 57.5%, nd 54.2% in men nd 72.3%, 65.1%, nd 59.6% in women, P <.5). Although the prevlence of NAFLD in women ws higher thn tht in men < 5 yers nd the reverse ws evident t > 5 yers, no significnt difference ws found in the prevlence of NAFLD etween men nd women t different ges (Figure 1A, P >.5). When ptients were divided into three groups ccording to durtion of dietes, tht is, < 5 yers, 5-1 yers, nd > 1 yers, the prevlence rtes of NAFLD were 74.9%, 65.5%, nd 5.7%, respectively. This indictes tht the prevlence of NAFLD decresed significntly s dietes ws prolonged (Figure 1B, P <.5). This trend persisted even when ptients were clssified y sex (72.3%, 65.6%, nd 47.1% in men nd 76.5%, 65.4%, nd 52.6% in femles, respectively, P <.5). No significnt difference ws indicted in the prevlence rte of NAFLD etween men nd women with different durtions of dietes (Figure 1B, P >.5). Prevlence of NAFLD in T2DM with or without microngiopthic complictions The incidence of NAFLD ws found to correlte negtively with DN, s shown in Figure 2A (r = -.154, P <.5). The generl prevlence of NAFLD in T2DM with nd without DN ws 49.4% nd 65.9%, respectively (P <.5). This trend persisted even when ptients were strtified y sex (r = -.13 in men, r = -.17 in women, 3136 My 28, 13 Volume 19 Issue

4 A B 1 Prevlence of NAFLD in T2DM ptients with different ge rges Prevlence of NAFLD with different durtion of dietes Below 5 yr Between 5- yr Aove yr Below 5 yr Between 5- yr Aove yr Below 5 yr Between 5- yr Aove yr Less thn 5 yr 5-1 yr Longer thn 1 yr Less thn 5 yr 5-1 yr Longer thn 1 yr Less thn 5 yr 5-1 yr Longer thn 1 yr Figure 1 Prevlence of nonlcoholic ftty liver disese in type 2 dietes mellitus ptients ccording to different ge rnges nd durtions of dietes. A: Prevlence of nonlcoholic ftty liver disese (NAFLD) in ptients ged < 5, 5-, nd > yers ws 73.4%, 61.6%, nd 57.8%, respectively, indicting tht the prevlence of NAFLD decresed significntly with incresing ge ( P <.1 vs group elow 5 yers). In men (74.5%, 57.5%, nd 54.2%, respectively, P <.1 vs group elow 5 yers) nd women (72.3%, 65.1%, nd 59.6%, respectively, P <.5 vs group elow 5 yers), the prevlence of NAFLD decresed significntly with incresing ge. The prevlence of NAFLD in men ws higher thn in women (74.5% nd 72.3%, respectively, P >.5) in the < 5 yers ge group; however, the reverse ws evident in the > 5 yers ge group (57.5% nd 65.1%, respectively, in the 5- yers ge group, nd 54.2% nd 59.6%, in the > yers ge group, oth P >.5); B: Prevlence of NAFLD, ccording to durtion of dietes, ws 74.9%, 65.5%, nd 5.7% for < 5, 5-1, nd > 1 yers, respectively. Prevlence of NAFLD decresed significntly with prolonged course of dietes ( P <.1 vs group less thn 5 yers). This trend persisted even when ptients were strtified y sex (72.3%, 65.6%, nd 47.1%, respectively, in men, nd 76.5%, 65.4%, nd 52.6% in women, P <.1 vs group less thn 5 yers). There were no significnt differences in the prevlence of NAFLD etween men nd women with different durtions of dietes (P >.5). T2DM: Type 2 dietes mellitus. A Prevlence of NAFLD with or without DN Without DN With DN Without DN With DN Without DN With DN B Prevlence of NAFLD with or without DPN Without DPN With DPN Without DPN With DPN Without DPN With DPN C Prevlence of NAFLD with or without DR Without DR With DR Without DR With DR Without DR With DR Figure 2 Prevlence of nonlcoholic ftty liver disese in T2DM with or without microngiopthy complictions. A: Incidence of nonlcoholic ftty liver disese (NAFLD) negtively correlted with DN (r = -.154, P <.5). This trend persisted even when ptients were strtified y sex (r = -.13 in men, r = -.17 in women, oth P <.5). Prevlence of NAFLD in T2DM with nd without DN ws 49.4% nd 65.9%, respectively ( P <.1 vs group without DN). Prevlence of NAFLD in men without DN ws significntly higher thn in ptients with DN (63.3% nd 49.3%, respectively, P <.1 vs the group without DN). Prevlence of NAFLD in women without DN ws significntly higher thn in ptients with DN (67.5% nd 49.5%, respectively, P <.1 vs the group without DN); B: Incidence of NAFLD negtively correlted with DPN (r = -.86, P <.5). This trend persisted even when ptients were strtified y sex (r = -.95 in men, r = -.84 in women, oth P <.5). The generl prevlence of NAFLD in T2DM with nd without DPN ws 57.2% nd 65.6%, respectively ( P <.1 vs the group without DPN). Prevlence of NAFLD in men without DPN ws significntly higher thn in ptients with DPN (63.9% nd 54.5%, respectively, P <.5 vs the group without DPN). Prevlence of NAFLD in women without DPN ws lso significntly higher thn tht in ptients with DPN (66.9% nd 58.6%, respectively, P <.5 vs the group without DPN); C: Incidence of NAFLD negtively correlted with DR (r = -.114, P <.5). This trend persisted even when ptients were strtified y sex (r = in men, r = -.76 in women, oth P <.5). Prevlence of NAFLD in T2DM with nd without DR ws 54.9% nd 66.1%, respectively ( P <.1 vs the group without DR). Furthermore, the Prevlence of NAFLD in men without DR ws significntly higher thn tht in ptients with DR (66.9% nd 49.5%, respectively, P <.1 vs the group without DR). Prevlence of NAFLD in women without DR ws lso significntly higher thn tht in ptients with DR (65.5% nd 58.1%, respectively, P <.5 vs the group without DR) My 28, 13 Volume 19 Issue

5 Tle 2 Risk fctors for nonlcoholic ftty liver disese Vriles SE P vlue OR 95%CI Totl ptients with T2DM logbmi logwc logtg FBG DBP SBP Durtion of dietes DR DPN DN loghdl Mle ptients with T2DM logbmi logtg DBP Durtion of dietes loghdl Femle ptients with T2DM logbmi logtg FBG SBP Durtion of dietes DPN DR DN T2DM: Type 2 dietes mellitus; WC: Wist circumference; TG: Triglyceride; BMI: Body mss index; FBG: Fsting lood glucose; SBP: Systolic lood pressure; DBP: Distolic lood pressure; HDL: Highdensity lipoprotein; DR: Dietic retinopthy; DPN: Dietic peripherl neuropthy; DN: Dietic nephropthy. oth P <.5). The prevlence of NAFLD in men without DN ws significntly higher thn tht of ptients with DN (63.3% nd 49.3%, respectively, P <.5). Similrly, the prevlence of NAFLD in women without DN is significntly higher thn tht of ptients with DN (67.5% nd 49.5%, respectively, P <.5). The incidence of NAFLD ws found to correlte negtively with DPN, s shown in Figure 2B (r = -.86, P <.5). The generl prevlence of NAFLD in T2DM with nd without DPN ws 57.2% nd 65.6%, respectively (P <.5). This trend lso persisted when ptients were strtified y sex (r = -.95 in men, r = -.84 in women, oth P <.5). The prevlence of NAFLD in men without DPN ws significntly higher thn tht of ptients with DPN (63.9% nd 54.5%, respectively, P <.5). Similr results were found in women (66.9% nd 58.6%, respectively, P <.5). The incidence of NAFLD ws negtively correlted with DR, s shown in Figure 2C (r = -.114, P <.5). The generl prevlence of NAFLD in T2DM with nd without DR ws 54.9% nd 66.1%, respectively (P <.5). This trend persisted even when ptients were strtified y sex (r = in men, r = -.76 in women, oth P <.5). The prevlence of NAFLD in men without DR ws significntly higher thn tht of ptients with DR (66.9% nd 49.5%, respectively, P <.5). Similr results were determined in women (65.5% nd 58.1%, respectively, P <.5). Risk fctors for the development of NAFLD in ptients with T2DM With NAFLD s the dependent vrile, the vriles tht were independently ssocited with NAFLD in T2DM ptients were identified y inry stepwise logistic regression. Independent predictors of NAFLD were BMI (OR for log BMI: ; 95%CI: ), WC (OR for log WC: ; 95%CI: ), TG (OR for log TG: 7.79; 95%CI: ), FBG (OR = 1.8; 95%CI: ), distolic lood pressure (DBP) (OR = 1.3; 95%CI: ), systolic lood pressure (SBP) (OR = 1.3; 95%CI: ), durtion of dietes (OR =.96; 95%CI: ), DR (OR =.71; 95%CI: ), DPN (OR =.69; 95%CI:.5-.95), DN (OR =.32; 95%CI: ), nd HDL (OR for log HDL:.17; 95%CI:.3-.89) (Tle 2). However, the risk fctors for NAFLD in men nd women were not identicl. Independent predictors of NAFLD in men were BMI (OR for log BMI: ; 95%CI: ), TG (OR for log TG: 37.88; 95%CI: ), DBP (OR = 1.9; 95%CI: ), durtion of dietes (OR =.94; 95%CI:.9-.98), nd HDL (OR: for log HDL:.1; 95%CI: -.21) (Tle 2). Independent predictors of NAFLD in women were BMI (OR for log BMI: ; 95%CI: ), TG (OR for log TG: 3.48; 95%CI: ), FBG (OR = 1.22; 95%CI: ), SBP (OR = 1.4; 95%CI: ), durtion of dietes (OR =.96; 95%CI: ), DPN (OR =.65; 95%CI: ), DR (OR =.61; 95%CI: ), nd DN (OR =.29; 95%CI: ) (Tle 2). DISCUSSION NAFLD represents n importnt urden of disese for ptients with T2DM; however, the mgnitude of the prolem is currently unknown. In this study, the prevlence of NAFLD in hospitlized Chinese T2DM ptients ws clculted t 61%. This prevlence is lower thn tht reported y Lu et l [2] in 9 (75.18%) ut mrkedly higher compred with tht reported y Zhou et l [3] conducted 5 yers go (42.1%). A limittion of this study ws tht the dignosis of NAFLD ws sed on ultrsound imging. The ptients did not undergo liver iopsy nd histologicl exmintion, which is the gold stndrd technique for identifying stetosis. The sensitivity of ultrsonogrphy in detecting 3138 My 28, 13 Volume 19 Issue

6 stetosis vries etween % nd 94% nd is dependent on the degree of stetosis. In prticulr, sensitivity is significntly low when the degree of stetosis is < 3% [5,8]. Furthermore, some prticipnts with norml ultrsound scns my hve undignosed heptic firosis nd thus e considered severe cse of NAFLD [6]. Therefore, the cses tht were potentilly misclssified y ultrsonogrphy might hve resulted in n underestimted prevlence of NAFLD. This limittion might hve ttenuted the mgnitude of our effect mesures to null. The findings of this study my then e considered conservtive estimtes of the prevlence of NAFLD in hospitlized Chinese T2DM ptients. This study reveled tht the prevlence of NAFLD in mle hospitlized T2DM ptients ws 59.1%, which ws slightly lower thn tht in femle ptients (62.1%), ut without sttisticl significnce. When ptients were divided into three groups ccording to their ge (i.e., < 5, 5-, nd > yers), the prevlence of NAFLD in women ws higher thn in men ged < 5 yers, wheres the reverse ws evident when ge ws > 5 yers. However, no significnt difference ws indicted in the prevlence of NAFLD etween mle nd femle ptients t different ges. This finding differs from tht of Zhou et l [3], who reported tht the prevlence of ftty liver in ptients < 5 yers old ws significntly higher in men thn women; however, the reverse ws evident when prticipnts were older thn 5 yers. In the present study, severl mle ptients with NFALD, especilly those ged < 5 yers, were excluded for overdrinking. With this fctor considered, the prevlence of NAFLD in mle hospitlized T2DM ptients my e significntly higher thn tht of femle ptients. In our study, ptients were ssessed ccording to three ge groups. The prevlence rtes of NAFLD significntly decresed s ge incresed. This trend persisted even when the ptients were strtified y sex. These oservtions re inconsistent with those of Trgher et l [5], who reported tht the prevlence of NAFLD incresed with ge (i.e., 65.4% mong prticipnts ged -59 yers nd 74.6% mong those ged yers; P <.1). By contrst, Lu et l [2] found tht the prevlence of NAFLD in Chinese T2DM ptients did not increse with ge. In prticulr, T2DM ptients in Chin ged -59 yers re more prone to NAFLD. These findings re consistent with those pulished in review y Duvnjk et l [9], which reports tht the highest prevlence of NAFLD occurs in those ged - yers. A potentil explntion for these oservtions is tht middle-ged persons re often too usy to prticipte in physicl exercise nd re more likely to dine outside of the home, wheres older nd retired persons my hve more time for physicl exercise nd devote more ttention to their lifestyle. These ehviors mong middle-ged persons my e one reson why Chinese ptients with T2DM re more vulnerle to NAFLD, considering tht the prevlence of NAFLD does not increse with ge [2]. Ptients were lso ssessed ccording to the durtion of dietes (i.e., < 5, 5-1, nd > 1 yers). The prevlence rtes of NAFLD decresed significntly with the prolonged course of dietes. This trend persisted even when ptients were strtified y sex. No significnt difference ws oserved in the prevlence of NAFLD etween mle nd femle ptients with different durtions of dietes. These findings contrdict those of Bnerjee et l [1], who found tht longer durtion of T2DM ws significntly ssocited with NAFLD. The ssocition of shorter durtion of dietes with liver disese hs een previously descried. A possile explntion for this ssocition my e tht greter degree of hyperinsulinemi in erly T2DM increses the uptke of free ftty cids (FFAs) y heptocytes [6]. Popović et l [11] presented significnt negtive correltion etween the durtion of dietes nd fsting insulinemi s well s insulin resistnce ssessed y homeosttic model ssessment-insulin resistnce index. Incresed fsting insulinemi nd heptic insulin resistnce my trigger reduced ctolism of lipoproteins rich in TGs nd n incresed heptic very LDL production vi chnges in the rte of polipoprotein B synthesis nd degrdtion, s well s de novo lipogenesis or incresed FFA flux from dipose tissue into the liver [12]. In this study, we demonstrted tht the generl prevlence of dietic microngiopthy complictions (i.e., DN, DPN nd DR) incresed significntly with ge incresed (dt not shown). This trend persisted even when the ptients were strtified y sex. When the ptients were strtified y durtion of T2DM, the prevlence rtes of dietic microngiopthy complictions incresed significntly with prolonged durtion of T2DM (dt not shown). In previous reports, the ge nd durtion of dietes were common risk fctors for the three microvsculr complictions of T2DM [13-17]. Thus, chronic microvsculr dietic complictions increse grdully with prolonged durtion of T2DM, nd the clinicl symptoms tend to worsen progressively. Consequently, these ptients need to py more ttention to their lifestyle nd drug therpy. Therefore, the incidence of NAFLD does not increse with prolonged durtion of T2DM. The development of NAFLD is multifceted cscde of physiologicl nd iochemicl events, including genetic, environmentl, metolic, nd stress-relted fctors; the exct risk fctors for NAFLD hve not een clerly identified [18]. On the sis of the univrite nlysis results, ptients dignosed with NAFLD were significntly younger nd hd shorter durtion of dietes thn those without NAFLD. The BW, WC, BMI, SBP, DBP, FBG, HA1c, nd TG were significntly higher, nd HDL cholesterol ws significntly lower in ptients with NAFLD (Tle 1, P <.5). Multivrite nlysis identified the following s independent pre My 28, 13 Volume 19 Issue

7 dictors of NAFLD: BMI, WC, TG, FBG, DBP, SBP, durtion of dietes, DR, DPN, DN, nd HDL. This oservtion is consistent with the findings reported in literture tht the prevlence of NAFLD is closely ssocited with oesity, dyslipidemi, hypertension, nd glucose intolernce, cluster of metolic disorders tht is now recognized s metolic syndrome [1,18,19]. However, the negtive correltions etween the prevlence of NAFLD nd the durtion of dietes, DR, DPN, nd DN identified in this study re inconsistent with the dt reported in previous studies [1]. Given the negtive correltions etween the prevlence of NAFLD s well s the durtion of dietes nd dietic chronic microvsculr complictions, more ttention should e given to lifestyle nd drug therpy, prticulrly in ptients presenting n ggrvtion in ny of the clinicl symptoms mentioned ove. Despite the difference in the independent risk fctors for NAFLD etween men (Tle 2) nd women (Tle 2), oth positively correlted with BMI, TG, nd hypertension nd negtive correltion with the durtion of dietes. In men, the prevlence of NAFLD positively correlted with DBP ut negtively with HDL (Tle 2). In women, the prevlence of NAFLD positively correlted with FBG nd SBP ut negtively with DPN, DR nd DN (Tle 2). According to previous study, SBP represents the most prevlent type in oese women, eing stronger predictor of crdiovsculr disese thn DBP []. Therefore, the regultion of SBP is more criticl for women. Although most ptients with NAFLD presented with non-progressive lnd stetosis, few others developed histologicl sutype of nonlcoholic stetoheptitis (NASH), which cn develop to cirrhosis, heptocellulr crcinom, nd liver-cncer-relted deth [9,21,22], especilly for NASH ptients with T2DM [21,23,24]. Thus, specilists hve considered tht NAFLD my not e completely enign disorder [9,25]. On the contrry, we consider NAFLD enign condition ecuse of the negtive reltionship etween the prevlence of NAFLD with ge nd durtion of T2DM. No tretment to llevite NAFLD or prevent its progression hs een scientificlly proven. However, vrious therpeutic lterntives imed t interfering with the risk fctors involved in the pthogenesis of this disorder hve een pplied to prevent the progression of NAFLD to end-stge liver disese. The most importnt therpeutic mesure is to increse insulin sensitivity y motivting ptients to chnge their lifestyle hits, prticulrly y diet modifiction nd prticiption in physicl ctivities to lose weight [26,27]. Tushuizen et l [28] reported tht fter 44 wk of exentide therpy, ptients experienced 73% reduction in heptic ft content (i.e., from seline of 15.8% to 4.3%), s evluted y proton mgnetic resonnce spectroscopy. This finding is consistent with tht reported y Ding et l [29] on the reduced heptic lipid content in exentide-treted o/o or oese mice compred with plceo-treted mice. Lzo et l [3] reported tht 12-mo intensive lifestyle intervention in ptients with T2DM significntly reduced stetosis nd NAFLD. In ddition, Lo et l [24] hve reported tht diet-induced NASH firosis is excerted y dietes nd ttenuted y insulin therpy. On the sis of these findings, we elieve tht NAFLD is reversile, nd ptients my enefit from its erly dignosis nd tretment [31]. In conclusion, the results of this study suggest tht NAFLD is extremely common in people with T2DM, positively correltes with BMI, WC, TG, FBG, DBP, nd SBP, nd negtively correltes with the durtion of dietes, DR, DPN, DN, nd HDL. Given tht heptic ft content cn e reversed with lifestyle chnges nd drugs, NAFLD should e included in future preventive pulic helth inititives, nd the ffected individuls should e motivted to dopt helthier lifestyle [27]. Ptients with T2DM should e lwys ssessed for NAFLD to ensure erly dignosis nd entry into proper nd thorough medicl cre. Future efforts should e directed towrd strengthening erly dignosis, intensive lood glucose nd lood pressure control, nd effective dyslipidemi correction to prevent nd minimize the occurrence of NAFLD. COMMENTS Bckground Dietes is n independent risk fctor for the development of nonlcoholic ftty liver disese (NAFLD) nd its progression to more dvnced liver diseses, including firosis, cirrhosis, nd heptocellulr crcinom. NAFLD nd dietic microngiopthy complictions represent importnt urdens of disese for ptients with type 2 dietes mellitus (T2DM), Previous studies hve shown tht the prevlence of NAFLD nd microngiopthy complictions in ptients with T2DM significntly correlte with ge nd durtion of T2DM. However, few studies hve focused on the reltionship etween NAFLD nd dietic microngiopthy complictions. Reserch frontiers Mny studies hve reported tht individuls with NAFLD re older, more likely to e mle, nd hve longer durtion of dietes thn those without NAFLD. However, recently, conflicting results hve shown tht prticipnts with definite stetosis re significntly younger nd hve shorter durtions of dietes thn the comined norml/proly norml groups. Further studies re required to scertin the differences in the prevlence of NAFLD etween the sexes, nd the reltionships etween ge, durtion of dietes, nd prevlence of NAFLD. Innovtions nd rekthroughs The reltively lrger cross-sectionl study of inptients with T2DM in Qingdo, Chin showed tht the prevlence of NAFLD ws 61%. However, sed on the finding tht the prevlence of NAFLD ws negtively correlted with ge nd durtion of T2DM, the uthors elieve tht NAFLD is enign process. Applictions Our results suggest tht ptients with T2DM should e lwys ssessed for NAFLD to ensure erly dignosis nd entry into proper nd thorough medicl cre. Future efforts should e directed t strengthening erly dignosis, intensive lood glucose nd pressure control, nd effective dyslipidemi correction to prevent nd minimize the occurrence of NAFLD. Terminology NAFLD is defined s the presence of definite heptic stetosis on ultrsound scn in the sence of secondry cuse for heptic stetosis. Dietic microvsculr complictions included dietic nephropthy (DN), dietic peripherl neuropthy (DPN), nd dietic retinopthy (DR). DN is defined y incresed urinry lumin excretion in the sence of urinry trct infection or other renl normlities. DPN is dignosed in the presence of persistent numness, pr- 31 My 28, 13 Volume 19 Issue

8 esthesi, loss of hering of the tuning fork nd sense of virtion, nd filure to elicit knee nd/or nkle jerk. DR is dignosed in the presence of retinl hemorrhges, exudtes, nd mculr edem. Peer review This ws good descriptive study in which the uthors evluted the correltion etween NAFLD nd microvsculr complictions in Chinese T2DM ptients. The results re interesting nd suggest tht NAFLD is likely enign process nd efforts should e directed t erly dignosis, intensive lood glucose nd lood pressure control, nd effective dyslipidemi correction, which is of clinicl interest. REFERENCES 1 El-Serg HB, Trn T, Everhrt JE. Dietes increses the risk of chronic liver disese nd heptocellulr crcinom. Gstroenterology 4; 126: [PMID: DOI: 1.153/j.gstro ] 2 Lu H, Zeng L, Ling B, Shu X, Xie D. High prevlence of coronry hert disese in type 2 dietic ptients with nonlcoholic ftty liver disese. Arch Med Res 9; : [PMID: DOI: 1.116/j.rcmed.9.7.9] 3 Zhou J, Ji WP, Bo YQ, M XJ, Lu W, Yu M, Pn JM, Hu C, Xing KS. [Study on prevlence nd risk fctors of ftty liver of ptients with type 2 dietes]. Zhonghu Yi Xue Zzhi 7; 87: [PMID: 11543] 4 Yng W, Lu J, Weng J, Ji W, Ji L, Xio J, Shn Z, Liu J, Tin H, Ji Q, Zhu D, Ge J, Lin L, Chen L, Guo X, Zho Z, Li Q, Zhou Z, Shn G, He J. Prevlence of dietes mong men nd women in Chin. N Engl J Med 1; 362: [PMID: DOI: 1.156/NEJMo98292] 5 Trgher G, Bertolini L, Pdovni R, Rodell S, Tessri R, Zenri L, Dy C, Arcro G. Prevlence of nonlcoholic ftty liver disese nd its ssocition with crdiovsculr disese mong type 2 dietic ptients. Dietes Cre 7; 3: [PMID: DOI: /dc6-2247] 6 Willimson RM, Price JF, Glncy S, Perry E, Nee LD, Hyes PC, Frier BM, Vn Look LA, Johnston GI, Reynolds RM, Strchn MW. Prevlence of nd risk fctors for heptic stetosis nd nonlcoholic Ftty liver disese in people with type 2 dietes: the Edinurgh Type 2 Dietes Study. Dietes Cre 11; 34: [PMID: DOI: /dc1-2229] 7 Alwkeel JS, Al-Suwid A, Isnni AC, Al-Hri A, Alm A. Concomitnt mcro nd microvsculr complictions in dietic nephropthy. Sudi J Kidney Dis Trnspl 9; : 2-9 [PMID: ] 8 Fierintenu-Brticevici C, Din I, Petrisor A, Trius L, Negrenu L, Crstoiu C. Noninvsive investigtions for non lcoholic ftty liver disese nd liver firosis. World J Gstroenterol 1; 16: [PMID: DOI: / wjg.v16.i ] 9 Duvnjk M, Lerotić I, Brsić N, Tomsić V, Virović Jukić L, Velgić V. Pthogenesis nd mngement issues for nonlcoholic ftty liver disese. World J Gstroenterol 7; 13: [PMID: ] 1 Bnerjee S, Ghosh US, Dutt S. Clinicopthologicl profile of heptic involvement in type-2 dietes mellitus nd its significnce. J Assoc Physicins Indi 8; 56: [PMID: ] 11 Popović L, Zmklr M, Llić K, Vsović O. [Anlysis of the effect of dietes type 2 durtion on et cell secretory function nd insulin resistnce]. Srp Arh Celok Lek 6; 134: [PMID: ] 12 Meshkni R, Adeli K. Heptic insulin resistnce, metolic syndrome nd crdiovsculr disese. Clin Biochem 9; 42: [PMID: ] 13 Liu Z, Fu C, Wng W, Xu B. Prevlence of chronic complictions of type 2 dietes mellitus in outptients - cross-sectionl hospitl sed survey in urn Chin. Helth Qul Life Outcomes 1; 8: 62 [PMID: DOI: / ] 14 Chorny A, Lifshits T, Krtz A, Levy J, Golfr D, Zlotnik A, Knyzer B. [Prevlence nd risk fctors for dietic retinopthy in type 2 dietes ptients in Jewish nd Bedouin popultions in southern Isrel]. Hrefuh 11; 15: 96-91, 935 [PMID: ] 15 Prdeep R, Anjn RM, Unnikrishnn R, Gnesn A, Mohn V, Rem M. Risk fctors for microvsculr complictions of dietes mong South Indin sujects with type 2 dietes--the Chenni Urn Rurl Epidemiology Study (CURES) Eye Study-5. Dietes Technol Ther 1; 12: [PMID: DOI: 1.189/di.1.69] 16 Prdeep R, Rem M, Vignesh J, Deep M, Deep R, Mohn V. Prevlence nd risk fctors for dietic neuropthy in n urn south Indin popultion: the Chenni Urn Rurl Epidemiology Study (CURES-55). Diet Med 8; 25: [PMID: DOI: / j x] 17 Yokoym H, Yokot Y, Td J, Knno S. Dietic neuropthy is closely ssocited with rteril stiffening nd thickness in Type 2 dietes. Diet Med 7; 24: [PMID: DOI: /j x] 18 Fng JG, Zhu J, Li XJ, Li R, Di F, Song XM, Chen L, Li F, Chen SY. [Epidemiologicl survey of prevlence of ftty liver nd its risk fctors in generl dult popultion of Shnghi]. Zhonghu Gn Zng Bing Zzhi 5; 13: [PMID: ] 19 Trntino G, Sldlmcchi G, Conc P, Aren A. Nonlcoholic ftty liver disese: further expression of the metolic syndrome. J Gstroenterol Heptol 7; 22: [PMID: ] Trntino G, Pizz G, Colo A, Psnisi F, Conc P, Colicchio P, Finelli C, Contldo F, Di Somm C, Svstno S. Heptic stetosis in overweight/oese femles: new screening method for those t risk. World J Gstroenterol 9; 15: [PMID: ] 21 Lm B, Younossi ZM. Tretment options for nonlcoholic ftty liver disese. Therp Adv Gstroenterol 1; 3: [PMID: DOI: / X ] 22 Buginesi E, Vnni E, Mrchesini G. NASH nd the risk of cirrhosis nd heptocellulr crcinom in type 2 dietes. Curr Di Rep 7; 7: [PMID: ] 23 Adms LA, Hrmsen S, St Suver JL, Chrtchroenwitthy P, Enders FB, Therneu T, Angulo P. Nonlcoholic ftty liver disese increses risk of deth mong ptients with dietes: community-sed cohort study. Am J Gstroenterol 1; 15: [PMID: 1459 DOI: 1.138/ jg.1.18] 24 Lo L, McLennn SV, Willims PF, Bonner J, Chowdhury S, McCughn GW, Gorrell MD, Yue DK, Twigg SM. Dietes is progression fctor for heptic firosis in high ft fed mouse oesity model of non-lcoholic stetoheptitis. J Heptol 11; 55: [PMID: DOI: 1.116/ j.jhep ] 25 Trntino G, Conc P, Riccio A, Trntino M, Di Minno MN, Chinese D, Psnisi F, Contldo F, Scopcs F, Cpone D. Enhnced serum concentrtions of trnsforming growth fctor-et1 in simple ftty liver: is it relly enign? J Trnsl Med 8; 6: 72 [PMID: 193 DOI: / ] 26 Rszej-Wyszomirsk J, Lwniczk M, Mrlicz W, Miezyńsk-Kurtycz J, Milkiewicz P. [Non-lcoholic ftty liver disese--new view]. Pol Merkur Lekrski 8; 24: [PMID: ] 27 Frrell GC, Lrter CZ. Nonlcoholic ftty liver disese: from stetosis to cirrhosis. Heptology 6; 43: S99-S112 [PMID: DOI: 1.12/hep.973] 3141 My 28, 13 Volume 19 Issue

9 28 Tushuizen ME, Bunck MC, Pouwels PJ, vn Weserghe JH, Dimnt M, Heine RJ. Incretin mimetics s novel therpeutic option for heptic stetosis. Liver Int 6; 26: [PMID: DOI: / j x] 29 Ding X, Sxen NK, Lin S, Gupt NA, Anni FA. Exendin-4, glucgon-like protein-1 (GLP-1) receptor gonist, reverses heptic stetosis in o/o mice. Heptology 6; 43: [PMID: DOI: 1.12/hep.216] 3 Lzo M, Solg SF, Horsk A, Bonekmp S, Diehl AM, Brncti FL, Wgenknecht LE, Pi-Sunyer FX, Khn SE, Clrk JM. Effect of 12-month intensive lifestyle intervention on heptic stetosis in dults with type 2 dietes. Dietes Cre 1; 33: [PMID: 6619 DOI: / dc1-856] 31 Cusi K. Nonlcoholic ftty liver disese in type 2 dietes mellitus. Curr Opin Endocrinol Dietes Oes 9; 16: [PMID: DOI: 1.197/MED.13e ] P- Reviewers Buechler C, Hsieh PS, Trntino G S- Editor Wen LL L- Editor Kerr C E- Editor Zhng DN 3142 My 28, 13 Volume 19 Issue