1

Introduction

pÉÇÉåí~êó=äáÑÉëíóäÉë=ÅçìéäÉÇ=ïáíÜ=ÉñÅÉëëáîÉ=Å~äçêáÅ=áåí~âÉ=Ü~îÉ=ÄÉÉå=ã~àçê=ÇÉíÉêãáå~åíëíç=íÜÉ=ÉñéäçëáîÉ=áåÅêÉ~ëÉ=áå=íÜÉ=éêÉî~äÉåÅÉ=çÑ=çÄÉëáíó=~åÇ=íóéÉ=O=Çá~ÄÉíÉë=ãÉääáíìë=EqOajFKbåÇçÅêáåçäçÖáëíë= ~êÉ= ÉåÅçìåíÉêáåÖ= çå= ~= Ç~áäó= Ä~ëáë= é~íáÉåíë= ïáíÜ= çÄÉëáíóJêÉä~íÉÇÅçãéäáÅ~íáçåëI=ëìÅÜ=~ë=ãÉí~ÄçäáÅ=ëóåÇêçãÉ=EjÉípF=~åÇ=qOajK=qÜÉ=ÉéáÇÉãáÅ=çÑ=qOaj=Ü~ëÇêáîÉå= ÜÉ~äíÜ= Å~êÉ= éêçîáÇÉêë= íç= ÖáîÉ= áåÅêÉ~ëáåÖ= ~ííÉåíáçå= íç= íÜÉ= É~êäó= Çá~Öåçëáë= ~åÇíêÉ~íãÉåí=çÑ=Çá~ÄÉíáÅ=ÅçãéäáÅ~íáçåëK=eçïÉîÉêI=åçí=ìåíáä=êÉÅÉåíäó=Ü~ë=åçåJ~äÅçÜçäáÅ=Ñ~ííó=äáîÉêÇáëÉ~ëÉ=Ek^ciaF=ÄÉÉå=êÉÅçÖåáòÉÇ=~ë=~åçíÜÉê=Åçããçå=ÅçãéäáÅ~íáçå=çÑ=é~íáÉåíë=ïáíÜ=qOajíÜ~í=êÉèìáêÉë=ëéÉÅá~ä=~ííÉåíáçåK=oÉ~ëçåë=Ñçê=íÜáë=ã~ó=ÄÉ=êÉä~íÉÇ=íç=íÜÉ= ä~Åâ=çÑ=~ï~êÉåÉëë~Äçìí= íÜÉ= áåÅêÉ~ëÉÇ= ëìëÅÉéíáÄáäáíó= íç= Ñ~ííó= äáîÉê= ÇáëÉ~ëÉ= çÑ= é~íáÉåíë=ïáíÜ= qOajI= áåÜÉêÉåíÇáÑÑáÅìäíáÉë=áå=ã~âáåÖ=íÜÉ=Çá~Öåçëáë=~åÇ=áåÅçãéäÉíÉ=ìåÇÉêëí~åÇáåÖ=~Äçìí=íÜÉ=å~íìê~ä=ÜáëíçêóçÑ=íÜÉ=ÇáëÉ~ëÉK=qÜÉ=ã~å~ÖÉãÉåí=çÑ=é~íáÉåíë=ïáíÜ=k^cia=Ü~ë=íê~Çáíáçå~ääó=ÄÉäçåÖÉÇ=íç=íÜÉêÉ~äã=çÑ=ÜÉé~íçäçÖáëíëI=Äìí=êÉ~äáò~íáçå=íÜ~í=íÜÉ=ã~àçêáíó=çÑ=çÄÉëÉ=çê=qOaj=é~íáÉåíë=ã~ó=Ü~îÉ~= Ñ~ííó= äáîÉê= Ü~ë= ÄÉÅçãÉ= ~= åÉï= ~åÇ= ÅçåÅÉêåáåÖ= ãÉÇáÅ~ä= ÇáäÉãã~= Ñçê= éêáã~êó= Å~êÉéÜóëáÅá~åë= ~åÇ= ÉåÇçÅêáåçäçÖáëíëK= qÜáë= ÅÜ~éíÉê= ïáää= ÄêáÉÑäó= êÉîáÉï= çìê= ÅìêêÉåí= âåçïäÉÇÖÉ~Äçìí=k^cia=íêóáåÖ=íç=éáÉÅÉ=íçÖÉíÜÉê=çìê=áåÅçãéäÉíÉ=âåçïäÉÇÖÉ=çÑ=íÜÉ=ÇáëÉ~ëÉ=~åÇ=ïÉáÖÜíáåíç=íÜÉ=ÅçåíêçîÉêëó=çå=ïÜÉíÜÉê=íÜáë=ÅçåÇáíáçå=Å~êêáÉë=~å=áåÇÉéÉåÇÉåí=~åÇ=áåÜÉêÉåí=ÜÉ~äíÜêáëâ=çê=áí=áë=ëáãéäó=~å=ÉéáéÜÉåçãÉåçå=çÑ=~=ëí~íÉ=çÑ=áåëìäáå=êÉëáëí~åÅÉ=~åÇ=~Äåçêã~ä=ÖäìÅçëÉãÉí~ÄçäáëãK=

Non-alcoholic fatty liver disease (NAFLD) indiabetes: distraction or impending disaster?

Romina Lomonaco MD, Assistant Professor Division of Endocrinology, Diabetes and Metabolism, University of Florida,Gainesville, Florida, USA

Kenneth Cusi MD, Chief and Professor Division of Endocrinology, Diabetes and Metabolism, University of Florida,Gainesville, Florida and the Malcom Randall Veterans Affairs Medical Center(VAMC), Gainesville, Florida, USA

Chapter 21

Natural history

NAFLD and liver disease progression

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Evidence-based Management of Diabetes

2

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21 Non-alcoholic fatty liver disease (NAFLD) in diabetes: distraction or impending disaster?

3

Table 1. Natural history of NASH: disease progression in studies with paired liver biopsies.

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^å=~ëéÉÅí=çÑ= íÜÉëÉ=ëíìÇáÉë= íÜ~í= Ü~ë= áãéçêí~åí= ÅäáåáÅ~ä= áãéäáÅ~íáçåë= áë= íÜÉ=çîÉê~ää= ä~Åâ=çÑÅçêêÉä~íáçå=ÄÉíïÉÉå=éä~ëã~=~ãáåçíê~åëÑÉê~ëÉë=äÉîÉäë=~åÇ=ÅÜ~åÖÉë=áå=äáîÉê=ÑáÄêçëáë=çîÉê=íáãÉKtÜáäÉ= ëçãÉ= ëíìÇáÉë= Ü~îÉ= ÑçìåÇ= ~= ïÉ~â= ÅçêêÉä~íáçå= ÄÉíïÉÉå= äáîÉê= ÇáëÉ~ëÉ= ~åÇ= éä~ëã~~ãáåçíê~åëÑÉê~ëÉë=TI=NMI=ãçëí=ëíìÇáÉë=Ü~îÉ=åçí=ÑçìåÇ=íÜÉã=~äçåÉ=íç=ÄÉ=îÉêó=ìëÉÑìä=áå=éêÉÇáÅíáåÖÇáëÉ~ëÉ= ëÉîÉêáíó= çê= íêÉ~íãÉåí= êÉëéçåëÉ= NNJNPI= NRK= eçïÉîÉêI= áå= ÅçãÄáå~íáçå= ïáíÜ= ÅçããçåÅäáåáÅ~ä=êáëâ=Ñ~Åíçêë=ëìÅÜ=~ë=çÄÉëáíó=~åÇ=Çá~ÄÉíÉëI=~ë=ïÉää=~ë=äáîÉê=áã~ÖáåÖ=EáKÉK=ëíÉ~íçëáë=çåìäíê~ëçìåÇFI=íÜÉó=ã~ó=ÄÉ=ÜÉäéÑìä=Ñçê=~ëëÉëëáåÖ=êáëâ=çÑ=k^ciaK=cçê=áåëí~åÅÉI=ÉäÉî~íÉÇ=éä~ëã~~ãáåçíê~åëÑÉê~ëÉë= áå= íÜÉ= éêÉëÉåÅÉ= çÑ= ÄçíÜ= ÜáÖÜ= ÅÜçäÉëíÉêçä= ~åÇ= íêáÖäóÅÉêáÇÉë= EqdF= ï~ë~ëëçÅá~íÉÇ=ïáíÜ=k^cia= áå=UPB=çÑ=é~íáÉåíë= áå= íÜÉ=a~ää~ë=eÉ~êí=píìÇó= NSK= få= ëçãÉ=ëíìÇáÉëÉäÉî~íÉÇ= äáîÉê= ~ãáåçíê~åëÑÉê~ëÉë= ïÉêÉ= áåÇáÅ~íáîÉ= çÑ= ïçêëÉ= ÜÉé~íáÅ= áåëìäáå= êÉëáëí~åÅÉ= ~åÇçîÉê~ää=éêçÖåçëáë=áå=k^cia=NQI=NTK=qÜÉëÉ=~Äåçêã~äáíáÉëI=ÅçãÄáåÉÇ=ïáíÜ=ä~Äçê~íçêó=áåÇáÅ~íçêëçÑ= ~Çî~åÅÉÇ= äáîÉê= ÇáëÉ~ëÉ= EëìÅÜ= ~ë= éä~ëã~= äçï= éä~íÉäÉí= Åçìåí= ~åÇ= ÉäÉî~íÉÇ= ÄáäáêìÄáåFI= ~êÉÅäÉ~êäó=ìëÉÑìä=áåÇáÅ~íçêë=çÑ=~Çî~åÅÉÇ=äáîÉê=ÇáëÉ~ëÉ=Äìí=åçí=îÉêó=ëÉåëáíáîÉ=Ñçê=~å=É~êäó=Çá~ÖåçëáëKqÜÉ=íêìÉ=ÇáäÉãã~=áë=íÜÉ=Çá~Öåçëáë=çÑ=k^ciaI=~åÇ=áå=é~êíáÅìä~ê=çÑ=k^peI=áå=íÜÉ=É~êäó=ëí~ÖÉëçÑ=íÜÉ=ÇáëÉ~ëÉ=ïÜÉå=ãáäÇ=íç=ãçÇÉê~íÉ=äáîÉê=ÑáÄêçëáë=áë=éêÉëÉåíK=qÜáë=áë=~å=áãéçêí~åí=ÇáëíáåÅíáçåÄÉÅ~ìëÉ=äçåÖJíÉêã=éêçÖåçëáë=çÑ=äáîÉê=ÇáëÉ~ëÉ=ëÉÉãë=íç=Öç=Ü~åÇJáåJÜ~åÇ=ïáíÜ=íÜÉ=ÇÉîÉäçéãÉåíçÑ= ëíÉ~íçÜÉé~íáíáëI= ~åÇ= áå=é~êíáÅìä~êI= çÑ= ÑáÄêçëáëK= få= íÜáë= ëÉííáåÖI= äáîÉê= ÉåòóãÉë=Ü~îÉ=ÄÉÉå=çÑÇáë~ééçáåíáåÖ=Çá~ÖåçëíáÅ=î~äìÉ=NTJONI=~åÇ=ïÜÉå=ïáíÜáå=íÜÉ=åçêã~ä=ê~åÖÉI=çÑÑÉê=~=Ñ~äëÉ=ëÉåëÉ=çÑëÉÅìêáíóK=j~åó=êÉÅÉåí=ëíìÇáÉë=êÉéçêí=íÜÉ=éêÉëÉåÅÉ=çÑ=~Çî~åÅÉÇ=k^pe=ÉîÉå=ïáíÜ=åçêã~ä=äáîÉê~ãáåçíê~åëÑÉê~ëÉë=UI=NQI=OOI=OPI=Äìí=ã~ó=ìåÇÉêÉëíáã~íÉ= äáîÉê= Ñ~í=~ÅÅìãìä~íáçå= áå=é~íáÉåíë=ïáíÜqOaj=OQK=få=ëìãã~êóI=íÜÉëÉ=ÑáåÇáåÖë=Ü~îÉ=áãéçêí~åí=áãéäáÅ~íáçåë=áå=íÜÉ=Å~êÉ=çÑ=é~íáÉåíë=ïáíÜk^ciaK= ^äíÜçìÖÜ= íÜÉó= ÅçìäÇ= ÄÉ= áåÇáÅ~íáîÉ= çÑ= ëÉîÉêÉ= ãÉí~ÄçäáÅ= ÇáëÉ~ëÉ= ~åÇ= Ñ~ííó= äáîÉêáåÑáäíê~íáçåI=áåÅêÉ~ëÉÇ=äáîÉê=~ãáåçíê~åëÑÉê~ëÉë=~êÉ=éççê=ÖìáÇÉë=Ñçê=íÜÉ=çîÉê~ää=ã~å~ÖÉãÉåí=çÑé~íáÉåíë=ïáíÜ=k^cia=~åÇ=ÅìêêÉåíäó=çåäó=~=äáîÉê=Äáçéëó=Å~å=~ÅÅìê~íÉäó=ÇÉíÉêãáåÉ=íÜÉ=ëÉîÉêáíóçÑ=k^cia=~åÇ=åÉÉÇ=Ñçê=íêÉ~íãÉåíK=

NAFLD and long-term mortality

tÜÉíÜÉê= k^cia= áë= ~ëëçÅá~íÉÇ= ïáíÜ= ~å= áåÅêÉ~ëÉÇ= êáëâ= çÑ= éêÉã~íìêÉ= ÇÉ~íÜ= áë= ÜáÖÜäóÅçåíêçîÉêëá~äI= ~åÇ=~í= íÜÉ=éêÉëÉåí= íáãÉI=Ü~ë=åç=ÇÉÑáåáíáîÉ=~åëïÉêK=^Ö~áåI= ëíìÇáÉë=Ü~îÉ=ÄÉÉåéä~ÖìÉÇ= Äó= ëÜçêíÅçãáåÖë= ëìÅÜ= ~ë= ëã~ää= ë~ãéäÉ= ëáòÉI= é~íáÉåí= ëÉäÉÅíáçå= Äá~ëI= ä~Åâ= çÑëí~åÇ~êÇáòÉÇ=ÑçääçïJìé=~åÇ=íÜÉ=éêÉëÉåÅÉ=çÑ=çîÉêä~ééáåÖ=Å~êÇáçî~ëÅìä~ê=êáëâ=Ñ~Åíçêë=íóéáÅ~ä=çÑé~íáÉåíë=ïáíÜ=k^ciaK=få=ã~åó=ëíìÇáÉëI=~ÑíÉê=íÜÉ=áåáíá~ä=Ä~ëÉäáåÉ=Çá~Öåçëáë=çÑ=k^peI=åç=äáîÉêÄáçéëó=ÅçåÑáêãÉÇ=íÜÉ=ëÉîÉêáíó=çÑ=äáîÉê=ÇáëÉ~ëÉ=Eçê=áíë=êÉëçäìíáçåF=~í=íÜÉ=ÉåÇ=çÑ=íÜÉ=çÄëÉêî~íáçåéÉêáçÇK= qÜáë= áë= áãéçêí~åí= ÄÉÅ~ìëÉ= ~ë=ã~åó= ~ë=úNUJORB=çÑ= é~íáÉåíë= Ü~îÉ= áãéêçîÉãÉåí= çêêÉëçäìíáçå=çÑ=k^pe=çîÉê=íáãÉ=TI=ORJOTK=qÜìëI= áí=êÉã~áåë=ìåÅäÉ~ê=ïÜÉíÜÉê=íÜÉ=çîÉê~ää=ãçêí~äáíóêÉéçêíÉÇ=áå=íÜÉëÉ=ëíìÇáÉë=ï~ë=äáåâÉÇ=íç=äáîÉê=ÇáëÉ~ëÉ=çê=~ëëçÅá~íÉÇ=ãÉí~ÄçäáÅ=Ñ~ÅíçêëK=

Evidence-based Management of Diabetes

4

21 Non-alcoholic fatty liver disease (NAFLD) in diabetes: distraction or impending disaster?

5

Table 2. Long-term liver-related and overall mortality in middle-aged patients withNAFLD.

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Evidence-based Management of Diabetes

6

Figure 1. Overall survival of subjects with NAFLD, divided among those with only fattyliver or subjects with fat and any type of inflammation, ballooning, or fibrosis. Adapted fromSoderberg C, et al 26. Reprinted with permission from John Wiley and Sons, © 2009.

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ëáãéäÉ=ëíÉ~íçëáë= EQTKNB=îëK=PQKPBFK=bâëíÉÇí=Éí=~ä T ÑçìåÇ=åç= äáîÉêJêÉä~íÉÇ=ãçêí~äáíó=~ÑíÉê=NQóÉ~êë=çÑ=ÑçääçïJìé=áå=é~íáÉåíë=ïáíÜ=ëáãéäÉ=ëíÉ~íçëáë=Åçãé~êÉÇ=íç=OKUB=áå=é~íáÉåíë=ïáíÜ=k^pe~åÇ=~=OKRJÑçäÇ=áåÅêÉ~ëÉ=áå=çîÉê~ää=ãçêí~äáíóK=fÑ=íÜÉ=Ç~í~=çÑ=~ää=ëíìÇáÉë=áå=q~ÄäÉ=O=~êÉ=í~âÉå=íçÖÉíÜÉêIáí=~ééÉ~êë=íÜ~í=~ÑíÉê=NN=óÉ~êë=çÑ=ÑçääçïJìé=é~íáÉåíë=ïáíÜ=k^pe=ÉîÉå=Ü~îÉ=~=ïçêëÉ=éêçÖåçëáë=íÜ~åé~íáÉåíë=ïáíÜ= ëáãéäÉ= ëíÉ~íçëáë= ÑçääçïÉÇ= Ñçê= NT= óÉ~êëI=ïáíÜ= ~= ÑáîÉJÑçäÇ= áåÅêÉ~ëÉ= áå= äáîÉêJêÉä~íÉÇãçêí~äáíó=~åÇ=ÜáÖÜÉê=çîÉê~ää=ãçêí~äáíóK=tÜ~í=áë=ìåèìÉëíáçå~ÄäÉ=áë=íÜ~í=é~íáÉåíë=ïáíÜ=k^ciaJêÉä~íÉÇÅáêêÜçëáë=~êÉ=~í=~=ãìÅÜ=ÜáÖÜÉê= êáëâ=çÑ= äáîÉêJêÉä~íÉÇ=~åÇ=çîÉê~ää=ãçêí~äáíóI=ïáíÜ=RJNM=óÉ~êë= äáîÉêJêÉä~íÉÇ=ãçêí~äáíó=ÄÉáåÖ=~ë=ÜáÖÜ=~ë=NOKNB=~åÇ=çîÉê~ää=ãçêí~äáíó=OQKPB=POJPRK

NAFLD in patients with type 2 diabetes mellitus

få=íÜÉ=ä~ëí=ÇÉÅ~ÇÉI=~=åìãÄÉê=çÑ=ÉéáÇÉãáçäçÖáÅ~ä=~åÇ=ÅäáåáÅ~ä=íê~åëä~íáçå~ä=ëíìÇáÉë=Ü~îÉ=äÉÇíç=~å=áåÅêÉ~ëÉÇ=~ï~êÉåÉëë=~Äçìí=íÜÉ=ÅäçëÉ=äáåâ=ÄÉíïÉÉå=k^cia=~åÇ=qOajK=_çíÜ=ÅçåÇáíáçåëÑêÉèìÉåíäó= ÅçÉñáëí= ïáíÜ= ëÉîÉêÉ= ÜÉé~íáÅ= áåëìäáå= êÉëáëí~åÅÉ= éä~óáåÖ= ~= âÉó= êçäÉ= áå= íÜÉé~íÜçéÜóëáçäçÖó= çÑ= íÜÉ= ÇáëÉ~ëÉK= béáÇÉãáçäçÖáÅ~ä= ëíìÇáÉë= êÉîÉ~ä= íÜ~í= ÉäÉî~íÉÇ= éä~ëã~~ãáåçíê~åëÑÉê~ëÉ=äÉîÉäë=~êÉ=~ëëçÅá~íÉÇ=ïáíÜ=~=ÖêÉ~íÉê=êáëâ=çÑ=Ü~îáåÖ=Çá~ÄÉíÉë=PSJQNK=jçêÉçîÉêIÉîÉå= éä~ëã~= ~ä~åáåÉ= ~ãáåçíê~åëÑÉê~ëÉ= E^iqF= ïáíÜáå= íÜÉ= Úåçêã~äÛ= ê~åÖÉ= áë= ~ëëçÅá~íÉÇ= ïáíÜÜáÖÜÉê=Çá~ÄÉíÉë= áåÅáÇÉåÅÉI= áåÇÉéÉåÇÉåíäó=çÑ=Åä~ëëáÅ~ä=éêÉÇáÅíçêë= EáKÉK=_jfI=éä~ëã~=ÖäìÅçëÉäÉîÉäëI=éêÉëÉåÅÉ=çÑ= íÜÉ=jÉípF=PTI=QOI=QPK=qÜÉ=éêÉî~äÉåÅÉ=çÑ=~Äåçêã~ä=ÖäìÅçëÉ=ãÉí~Äçäáëã=áåé~íáÉåíë= ïáíÜ= k^cia= Ä~ëÉÇ= çåäó= çå= ëÉäÑJêÉéçêíÉÇ= Çá~Öåçëáë= çê= ~= Ñ~ëíáåÖ= éä~ëã~= ÖäìÅçëÉê~åÖÉë= ÄÉíïÉÉå= V= íç= PNB UI= QQI= QRK= eçïÉîÉêI= ïÜÉå= ëíìÇáÉë= Ü~îÉ= ëóëíÉã~íáÅ~ääó= ëÅêÉÉåÉÇé~íáÉåíë=ïáíÜ=k^cia= Ñçê= áãé~áêÉÇ=ÖäìÅçëÉ= íçäÉê~åÅÉ= EfdqF= çê= qOaj=ïáíÜ= ~å= çê~ä= ÖäìÅçëÉíçäÉê~åÅÉ=íÉëí=EldqqF=íÜÉ=íêìÉ=ê~íÉ=çÑ=~Äåçêã~ä=ÖäìÅçëÉ=ãÉí~Äçäáëã=áë=ãìÅÜ=ÜáÖÜÉêK=få=çìêÉñéÉêáÉåÅÉI=ïÜÉå=çÄÉëÉ=é~íáÉåíë=ÄÉäáÉîÉÇ= íç=Ü~îÉ=åçêã~ä=ÖäìÅçëÉ=ãÉí~Äçäáëã=EÄó=ÄçíÜ= íÜÉé~íáÉåí=~åÇ=éêáã~êó=Å~êÉ=éêçîáÇÉêF=~êÉ=ëóëíÉã~íáÅ~ääó=ëÅêÉÉåÉÇ=ïáíÜ=~å=ldqqI=íÜÉ=éêÉî~äÉåÅÉçÑ= éêÉÇá~ÄÉíÉë= Eáãé~áêÉÇ= Ñ~ëíáåÖ= ÖäìÅçëÉ= xfcdzI= fdqF= ~åÇ= åÉïäó= Çá~ÖåçëÉÇ= qOaj= áëÅçåëáÇÉê~Ääó=ÜáÖÜÉê=áå=é~íáÉåíë=ïáíÜ=k^cia=îÉêëìë=ã~íÅÜÉÇ=Åçåíêçäë=ïáíÜçìí=~=Ñ~ííó=äáîÉê=EUPBîëK=PUBI=éYMKMMNFK=m~íáÉåíë=ïáíÜ=k^cia=Ü~Ç=~å=~ééêçñáã~íÉäó=íÜêÉÉJÑçäÇ=ÜáÖÜÉê=ê~íÉ=çÑ=åÉïäóÇá~ÖåçëÉÇ=qOaj=QSK=lÑ=åçíÉI=íÜÉ=îÉêó=ÜáÖÜ=ê~íÉ=çÑ=~Äåçêã~ä=ÖäìÅçëÉ=ãÉí~Äçäáëã=áå=íÜáë=ÅçÜçêíï~ë= äáâÉäó= êÉä~íÉÇ= íç=~=ÜáÖÜ=éêÉî~äÉåÅÉ=çÑ=âåçïå=êáëâ= Ñ~Åíçêë= Ñçê= íÜÉ=ÇÉîÉäçéãÉåí=çÑ=qOajEëìÅÜ=~ë=ÜáÖÜ=ê~íÉë=çÑ=ëÉÇÉåí~êáëãI=çÄÉëáíó=~åÇ=eáëé~åáÅ=~åÅÉëíêóFI=Äìí=ëáãáä~ê=ÜáÖÜ=éêÉî~äÉåÅÉê~íÉë=çÑ=fdq=~åÇ=qOaj=Eê~åÖáåÖ=Ñêçã=PPB=íç=SOBF=Ü~îÉ=ÄÉÉå=êÉÅÉåíäó=êÉéçêíÉÇ=áå=ëíìÇáÉëÑêçã=`Üáå~=QTI=g~é~å=QU ~åÇ=áå=~=éêÉÇçãáå~åíäó=bìêçéÉ~å=éçéìä~íáçå=Ñêçã=^ìëíê~äá~=QVK=

tÜáäÉ=qOaj= áë=ãçêÉ=Åçããçå= áå=k^ciaI= íÜÉ=å~íìêÉ=çÑ= íÜáë= êÉä~íáçåëÜáé= áë= áåÅçãéäÉíÉäóìåÇÉêëíççÇ=~åÇ=áí=êÉã~áåë=íç=ÄÉ=Éëí~ÄäáëÜÉÇ=áÑ=ÜÉé~íáÅ=ëíÉ~íçëáë=éêÉÅÉÇÉë=íÜÉ=ÇÉîÉäçéãÉåíçÑ= ëíÉ~íçëáë= ~åÇ= ÇáêÉÅíäó= ÅçåíêáÄìíÉë= íç= íÜÉ= ÇÉîÉäçéãÉåí= çÑ= Çá~ÄÉíÉëI= çê= áë= ~å= ~ëëçÅá~íÉÇÅçåÇáíáçå=ãçêÉ=ÅäçëÉäó=ãáêêçêáåÖ=íÜÉ=ëí~íÉ=çÑ=áåëìäáå=êÉëáëí~åÅÉK=aÉÑÉÅíë=áå=~ÇáéçëÉ=íáëëìÉ=~êÉïÉää=Éëí~ÄäáëÜÉÇ= áå=çÄÉëáíó=~åÇ=qOaj=RMI=RNK=qÜÉ=é~íÜçÖÉåÉëáë=çÑ=k^cia= áå= íÜÉ=ëÉííáåÖ=çÑáåëìäáå=êÉëáëí~åÅÉ=áåîçäîÉë=~=ÅêçëëJí~äâ=ÄÉíïÉÉå=~ÇáéçëÉ=íáëëìÉ=~åÇ=í~êÖÉí=íáëëìÉë=ëìÅÜ=~ë=íÜÉäáîÉê=~åÇ=ëâÉäÉí~ä=ãìëÅäÉ RMI=ROK=lîÉêëìééäó=çÑ=ÑêÉÉ=Ñ~ííó=~ÅáÇë=Ecc^F=íç=íÜÉ=äáîÉê=Ñêçã=áåëìäáåêÉëáëí~åí=~ÇáéçëÉ=íáëëìÉ=~åÇ=~=ëí~íÉ=çÑ=äçÅ~ä=EÜÉé~íáÅF=~åÇ=ëóëíÉãáÅ=ÅÜêçåáÅ=áåÑä~ãã~íáçå=~êÉ~í= ÅÉåíÉê= ëí~ÖÉ= áå= íÜÉ= ÇÉîÉäçéãÉåí= çÑ= ëíÉ~íçëáë= ~åÇ= k^pe= NQI= NUI= RPI= RQK= få= íÜÉ= ëÉííáåÖ= çÑÉñÅÉëëáîÉ= cc^= ëìééäóI= ÄçíÜ= ÅÜêçåáÅ= ÜóéÉêÖäóÅÉãá~= ~åÇ= ÜóéÉêáåëìäáåÉãá~= éêçãçíÉ= ÜÉé~íáÅíêáÖäóÅÉêáÇÉ=ëóåíÜÉëáë=~åÇ=áåÅêÉ~ëÉ=íÜÉ=ëÉÅêÉíáçå=çÑ=siaiK=eçïÉîÉêI= áí=ãìëí=ÄÉ=êÉÅçÖåáòÉÇ

21 Non-alcoholic fatty liver disease (NAFLD) in diabetes: distraction or impending disaster?

7

íÜ~í=~äíÜçìÖÜ=ÇÉ=åçîç äáéçÖÉåÉëáë=EakiF=áë=áåÅêÉ~ëÉÇ=áå=k^ciaI=áí=ÅçåíêáÄìíÉë=äÉëë=íç=íÜÉ=íçí~äÜÉé~íáÅ=íêáÖäóÅÉêáÇÉ=éççä=EúOMJORBF=íÜ~å=Ñ~ííó=~ÅáÇë=Ñêçã=~ÇáéçëÉ=íáëëìÉ=EúSMBF=áå=k^cia=RRKlîÉêëÉÅêÉíáçå=çÑ=siai=ã~ó=ÄÉ=~å=~Ç~éí~íáçå=íç=éêÉîÉåí=ã~ëëáîÉ=ëíÉ~íçëáë=~åÇ=ã~ó=Éñéä~áå=ïÜóëç= ÑêÉèìÉåíäó=ÜáÖÜ=éä~ëã~= íêáÖäóÅÉêáÇÉëI= äçï=ÜáÖÜJÇÉåëáíó= äáéçéêçíÉáå= EeaiJ`FI=~åÇ= áåÅêÉ~ëÉÇÑçêã~íáçå=çÑ=ëã~ääI=ÇÉåëÉ=äçïJÇÉåëáíó=äáéçéêçíÉáå=EiaiJ`F=~êÉ=ëç=Åçããçå=áå=é~íáÉåíë=ïáíÜ=jÉípIqOaj=~åÇ=k^cia=QSI=RSK=få=é~íáÉåíë=ïáíÜ=ëíÉ~íçëáë=íÜÉêÉ=áë=~=Ñ~áäìêÉ=çÑ=áåëìäáå=íç=ëìééêÉëë=siaiëÉÅêÉíáçå=RTI=RU=~åÇ=ëÉÅêÉíáçå=ê~íÉë=çÑ= íÜÉ= äáéçéêçíÉáå= áåÅêÉ~ëÉ= áå=éêçéçêíáçå=íç= íÜÉ=ëÉîÉêáíó=çÑáåíê~ÜÉé~íáÅ=íêáÖäóÅÉêáÇÉ=~ÅÅìãìä~íáçå=RVK=oÉëáëí~åÅÉ=íç=áåëìäáåÛë=~Åíáçå=íç=ëìééêÉëë=ÖäìÅçëÉ=~åÇsiai=ëÉÅêÉíáçå=áå=é~íáÉåíë=ïáíÜ=qOaj=ã~ó=~ÅÅçìåí=Ñçê=íÜÉ=çÄëÉêî~íáçå=íÜ~í=Çá~ÄÉíÉë=Åçåíêçäã~ó=ÄÉ=ãçêÉ=ÇáÑÑáÅìäí= íç=~ÅÜáÉîÉ=~åÇ=êÉèìáêÉ=ÜáÖÜÉê= áåëìäáå=ÇçëÉë= áå=é~íáÉåíë=ïáíÜ=qOaj=~åÇk^cia=SMK=eçïÉîÉêI=ÜÉé~íáÅ=ëíÉ~íçëáë=ã~ó=ÄÉ=~ãÉäáçê~íÉÇ=~åÇ=éä~ëã~=íêáÖäóÅÉêáÇÉë=áãéêçîÉÇÄó=ÖççÇ=ÖäóÅÉãáÅ=Åçåíêçä=áå=é~íáÉåíë=ïáíÜ=qOaj=~åÇ=k^cia=E`ìëá=Éí=~äI=ìåéìÄäáëÜÉÇFK

qOaj= áë= ~äëç= ~ëëçÅá~íÉÇ= ïáíÜ= ïçêëÉ= äáîÉê= ÇáëÉ~ëÉ= ~äíÜçìÖÜ= íÜÉ= ìåÇÉêäóáåÖ= ãÉÅÜ~åáëãëêÉã~áå=ìåÅäÉ~ê=UI=RQK=cçê=áåëí~åÅÉI=áå=ÉéáÇÉãáçäçÖáÅ~ä=ëíìÇáÉë=qOaj=áë=~ëëçÅá~íÉÇ=ïáíÜ=~=íïçJ=íçÑçìêJÑçäÇ=áåÅêÉ~ëÉ=áå=~Çî~åÅÉÇ=äáîÉê=ÇáëÉ~ëÉ=PI=TI=ÅáêêÜçëáë=Q ~åÇ=ÜÉé~íçÅÉääìä~ê=Å~êÅáåçã~=QI=VI=SNISO EffÄL_FK= qÜÉ= éêÉëÉåÅÉ= çÑ= qOaj= áå= é~íáÉåíë=ïáíÜ=k^cia= áë= ~ëëçÅá~íÉÇ=ïáíÜ=ãçêÉ= ëÉîÉêÉÜÉé~íáÅ=~åÇ=~ÇáéçëÉ=íáëëìÉ=áåëìäáå=êÉëáëí~åÅÉ=NQI=NUI=QS ~åÇ=ãìÅÜ=ïçêëÉ=äáîÉê=ÜáëíçäçÖóI=áåÅäìÇáåÖÑêÉèìÉåíäó= ~Çî~åÅÉÇ= äáîÉê= ÑáÄêçëáë= çê= ÅáêêÜçëáë= OI= SJUI= NMI= NNI= NQI= NUI= OPI= QNI= QSI= SPK= eçïÉîÉêI= ïÉääJÅçåíêçääÉÇ=äçåÖJíÉêã=éêçëéÉÅíáîÉ=ëíìÇáÉë=çå=íÜÉ=å~íìê~ä=Üáëíçêó=çÑ=k^cia=áå=qOaj=~êÉ=ä~ÅâáåÖK=

få= ëìãã~êóI= íÜÉ= ~î~áä~ÄäÉ= ÉîáÇÉåÅÉ= Å~ääë= Ñçê= ÉåÇçÅêáåçäçÖáëíë= íç= ÄÉ= ~ï~êÉ= ~Äçìí= íÜÉéçëëáÄäÉ=êçäÉ=çÑ=k^cia=áå=é~íáÉåíë=ïáíÜ=qOajK=tÜáäÉ=íÜÉ=ÉîáÇÉåÅÉ= áë=ëíáää= äáãáíÉÇI=íÜÉ=Ç~í~êÉîáÉïÉÇ=ëìÖÖÉëíë=íÜ~í=íÜÉ=éêÉëÉåÅÉ=çÑ=k^cia=ã~ó=éä~ó=~=é~íÜçÖÉåáÅ=êçäÉI=çê=~í=äÉ~ëí=ÄÉ=~Ü~ääã~êâ=çÑI=ÑìíìêÉ=qOajK=fí=ã~ó=~äëç=áÇÉåíáÑó=~=ëìÄëÉí=çÑ=é~íáÉåíë=ïáíÜ=ãçêÉ=ëÉîÉêÉ=ÜÉé~íáÅáåëìäáå=êÉëáëí~åÅÉ=íÜ~í=~êÉ=ãçêÉ=éêçåÉ=íç=íÜÉ=ÇÉîÉäçéãÉåí=çÑ=ÇóëäáéáÇÉãá~=~åÇ=~í=êáëâ=çÑ=É~êäáÉêçê~ä=~ÖÉåí= Ñ~áäìêÉK=cáå~ääóI= íÜÉ=~ëëçÅá~íáçå=çÑ=qOaj=~åÇ=k^pe=éä~ÅÉë= íÜÉëÉ=é~íáÉåíë=~í=~åáåÅêÉ~ëÉÇ= êáëâ=çÑ= ëÉîÉêÉ= äáîÉê=ÇáëÉ~ëÉI= áåÅäìÇáåÖ=ÜÉé~íçÅÉääìä~ê= Å~êÅáåçã~K=q~âÉå= íçÖÉíÜÉêIíÜÉêÉ= áë=~=ÅçãéÉääáåÖ=åÉÉÇ=íç=ÇÉîÉäçé=åçåJáåî~ëáîÉ=ï~óë=íç=Éëí~ÄäáëÜ=~å=É~êäó=Çá~Öåçëáë=çÑk^pe=áå=é~íáÉåíë=ïáíÜ=qOajI=çê=áå=ëÉäÉÅíÉÇ=é~íáÉåíëI=éÉêÑçêã=~=äáîÉê=Äáçéëó=EáKÉK=íÜçëÉ=ïáíÜãçêÉ=êáëâ=Ñ~Åíçêë=Ñçê=k^peI=äáîÉê=~ãáåçíê~åëÑÉê~ëÉë=[íÜêÉÉJÑçäÇ=ìééÉê=äáãáí=çÑ=åçêã~äI=ÅäáåáÅ~äçê=áã~ÖáåÖ=ëìëéáÅáçå=çÑ=~Çî~åÅÉÇ=äáîÉê=ÇáëÉ~ëÉFK=

T2DM, NAFLD and cardiovascular disease (CVD)

tÜÉíÜÉê=íÜÉ=éêÉëÉåÅÉ=çÑ=k^cia=ÅçåÑÉêë=~å=áåÅêÉ~ëÉÇ=êáëâ=çÑ=`sa=ÄÉóçåÇ=íÜÉ=éêÉëÉåÅÉçÑ=íê~Çáíáçå~ä=êáëâ=Ñ~Åíçêë=áë=~å=~êÉ~=Ö~íÜÉêáåÖ=ëìÄëí~åíá~ä=~ííÉåíáçåK=píìÇáÉë=Ü~îÉ=êÉéçêíÉÇ=íÜ~íé~íáÉåíë=ïáíÜ=ÉäÉî~íÉÇ= äáîÉê= ~ãáåçíê~åëÑÉê~ëÉë=Ü~îÉ=~=ãìÅÜ=ÜáÖÜÉê=cê~ãáåÖÜ~ã= êáëâ= ëÅçêÉ~åÇLçê=Å~êÇáçî~ëÅìä~ê=ÉîÉåíë=Åçãé~êÉÇ=íç=íÜçëÉ=ïáíÜ=åçêã~ä=äáîÉê=~ãáåçíê~åëÑÉê~ëÉë QOI=SQJSSKqÜÉ=~ëëçÅá~íáçå=çÑ=k^cia=ïáíÜ=íÜÉ=jÉíp=Ü~ë=äÉÇ=íç=íÜÉ=ÅçååÉÅíáçå=ÄÉíïÉÉå=Ñ~ííó=äáîÉê=~åÇíÜÉ=ÇÉîÉäçéãÉåí=çÑ=`saK=qÜÉ=ëíìÇáÉë= äáåâáåÖ=`sa=ïáíÜ=k^cia=Å~å=ÄÉ=ÇáîáÇÉÇ= áåíç= íÜêÉÉã~àçê=Å~íÉÖçêáÉëW=

� ëã~ää=ëíìÇáÉë=ëìÖÖÉëíáåÖ=`sa=çÅÅìêë=ãçêÉ=Åçããçåäó=áå=íÜÉ=éêÉëÉåÅÉ=çÑ=k^pe=íÜ~å=áåíÜÉ=ÖÉåÉê~ä=éçéìä~íáçå=çê=ëìÄàÉÅíë=ïáíÜçìí=k^cia=TI=NOI=OUI=OVI=QNI=SSI=STX=

Evidence-based Management of Diabetes

8

� ÅêçëëJëÉÅíáçå~ä= ëíìÇáÉë= ïáíÜ= ëìêêçÖ~íÉ= ãÉ~ëìêÉë= çÑ= ~íÜÉêçëÅäÉêçëáë= áå= é~íáÉåíë= ïáíÜk^cia=Åçãé~êÉÇ=íç=ÅçåíêçäëX=~åÇ=

� äçåÖáíìÇáå~ä= ëíìÇáÉë= çÑ= Å~êÇáçî~ëÅìä~ê= ÉîÉåíë= áå= é~íáÉåíë= ïáíÜ= ~åÇ= ïáíÜçìí= k^cia= ~íÄ~ëÉäáåÉ=Eq~ÄäÉ=PFK=

21 Non-alcoholic fatty liver disease (NAFLD) in diabetes: distraction or impending disaster?

9

Table 3. Studies assessing cardiovascular burden in patients with and without NAFLD.

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Evidence-based Management of Diabetes

10

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21 Non-alcoholic fatty liver disease (NAFLD) in diabetes: distraction or impending disaster?

11

Figure 2. Dysfunctional adipose tissue leads to excessive free fatty acids (FFA) in theliver. This promotes triglyceride accumulation, hepatocyte lipotoxicity with necrosis,inflammation, and eventually disease progression to fibrosis, cirrhosis or hepatocellularcarcinoma. The metabolic consequences are hyperglycemia, hyperinsulinemia,dyslipidemia and subclinical inflammation, all leading to premature cardiovasculardisease. NAFLD: nonalcoholic fatty liver disease, NASH: nonalcoholic steatohepatitis,HDL-C: high-density lipoprotein cholesterol, sd LDL-C: small dense low-density lipoproteincholesterol.

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NAFLD: whom to screen and how to treat?

Diagnosis and screening

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oçìíáåÉ=ëÅêÉÉåáåÖ=Ñçê=k^cia=Å~ååçí=ÄÉ=êÉÅçããÉåÇÉÇ=~í=íÜáë=íáãÉ=áå=~ää=çÄÉëÉ=é~íáÉåíëÖáîÉå=çìê=áåÅçãéäÉíÉ=ìåÇÉêëí~åÇáåÖ=~Äçìí=íÜÉ=å~íìê~ä=Üáëíçêó=çÑ=íÜÉ=ÇáëÉ~ëÉI=Ñ~Åíçêë=äÉ~ÇáåÖíç=ÇáëÉ~ëÉ=éêçÖêÉëëáçå= ~åÇ= íêÉ~íãÉåí= ÅÜçáÅÉë=ïáíÜçìí=ÇÉÑáåáíáîÉ= ÉåÇéçáåíëK=^í= íÜÉ=éêÉëÉåííáãÉI= ëÅêÉÉåáåÖ= ëÜçìäÇ= ÑçÅìë= çåäó= çå= íÜçëÉ= ~í= íÜÉ= ÜáÖÜÉëí= êáëâ= çÑ= Ü~îáåÖ= ëíÉ~íçÜÉé~íáíáëEk^peF=ìåíáä=~=ëáãéäÉI=åçåJáåî~ëáîÉ=ëÅêÉÉåáåÖ=íÉëí=ïáíÜ=~ÇÉèì~íÉ=ëÉåëáíáîáíó=~åÇ=ëéÉÅáÑáÅáíó=áë~î~áä~ÄäÉK= qÜÉëÉ= áåÅäìÇÉ= é~íáÉåíë=ïáíÜ= ëóãéíçãë= EáKÉK= êáÖÜí= ìééÉê= èì~Çê~åí= ÇáëÅçãÑçêíF= çê~Äåçêã~ä= äáîÉê=ÄáçÅÜÉãáëíêáÉë= Eáå=é~êíáÅìä~êI= ÉäÉî~íÉÇ=~ãáåçíê~åëÑÉê~ëÉëFK=m~íáÉåíë= áå=ïÜçãäáîÉê=ëíÉ~íçëáë=áë=~å=áåÅáÇÉåí~ä=ÑáåÇáåÖ=ÇÉíÉÅíÉÇ=çå=áã~ÖáåÖI=~êÉ=~ëóãéíçã~íáÅ=~åÇ=Ü~îÉ=åçêã~äéä~ëã~=~ãáåçíê~åëÑÉê~ëÉ= äÉîÉäëI=~= äáîÉê=Äáçéëó=~í= íÜÉ=ÅìêêÉåí= íáãÉ= áë=åçí= êÉÅçããÉåÇÉÇ= UOKeçïÉîÉêI= ~ë= çìíäáåÉÇ= É~êäáÉêI= éä~ëã~= ~ãáåçíê~åëÑÉê~ëÉ= äÉîÉäë= Ü~îÉ= ~= éççê= ëÉåëáíáîáíó= ~ë= ~ëÅêÉÉåáåÖ=íÉëí=~åÇ=~êÉ=çÑíÉå=ïáíÜáå=åçêã~ä=äáãáíë=áå=k^ciaLk^peK=tÜáäÉ=~=äáîÉê=ìäíê~ëçìåÇã~ó=~ëëáëí= áå= íÜÉ=Çá~ÖåçëáëI= áí= Å~ååçí=ÄÉ= êçìíáåÉäó= êÉÅçããÉåÇÉÇI=ÖáîÉå= áíë=Åçëí=~åÇ= ä~êÖÉåìãÄÉê=çÑ=é~íáÉåíë=ïáíÜ=jÉíp=çê=qOaj=~åÇ=k^ciaK=få=~ÇÇáíáçåI=áíë=ëÉåëáíáîáíó=áë=éççê=~í=äçïíç=ãçÇÉê~íÉ=ÇÉÖêÉÉë=çÑ=ëíÉ~íçëáë=~åÇ=áí=ÇÉÅêÉ~ëÉë=ÑìêíÜÉê=ïáíÜ=áåÅêÉ~ëáåÖ=ÅÉåíê~ä=~ÇáéçëáíóK

Evidence-based Management of Diabetes

12

^í=éêÉëÉåíI=ã~ÖåÉíáÅ=êÉëçå~åÅÉ=áã~ÖáåÖ=~åÇ=ëéÉÅíêçëÅçéó=EjopF=êÉã~áåë=íÜÉ=ÖçäÇ=ëí~åÇ~êÇÑçê=ãÉ~ëìêáåÖ=äáîÉê=íêáÖäóÅÉêáÇÉ=ÅçåíÉåí=Äìí=áë=~î~áä~ÄäÉ=çåäó=áå=~Å~ÇÉãáÅ=ÅÉåíÉêë=~ë=áí=êÉèìáêÉëëéÉÅá~äáòÉÇ= ëçÑíï~êÉ= ~åÇ= áåíÉêéêÉí~íáçå= áë= ä~Äçê= áåíÉåëáîÉK= eçïÉîÉêI= ïÜáäÉ= áí= Ü~ë= ~= ÅäçëÉÅçêêÉä~íáçå=ïáíÜ=äáîÉê=Ñ~í=ÅçåíÉåí=Éëíáã~íÉÇ=Ñêçã=äáîÉê=ÄáçéëáÉë=E`ìëá=Éí=~äI=ìåéìÄäáëÜÉÇF=áí=Ü~ë~=äçï=ëÉåëáíáîáíó=Ñçê=åÉÅêçáåÑä~ãã~íáçå=~åÇ=ÑáÄêçëáëK

råÑçêíìå~íÉäóI=åç=áã~ÖáåÖ=íÉÅÜåáèìÉ=Å~å=êÉéä~ÅÉ=~=äáîÉê=Äáçéëó=áå=ÅçåÑáêãáåÖ=íÜÉ=Çá~ÖåçëáëçÑ=k^peK=^= äáîÉê=Äáçéëó=ã~ó=ÄÉ=~=êÉ~ëçå~ÄäÉ=~ééêç~ÅÜ=íç=Çá~ÖåçëÉ=k^pe=~åÇ=ëí~ÖÉ=íÜÉÇáëÉ~ëÉ= EáKÉK= ëÉîÉêáíó= çÑ= ÑáÄêçëáëF= áå= áåÇáîáÇì~äë= ïÜç= ~êÉ= ~í= íÜÉ= ÜáÖÜÉëí= êáëâ= çÑ= ÇáëÉ~ëÉéêçÖêÉëëáçå=ëìÅÜ=~ë= áå=çÄÉëáíóI=jÉíp=~åÇLçê=qOajI=é~íáÉåíë=ïáíÜ=ëóãéíçãë=~åÇLçê= áå= íÜÉéêÉëÉåÅÉ= çÑ= ÉäÉî~íÉÇ= äáîÉê= ÉåòóãÉëI= ~åÇ= áÑ= íÜÉ= áåÑçêã~íáçå= çÄí~áåÉÇ= ïáää= éêçãéí= ~= ãçêÉ~ÖÖêÉëëáîÉ=íêÉ~íãÉåí=~ééêç~ÅÜK=qÜÉêÉ=~êÉ=íÜêÉÉ=ÖÉåÉê~ä=áåÇáÅ~íáçåë=Ñçê=äáîÉê=ÄáçéëóW=

� íç=ÅçåÑáêã=íÜÉ=Çá~Öåçëáë=~åÇ=Éëí~ÄäáëÜ=íÜÉ=éêÉëÉåÅÉ=çÑ=k^peX=� íç=ÇÉíÉêãáåÉ=íÜÉ=éêçÖåçëáë=Ä~ëÉÇ=çå=íÜÉ=ëÉîÉêáíó=çÑ=äáîÉê=ÑáÄêçëáëX=~åÇLçê=� áåÅäìëáçå=áåíç=~=ÅäáåáÅ~ä=íêá~ä=áå=~å=~Å~ÇÉãáÅ=ÅÉåíÉêK=

^=äáîÉê=Äáçéëó=ëÜçìäÇ=ÄÉ=ÅçåëáÇÉêÉÇ=çåäó=~ÑíÉê=~å=áåJÇÉéíÜ=ÇáëÅìëëáçå=ïáíÜ=íÜÉ=é~íáÉåí=~ÄçìííÜÉ=ÄÉåÉÑáíë=~åÇ=êáëâë=çÑ=íÜÉ=éêçÅÉÇìêÉK=få=ÅäáåáÅ~ä=éê~ÅíáÅÉ=áí=áë=ÇçåÉ=ìåÅçããçåäó=ÖáîÉå=íÜÉÜáÖÜ=éêÉî~äÉåÅÉ=çÑ=k^cia=~åÇ=íÜÉ=ä~Åâ=çÑ=ëéÉÅáÑáÅ=äçåÖJíÉêã=éÜ~êã~ÅçäçÖáÅ~ä=íÜÉê~éáÉëK=qÜáëï~íÅÜÑìä=ï~áíáåÖ=~ééêç~ÅÜ=ã~ó=ëççå=ÅÜ~åÖÉ=~ë=åÉï=ÉÑÑÉÅíáîÉ=íêÉ~íãÉåíë=ÉãÉêÖÉK=

cáå~ääóI= íÜÉêÉ= áë=~å=~ÅíáîÉ=ëÉ~êÅÜ=Ñçê=ëáãéäÉI=êÉäá~ÄäÉ=~åÇ=áåÉñéÉåëáîÉ=ï~óë=íç=ëÅêÉÉå=íÜÉä~êÖÉ=åìãÄÉê=çÑ=çÄÉëÉ=~åÇ=Çá~ÄÉíáÅ=é~íáÉåíë=íÜ~í=~êÉ=ÅìêêÉåíäó=ÄÉáåÖ=ãáëëÉÇ=ïáíÜ=k^cia=çêk^peK=bÑÑçêíë=áåÅäìÇÉ=íÜÉ=ìëÉ=çÑ=éä~ëã~=Äáçã~êâÉêë=~åÇ=åçîÉä=áã~ÖáåÖ=íÉÅÜåáèìÉë=ëìÅÜ=~ëíê~åëáÉåí=Éä~ëíçÖê~éÜó=UMI=UOK=tÜáäÉ=íÜÉëÉ=~ééêç~ÅÜÉë=~êÉ=éêçãáëáåÖ=íÜÉó=~ï~áí=ãçêÉ=ÇÉÑáåáíáîÉî~äáÇ~íáçå=ÄÉÑçêÉ=ÄÉáåÖ=êÉÅçããÉåÇÉÇ=áå=íÜÉ=êçìíáåÉ=ëÅêÉÉåáåÖ=çÑ=k^ciaK

Treatment

Lifestyle interventionfí= áë= ïÉää= âåçïå= íÜ~í= äáÑÉëíóäÉ= áåíÉêîÉåíáçåë= íÜ~í= êÉëìäí= áå= ïÉáÖÜí= äçëëI= ëìÅÜ= ~ë= ÇáÉí= ~åÇ

ÉñÉêÅáëÉI=ÇÉÅêÉ~ëÉ=`sa=~åÇ=ÇÉä~ó=íÜÉ=ÇÉîÉäçéãÉåí=çÑ=qOaj=UPK=eçïÉîÉêI=íÜÉ=ãçëí=ÉÑÑÉÅíáîÉäáÑÉëíóäÉ= áåíÉêîÉåíáçå= áå=k^cia=êÉã~áåë=ìåÅäÉ~ê=ÄÉÅ~ìëÉ=íÜÉêÉ=~êÉ=åç=ä~êÖÉI= äçåÖJíÉêã=íêá~äëKtÉáÖÜí=äçëë=ÅäÉ~êäó=áãéêçîÉë=ÜÉé~íáÅ=ëíÉ~íçëáëK=lêäáëí~í=Å~å=Ñ~Åáäáí~íÉ=ïÉáÖÜí=äçëë=Äìí=ÇçÉë=åçíÜ~îÉ= ~å= áåíêáåëáÅ= ÉÑÑÉÅí= çå= äáîÉê= ÜáëíçäçÖó= áå=k^pe= UQI= URK= ^=≥TB=ïÉáÖÜí= äçëë=ïáíÜ= äáÑÉëíóäÉáåíÉêîÉåíáçå=EOMM=ãáåìíÉë=~=ïÉÉâ=çÑ=ãçÇÉê~íÉ=éÜóëáÅ~ä=~ÅíáîáíóF=Å~å=ëáÖåáÑáÅ~åíäó=áãéêçîÉ=äáîÉêëíÉ~íçëáëI=äçÄìä~ê=áåÑä~ãã~íáçå=~åÇ=Ä~ääççåáåÖI=Äìí=åçí=ÑáÄêçëáë=áå=çÄÉëÉ=é~íáÉåíë=ïáíÜ=ÄáçéëóJéêçîÉå=k^pe=USK=oÉÇìÅíáçå=áå=ëíÉ~íçëáë=ê~åÖáåÖ=ÄÉíïÉÉå=OMB=íç=UNB=EãÉ~ëìêÉÇ=Äó=íÜÉ=ÖçäÇJëí~åÇ~êÇ=jop=íÉÅÜåáèìÉF=Ü~ë=ÄÉÉå=êÉéçêíÉÇ= áå=ãìäíáéäÉ=ëíìÇáÉë=ÉáíÜÉê=Äó=ÇáÉí=~äçåÉ= UTJVM çêÅçãÄáåÉÇ=ïáíÜ=ÉñÉêÅáëÉ=UUI=VNJVQI=ÄÉáåÖ=éêçéçêíáçå~ä=íç=íÜÉ=áåíÉåëáíó=çÑ=íÜÉ=äáÑÉëíóäÉ=áåíÉêîÉåíáçåKeçïÉîÉêI=ÄÉÅ~ìëÉ=~=äáîÉê=Äáçéëó=ï~ë=åçí=ÇçåÉ=áå=íÜÉëÉ=ëíìÇáÉëI=íÜÉáê=áãé~Åí=çå=çíÜÉê=~ëéÉÅíëçÑ= äáîÉê= ÜáëíçäçÖó= êÉã~áå= íç=ÄÉ=Éëí~ÄäáëÜÉÇK= qÜÉ=çåäó= ëíìÇó= ìëáåÖ=ÄçíÜ= äáîÉê=jop=~åÇ= äáîÉêÄáçéëáÉë=áå=é~íáÉåíë=ïáíÜ=k^pe=êÉéçêíÉÇ=íÜ~í=ÇáÉí=éäìë=éáçÖäáí~òçåÉ=äÉÇ=íç=~=ROB=êÉÇìÅíáçå=áåäáîÉê=ëíÉ~íçëáë= íÜ~í=ÅçêêÉä~íÉÇ=ïáíÜ=~=RMB=ãÉ~å=ÇÉÅêÉ~ëÉ= áå=ëíÉ~íçëáëI=Ä~ääççåáåÖJåÉÅêçëáë

21 Non-alcoholic fatty liver disease (NAFLD) in diabetes: distraction or impending disaster?

13

~åÇ= áåÑä~ãã~íáçå= çå= äáîÉê= ÜáëíçäçÖó= VRK= oçìñJÉåJv= Ö~ëíêáÅ= Äóé~ëë= Eovd_F= çê= ä~é~êçëÅçéáÅ~Çàìëí~ÄäÉ= Ö~ëíêáÅ= Ä~åÇáåÖ= Ei^d_F= áãéêçîÉ= ãÉí~ÄçäáÅ= ~åÇ= ÜáëíçäçÖáÅ~ä= ~Äåçêã~äáíáÉë= áåk^peK=eçïÉîÉêI=ÅÜ~åÖÉë=áå=äáîÉê=ÑáÄêçëáë=Ü~îÉ=ÄÉÉå=ãìÅÜ=äÉëë=éêÉÇáÅí~ÄäÉ=~åÇ=ëçãÉ=ëíìÇáÉëêÉéçêí= íÜ~í= áí=ã~ó=ÉîÉå=ïçêëÉå= ÑçääçïáåÖ=Ä~êá~íêáÅ=ëìêÖÉêó= VSI=VTK=^î~áä~ÄäÉ=Ä~êá~íêáÅ=ëìêÖÉêóëíìÇáÉë=Ü~îÉ=ÄÉÉå=êÉíêçëéÉÅíáîÉ=~åÇ=éççêäó=ëí~åÇ~êÇáòÉÇ=áå=íÉêãë=çÑ=éêÉJ=~åÇ=éçëíJëìêÖáÅ~äÇáÉí~êó= éêçÅÉÇìêÉë= ~åÇ= ä~Åâ= çÑ= áåJÇÉéíÜ=ãÉí~ÄçäáÅ= íÉëíáåÖK= qÜÉêÉ= áë= ~å= ìêÖÉåí= åÉÉÇ= Ñçê= ~ÅçåíêçääÉÇI= äçåÖJíÉêã= Ä~êá~íêáÅ= ëìêÖÉêó= ëíìÇó= íç= íÉëí= íÜÉ= ÄÉëí= ~ééêç~ÅÜ= Ñçê= é~íáÉåíë= ïáíÜk^ciaK=

Pharmacological intervention^í=íÜÉ=éêÉëÉåí= íáãÉ=çåäó=îáí~ãáå=b=~åÇ=éáçÖäáí~òçåÉ=Ü~îÉ=éêçîÉå=ÉÑÑÉÅíáîÉ=~åÇ=ë~ÑÉ=Ñçê= íÜÉ

íêÉ~íãÉåí=çÑ=k^pe=áå=ëÜçêíJíÉêã=ëíìÇáÉë=ESJOQ=ãçåíÜëFK=eçï=îáí~ãáå=b=ÄÉåÉÑáíë=äáîÉê=ÜáëíçäçÖóáå=é~íáÉåíë=ïáíÜ=k^pe=áë=ìåâåçïå=Äìí=áí=~ééÉ~êë=íç=~ãÉäáçê~íÉ=çñáÇ~íáîÉ=ëíêÉëë=VUJNMMK=eçïÉîÉêIáíë=ÉÑÑáÅ~Åó=ï~ë=ÅçåÅäìëáîÉäó=ÇÉãçåëíê~íÉÇ=çåäó=áå=åçåJÇá~ÄÉíáÅ=ëìÄàÉÅíë=ïáíÜ=k^pe=OTK

máçÖäáí~òçåÉI=~å=~Öçåáëí=çÑ=mm^oγ ãçëí=~ÄìåÇ~åí= áå=~ÇáéçÅóíÉë=NMNI=NMOI= áãéêçîÉë=~ÇáéçëÉíáëëìÉLÜÉé~íáÅ=áåëìäáå=~Åíáçå=~åÇ=áãéêçîÉë=äáîÉê=ÜáëíçäçÖó=áå=é~íáÉåíë=ïáíÜ=k^pe=OI=NMPK=få=é~íáÉåíëïáíÜ= éêÉÇá~ÄÉíÉë= çê= qOaj= ~åÇ= k^peI= äáîÉê= ëíÉ~íçëáë= ÇÉÅêÉ~ëÉë= Äó= úRMB= ~åÇåÉÅêçáåÑä~ãã~íáçå=áãéêçîÉë=áå=URB=çÑ=ëìÄàÉÅíë=NMQK=qÜÉëÉ=êÉëìäíë=ïÉêÉ=ä~íÉê=ÅçåÑáêãÉÇ=áå=íïçê~åÇçãáòÉÇ=ÅçåíêçääÉÇ=íêá~äë=áå=é~íáÉåíë=ïáíÜ=k^pe=ïáíÜçìí=Çá~ÄÉíÉë=OTI=NMRI=~äíÜçìÖÜ=íÜÉ=êÉëìäíëïÉêÉ=äÉëë=áãéêÉëëáîÉ=éÉêÜ~éë=ÇìÉ=íç=íÜÉ=äçïÉê=ÇçëÉë=ìëÉÇ=EPMãÖ=éÉê=Ç~ó=îÉêëìë=QRãÖ=éÉêÇ~ó=Äó=_ÉäÑçêí=Éí=~ä NMQFK=qÜÉ=mfsbkp=ëíìÇó=OT ê~åÇçãáòÉÇ=OQT=é~íáÉåíë=íç=îáí~ãáå=b=EUMMfr=éÉêÇ~óFI=éáçÖäáí~òçåÉ=PMãÖLÇ~óI=çê=éä~ÅÉÄçK=qÜÉ=éêáã~êó=ÉåÇéçáåí=EÜáëíçäçÖáÅ~ä=áãéêçîÉãÉåí=áå=≥OÖê~ÇÉë= áå= íÜÉ= k^cia= ^Åíáîáíó= pÅçêÉ= ïáíÜ= ~í= äÉ~ëí= ~= NJéçáåí= áãéêçîÉãÉåí= áå= ÜÉé~íçÅÉääìä~êÄ~ääççåáåÖ=~åÇ=NJéçáåí=áå=ÉáíÜÉê=íÜÉ=äçÄìä~ê=áåÑä~ãã~íáçå=çê=ëíÉ~íçëáë=ëÅçêÉI=~åÇ=åç=áåÅêÉ~ëÉ=áåíÜÉ= ÑáÄêçëáë=ëÅçêÉF=ï~ë= êÉ~ÅÜÉÇ=Äó=QPBI=PQB=~åÇ=NUB=çÑ=é~íáÉåíë= íêÉ~íÉÇ=ïáíÜ=îáí~ãáå=bIéáçÖäáí~òçåÉ=çê=éä~ÅÉÄçI=êÉëéÉÅíáîÉäó=EëáÖåáÑáÅ~åí=~í=~=éZMKMQ=îÉêëìë=éä~ÅÉÄç=çåäó=Ñçê=îáí~ãáå=bFKeçïÉîÉêI=íïç=Ñ~Åíçêë=~ÑÑÉÅíÉÇ=íÜÉ=çìíÅçãÉ=çÑ=éáçÖäáí~òçåÉ=áå=íÜÉ=ëí~íáëíáÅ~ä=~å~äóëáëW=

� é~íáÉåíë=íÜ~í=ÇáÇ=åçí=Ü~îÉ=Ä~ääççåáåÖ=~í=Ä~ëÉäáåÉI=~=ÅçãéçåÉåí=çÑ=íÜÉ=éêáã~êó=ÜáëíçäçÖáÅ~äçìíÅçãÉI= ïÉêÉ= ÅçåëáÇÉêÉÇ= ~ë= åçåJêÉëéçåÇÉêë= ~åÇ= ãçêÉ= éÉçéäÉ= áå= íÜÉ= éáçÖäáí~òçåÉîÉêëìë=îáí~ãáå=b=~êã=ä~ÅâÉÇ=Ä~ääççåáåÖ=~í=ëíìÇó=Éåíêó=EOUB=îëK=NUBFX=~åÇ=

� é~íáÉåíë=íÜ~í=ÇáÇ=åçí=Ü~îÉ=íÜÉ=ëÉÅçåÇ=Äáçéëó=ïÉêÉ=~äëç=ÅçåëáÇÉêÉÇ=~ë=åçåJêÉëéçåÇÉêëK=

^Ö~áåI=ãçêÉ= é~íáÉåíë= áå= íÜÉ= éáçÖäáí~òçåÉ= ~êã= ÇáÇ= åçí= Ü~îÉ= ~= ëÉÅçåÇ= äáîÉê= Äáçéëó= ENPBîÉêëìë=RB=çå=îáí~ãáå=bFK=_çíÜ=íÜÉê~éáÉë=ïÉêÉ=Éèì~ääó=ÉÑÑÉÅíáîÉ=áå=ëìÄàÉÅíë=ïáíÜ=Ä~ääççåáåÖ=~íÄ~ëÉäáåÉI=íÜÉ=Ü~ääã~êâ=çÑ=k^pe=EéáçÖäáí~òçåÉW=ROBI=îáí~ãáå=bW=QTB=~åÇ=éä~ÅÉÄçW=OPBI=ÄçíÜëáÖåáÑáÅ~åíäó= ÄÉííÉê= îëK= éä~ÅÉÄçFK= _çíÜ= ~ÖÉåíë= ÇÉÅêÉ~ëÉÇ= ÜÉé~íáÅ= ëíÉ~íçëáë= EéZMKMMR= Ñçêîáí~ãáå=b=~åÇ=éYMKMMN=Ñçê=éáçÖäáí~òçåÉF=~åÇ=äçÄìä~ê=áåÑä~ãã~íáçå=EéZMKMO=Ñçê=îáí~ãáå=b=~åÇéZMKMMQ= Ñçê=éáçÖäáí~òçåÉFI=Äìí=ÇáÇ=åçí= ~äíÉê= äáîÉê= ÑáÄêçëáëK=oÉëçäìíáçå=çÑ=k^pe=çÅÅìêêÉÇ= áåPSB= çÑ= é~íáÉåíë= çå= îáí~ãáå= b= EéZMKMR= îëK= éä~ÅÉÄçFI= QTB= çå= éáçÖäáí~òçåÉ= EéZMKMMN= îëKéä~ÅÉÄçF=~åÇ=ONB=çå=éä~ÅÉÄçK=cáå~ääóI=áí=ãìëí=ÄÉ=âÉéí=áå=ãáåÇ=íÜ~í=íÜÉêÉ=áë=ëíáää=ÅçåÅÉêå=~ÄçìííÜÉ= äçåÖJíÉêã=ë~ÑÉíó= çÑ= éáçÖäáí~òçåÉ= êÉÖ~êÇáåÖ=ÜÉ~êí= Ñ~áäìêÉI= ÄçåÉ= äçëë= ~åÇ=Ää~ÇÇÉê= Å~åÅÉêEbìêçéÉ~å=jÉÇáÅáåÉë=^ÖÉåÅóI= gìåÉ=NRI=OMNNI= ÜííéWLLïïïKÉã~KÉìêçé~KÉìLÉã~F= NMSK=^í= íÜÉéêÉëÉåí= ãçãÉåíI= íÜÉ= ca^= êÉÅçããÉåÇë= ~îçáÇ~åÅÉ= çÑ= éáçÖäáí~òçåÉ= áÑ= ~= é~íáÉåí= Ü~ë= ~ÅíáîÉ

Evidence-based Management of Diabetes

14

Ää~ÇÇÉê=Å~åÅÉêI=~åÇ=Å~ìíáçå=áÑ=~=é~íáÉåí=Ü~ë=~=éêáçê=Üáëíçêó=çÑ=íÜÉ=ÇáëÉ~ëÉ=ìåíáä=ãçêÉ=ÇÉÑáåáíáîÉÇ~í~=ÄÉÅçãÉë= ~î~áä~ÄäÉK=eçïÉîÉêI= Å~êÇáçî~ëÅìä~ê= ÇáëÉ~ëÉ=Ü~ë=ÄÉÉå= êÉéçêíÉÇ= íç=ÇÉÅêÉ~ëÉïáíÜ=éáçÖäáí~òçåÉ=áå=é~íáÉåíë=ïáíÜ=qOaj=UMK=

líÜÉê= éÜ~êã~ÅçäçÖáÅ~ä= ~ÖÉåíë= ìëÉÇ= íç= íêÉ~í= qOaj= Ü~îÉ= ÄÉÉå= íêáÉÇ= áå= k^pe= ëìÅÜ= ~ëãÉíÑçêãáå= NMTI= NMU ~åÇ= áåÅêÉíáåJãáãÉíáÅë= ëìÅÜ= ~ë= ÉñÉå~íáÇÉ= NMVI= NNM çê= äáê~ÖäìíáÇÉ= NNNK= pÉîÉê~äìåÅçåíêçääÉÇ=íêá~äë=ïáíÜ=ãÉíÑçêãáå=RQI=NMPI=NNOJNNS=áå=é~íáÉåíë=ïáíÜ=k^cia=Ü~îÉ=ëÜçïå=~=êÉÇìÅíáçåáå=éä~ëã~=~ãáåçíê~åëÑÉê~ëÉë=Äìí=íÜÉ=ÄáÖì~åáÇÉ=ÇçÉë=åçí=áãéêçîÉ=äáîÉê=ÜáëíçäçÖó=NMPI=NNPI=NNRI=NNTKqÜÉ=áåÅêÉíáåJãáãÉíáÅë=ÉñÉå~íáÇÉ=~åÇ=äáê~ÖäìíáÇÉ=Ü~îÉ=ÖÉåÉê~íÉÇ=ëáÖåáÑáÅ~åí=áåíÉêÉëí=ÄÉÅ~ìëÉíÜÉó= áåÇìÅÉ= ïÉáÖÜí= äçëë= ~åÇ= ÉñÉåÇáåJQ= ~ãÉäáçê~íÉë= ÜÉé~íáÅ= áåëìäáå= êÉëáëí~åÅÉ= ~åÇíêáÖäóÅÉêáÇÉ= ~ÅÅìãìä~íáçå= áå= îáîç NNUK= jçêÉçîÉêI= dimJN= êÉÅÉéíçêë= ~êÉ= éêÉëÉåí= áå= Üìã~åÜÉé~íçÅóíÉë= NNVI= NOMK= bñÉå~íáÇÉ= Ü~ë= ÄÉÉå= êÉéçêíÉÇ= íç= áãéêçîÉ= ÜÉé~íáÅ= mm^oγLmm^oαÉñéêÉëëáçåI=^âí=~åÇ=^jmh=éÜçëéÜçêóä~íáçå= áå=ÜÉé~íçÅóíÉë=Ñêçã=é~íáÉåíë=ïáíÜ=k^pe=NNVKtÜáäÉ= ÄçíÜ= ~ÖÉåíë= ÉñÉå~íáÇÉ= NMVI= NNM ~åÇ= äáê~ÖäìíáÇÉ= NNN ~ééÉ~ê= éêçãáëáåÖI= ê~åÇçãáòÉÇIÅçåíêçääÉÇ=ëíìÇáÉë=ìëáåÖ=äáîÉê=ÜáëíçäçÖó=~ë=íÜÉ=ã~áå=ÉåÇéçáåí=~êÉ=åÉÉÇÉÇ=ÄÉÑçêÉ=íÜÉáê=ìëÉ=Å~åÄÉ=êÉÅçããÉåÇÉÇ=Ñçê=íÜÉ=íêÉ~íãÉåí=çÑ=k^peK=

Conclusions

NAFLD in T2DM: distraction or impending disaster?

cçê= ÇÉÅ~ÇÉëI= ~ííÉåíáçå= çÑ= íÜÉ= é~íáÉåí= ïáíÜ= qOaj= Ü~ë= ÑçÅìëÉÇ= çå= íÜÉ= Åçåíêçä= çÑÜóéÉêÖäóÅÉãá~=~åÇ=çÑ=êáëâ=Ñ~Åíçêë=~ëëçÅá~íÉÇ=ïáíÜ=ã~Åêçî~ëÅìä~ê=ÇáëÉ~ëÉK=qÜÉ=ÉéáÇÉãáÅ=çÑçÄÉëáíó=åçï=Ñ~ÅÉë=ÉåÇçÅêáåçäçÖáëíë=ïáíÜ=åÉï=ÅÜ~ääÉåÖÉëK=^ãçåÖ=íÜÉã=áë=íÜÉ=åÉÉÇ=íç=áÇÉåíáÑóÉ~êäó= ÅçãéäáÅ~íáçåë= êÉä~íÉÇ= íç= çÄÉëáíó= áå= íÜÉ= ëÉííáåÖ= çÑ= qOajK= få= íÜáë= ëÉåëÉI= k^cia= áë= ~Åçããçå=ÅçãéäáÅ~íáçå=çÑ=é~íáÉåíë=ïáíÜ=qOaj=íÜ~í=êÉèìáêÉë=ëéÉÅá~ä=~ííÉåíáçåK=eçïÉîÉêI=áí=ÇçÉëåçí=Ñáí=~ë=ëìÅÜ=áåíç=íÜÉ=íê~Çáíáçå~ä=êÉ~äã=çÑ=Çá~ÄÉíáÅ=ÅçãéäáÅ~íáçåë=EáKÉK=ãáÅêçJ=çê=ã~Åêçî~ëÅìä~êÇáëÉ~ëÉF= Äìí= ê~íÜÉê= áåíç= ~= åÉï= ÖÉåêÉ= çÑ= äáéçíçñáÅáíóJêÉä~íÉÇ= ÅçãéäáÅ~íáçåë= áå= Çá~ÄÉíÉëK`äáåáÅá~åë=áå=ÖÉåÉê~ä=~êÉ=ìåÅçãÑçêí~ÄäÉ=ïáíÜ=~=ÅçåÇáíáçå=íÜ~í=Å~ååçí=ÄÉ=Çá~ÖåçëÉÇ=çê=ÑçääçïÉÇïáíÜ=~=ÄäççÇ=íÉëíI=~åÇ=íÜ~í=íÜÉ=å~íìê~ä=Üáëíçêó=çÑ=íÜÉ=ÇáëÉ~ëÉ=áë=éççêäó=ìåÇÉêëíççÇK=eçïÉîÉêIíÜÉ=åÉÉÇ=Ñçê=ëéÉÅá~ä=~ííÉåíáçå=~Äçìí=k^cia=áå=qOaj=áë=Ä~ëÉÇ=çå=ëçãÉ=âÉó=ÑáåÇáåÖëW=

� êÉ~äáò~íáçå=íÜ~í=íÜÉ=ã~àçêáíó=çÑ=é~íáÉåíë=ïáíÜ=qOaj=E[TMBF=Ü~îÉ=~=Ñ~ííó=äáîÉê=~åÇ=~=ä~êÖÉéêçéçêíáçå=çÑ=íÜÉëÉ=Ü~îÉ=k^pe=E≥RMB\FX=

� ëÉîÉêÉ=ëíÉ~íçÜÉé~íáíáë=~åÇ=ÇáëÉ~ëÉ=éêçÖêÉëëáçå=çÅÅìêë=ãçêÉ=çÑíÉå=áå=qOajX=� ã~åó=ãÉÅÜ~åáëãë=~í=éä~ó=áå=k^cia=ëìÖÖÉëí=íÜ~í= áåÅêÉ~ëÉÇ=`sa=áë=~=êÉ~ä=éçëëáÄáäáíóI

~ÄçîÉ=~åÇ=ÄÉóçåÇ=íê~Çáíáçå~ä=êáëâ=Ñ~Åíçêë=áå=é~íáÉåíë=ïáíÜ=qOajX=� éáçÖäáí~òçåÉ=êÉã~áåë=~ë=íÜÉ=ãçëí=ÉÑÑÉÅíáîÉ=íêÉ~íãÉåí=Ñçê=k^pe=áå=é~íáÉåíë=ïáíÜ=qOaj=NMQK=

tÜáäÉ=äáÑÉëíóäÉ=áåíÉêîÉåíáçå=êÉã~áåë=íÜÉ=ÅçêåÉêëíçåÉ=çÑ=íêÉ~íãÉåí=Ñçê=k^cia=~åÇ=íÜÉ=äçåÖJíÉêã= ë~ÑÉíó= çÑ= qwaë= áë= ìåÇÉê= ÅäçëÉ= ëÅêìíáåóI= éáçÖäáí~òçåÉ= ïáää= ëççå= ÄÉ= ÖÉåÉêáÅ= áå= ã~åóÅçìåíêáÉëK=^=Çá~Öåçëáë=çÑ=k^pe=áå=~=é~íáÉåí=ïáíÜ=qOaj=ã~ó=ÉåÅçìê~ÖÉ=áíë=ìëÉ=~í=~å=É~êäáÉêëí~ÖÉ= ïáíÜáå= íÜÉ= Çá~ÄÉíÉë= íêÉ~íãÉåí= ~äÖçêáíÜã= íç= êÉîÉêëÉ= íÜÉ= ãÉí~ÄçäáÅ= ~åÇ= äáîÉêJëéÉÅáÑáÅ~Äåçêã~äáíáÉë=çÑ=íÜÉ=ÇáëÉ~ëÉK=

21 Non-alcoholic fatty liver disease (NAFLD) in diabetes: distraction or impending disaster?

15

få= ëìãã~êóI= ~äíÜçìÖÜ= çìê= ÅìêêÉåí= âåçïäÉÇÖÉ= ~Äçìí= k^cia= áë= áåÅçãéäÉíÉ= ~åÇ= ã~åó~ëéÉÅíë=êÉã~áå=ÅçåíêçîÉêëá~äI= áí= áë= äáâÉäó=íÜ~í=íÜáë=ÅçåÇáíáçå=Å~êêáÉë=~å=áåÜÉêÉåí=ÜÉ~äíÜ=êáëâ=íçã~åó=é~íáÉåíë=ïáíÜ=qOajK=låäó=çìê=~ï~êÉåÉëë=~åÇ=~=éêç~ÅíáîÉ=~ééêç~ÅÜ=áå=íÜÉ=Çá~Öåçëáë=~åÇíêÉ~íãÉåí=çÑ=k^cia=áå=qOaj=ã~ó=~îÉêí=~å=áãéÉåÇáåÖ=Çáë~ëíÉê=äççãáåÖ=çå=íÜÉ=ÜçêáòçåK=

Acknowledgement

qÜáë=ïçêâ=ï~ë=ëìééçêíÉÇ=Äó=íÜÉ=_ìêêçìÖÜë=tÉääÅçãÉ=cìåÇ=Eh`F=~åÇ=~=s^=jÉêáí=^ï~êÇ=ENfMN=`uMMMNSTJMNX=h`FX=~äëç=Äó=íÜÉ=sÉíÉê~åë=^ÑÑ~áêë=jÉÇáÅ~ä=oÉëÉ~êÅÜ=cìåÇ=~åÇ=Äó=^ï~êÇkìãÄÉê=ri=NooMORTST= Ñêçã= íÜÉ=k~íáçå~ä=`ÉåíÉê= Ñçê=oÉëÉ~êÅÜ=oÉëçìêÅÉëK= qÜÉ=ÅçåíÉåí= áëëçäÉäó=íÜÉ=êÉëéçåëáÄáäáíó=çÑ=íÜÉ=~ìíÜçêë=~åÇ=ÇçÉë=åçí=åÉÅÉëë~êáäó=êÉéêÉëÉåí=íÜÉ=çÑÑáÅá~ä=îáÉïë=çÑíÜÉ=k~íáçå~ä=`ÉåíÉê=Ñçê=oÉëÉ~êÅÜ=oÉëçìêÅÉë=çÑ=íÜÉ=k~íáçå~ä=fåëíáíìíÉë=çÑ=eÉ~äíÜK=

Evidence-based Management of Diabetes

16

Key points Evidence level

� k^cia=áë=íÜÉ=ãçëí=Åçããçå=Å~ìëÉ=çÑ=ÅÜêçåáÅ=äáîÉê=ÇáëÉ~ëÉ=~åÇ=~ëã~åó= ~ë= ≥QMB= çÑ= é~íáÉåíë= ïáíÜ= k^cia= Ü~îÉ= ëíÉ~íçÜÉé~íáíáëEk^peFK==k^pe=ã~ó=éêçÖêÉëë=íç=~Çî~åÅÉÇ=ÑáÄêçëáë=áå=~=ëáÖåáÑáÅ~åíåìãÄÉê=çÑ=é~íáÉåíë=~åÇ=áë=~=ã~àçê=Å~ìëÉ=çÑ=ÅêóéíçÖÉåáÅ=ÅáêêÜçëáëK

� lÄÉëáíó=~åÇ=Çá~ÄÉíÉë=EÄçíÜ=êÉä~íÉÇ=íç=ÇóëÑìåÅíáçå~ä=~ÇáéçëÉ=íáëëìÉ~åÇ= áåëìäáå= êÉëáëí~åÅÉFI= çê= íÜÉ= éêÉëÉåÅÉ= çÑ= ~Çî~åÅÉÇ= ÜÉé~íáÅÑáÄêçëáë= çå= ~= äáîÉê= ÄáçéëóI= ~êÉ= Ñ~Åíçêë= ~ëëçÅá~íÉÇ= ïáíÜ= k^peéêçÖêÉëëáçå=~åÇ=éççê=äçåÖJíÉêã=éêçÖåçëáëK

� tÜÉíÜÉê=k^cia=áë=~ëëçÅá~íÉÇ=ïáíÜ=~å=áåÅêÉ~ëÉÇ=êáëâ=çÑ=éêÉã~íìêÉÇÉ~íÜ= êÉã~áåë= ìåâåçïåK= bîáÇÉåÅÉ= ëìÖÖÉëíë= íÜ~í= é~íáÉåíë= ïáíÜk^pe= ~êÉ= ~í= áåÅêÉ~ëÉÇ= çÑ= äáîÉêJêÉä~íÉÇ= ãçêÄáÇáíó= ~åÇ= ãçêí~äáíóIä~êÖÉäó=~ëëçÅá~íÉÇ=ïáíÜ=íÜÉ=ëÉîÉêáíó=çÑ=äáîÉê=ÑáÄêçëáëK=

� qÜÉ=êÉä~íáçåëÜáé=ÄÉíïÉÉå=Çá~ÄÉíÉë=~åÇ=k^cia=áë=ÅçãéäÉñK==lÄÉëÉé~íáÉåíë= ïáíÜ= k^cia= ~êÉ= ~í= áåÅêÉ~ëÉÇ= êáëâ= çÑ= éêÉÇá~ÄÉíÉë= EfcdIfdqF=~åÇ=çÑ=åÉïäó=Çá~ÖåçëÉÇ=qOaj=Åçãé~êÉÇ=íç=é~íáÉåíë=ïáíÜçìík^ciaK=píêçåÖ=ÅçåëáÇÉê~íáçå=ëÜçìäÇ=ÄÉ=ÖáîÉå=íç=ëÅêÉÉå=é~íáÉåíëïáíÜ=k^cia=Ñçê=qOaj=íç=Éëí~ÄäáëÜ=~å=É~êäó=Çá~Öåçëáë=çÑ=Çá~ÄÉíÉë~åÇ=ÄÉÅ~ìëÉ=é~íáÉåíë=ïáíÜ=qOaj=~åÇ=k^pe=ÇÉîÉäçé=ïçêëÉ=äáîÉêÇáëÉ~ëÉ= ~åÇ= Ü~îÉ= ~= íïçJ= íç= ÑçìêJÑçäÇ= áåÅêÉ~ëÉ= áå= ~Çî~åÅÉÇ= äáîÉêÇáëÉ~ëÉI=ÅáêêÜçëáë=~åÇ=ÜÉé~íçÅÉääìä~ê=Å~êÅáåçã~K==

� qÜÉ=ãÉÅÜ~åáëãë=~í=éä~ó=áå=é~íáÉåíë=ïáíÜ=k^cia=ëìééçêí=íÜÉ=åçíáçåíÜ~í= íÜáë= ÅçåÇáíáçå= Å~êêáÉë= ~å= áåÅêÉ~ëÉÇ= êáëâ= çÑ= `saK= eçïÉîÉêÇáêÉÅí= íÜÉ= ÉîáÇÉåÅÉ= áë= ïÉ~â= ~åÇ= áåÅçåÅäìëáîÉK= içåÖJíÉêãéêçëéÉÅíáîÉ=ëíìÇáÉë=~êÉ=åÉÉÇÉÇ=íç=Ñìääó=Éëí~ÄäáëÜ=íÜÉ=å~íìêÉ=çÑ=íÜáë~ëëçÅá~íáçåI=Äìí=áå=íÜÉ=ãÉ~åíáãÉI=~ÖÖêÉëëáîÉ=íêÉ~íãÉåí=çÑ=`s=êáëâÑ~Åíçêë=~ééÉ~êë=ï~êê~åíÉÇ=áå=íÜáë=éçéìä~íáçåK

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References

NK ^Ç~ãë=i^I=^åÖìäç=mK=oÉÅÉåí=ÅçåÅÉéíë=áå=åçåJ~äÅçÜçäáÅ=Ñ~ííó=äáîÉê=ÇáëÉ~ëÉK=aá~ÄÉí=jÉÇ OMMRX=OOW=NNOVJPPKOK jìëëç=dI=d~ãÄáåç=oI=`~ëë~ÇÉê=jK=kçåJ~äÅçÜçäáÅ=Ñ~ííó=äáîÉê=ÇáëÉ~ëÉ=Ñêçã=é~íÜçÖÉåÉëáë=íç=ã~å~ÖÉãÉåíW=~å

ìéÇ~íÉK=lÄÉë=oÉî OMNMX=NNW=QPMJQRKPK mçêÉé~=iI=o~ó=gdI=p~åÅÜÉòJoçãÉì=mI=Éí=~äK=kÉïäó=Çá~ÖåçëÉÇ=Çá~ÄÉíÉë=ãÉääáíìë=~ë=~=êáëâ=Ñ~Åíçê=Ñçê=ëÉêáçìë=äáîÉê

ÇáëÉ~ëÉK=`j^g OMNMX=NUOW=bROSJPNKQK pí~êäÉó= _nI= `~äÅ~Öåç= `gI= e~êêáëçå= p^K= kçå~äÅçÜçäáÅ= Ñ~ííó= äáîÉê= ÇáëÉ~ëÉ= ~åÇ= ÜÉé~íçÅÉääìä~ê= Å~êÅáåçã~W= ~

ïÉáÖÜíó=ÅçååÉÅíáçåK=eÉé~íçäçÖó OMNMX=RNW=NUOMJPOKRK `ä~êâ=gjI=_ê~åÅ~íá=ciI=aáÉÜä=^jK=kçå~äÅçÜçäáÅ=Ñ~ííó=äáîÉê=ÇáëÉ~ëÉK=d~ëíêçÉåíÉêçäçÖó OMMOX=NOOW=NSQVJRTKSK ^åÖìäç= mI= hÉ~ÅÜ= g`I=_~ííë= hmI= Éí= ~äK= fåÇÉéÉåÇÉåí= éêÉÇáÅíçêë= çÑ= äáîÉê= ÑáÄêçëáë= áå= é~íáÉåíë=ïáíÜ= åçå~äÅçÜçäáÅ

ëíÉ~íçÜÉé~íáíáëK=eÉé~íçäçÖó=NVVVX=PMW=NPRSJSOKTK bâëíÉÇí=jI=cê~åòÉå=ibI=j~íÜáÉëÉå=riI=Éí=~äK=içåÖJíÉêã=ÑçääçïJìé=çÑ=é~íáÉåíë=ïáíÜ=k^cia=~åÇ=ÉäÉî~íÉÇ=äáîÉê

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21 Non-alcoholic fatty liver disease (NAFLD) in diabetes: distraction or impending disaster?

17

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Evidence-based Management of Diabetes

18

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21 Non-alcoholic fatty liver disease (NAFLD) in diabetes: distraction or impending disaster?

19

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Evidence-based Management of Diabetes

20

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21 Non-alcoholic fatty liver disease (NAFLD) in diabetes: distraction or impending disaster?

21

Evidence-based Management of Diabetes

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