hyperiltration [282]
,aphenomenonthathasbeenshowntocorrelatewiththenumberof cigarettes smoked Fig.
7.4 . Nowadays, therefore, alongside the coronary system, the
kidneysshouldbeviewedasthesecondorgansystemendangeredbytheharmfuleffects ofsmoking.Cigarettesmokingencouragestheprogressionofnephropathyinbothtype1
andtype2diabetes [290]
.Incontrast–althoughasubjectofcontroversyinthepast–asso- ciationshavenotnecessarilybeenfoundbetweendiabeticretinopathyandcigarettesmok-
ingseeSect.7.2.1.Ina1-yearprospectivestudy,nephropathyprogressionwasdetected in53ofsmokersand33ofex-smokers,comparedwithonly11ofnon-smokers
[291] . Similar results have been obtained in smokers, based on self-reported smoking
behaviour [279]
.Aninvestigationconductedin574type2diabeticpatients,aged40–60
500 450
400 350
300 250
200 150
100 50
−30 30
60 90
120 150 180 210 240 270 300
−30 1,0
2,0 3,0
30 60
90 120
150 180 210 240 270 300
Time [min]
Time [min] p 0,001
p 0,01 Plasma insulin [pmoll]
Plasma C-peptide [nmoll]
Fig. 7.1
Plasmainsulinand C-peptideconcentrationsin
fastingNIDDMpatientsand effectoforalglucoseloading
with75g [276]
.Opencircle non-smokers;illedcircle
smokers
40 30
F-ANOVA = 6,8; P 0,001
20
Insulin-mediated total glucose disposal [µmolmin x kg FFM]
10
0 n=12
Number of cigarettes smoked per day
10 n=5 10–19 n=10
20 n=13
Fig. 7.2
Therateoftotal insulin-mediatedglucose
disposalinrelationtothe numberofcigarettessmoked
perday [276]
100 []
50
Survival rate [] Smoker
n = 22 Nonsmoker
n = 30
1 2
3 4
Years
5
Fig. 7.3
Five-yearsurvivalrate ofdiabeticnon-smokersand
smokersrequiringdialysis therapyforadvanced
nephropathy [293]
Fig. 7.4
Meannocturnal urinaryalbuminexcretionin
patientswithtype1diabetes, classiiedonthebasisof
smokinghabit [285]
.The verticalbarsshowthe
standarderror
6 5
4 3
2 1
Urinary albumin excretion [µgmin]
p 0,003
Non-smokers light smokers
smokers
100 ng Cml n=166
100–500 ng Cml n=26
500 ng Cml n=46
years,identiiedslightlyraisedbloodpressure,slightlyraisedtotalcholesterolandHbA
1c
asriskfactorsforthedevelopmentofdiabeticnephropathy
[292] .
Smokingamongadolescentswithtype1diabetesisassociatedwithanincreaseinmor- talityandhospitaladmissions,includingnumberoftreatmentdays,andthesepatientsfeel
“unwell”.Sincedetailsonsmokingbehaviourprovidedbydiabeticpatientsareknownto beimpreciseandunreliable,urinarycotininemeasurementshaveprovedusefulformoni-
toringcigaretteconsumption [293]
.AccordingtotheresultssummarisedinFig. 7.3
,fol- lowingassignmenttogroupsonthebasisofurinarycotinineexcretionthesmokingstatus
oftype1diabeticpatientscorrelatedwiththeextentofrenalalbuminexcretion [293]
. Bloodpressureintype1diabeticsisincreased,dependingonthenumberofcigarettes
smoked [281,294]
;however,theseindingshavebeencontested [293]
.Incontrast,passive smokingbychildrenandadultshasbeenshowntohaveadverseimplicationsforthepro-
gressionofdiabetese.g.basedonHbA
1c
measurements [295]
. Overall,themedicalprofessionshouldseriouslyurgemenandwomenwithdiabetesto
giveupsmoking,particularlysincetheprogressionofthediseasehasbeenshowntobe acceleratedbysmoking,asconirmedbymajornationalstudies
[259,296] .
7.5 Gastrointestinal Tract
Accordingtooneolderstudyin456patients,associationswerefoundbetweengastroin- testinaldiseaseandingestionofaspirinornon-steroidalanti-inlammatorydrugsNSAIDs,
butnocorrelationsweredetectedwithsmokingoralcohol [297]
.Smokingisknownto modifythebloodglucoseresponsetoanoralglucoseload,possiblybyalteringgastroin-
testinaltractmotility:thisisrelectedinhigherserummotilinahormonesecretedbythe stomachinsmokersthaninnon-smokers
[298] .
7.5.1 Oesophageal Cancer
Afterlungcancer,cancersoftheoesophagusarethecommonestsmoking-relatedtumours [299, 300]
. One possible cause is thought to be the UDP-glucuronyltransferase 1A7 UGT1A7systemwhichdetoxiiestobaccocarcinogens;thisisgeneticallyalteredinvari-
ousindividuals,andtheriskfororolaryngealcancersisincreasedinsubjectswithlow- activityUGT1A7genotypeswhoareheavysmokersOR=6.1;CI:1.5–25orlightsmokers
OR=3.7;CI:1.1–12 [301]
.Inaddition,tobaccosmokeisregardedasthetargetforthe p53gene
[302] .Thesetumoursarecausedbycontactcarcinogens,particularlysincethese
arecondensedinthepharynx,thenclearedbythelungsandtransportedtotheoesophageal mucosawheretheyproduceneoplasia
[303] .
Theriskofoesophagealcancerincreaseswithdurationofsmokingandfallsfollowing smokingcessation,ashasbeenconirmedinaUSstudyOR=2.1,andtheriskissome-
whatreducedbyiltercigarettescomparedwithnon-iltercigarettes [304]
.Inamulti-ethnic
study,currentcigarettesmokingwasasigniicantriskfactorforoesophagealcancers:the association was strongest for oesophageal adenocarcinomas OR = 2.80; CI: 1.8–4.3,
intermediateforgastriccardiaadenocarcinomasOR=2.12;CI:1.5–3.1,andweakerfor distalgastricadenocarcinomasOR=1.50;CI:1.1–2.1
[305] .IntheUSA,80ofcases
of oesophageal cancer observed in the 1990s were related to smoking. Alcohol intake potentiatesthecarcinogeniceffectofsmoking
[306,307] .Theoddsratioforadenocarci-
nomaofthedistaloesophagusforcurrentsmokershasbeenreportedat2.3CI:1.4–3.9 comparedwith1.9forex-smokersCI:1.2–3.0.Drinkersfourormoreglassesofwhisky
dayalsohaveanoddsratioof2.3CI:1.3–4.3,andanadditiveeffectofalcoholand smokingislikely
[308] .
7.5.2 Gastrointestinal Ulcers
Pepticulcersshowaparticularassociationwithsmoking,asdemonstratedbyawealthof publicationsintheliteraturefromthe1950stothe1980s.Accordingtoonemeta-analysis,
24ofallpepticulcersareattributabletoNSAIDs,48toHelicobacterpyloriand23 to cigarette smoking
[309] . Women who smoke are twice as likely as non-smokers to
developpepticulcers,anditisestimatedthatapproximately20ofincidentpepticulcer casesamongUSwomenareattributabletocigarettesmoking
[310] .AlargerPolishstudy
conductedineightdifferentregionsunderlinestheseindings [311]
,althoughotherauthors considersmokingunlikeHelicobacterpyloriinfectionnottobeanindependentfactor
forulcerdevelopment [312]
. Onthebasisofendoscopyindings,anassociationhasbeenreportedbetweencigarette
smokingandHelicobacterpyloriinfection [313]
,withtheresultthatincreasedsusceptibility toHelicobacterpylorimaybeassumed.GastritiscausedbyHelicobacterpyloriorbysmok-
ingisassociatedwithreducedconcentrationsoftheintragastricepidermalgrowthfactor EGF,asubstancefoundinthemucosaandproducedinincreasedquantitieswhenulcers
develop;however,thisgrowthfactordidnotplayaroleinthepathogenesisofduodenalulcer [314]
.ExperimentalanimalworkindicatesthatsmokingreducesEGF-inducedangiogenesis anddelaysulcerhealing
[315] .Inaddition,smokingdepressesgastricmucosalbloodlowas
wellastheproductionofNObyinhibitingNOsynthase [316]
. OnestudyfromSpaininHelicobacterpylori-positivepatientsdidnotrevealanyasso-
ciationbetweenHelicobacterpyloriinfectionandalcoholconsumptionorsmoking [317]
. Smokingwasalsonotanadditionalriskfactorfordyspepsia
[318] .Wheresmokershad
successfullyundergonetherapytoeradicateHelicobacterpylori,cigarettesmokingdidnot increasetherecurrenceofpepticulcers
[319] .
Duodenalulcersarealsoprovokedbysmoking,andsmokershavebeenreportedto havemorerelapsesandbleedingepisodesthanex-smokersornon-smokers63.3vs.31.2
vs.34.5forrelapses.Ulcerbleedingoccurredinsmokers,butnotinresponsetonicotine intake
[320] .Ithasbeenestablishedthatsmokingencouragesthedevelopmentofduode-
nal ulcers by inhibiting duodenal mucosal bicarbonate secretion, an important defence mechanismagainstacidandpepticdamage
[321] .Moreover,serumpepsinogenIlevels
areelevatedinsmokersbecauseofaugmentedpepsinsecretorycapacity [322]
.