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Diabetesmellitus
FromWikipedia,thefreeencyclopedia

Diabetesmellitus(DM),commonlyreferredtoasdiabetes,isagroupofmetabolicdiseasesinwhichthereare
highbloodsugarlevelsoveraprolongedperiod.[2]Symptomsofhighbloodsugarincludefrequenturination,
increasedthirst,andincreasedhunger.Ifleftuntreated,diabetescancausemanycomplications.[3]Acute
complicationscanincludediabeticketoacidosis,nonketotichyperosmolarcoma,ordeath.[4]Seriouslongterm
complicationsincludeheartdisease,stroke,chronickidneyfailure,footulcers,anddamagetotheeyes.[3]

Diabetesmellitus

Diabetesisduetoeitherthepancreasnotproducingenoughinsulinorthecellsofthebodynotresponding
properlytotheinsulinproduced.[5]Therearethreemaintypesofdiabetesmellitus:
Type1DMresultsfromthepancreas'sfailuretoproduceenoughinsulin.Thisformwaspreviously
referredtoas"insulindependentdiabetesmellitus"(IDDM)or"juvenilediabetes".Thecauseis
unknown.[3]
Type2DMbeginswithinsulinresistance,aconditioninwhichcellsfailtorespondtoinsulinproperly.[3]
Asthediseaseprogressesalackofinsulinmayalsodevelop.[6]Thisformwaspreviouslyreferredtoas
"noninsulindependentdiabetesmellitus"(NIDDM)or"adultonsetdiabetes".Theprimarycauseis
excessivebodyweightandnotenoughexercise.[3]
Gestationaldiabetesisthethirdmainformandoccurswhenpregnantwomenwithoutaprevioushistory
ofdiabetesdevelophighbloodsugarlevels.[3]
Preventionandtreatmentinvolvemaintainingahealthydiet,regularphysicalexercise,anormalbodyweight,
andavoidinguseoftobacco.Controlofbloodpressureandmaintainingproperfootcareareimportantfor
peoplewiththedisease.Type1DMmustbemanagedwithinsulininjections.[3]Type2DMmaybetreatedwith
medicationswithorwithoutinsulin.[7]Insulinandsomeoralmedicationscancauselowbloodsugar.[8]Weight
losssurgeryinthosewithobesityissometimesaneffectivemeasureinthosewithtype2DM.[9]Gestational
diabetesusuallyresolvesafterthebirthofthebaby.[10]
Asof2015,anestimated415millionpeoplehaddiabetesworldwide,[11]withtype2DMmakingupabout90%
ofthecases.[12][13]Thisrepresents8.3%oftheadultpopulation,[13]withequalratesinbothwomenandmen.[14]
Asof2014,trendssuggestedtheratewouldcontinuetorise.[15]Diabetesatleastdoublesaperson'sriskofearly
https://en.wikipedia.org/wiki/Diabetes_mellitus

Universalbluecirclesymbolfordiabetes. [1]
Classificationandexternalresources
Specialty

Endocrinology

ICD10

E10(http://apps.who.int/classification
s/icd10/browse/2016/en#/E10)E14
(http://apps.who.int/classifications/icd
10/browse/2016/en#/E14)

ICD9CM

250(http://www.icd9data.com/getIC
D9Code.ashx?icd9=250)

MedlinePlus 001214(http://www.nlm.nih.gov/me
dlineplus/ency/article/001214.htm)
eMedicine

med/546(http://www.emedicine.com/
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death.[3]From2012to2015,approximately1.5to5.0milliondeathseachyearresultedfromdiabetes.[7][11]The
globaleconomiccostofdiabetesin2014wasestimatedtobeUS$612billion.[16]IntheUnitedStates,diabetes
cost$245billionin2012.[17]

Contents

med/topic546.htm)emerg/134(http://
www.emedicine.com/emerg/topic134.
htm#)
PatientUK Diabetesmellitus(http://patient.info/
doctor/managementoftype1diabete
s)
MeSH

1 Signsandsymptoms
1.1 Diabeticemergencies
1.2 Complications
2 Causes
2.1 Type1
2.2 Type2
2.3 Gestationaldiabetes
2.4 Othertypes
3 Pathophysiology
4 Diagnosis
5 Prevention
6 Management
6.1 Lifestyle
6.2 Medications
6.3 Surgery
6.4 Support
7 Epidemiology
8 History
8.1 Etymology
9 Societyandculture
9.1 Naming
10 Otheranimals
11 Research
12 References
13 Furtherreading
14 Externallinks

C18.452.394.750(https://www.nlm.ni
h.gov/cgi/mesh/2016/MB_cgi?mode=
&term=Diabetes&field=entry#TreeC
18.452.394.750)

Videoexplanation

Signsandsymptoms
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Theclassicsymptomsofuntreateddiabetesareweightloss,polyuria(increasedurination),polydipsia
(increasedthirst),andpolyphagia(increasedhunger).[18]Symptomsmaydeveloprapidly(weeksor
months)intype1DM,whiletheyusuallydevelopmuchmoreslowlyandmaybesubtleorabsentin
type2DM.
Severalothersignsandsymptomscanmarktheonsetofdiabetesalthoughtheyarenotspecifictothe
disease.Inadditiontotheknownonesabove,theyincludeblurryvision,headache,fatigue,slow
healingofcuts,anditchyskin.Prolongedhighbloodglucosecancauseglucoseabsorptioninthelens
oftheeye,whichleadstochangesinitsshape,resultinginvisionchanges.Anumberofskinrashes
thatcanoccurindiabetesarecollectivelyknownasdiabeticdermadromes.

Diabeticemergencies
Lowbloodsugariscommoninpersonswithtype1andtype2DM.Mostcasesaremildandarenot
consideredmedicalemergencies.Effectscanrangefromfeelingsofunease,sweating,trembling,and
increasedappetiteinmildcasestomoreseriousissuessuchasconfusion,changesinbehaviorsuchas
aggressiveness,seizures,unconsciousness,and(rarely)permanentbraindamageordeathinsevere
cases.[19][20]Moderatehypoglycemiamayeasilybemistakenfordrunkenness[21]rapidbreathingand
sweating,cold,paleskinarecharacteristicofhypoglycemiabutnotdefinitive.[22]Mildtomoderate
casesareselftreatedbyeatingordrinkingsomethinghighinsugar.Severecasescanleadto
unconsciousnessandmustbetreatedwithintravenousglucoseorinjectionswithglucagon.

Overviewofthemostsignificantsymptomsofdiabetes

People(usuallywithtype1DM)mayalsoexperienceepisodesofdiabeticketoacidosis,ametabolicdisturbancecharacterizedbynausea,vomitingandabdominal
pain,thesmellofacetoneonthebreath,deepbreathingknownasKussmaulbreathing,andinseverecasesadecreasedlevelofconsciousness.[23]
Ararebutequallyseverepossibilityishyperosmolarnonketoticstate,whichismorecommonintype2DMandismainlytheresultofdehydration.[23]

Complications
Allformsofdiabetesincreasetheriskoflongtermcomplications.Thesetypicallydevelopaftermanyyears(1020),butmaybethefirstsymptominthosewho
haveotherwisenotreceivedadiagnosisbeforethattime.
Themajorlongtermcomplicationsrelatetodamagetobloodvessels.Diabetesdoublestheriskofcardiovasculardisease[24]andabout75%ofdeathsindiabetics
areduetocoronaryarterydisease.[25]Other"macrovascular"diseasesarestroke,andperipheralvasculardisease.

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Theprimarycomplicationsofdiabetesduetodamageinsmallbloodvesselsincludedamagetotheeyes,kidneys,andnerves.[26]Damagetotheeyes,knownas
diabeticretinopathy,iscausedbydamagetothebloodvesselsintheretinaoftheeye,andcanresultingradualvisionlossandblindness.[26]Damagetothe
kidneys,knownasdiabeticnephropathy,canleadtotissuescarring,urineproteinloss,andeventuallychronickidneydisease,sometimesrequiringdialysisor
kidneytransplant.[26]Damagetothenervesofthebody,knownasdiabeticneuropathy,isthemostcommoncomplicationofdiabetes.[26]Thesymptomscan
includenumbness,tingling,pain,andalteredpainsensation,whichcanleadtodamagetotheskin.Diabetesrelatedfootproblems(suchasdiabeticfootulcers)
mayoccur,andcanbedifficulttotreat,occasionallyrequiringamputation.Additionally,proximaldiabeticneuropathycausespainfulmusclewastingand
weakness.
Thereisalinkbetweencognitivedeficitanddiabetes.Comparedtothosewithoutdiabetes,thosewiththediseasehavea1.2to1.5foldgreaterrateofdeclinein
cognitivefunction.[27]

Causes
Diabetesmellitusisclassifiedintofourbroadcategories:type1,type2,gestationaldiabetes,and
"otherspecifictypes".[5]The"otherspecifictypes"areacollectionofafewdozenindividual
causes.[5]Diabetesisamorevariablethanoncethoughtandpeoplemayhavecombinationsof
forms.[29]Theterm"diabetes",withoutqualification,usuallyreferstodiabetesmellitus.

Type1
Type1diabetesmellitusischaracterizedbylossoftheinsulinproducingbetacellsoftheisletsof
Langerhansinthepancreas,leadingtoinsulindeficiency.Thistypecanbefurtherclassifiedas
immunemediatedoridiopathic.Themajorityoftype1diabetesisoftheimmunemediated
nature,inwhichaTcellmediatedautoimmuneattackleadstothelossofbetacellsandthus
insulin.[30]Itcausesapproximately10%ofdiabetesmellituscasesinNorthAmericaandEurope.
Mostaffectedpeopleareotherwisehealthyandofahealthyweightwhenonsetoccurs.Sensitivity
andresponsivenesstoinsulinareusuallynormal,especiallyintheearlystages.Type1diabetes
canaffectchildrenoradults,butwastraditionallytermed"juvenilediabetes"becauseamajority
ofthesediabetescaseswereinchildren.

Comparisonoftype1and2diabetes[12]
Feature
Type1diabetes Type2diabetes
Onset
Ageatonset
Bodysize
Ketoacidosis
Autoantibodies

Sudden

Mostlyinchildren Mostlyinadults
Thinornormal[28] Oftenobese
Common

Rare

Usuallypresent

Absent

Endogenousinsulin Loworabsent
Concordance
50%
inidenticaltwins
Prevalence

Gradual

~10%

Normal,decreased
orincreased
90%
~90%

"Brittle"diabetes,alsoknownasunstablediabetesorlabilediabetes,isatermthatwastraditionallyusedtodescribethedramaticandrecurrentswingsinglucose
levels,oftenoccurringfornoapparentreasonininsulindependentdiabetes.Thisterm,however,hasnobiologicbasisandshouldnotbeused.[31]Still,type1
diabetescanbeaccompaniedbyirregularandunpredictablehighbloodsugarlevels,frequentlywithketosis,andsometimeswithseriouslowbloodsugarlevels.

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Othercomplicationsincludeanimpairedcounterregulatoryresponsetolowbloodsugar,infection,gastroparesis(whichleadstoerraticabsorptionofdietary
carbohydrates),andendocrinopathies(e.g.,Addison'sdisease).[31]Thesephenomenaarebelievedtooccurnomorefrequentlythanin1%to2%ofpersonswith
type1diabetes.[32]
Type1diabetesispartlyinherited,withmultiplegenes,includingcertainHLAgenotypes,knowntoinfluencetheriskofdiabetes.Theincreaseofincidenceof
type1diabetesreflectsthemodernlifestyle.[33]Ingeneticallysusceptiblepeople,theonsetofdiabetescanbetriggeredbyoneormoreenvironmentalfactors,[34]
suchasaviralinfectionordiet.Severalviruseshavebeenimplicated,buttodatethereisnostringentevidencetosupportthishypothesisinhumans.[34][35]Among
dietaryfactors,datasuggestthatgliadin(aproteinpresentingluten)mayplayaroleinthedevelopmentoftype1diabetes,butthemechanismisnotfully
understood.[36][37]

Type2
Type2DMischaracterizedbyinsulinresistance,whichmaybecombinedwithrelativelyreducedinsulinsecretion.[5]Thedefectiveresponsivenessofbody
tissuestoinsulinisbelievedtoinvolvetheinsulinreceptor.However,thespecificdefectsarenotknown.Diabetesmellituscasesduetoaknowndefectare
classifiedseparately.Type2DMisthemostcommontypeofdiabetesmellitus.
Intheearlystageoftype2,thepredominantabnormalityisreducedinsulinsensitivity.Atthisstage,highbloodsugarcanbereversedbyavarietyofmeasuresand
medicationsthatimproveinsulinsensitivityorreducetheliver'sglucoseproduction.
Type2DMisdueprimarilytolifestylefactorsandgenetics.[38]Anumberoflifestylefactorsareknowntobeimportanttothedevelopmentoftype2DM,
includingobesity(definedbyabodymassindexofgreaterthan30),lackofphysicalactivity,poordiet,stress,andurbanization.[12]Excessbodyfatisassociated
with30%ofcasesinthoseofChineseandJapanesedescent,6080%ofcasesinthoseofEuropeanandAfricandescent,and100%ofPimaIndiansandPacific
Islanders.[5]Eventhosewhoarenotobeseoftenhaveahighwaisthipratio.[5]
Dietaryfactorsalsoinfluencetheriskofdevelopingtype2DM.Consumptionofsugarsweeteneddrinksinexcessisassociatedwithanincreasedrisk.[39][40]The
typeoffatsinthedietisalsoimportant,withsaturatedfatsandtransfattyacidsincreasingtheriskandpolyunsaturatedandmonounsaturatedfatdecreasingthe
risk.[38]Eatinglotsofwhitericealsomayincreasetheriskofdiabetes.[41]Alackofexerciseisbelievedtocause7%ofcases.[42]

Gestationaldiabetes
Gestationaldiabetesmellitus(GDM)resemblestype2DMinseveralrespects,involvingacombinationofrelativelyinadequateinsulinsecretionand
responsiveness.Itoccursinabout210%ofallpregnanciesandmayimproveordisappearafterdelivery.[43]However,afterpregnancyapproximately510%of
womenwithgestationaldiabetesarefoundtohavediabetesmellitus,mostcommonlytype2.[43]Gestationaldiabetesisfullytreatable,butrequirescarefulmedical
supervisionthroughoutthepregnancy.Managementmayincludedietarychanges,bloodglucosemonitoring,andinsomecases,insulinmayberequired.
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Thoughitmaybetransient,untreatedgestationaldiabetescandamagethehealthofthefetusormother.Riskstothebabyincludemacrosomia(highbirthweight),
congenitalheartandcentralnervoussystemabnormalities,andskeletalmusclemalformations.Increasedlevelsofinsulininafetus'sbloodmayinhibitfetal
surfactantproductionandcauserespiratorydistresssyndrome.Ahighbloodbilirubinlevelmayresultfromredbloodcelldestruction.Inseverecases,perinatal
deathmayoccur,mostcommonlyasaresultofpoorplacentalperfusionduetovascularimpairment.Laborinductionmaybeindicatedwithdecreasedplacental
function.ACaesareansectionmaybeperformedifthereismarkedfetaldistressoranincreasedriskofinjuryassociatedwithmacrosomia,suchasshoulder
dystocia.

Othertypes
Prediabetesindicatesaconditionthatoccurswhenaperson'sbloodglucoselevelsarehigherthannormalbutnothighenoughforadiagnosisoftype2DM.Many
peopledestinedtodeveloptype2DMspendmanyyearsinastateofprediabetes.
Latentautoimmunediabetesofadults(LADA)isaconditioninwhichtype1DMdevelopsinadults.AdultswithLADAarefrequentlyinitiallymisdiagnosedas
havingtype2DM,basedonageratherthanetiology.
Somecasesofdiabetesarecausedbythebody'stissuereceptorsnotrespondingtoinsulin(evenwheninsulinlevelsarenormal,whichiswhatseparatesitfrom
type2diabetes)thisformisveryuncommon.Geneticmutations(autosomalormitochondrial)canleadtodefectsinbetacellfunction.Abnormalinsulinaction
mayalsohavebeengeneticallydeterminedinsomecases.Anydiseasethatcausesextensivedamagetothepancreasmayleadtodiabetes(forexample,chronic
pancreatitisandcysticfibrosis).Diseasesassociatedwithexcessivesecretionofinsulinantagonistichormonescancausediabetes(whichistypicallyresolvedonce
thehormoneexcessisremoved).Manydrugsimpairinsulinsecretionandsometoxinsdamagepancreaticbetacells.TheICD10(1992)diagnosticentity,
malnutritionrelateddiabetesmellitus(MRDMorMMDM,ICD10codeE12),wasdeprecatedbytheWorldHealthOrganizationwhenthecurrenttaxonomywas
introducedin1999.[44]
Otherformsofdiabetesmellitusincludecongenitaldiabetes,whichisduetogeneticdefectsofinsulinsecretion,cysticfibrosisrelateddiabetes,steroiddiabetes
inducedbyhighdosesofglucocorticoids,andseveralformsofmonogenicdiabetes.
"Type3diabetes"hasbeensuggestedasatermforAlzheimer'sdiseaseastheunderlyingprocessesmayinvolveinsulinresistancebythebrain.[45]
Thefollowingisacomprehensivelistofothercausesofdiabetes:[46]
Geneticdefectsofcellfunction
Maturityonsetdiabetesoftheyoung
MitochondrialDNAmutations
Geneticdefectsininsulinprocessingorinsulinaction
Defectsinproinsulinconversion
Insulingenemutations
Insulinreceptormutations
https://en.wikipedia.org/wiki/Diabetes_mellitus

Endocrinopathies
Growthhormoneexcess(acromegaly)
Cushingsyndrome
Hyperthyroidism
Pheochromocytoma
Glucagonoma
Infections
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Exocrinepancreaticdefects
Chronicpancreatitis
Pancreatectomy
Pancreaticneoplasia
Cysticfibrosis
Hemochromatosis
Fibrocalculouspancreatopathy

Cytomegalovirusinfection
CoxsackievirusB
Drugs
Glucocorticoids
Thyroidhormone
adrenergicagonists
Statins[47]

Pathophysiology
Insulinistheprincipalhormonethatregulatestheuptakeofglucosefromthebloodintomostcellsofthe
body,especiallyliver,muscle,andadiposetissue.Therefore,deficiencyofinsulinortheinsensitivityofits
receptorsplaysacentralroleinallformsofdiabetesmellitus.[48]
Thebodyobtainsglucosefromthreemainplaces:theintestinalabsorptionoffood,thebreakdownof
glycogen,thestorageformofglucosefoundintheliver,andgluconeogenesis,thegenerationofglucosefrom
noncarbohydratesubstratesinthebody.[49]Insulinplaysacriticalroleinbalancingglucoselevelsinthe
body.Insulincaninhibitthebreakdownofglycogenortheprocessofgluconeogenesis,itcanstimulatethe
transportofglucoseintofatandmusclecells,anditcanstimulatethestorageofglucoseintheformof
glycogen.[49]
Insulinisreleasedintothebloodbybetacells(cells),foundintheisletsofLangerhansinthepancreas,in
responsetorisinglevelsofbloodglucose,typicallyaftereating.Insulinisusedbyabouttwothirdsofthe
body'scellstoabsorbglucosefromthebloodforuseasfuel,forconversiontootherneededmolecules,orfor
storage.Lowerglucoselevelsresultindecreasedinsulinreleasefromthebetacellsandinthebreakdownof
glycogentoglucose.Thisprocessismainlycontrolledbythehormoneglucagon,whichactsintheopposite
mannertoinsulin.[50]

Thefluctuationofbloodsugar(red)andthesugar
loweringhormoneinsulin(blue)inhumansduring
thecourseofadaywiththreemealsoneofthe
effectsofasugarrichvsastarchrichmealis
highlighted.

Iftheamountofinsulinavailableisinsufficient,ifcellsrespondpoorlytotheeffectsofinsulin(insulin
insensitivityorinsulinresistance),oriftheinsulinitselfisdefective,thenglucosewillnotbeabsorbedproperlybythebodycellsthatrequireit,anditwillnotbe
storedappropriatelyintheliverandmuscles.Theneteffectispersistentlyhighlevelsofbloodglucose,poorproteinsynthesis,andothermetabolicderangements,
suchasacidosis.[49]

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Whentheglucoseconcentrationinthebloodremainshighovertime,thekidneyswillreachathresholdof
reabsorption,andglucosewillbeexcretedintheurine(glycosuria).[51]Thisincreasestheosmoticpressureof
theurineandinhibitsreabsorptionofwaterbythekidney,resultinginincreasedurineproduction(polyuria)
andincreasedfluidloss.Lostbloodvolumewillbereplacedosmoticallyfromwaterheldinbodycellsand
otherbodycompartments,causingdehydrationandincreasedthirst(polydipsia).[49]

Diagnosis

Condition

WHOdiabetesdiagnosticcriteria[52][53]
2hourglucose
Fastingglucose

HbA1c

Unit

mmol/l(mg/dl)

mmol/l(mg/dl)

mmol/mol DCCT%

Normal

<7.8(<140)

<6.1(<110)

<42

<6.0

Impairedfastingglycaemia

<7.8(<140)

6.1(110)&<7.0(<126)

4246

6.06.4

Impairedglucosetolerance

7.8(140)

<7.0(<126)

4246

6.06.4

Diabetesmellitus

11.1(200)

7.0(126)

48

6.5

Mechanismofinsulinreleaseinnormalpancreatic
betacellsinsulinproductionismoreorless
constantwithinthebetacells.Itsreleaseistriggered
byfood,chieflyfoodcontainingabsorbableglucose.

Diabetesmellitusischaracterizedbyrecurrentorpersistenthighbloodsugar,andisdiagnosedbydemonstratinganyoneofthefollowing:[44]
Fastingplasmaglucoselevel7.0mmol/l(126mg/dl)
Plasmaglucose11.1mmol/l(200mg/dl)twohoursaftera75goralglucoseloadasinaglucosetolerancetest
Symptomsofhighbloodsugarandcasualplasmaglucose11.1mmol/l(200mg/dl)
Glycatedhemoglobin(HbA1C)48mmol/mol(6.5DCCT%).[54]
Apositiveresult,intheabsenceofunequivocalhighbloodsugar,shouldbeconfirmedbyarepeatofanyoftheabovemethodsonadifferentday.Itispreferable
tomeasureafastingglucoselevelbecauseoftheeaseofmeasurementandtheconsiderabletimecommitmentofformalglucosetolerancetesting,whichtakestwo
hourstocompleteandoffersnoprognosticadvantageoverthefastingtest.[55]Accordingtothecurrentdefinition,twofastingglucosemeasurementsabove
126mg/dl(7.0mmol/l)isconsidereddiagnosticfordiabetesmellitus.
PertheWorldHealthOrganizationpeoplewithfastingglucoselevelsfrom6.1to6.9mmol/l(110to125mg/dl)areconsideredtohaveimpairedfasting
glucose.[56]peoplewithplasmaglucoseatorabove7.8mmol/l(140mg/dl),butnotover11.1mmol/l(200mg/dl),twohoursaftera75goralglucoseloadare
consideredtohaveimpairedglucosetolerance.Ofthesetwoprediabeticstates,thelatterinparticularisamajorriskfactorforprogressiontofullblowndiabetes
mellitus,aswellascardiovasculardisease.[57]TheAmericanDiabetesAssociationsince2003usesaslightlydifferentrangeforimpairedfastingglucoseof5.6to
6.9mmol/l(100to125mg/dl).[58]
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Glycatedhemoglobinisbetterthanfastingglucosefordeterminingrisksofcardiovasculardiseaseanddeathfromanycause.[59]
Therarediseasediabetesinsipidushassimilarsymptomstodiabetesmellitus,butwithoutdisturbancesinthesugarmetabolism(insipidusmeans"withouttaste"in
Latin)anddoesnotinvolvethesamediseasemechanisms.Diabetesisapartofthewiderconditionknownasmetabolicsyndrome.

Prevention
Thereisnoknownpreventivemeasurefortype1diabetes.[3]Type2diabeteswhichaccountsfor8590%ofallcasescanoftenbepreventedordelayedby
maintaininganormalbodyweight,engaginginphysicalexercise,andconsumingahealthfuldiet.[3]Higherlevelsofphysicalactivityreducetheriskofdiabetes
by28%.[60]Dietarychangesknowntobeeffectiveinhelpingtopreventdiabetesincludemaintainingadietrichinwholegrainsandfiber,andchoosinggoodfats,
suchasthepolyunsaturatedfatsfoundinnuts,vegetableoils,andfish.[61]Limitingsugarybeveragesandeatinglessredmeatandothersourcesofsaturatedfatcan
alsohelppreventdiabetes.[61]Tobaccosmokingisalsoassociatedwithanincreasedriskofdiabetesanditscomplications,sosmokingcessationcanbean
importantpreventivemeasureaswell.[62]
Therelationshipbetweentype2diabetesandthemainmodifiableriskfactors(excessweight,unhealthydiet,physicalinactivityandtobaccouse)issimilarinall
regionsoftheworld.Thereisgrowingevidencethattheunderlyingdeterminantsofdiabetesareareflectionofthemajorforcesdrivingsocial,economicand
culturalchange:globalization,urbanization,populationageing,andthegeneralhealthpolicyenvironment.[63]

Management
Diabetesmellitusisachronicdisease,forwhichthereisnoknowncureexceptinveryspecificsituations.[64]Management
concentratesonkeepingbloodsugarlevelsasclosetonormal,withoutcausinglowbloodsugar.Thiscanusuallybe
accomplishedwithahealthydiet,exercise,weightloss,anduseofappropriatemedications(insulininthecaseoftype1
diabetesoralmedications,aswellaspossiblyinsulin,intype2diabetes).
Learningaboutthediseaseandactivelyparticipatinginthetreatmentisimportant,sincecomplicationsarefarlesscommon
andlesssevereinpeoplewhohavewellmanagedbloodsugarlevels.[65][66]ThegoaloftreatmentisanHbA1Clevelof

Overviewofmanagement

6.5%,butshouldnotbelowerthanthat,andmaybesethigher.[67]Attentionisalsopaidtootherhealthproblemsthatmay
acceleratethenegativeeffectsofdiabetes.Theseincludesmoking,elevatedcholesterollevels,obesity,highbloodpressure,
andlackofregularexercise.[67]Specializedfootweariswidelyusedtoreducetheriskofulceration,orreulceration,inatriskdiabeticfeet.Evidenceforthe
efficacyofthisremainsequivocal,however.[68]

Lifestyle
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Peoplewithdiabetescanbenefitfromeducationaboutthediseaseandtreatment,goodnutritiontoachieveanormalbodyweight,andexercise,withthegoalof
keepingbothshorttermandlongtermbloodglucoselevelswithinacceptablebounds.Inaddition,giventheassociatedhigherrisksofcardiovasculardisease,
lifestylemodificationsarerecommendedtocontrolbloodpressure.[69]

Medications
Medicationsusedtotreatdiabetesdosobyloweringbloodsugarlevels.Thereareanumberofdifferentclassesofantidiabeticmedications.Someareavailable
bymouth,suchasmetformin,whileothersareonlyavailablebyinjectionsuchasGLP1agonists.Type1diabetescanonlybetreatedwithinsulin,typicallywith
acombinationofregularandNPHinsulin,orsyntheticinsulinanalogs.
Metforminisgenerallyrecommendedasafirstlinetreatmentfortype2diabetes,asthereisgoodevidencethatitdecreasesmortality.[70]Itworksbydecreasing
theliver'sproductionofglucose.[71]Severalothergroupsofdrugs,mostlygivenbymouth,mayalsodecreasebloodsugarintypeIIDM.Theseincludeagentsthat
increaseinsulinrelease,agentsthatdecreaseabsorptionofsugarfromtheintestines,andagentsthatmakethebodymoresensitivetoinsulin.[71]Wheninsulinis
usedintype2diabetes,alongactingformulationisusuallyaddedinitially,whilecontinuingoralmedications.[70]Dosesofinsulinarethenincreasedto
effect.[70][72]
Sincecardiovasculardiseaseisaseriouscomplicationassociatedwithdiabetes,somehaverecommendedbloodpressurelevelsbelow130/80mmHg.[73]However,
evidencesupportslessthanorequaltosomewherebetween140/90mmHgto160/100mmHgtheonlyadditionalbenefitfoundforbloodpressuretargetsbeneath
thisrangewasanisolateddecreaseinstrokerisk,andthiswasaccompaniedbyanincreasedriskofotherseriousadverseevents.[74][75]A2016reviewfound
potentialharmtotreatinglowerthan140mmHg.[76]Amongmedicationsthatlowerbloodpressure,angiotensinconvertingenzymeinhibitors(ACEIs)improve
outcomesinthosewithDMwhilethesimilarmedicationsangiotensinreceptorblockers(ARBs)donot.[77]Aspirinisalsorecommendedforpeoplewith
cardiovascularproblems,howeverroutineuseofaspirinhasnotbeenfoundtoimproveoutcomesinuncomplicateddiabetes.[78]

Surgery
Apancreastransplantisoccasionallyconsideredforpeoplewithtype1diabeteswhohaveseverecomplicationsoftheirdisease,includingendstagekidney
diseaserequiringkidneytransplantation.[79]
Weightlosssurgeryinthosewithobesityandtypetwodiabetesisoftenaneffectivemeasure.[80]Manyareabletomaintainnormalbloodsugarlevelswithlittleor
nomedicationsfollowingsurgery[81]andlongtermmortalityisdecreased.[82]Therehoweverissomeshorttermmortalityriskoflessthan1%fromthe
surgery.[83]Thebodymassindexcutoffsforwhensurgeryisappropriatearenotyetclear.[82]Itisrecommendedthatthisoptionbeconsideredinthosewhoare
unabletogetboththeirweightandbloodsugarundercontrol.[84]

Support
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Incountriesusingageneralpractitionersystem,suchastheUnitedKingdom,caremaytakeplacemainlyoutsidehospitals,withhospitalbasedspecialistcare
usedonlyincaseofcomplications,difficultbloodsugarcontrol,orresearchprojects.Inothercircumstances,generalpractitionersandspecialistssharecareina
teamapproach.Hometelehealthsupportcanbeaneffectivemanagementtechnique.[85]

Epidemiology
Asof2016,422millionpeoplehavediabetesworldwide,[86]upfromanestimated382millionpeoplein
2013[13]andfrom108millionin1980.[86]Accountingfortheshiftingagestructureoftheglobalpopulation,
theprevalenceofdiabetesis8.5%amongadults,nearlydoubletherateof4.7%in1980.[86]Type2makesup
about90%ofthecases.[12][14]Somedataindicateratesareroughlyequalinwomenandmen,[14]butmale
excessindiabeteshasbeenfoundinmanypopulationswithhighertype2incidence,possiblyduetosex
relateddifferencesininsulinsensitivity,consequencesofobesityandregionalbodyfatdeposition,andother
contributingfactorssuchashighbloodpressure,tobaccosmokingandalcoholintake.[87][88]
TheWorldHealthOrganization(WHO)estimatesthatdiabetesmellitusresultedin1.5milliondeathsin
2012,makingitthe8thleadingcauseofdeath.[7][86]Howeveranother2.2milliondeathsworldwidewere
attributabletohighbloodglucoseandtheincreasedrisksofcardiovasculardiseaseandotherassociated
complications(e.g.kidneyfailure),whichoftenleadtoprematuredeathandareoftenlistedastheunderlying
causeondeathcertificatesratherthandiabetes.[86][89]Forexample,in2014,theInternationalDiabetes
Federation(IDF)estimatedthatdiabetesresultedin4.9milliondeathsworldwide,[15]usingmodellingto
estimatethetotalamountofdeathsthatcouldbedirectlyorindirectlyattributedtodiabetes.[16]

Ratesofdiabetesworldwidein2000(per1,000
inhabitants)worldaveragewas2.8%.
nodata

4552.5

7.5

52.560

7.515

6067.5

1522.5

67.575

22.530

7582.5

3037.5

82.5

Diabetesmellitusoccursthroughouttheworldbutismorecommon(especiallytype2)inmoredeveloped
37.545
countries.Thegreatestincreaseinrateshashoweverbeenseeninlowandmiddleincomecountries,[86]
wheremorethan80%ofdiabeticdeathsoccur.[90]Thefastestprevalenceincreaseisexpectedtooccurin
AsiaandAfrica,wheremostpeoplewithdiabeteswillprobablylivein2030.[91]Theincreaseinratesindevelopingcountriesfollowsthetrendofurbanizationand
lifestylechanges,includingincreasinglysedentarylifestyles,lessphysicallydemandingworkandtheglobalnutritiontransition,markedbyincreasedintakeof
foodsthatarehighenergydensebutnutrientpoor(oftenhighinsugarandsaturatedfats,sometimesreferredtoasthe"Westernstyle"diet).[86][91]

History

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Diabeteswasoneofthefirstdiseasesdescribed,[92]withanEgyptianmanuscriptfromc.1500BCE
mentioning"toogreatemptyingoftheurine".[93]Thefirstdescribedcasesarebelievedtobeoftype1
diabetes.[93]Indianphysiciansaroundthesametimeidentifiedthediseaseandclassifieditasmadhumehaor
"honeyurine",notingtheurinewouldattractants.[93]Theterm"diabetes"or"topassthrough"wasfirstused
in230BCEbytheGreekApolloniusofMemphis.[93]Thediseasewasconsideredrareduringthetimeofthe
Romanempire,withGalencommentinghehadonlyseentwocasesduringhiscareer.[93]Thisispossiblydue
tothedietandlifestyleoftheancients,orbecausetheclinicalsymptomswereobservedduringtheadvanced
stageofthedisease.Galennamedthedisease"diarrheaoftheurine"(diarrheaurinosa).Theearliestsurviving
workwithadetailedreferencetodiabetesisthatofAretaeusofCappadocia(2ndorearly3rdcenturyCE).
Hedescribedthesymptomsandthecourseofthedisease,whichheattributedtothemoistureandcoldness,
reflectingthebeliefsofthe"PneumaticSchool".Hehypothesizedacorrelationofdiabeteswithother
diseasesandhediscusseddifferentialdiagnosisfromthesnakebitewhichalsoprovokesexcessivethirst.His
workremainedunknownintheWestuntil1552,whenthefirstLatineditionwaspublishedinVenice.[94]

Diabetesmellitusdeathspermillionpersonsin2012
2891

164184

310404

92114

185209

4051879

115141

210247

142163

248309

Type1andtype2diabeteswereidentifiedasseparateconditionsforthefirsttimebytheIndianphysicians
SushrutaandCharakain400500CEwithtype1associatedwithyouthandtype2withbeingoverweight.[93]Theterm"mellitus"or"fromhoney"wasaddedby
theBritonJohnRolleinthelate1700stoseparatetheconditionfromdiabetesinsipidus,whichisalsoassociatedwithfrequenturination.[93]Effectivetreatment
wasnotdevelopeduntiltheearlypartofthe20thcentury,whenCanadiansFrederickBantingandCharlesHerbertBestisolatedandpurifiedinsulinin1921and
1922.[93]ThiswasfollowedbythedevelopmentofthelongactinginsulinNPHinthe1940s.[93]

Etymology
Theworddiabetes(/da.bitiz/or/da.bits/)comesfromLatindiabts,whichinturncomesfromAncientGreek(diabts)whichliterallymeans
"apasserthroughasiphon."[95]AncientGreekphysicianAretaeusofCappadocia(fl.1stcenturyCE)usedthatword,withtheintendedmeaning"excessive
dischargeofurine",asthenameforthedisease.[96][97]Ultimately,thewordcomesfromGreek(diabainein),meaning"topassthrough,"[95]whichis
composedof(dia),meaning"through"and(bainein),meaning"togo".[96]Theword"diabetes"isfirstrecordedinEnglish,intheformdiabete,ina
medicaltextwrittenaround1425.
Thewordmellitus(/mlats/or/mlts/)comesfromtheclassicalLatinwordmelltus,meaning"mellite"[98](i.e.sweetenedwithhoney[98]honeysweet[99]).
TheLatinwordcomesfrommell,whichcomesfrommel,meaning"honey"[98][99]sweetness[99]pleasantthing,[99]andthesuffixtus,[98]whosemeaningisthe
sameasthatoftheEnglishsuffix"ite".[100]ItwasThomasWilliswhoin1675added"mellitus"totheword"diabetes"asadesignationforthedisease,whenhe
noticedtheurineofadiabetichadasweettaste(glycosuria).ThissweettastehadbeennoticedinurinebytheancientGreeks,Chinese,Egyptians,Indians,and
Persians.
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Societyandculture
The1989"St.VincentDeclaration"[101][102]wastheresultofinternationaleffortstoimprovethecareaccordedtothosewithdiabetes.Doingsoisimportantnot
onlyintermsofqualityoflifeandlifeexpectancybutalsoeconomicallyexpensesduetodiabeteshavebeenshowntobeamajordrainonhealthand
productivityrelatedresourcesforhealthcaresystemsandgovernments.
Severalcountriesestablishedmoreandlesssuccessfulnationaldiabetesprogrammestoimprovetreatmentofthedisease.[103]
Peoplewithdiabeteswhohaveneuropathicsymptomssuchasnumbnessortinglinginfeetorhandsaretwiceaslikelytobeunemployedasthosewithoutthe
symptoms.[104]
In2010,diabetesrelatedemergencyroom(ER)visitratesintheUnitedStateswerehigheramongpeoplefromthelowestincomecommunities(526per10,000
population)thanfromthehighestincomecommunities(236per10,000population).Approximately9.4%ofdiabetesrelatedERvisitswerefortheuninsured.[105]

Naming
Theterm"type1diabetes"hasreplacedseveralformerterms,includingchildhoodonsetdiabetes,juvenilediabetes,andinsulindependentdiabetesmellitus
(IDDM).Likewise,theterm"type2diabetes"hasreplacedseveralformerterms,includingadultonsetdiabetes,obesityrelateddiabetes,andnoninsulin
dependentdiabetesmellitus(NIDDM).Beyondthesetwotypes,thereisnoagreeduponstandardnomenclature.
Diabetesmellitusisalsooccasionallyknownas"sugardiabetes"todifferentiateitfromdiabetesinsipidus.[106]

Otheranimals
Inanimals,diabetesismostcommonlyencounteredindogsandcats.Middleagedanimalsaremostcommonlyaffected.Femaledogsaretwiceaslikelytobe
affectedasmales,whileaccordingtosomesources,malecatsarealsomorepronethanfemales.Inbothspecies,allbreedsmaybeaffected,butsomesmalldog
breedsareparticularlylikelytodevelopdiabetes,suchasMiniaturePoodles.[107]Thesymptomsmayrelatetofluidlossandpolyuria,butthecoursemayalsobe
insidious.Diabeticanimalsaremorepronetoinfections.Thelongtermcomplicationsrecognisedinhumansaremuchrarerinanimals.Theprinciplesoftreatment
(weightloss,oralantidiabetics,subcutaneousinsulin)andmanagementofemergencies(e.g.ketoacidosis)aresimilartothoseinhumans.[107]

Research

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Inhalableinsulinhasbeendeveloped.[108]Theoriginalproductswerewithdrawnduetosideeffects.[108]Afrezza,underdevelopmentbypharmaceuticalscompany
MannKindCorporation,wasapprovedbytheFDAforgeneralsaleinJune2014.[109]Anadvantagetoinhaledinsulinisthatitmaybemoreconvenientandeasyto
use.[110]
Transdermalinsulinintheformofacreamhasbeendevelopedandtrialsarebeingconductedonpeoplewithtype2diabetes.[111][112]

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Furtherreading
PolonskyKS(2012)."ThePast200YearsinDiabetes".NewEnglandJournalofMedicine.367(14):133240.doi:10.1056/NEJMra1110560.
PMID23034021.

Externallinks
Diabetesmellitus(https://www.dmoz.org/Health/Conditions_and_Diseases/Endocrine_Disorders/Pancreas/Diabetes/)atDMOZ
IDFDiabetesAtlas(http://www.diabetesatlas.org/)
NationalDiabetesEducationProgram(http://ndep.nih.gov/)
Retrievedfrom"https://en.wikipedia.org/w/index.php?title=Diabetes_mellitus&oldid=742588432"
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