Tippingthebalance:Haemoglobinopathiesandtheriskofdiabetes
摘要: AIM:Toestablishalinkbetweentheriskofdiabeteswithhaemoglobinopathiesbyexaminingavailableevidenceoftheeffectsofironandbloodglucosehomeostasisfrommoleculartoepidemiologicalperspectives.METHODS:Asystematicliteraturesearchwasperformedusingelectronicliteraturedatabasesusingvarioussearchterms.TheInternationalDiabetesFederationWorldAtlaswasusedtogeneratealistofpopulationswithhighratesofdiabetes.PubMed,ScopusandGoogleScholarwereusedtoidentifywhichofthesepopulationsalsohadareportedprevalenceofhaemoglobinabnormalities.RESULTS:Abnormalitiesinironhomeostasisleadstoincreasesinreactiveoxygenspeciesintheblood.Thispromotesoxidativestresswhichcontributestoperipheralresistancetoinsulinintwoways:(1)reducedinsulin/insulinreceptorinteraction;and(2)β-celldysfunction.Hepcidiniscrucialintermsofmaintainingappropriateamountsofironinthebodyandisinturnaffectedbyhaemoglobinopathies.Hepcidinalsohasothermetaboliceffectsinplacessuchastheliverbutsofartheextentoftheseisnotwellunderstood.Itdoeshoweverdirectlycontrolthelevelsofserumferritin.Highserumferritinisfoundinobesepatientsandthosewithdiabetesandameta-analysisofthevariousstudiesshowsthathighserumferritindoesindeedincreasediabetesrisk.CONCLUSION:Fromanepidemiologicalstandpoint,itisplausiblethatthewell-documentedprotectiveeffectsofhaemoglobinopathieswithregardtomalariamayhavealsoofferedotherevolutionaryadvantages.Bycontributingtoperipheralinsulinresistance,haemoglobinopathiesmayhavehelpedtosculpttheso-calledthriftygenotype,whichhypotheticallyisadvantageousintimesoffamine.Theprevalencedatahoweverisnotextensiveenoughtoprovideconcreteassociationsbetweendiabetesandhaemoglobinopathies-moreprecisestudiesarerequired. ...
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