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Prediabetes - Wikipedia, the free encyclopedia

Prediabetes
FromWikipedia,thefreeencyclopedia

Prediabetesisthestateinwhich somebutnotallofthediagnostic criteriafordiabetesaremet.[1]Itis oftendescribedasthegrayarea betweennormalbloodsugarand diabeticlevels.

Prediabetes
Classificationandexternalresources ICD10 R73.0 (http://apps.who.int/classifications/icd10/browse/2010/en#/R73.0) ICD9 790.29(http://www.icd9data.com/getICD9Code.ashx? icd9=790.29)

Contents
1Classification 1.1Impairedfasting glycaemia 1.2Impaired glucosetolerance 2Signsandsymptoms 3Cause 3.1Genetics 4Pathophysiology 5Prevention 6Screening 7Diagnosis 8Management 9Prognosis 10Epidemiology 11References

MeSH D011236(http://www.nlm.nih.gov/cgi/mesh/2013/MB_cgi? field=uid&term=D011236)

Classification
Impairedfastingglycaemia
Mainarticle:Impairedfastingglycaemia Impairedfastingglycaemiaorimpairedfastingglucose(IFG)referstoaconditioninwhichthefasting bloodglucoseiselevatedabovewhatisconsiderednormallevelsbutisnothighenoughtobeclassifiedas diabetesmellitus.Itisconsideredaprediabeticstate,associatedwithinsulinresistanceandincreasedrisk ofcardiovascularpathology,althoughoflesserriskthanimpairedglucosetolerance(IGT).IFGsometimes progressestotype2diabetesmellitus.Thereisa50%riskover10yearsofprogressingtoovertdiabetes.A recentstudycitedtheaveragetimeforprogressionaslessthanthreeyears.[2]IFGisalsoariskfactorfor mortality.[3]

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Fastingbloodglucoselevelsareinacontinuumwithinagivenpopulation,withhigherfastingglucose levelscorrespondingtoahigherriskforcomplicationscausedbythehighglucoselevels.Impairedfasting glucoseisdefinedasafastingglucosethatishigherthantheupperlimitofnormal,butnothighenoughto beclassifiedasdiabetesmellitus.Somepatientswithimpairedfastingglucosecanalsobediagnosedwith impairedglucosetolerance,butmanyhavenormalresponsestoaglucosetolerancetest. WorldHealthOrganization(WHO)criteriaforimpairedfastingglucosediffersfromthe(American DiabetesAssociation)ADAcriteria,becausethenormalrangeofglucoseisdefineddifferently.Fasting glucoselevels100mg/dL(5.5mmol/L)andhigherhavebeenshowntoincreasecomplicationrates significantly.However,WHOoptedtokeepitsupperlimitofnormalatunder110mg/dLforfearof causingtoomanypeopletobediagnosedashavingimpairedfastingglucose,whereastheADAlowered theupperlimitofnormaltoafastingglucoseunder100mg/dL. WHOcriteria:fastingplasmaglucoselevelfrom6.1mmol/l(110mg/dL)to6.9mmol/L (125mg/dL).[4][5] ADAcriteria:fastingplasmaglucoselevelfrom5.6mmol/L(100mg/dL)to6.9mmol/L (125mg/dL).

Impairedglucosetolerance
Mainarticle:Impairedglucosetolerance Impairedglucosetolerance(IGT)isaprediabeticstateofdysglycemia,thatisassociatedwithinsulin resistanceandincreasedriskofcardiovascularpathology.IGTmayprecedetype2diabetesmellitusby manyyears.IGTisalsoariskfactorformortality.[3]

Signsandsymptoms
Prediabetestypicallyhasnodistinctsignsorsymptoms.Patientsshouldmonitorforsignsandsymptomsof type2diabetesmellitus.Theseincludethefollowing:[6] Constanthunger Unexplainedweightloss Weightgain Flulikesymptoms,includingweaknessandfatigue Blurredvision Slowhealingofcutsorbruises Tinglingorlossoffeelinginhandsorfeet Recurringgumorskininfections Recurringvaginalorbladderinfections

Cause
Sleepdisorders Familyhistoryofdiabetes Impairedglucoselevelsand/ormetabolicsyndrome

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Cardiovasculardisease Hypertension(highbloodpressure) Increasedtriglycerideslevels Lowlevelsofgoodcholesterol(HDL) Overweightorobese Womenwhohavehadgestationaldiabetes,hadhighbirthweightbabies(greaterthan9lbs.),and/or hasPolycysticOvarianSyndrome(PCOS)[7] Theseareassociatedwithinsulinresistanceandareriskfactorsforthedevelopmentoftype2diabetes mellitus.Thoseinthisstratum(IGTorIFG)areatincreasedriskofcardiovasculardisease.Ofthetwo, impairedglucosetolerancebetterpredictscardiovasculardiseaseandmortality.[8][9][10] Inaway,prediabetesisamisnomersinceitisanearlystageofdiabetes.Itisnowknownthatthehealth complicationsassociatedwithtype2diabetesoftenoccurbeforethemedicaldiagnosisofdiabetesis made.[11]

Genetics
Asthehumangenomeisfurtherexplored,itislikelythatmultiplegeneticanomaliesatdifferentlociwill befoundthatconfervaryingdegreesofpredispositiontotype2diabetes.[12]Type2DM,whichisthe conditionforwhichprediabetesisaprecursor,has90100%concordanceintwinsthereisnoHLA association.[13]However,geneticsplayarelativelysmallroleinthewidespreadoccurrenceoftype2 diabetes.Thiscanbelogicallydeducedfromthehugeincreaseintheoccurrenceoftype2diabeteswhich hascorrelatedwiththesignificantchangeinwesternlifestyle.[13]

Pathophysiology
Diabetesmellitus(DM)isagroupofmetabolicdiseasesthatarecharacterizedbyhyperglycemiaand defectsininsulinproductioninthepancreasand/orimpairedtolerancetoinsulineffects.DMisaleading causeofmorbidityandmortality.Becausethediseasecanbeinsidious,thediagnosisisoftendelayed. Effectsofthediseasecanbemacrovascular,asseeninthecardiovascularsystem/arthrosclerosis,or microvascular,asseenwithretinopathy,nephropathy,andneuropathy.[13] Normalglucosehomeostasisiscontrolledbythreeinterrelatedprocesses.Thereisgluconeogenesis (glucoseproductionthatoccursintheliver),uptakeandutilizationofglucosebytheperipheraltissuesof thebody,andinsulinsecretionbythepancreaticisletcells.Whattriggerstheproductionandreleaseof insulinfromthepancreasisthepresenceofglucoseinthebody.Themainfunctionofinsulinistoincrease therateoftransportofglucoseintocertaincellsofthebody,suchasstriatedmuscles,fibroblasts,andfat cells.Itisalsonecessaryfortransportofaminoacids,glycogenformationintheliverandskeletalmuscles, triglycerideformationfromglucose,nucleicacidsynthesis,andproteinsynthesis. Insulinenterscellsbyfirstbindingtotargetinsulinreceptors.DMandsomeofthosewithprediabeteshave impairedglucosetoleranceintheseindividuals,bloodglucoserisestoabnormallyhighlevels.Thismay befromalackofpancreatichormonereleaseorfailureoftargettissuestorespondtotheinsulinpresentor both.[13]

Prevention
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TheAmericanCollegeofEndocrinology(ACE)andtheAmericanAssociationofClinical Endocrinologists(AACE)havedevelopedlifestyleinterventionguidelinesforpreventingtheonsetoftype 2diabetes: Healthymeals(lowfat,lowsugar,lowsaltdiet) Physicalexercise(45minutesofexerciseperday,fivedaysaweek) Reducingweightbyaslittleas510percentcanhaveasignificantimpactonoverallhealth.

Screening
Fastingplasmaglucosescreeningshouldbeginatage3045andberepeatedatleasteverythreeyears. Earlierandmorefrequentscreeningshouldbeconductedinatriskindividuals.Theriskfactorsforwhich arelistedbelow: Familyhistory(parentorsibling) Dyslipidemia(triglycerides>200orHDL<35) Overweightorobesity(bodymassindex>25) Historyofgestationaldiabetesorinfantbornwithbirthweightgreaterthan9lb(4kg) Highriskethnicgroup Hypertension(systolicbloodpressure>140mmHgordiastolicbloodpressure>90mmHg) Priorfastingbloodglucose>99 Knownvasculardisease Markersofinsulinresistance(PCOS,acanthosisnigricans)[14][15]

Diagnosis
Prediabetesisusuallydiagnosedwithabloodtest: Fastingbloodsugar(glucose)levelof: 110to125mg/dL(6.1mMto6.9mM)WHOcriteria 100to125mg/dL(5.6mMto6.9mM)ADAcriteria Twohourglucosetolerancetestafteringestingthestandardized75Gmglucosesolutiontheblood sugarlevelof140to199mg/dL(7.8to11.0mM).[16] Glycatedhemoglobinbetween5.7and6.4percent[17] Levelsabovetheselimitswouldbeadiagnosisfordiabetes.

Management
Intensiveweightlossandlifestyleintervention,ifsustained,cansubstantiallyimproveglucosetolerance andpreventprogressionfromIGTtotype2diabetes.TheDiabetesPreventionProgram(DPP)[18]study founda16%reductionindiabetesriskforeverykilogramofweightloss.Reducingweightby7%through alowfatdietandperforming150minutesofexerciseaweekisthegoal.TheADAguidelines[19] recommendmodestweightloss(510%bodyweight),moderateintensityexercise(30minutesdaily),and smokingcessation.

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Forpatientswithsevereriskfactors,prescriptionmedicationmaybeappropriate.Thiscanbeconsideredin patientsforwhomlifestyletherapyhasfailedorisnotsustainableandwhoareathighriskfordeveloping type2diabetes.[20]Metformin[21]andacarbosehelppreventthedevelopmentoffrankdiabetes,andalso haveagoodsafetyprofile.Evidencealsosupportsthiazolidinedionesbuttherearesafetyconcerns,and dataonneweragentssuchasGLP1receptoragonists,DPP4inhibitorsormeglitinidesarelacking.[22]

Prognosis
Theprogressiontotype2diabetesmellitusisnotinevitableforthosewithprediabetes.Theprogression intodiabetesmellitusfromprediabetesisapproximately25%overthreetofiveyears[23]

Epidemiology
Studiesconductedfrom19881994indicatedthatatthattime,oftheUSpopulation4074yearsofage, 33.8%hadIFG,15.4%hadIGT,and40.1%hadprediabetes(IFG,IGT,orboth).Eighteenmillionpeople (6.3%ofthepopulation)hadtype2diabetesin2002.[24]

References
1. ^"prediabetes (http://web.archive.org/web/20090616022448/http://www.mercksource.com/pp/us/cns/cns_hl_dorlands_split.jsp ?pg=/ppdocs/us/common/dorlands/dorland/seven/000086054.htm)"at Dorland'sMedicalDictionary 2. ^NicholsGA,HillierTA,BrownJB(2007)."ProgressionFromNewlyAcquiredImpairedFastingGlusoseto Type2Diabetes"(http://care.diabetesjournals.org/cgi/content/full/30/2/228). DiabetesCare 30(2):228233. doi:10.2337/dc061392(http://dx.doi.org/10.2337%2Fdc061392).PMID17259486 (//www.ncbi.nlm.nih.gov/pubmed/17259486). 3. ^ a bBarrEL,ZimmetPZ,WelbornTA, etal. (2007)."Riskofcardiovascularandallcausemortalityin individualswithdiabetesmellitus,impairedfastingglucose,andimpairedglucosetolerance:theAustralian Diabetes,Obesity,andLifestyleStudy(AusDiab)". Circulation 116(2):1517. doi:10.1161/CIRCULATIONAHA.106.685628 (http://dx.doi.org/10.1161%2FCIRCULATIONAHA.106.685628).PMID17576864 (//www.ncbi.nlm.nih.gov/pubmed/17576864). 4. ^.WorldHealthOrganization."Definition,diagnosisandclassificationofdiabetesmellitusandits complications:ReportofaWHOConsultation.Part1.Diagnosisandclassificationofdiabetesmellitus" (http://www.who.int/diabetes/publications/en/).Retrieved20070529. 5. ^"Diagnosisandclassificationofdiabetesmellitus". DiabetesCare.28Suppl1:S3742.2005. PMID15618111(//www.ncbi.nlm.nih.gov/pubmed/15618111). 6. ^MayoClinicDiabetes:"Prediabetes".[1] (http://www.mayoclinic.com/health/prediabetes/DS00624/DSECTION=2).AccessedJan.27,2009. 7. ^ PowerofPrevention, AmericanCollegeofEndocrinology.Vol.1,issue2,May2009. http://www.powerofprevention.com/ 8. ^"ThePreventionorDelayofType2Diabetes,"ADA, DiabetesCare,25:742749,2002. 9. ^NationalDiabetesFactSheet(http://www.cdc.gov/diabetes/pubs/pdf/ndfs_2003.pdf) 10. ^Tominaga etal. (Jun1999)."Impairedglucosetoleranceisariskfactorforcardiovasculardisease,butnot impairedfastingglucose.TheFunagataDiabetesStudy". DiabetesCare 22(6):9204. 11. ^WebMD:Prediabetes(http://diabetes.webmd.com/guide/prediabetes).AccessedJan.27,2009. 12. ^UpToDate:Classificationofdiabetesmellitisandgeneticdiabeticsyndromes,Nov14,2007 13. ^ a b c dCotran,Kumar,Collins RobbinsPathologicBasisofDisease, SaundersSixthEdition,1999913 926.

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14. ^"ADA:StandardsofMedicalCareinDiabetes", DiabetesCare27:Supp1.515,2004. 15. ^"DiabetesGuidelinesTaskforce:AACEGuidelinesfortheManagementofDM", EndocrinPract1995, 1.149 16. ^Jellinger,PaulS."WhatYouNeedtoKnowaboutPrediabetes." PowerofPrevention, AmericanCollegeof Endocrinology.Vol.1,issue2,May2009.http://www.powerofprevention.com/ 17. ^NewGuidelinesUrgeA1CTestforDiabetesDiagnosis (http://www.nlm.nih.gov/medlineplus/news/fullstory_93511.html).HealthDay.December29,2009. 18. ^http://diabetes.niddk.nih.gov/dm/pubs/preventionprogram/ 19. ^https://www.diabetes.org/diabetesprevention/howtopreventdiabetes.jsp 20. ^UptoDate:Predictionandpreventionoftype2diabetesmellituswww.utdol.com/utd/content/topic.do? topicKey=diabetes. 21. ^LillyM,GodwinM(Apr2009)."Treatingprediabeteswithmetformin:systematicreviewandmeta analysis". CanadianFamilyPhysician 55(4):3639. 22. ^"AmericanCollegeofEndocrinologyConsensusStatementonthediagnosisandmanagementofprediabetes inthecontinuumofhyperglycemiaWhendotherisksofdiabetesbegin?" (http://www.aace.com/meetings/consensus/hyperglycemia/hyperglycemia.pdf)(PDF). AmericanCollegeof EndocrinologyTaskForceonPreDiabetes.Retrieved20080724. 23. ^Nathan etal. (Mar2007)."Impairedfastingglucoseandimpairedglucosetolerance:implicationsforcare". DiabetesCare 30(3):7539. 24. ^CDC:Diabetes.NationalDiabetesFactSheetUnitedStates,2003.

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