LOGOEfect of fenofbrate on amputation events in people with type 2 diabetes mellitus (FIELD study) : a prespecifed analysis of a randomised controlled trial2nd Journal readingSuryadi Syam1IntroductionIn the USA in 2001, at least one amputation due to diabetes occurred every 2 h, with an annual cost exceeding US$1 billion!"ithmanagement o# reversible #actors, probably around one in ten patients with diabetes will eventually need at least one amputation2The aim of FIELD studylong$term lipid$lowering treatment with #eno#ibrate adverse macrovascular and microvascular outcomes in type 2 diabetes, including amputations%Methods& aged '0()' years & diagnosis o# type 2 *+ according to ",- criteria& an initial plasma total cholesterol concentration %!0 mmol./ ( !' mmol./ & a total cholesterol.,*/$cholesterol ratio o# 01!0& a plasma triglyceride concentration 1!0 mmol./ ( '!0 mmol./ &without needing lipid$modi#ying treatmentPatients& Individuals with renal impairment, & chronic liver disease,& symptomatic gallbladder disease,& experienced a cardiovascular event within the % months be#ore recruitmentInclusion criteria Exclusion criteria1Procedures'Procedures& +a2or amputations were de#ined as those above the an3le & +inor amputations as those below the an3le

Statistical analysis7Table 1: Baseline characteristics and medication4Table 2: Baseline characteristics by subsequent lower-limb amputation, other cardiovascular event, or neither510Table : Baseline characteristics o! patients who had a lower-limb amputation, by presence o! lar"e-vessel disease11#i"ure 2: $!!ects o! !eno!ibrate on !irst and all amputation events12#i"ure : %umulative ris& curves o! time to !irst amputation 'minor, ma(or, any) event, by treatment "roup1%mechanisms for the microascular benefits of fenofibrate& reductions in mar3ers o# endothelial dys#unction and pro$in#lammatory mar3ers, including tumour necrosis #actor 6, interleu3in , and interleu3in 17 in plasma& reduced viscosity! & endothelial dependent vascular reactivity! & improved #low$mediated dilator response to hyperaemia with increased adiponectin concentrations and improved insulin sensitivity!& 8he drug might exert its antiangiogenic e##ects directly or by reducing tissue ischaemia through these actions!& 9eno#ibrate also activates A+: 3inase in endothelial cells via a peroxisome$proli#erating receptor$6 independent pathway& 9eno#ibrate could also be protective through the inhibition o# oxidative stress& ;europrotective e##ects in rodents11neuropathyabnormal #oot biomechanicsperipheral arterial disease9oot ulcers and in#ectionspoor wound healing:eripheral sensory neuropathy+otor and sensory neuropathyAutonomic neuropathy1'!i"h #is$ Patient to %m&utationPredictor %m&utationheight 1$$#old #or every 10 cmpoorglycaemic control!a history o#previous #oot ulcerlonger diabetes durationperipheral arterial diseasepresence o#neuropathy1'onclusion8reatment with #eno#ibrate was associated with a lower ris3 o# amputations, particularly minor amputations without 3nown large$vessel disease,8o prevent diabetes$related lower$limb amputations we can give longterm use o# #eno#ibrate, irrespective o# the presence o# dyslipidaemia, to patiens with 8ype 2 *+ who are at high ris3 #or amputation1)'#ITI'%L %PP#%I(%LI! Is the evidence o# this therapeutic aspect validesIs the observation o# the patient done #or enough time and completely< >esAre all o# the patient be analy=ed< >esAre the doctor and patient blind in the study< >es*o all o# the groups get the same action< >esAre the control and treatment group similar in the initial o# the study< >es1)II! Is the evidence o# this valid therapeutic aspectimportant%n"iostenstino"en%(PFactor B/ '2%di&sin%dhesie Protein %&o EP%I11TF#esistin%di&onectin9isfatin!(L-.Li&otransinPerili&inFF%sMIF 6alectin11+ E(M11Lactate%&elin!.#M.- D%- (7B(T%-(I BI.L.6I ?%-6 DI (E@#E(I (EL %DIP.(%(EL %DIP.(%(EL %DIP.(%%46ambar : Peran %di&onectin Pada !ati Dan .tot :@ado8asi et all/+,,AB%5Eambar F Her2a Adiponectin di 8ing3at Ieseptor @Hadowasi,2001ALOGO10EnCim sitoliti$ @atalisir hidrolisis tri"liserida intraselulerdalam Darin"an adi&osa/ otot &olos dan Dantun",S/EambarF :eran ,ormone Sensitive /ipase pada sel adiposa ( Barbara,2004)H"r"ne #ensiti$e %i&ase ( H#% )LOGO11#E67L%(I LIP.LI(I( 12?opyright C200% 8he Dndocrine SocietyLee/ '01!0 et al0 Endocrinolo"y +,,23144:++,11++,7/ets say someone has a brachial pressure o# 120mm,g and an an3le pressure o# 1%2mm,g!An3le brachial index J 1%2 . 120 J 1!1 /ets say someone has a brachial pressure o# 120mm,g and an an3le pressure o# 5mm,gAn3le brachial index J 5 . 120 J 0!4 8he #ollowing can be used as a guide to interpreting results o# an3le brachial index F;ormal 0!5 $ 1!2 Iis3 o# vascular #oot ulcer is small *e#inite vascular disease 0! $ 0!5 Iis3 o# vascular ulcer moderate and depends on other ris3 #actors Severe vascular disease /ess than 0! Iis3 o# vascular #oot ulcer very high

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