TYPE3DIABETESMELLITUS:BIOLOGICALMECHANISMSANDITSRELATIONSHIPWITHALZHEIMER'SDISEASE
Abstract
Type3diabetesmellitusisanemergingconceptualframeworkthatlinksmetabolicdysfunctionwithneurodegenerativeprocesses,particularlyAlzheimer’sdisease.Unlikeclassicaldiabetestypesthatprimarilyaffectperipheralglucoseregulation,type3diabetesdescribesinsulinresistanceandrelativeinsulindeficiencylocalizedwithinthebrain.Thisimpairmentdisruptsneuronalglucosemetabolism,leadingtocellularenergydeficits,oxidativestress,neuroinflammation,andprogressivesynapticdysfunction.CentraltothispathologyisalteredinsulinsignalingthroughthePI3K/Aktpathway,whichcontributestoamyloid-βaccumulation,tauhyperphosphorylation,mitochondrialdysfunction,andneuronalloss.Epidemiologicalevidenceindicatesthatindividualswithtype2diabeteshaveasignificantlyelevatedriskofdevelopingAlzheimer’sdisease,supportingthehypothesisthatmetabolicandneurodegenerativepathwaysarecloselyinterconnected.Understandingthesemechanismshighlightstheimportanceofinsulinsensitivity,metabolicregulation,andanti-inflammatorystrategiesinpreservingcognitivefunction.Althoughtype3diabetesisnotyetformallyrecognizedasaclinicaldiagnosis,growingexperimentalandclinicaldataunderscoreitsrelevanceinexplainingAlzheimer’spathophysiologyandguidingfuturetherapeuticapproaches.Continuedresearchmayopennewpreventiveandtreatmentstrategiesaimedatprotectingbrainhealththroughmetabolicintervention.