studies [229–232]
.SmokingincreasescirculatinglevelsofatherogenicLDLcholesterolby acceleratingthelipidconversionofHDLcholesterolanddelayingtheclearanceofLDL
cholesterolfromtheplasmacompartment [233]
. Accordingtoamorerecentstudyinwhichenergyintakeandbasalmetabolicratewere
calculatedin205womenand141men,cigarettesmokershadahigherenergyintakefrom fatthannon-smokers29vs.26,alowerintakefromcarbohydrates50vs.54anda
lowerintakeofvitaminC11vs.16mg [234]
. AnepidemiologicalstudyconductedinWestphaliainseveralthousandmenandwomen
showedthatthefrequencyofsubjectswithlowplasmaHDLcholesterolvalues0.907 mmolelinmen,1.166mmolelinwomenwasabout10higherinsmokersthaninex-
smokers or non-smokers [235]
. A study of cardiovascular risk factors in 166 cigarette smokersrevealedlowerserumHDLcholesterol0.76vs.0.81mmolelandhigherserum
triglycerides1.92vs.1.71mmolelincomparisonwithvaluesmeasuredin312non- smokers
[236] .Highertriglycerideandtotalcholesterollevelshavealsobeenreportedin
otherstudiesofsmokerscomparedwithnon-smokersandex-smokers [237–245]
.Ameta- analysisofdataobtainedinchildrenandadolescentsaged8–19yearsrevealedassocia-
tionsbetweensmokingornon-smokingstatus,andbloodlipidsandcholesterolfractions; theindingswereanalogoustothoseobtainedinadults
[228] .Plasmathiocyanatelevels,
measuredasanindicatoroftheextentoftobaccoexposureduringasmokingreduction programme, correlated signiicantly and inversely with HDL cholesterol and skinfold
thickness, but not with LDL cholesterol or triglycerides [230]
. The less an individual smoked,thegreaterwastheincreaseinHDLcholesterol.
Smokingduringpregnancyhasbeenfoundtoproducesigniicantdifferencesinvarious lipidparametersinthenewbornsofsmokermotherscomparedwiththenewbornsofnon-
smokermothers: LowerHDLcholesterol21vs.26mgdl
•
HighertotalcholesterolHDLcholesterolratio4.7vs.3.7
•
LowerapolipoproteinA-1105vs.129mgdl
•
HigherapolipoproteinBapolipoproteinA-1ratio0.44vs.0.3
•
Similardifferenceswerealsodetectedinthesmokerandnon-smokermothers [246]
.In adult smokers, the deleterious consequences for the coronaries are attributable to the
changesinHDLcholesterolandapolipoproteinA-1levels [226]
. AttemptstouseantioxidantsvitaminC,a-tocopheroltoreduceLDLoxidisabilitydue
to smoking or to block superoxide anion production by leucocytes have been largely unsuccessfulinvariousstudies
[247] ,ashavebeentheeffortstoreduceraisedplasma
levelsofsolubleintercellularadhesionmolecule-1sICAM-1orantibodiesagainstoxi- disedLDL
[248] .
Duringsmokingcessationtherapywithnicotineproductsinsmokersattemptingtoquit, triglycerides and HDL cholesterol are increased whereas LDL cholesterol is lowered
[249–251] . Plasma triglyceride levels after smoking cessation have shown varying
responses:unchangedvalueshavebeenfoundinsomestudies [229,232,252,253]
whereas a17.2reductionhasbeenreportedafter6weeksofsmokingcessation
[231] .Totalcho-
lesterol rises minimally 2.2 [254]
, and HDL cholesterol more markedly 20–30
[231,254] .TheextentoftheriseinHDLcholesterolcorrelatedwiththetypeofdiet,with
HDLcholesterolbeingincreasedmorerapidlybyahigh-fatthanalow-fatdiet [254]
.
7.4.2 Diabetes and Smoking
Peoplewithdiabeteshaveatendencytodevelopcomplicationssimplybecauseoftheir underlyingdisease.Theextensivebodyofsmoking-relatedindingspublishedduringthe
pasttwodecadesshouldmakediabeticpatientsandthephysicianswhotreatthemponder seriouslytheimplicationsoffailingtoquitsmoking.Speciiccomplicationssaidtobe
“supported”bysmokinginclude: Increasinginsulinresistance
•
Renalmicroangiopathywithincreasingalbuminuria
•
Progressionofatherosclerosisinthecoronaryarteriescoronaryheartdisease,myocar-
•
dialinfarction,stroke [255]
andtheperipheralbloodvesselsperipheralarterialocclu- sivedisease
[256] ResearchconductedintheNetherlands,USAandJapansuggeststhatcigarettesmoking
shouldalsoberegardedasariskfactorinitsownrightforthedevelopmentoftype2dia- betes
[257–261] ;however,acohortstudyinGreatBritainhasnotcorroboratedthistheory
[262] .Itremainsopentospeculationwhetherethnicormethodologicaldifferencesin
characterisingapersonwithdiabetesmightberesponsibleforthesediscrepantindings. AsdemonstratedbytheresultsfromalargeJapanesepatientpopulationTable
7.5 ,a
statisticallysigniicantassociationexistsbetweenpack-yearsofcigarettesmokingandthe riskforacquiringtype2diabetes.
Theassociationbetweendiabeticneuropathyandcigarettesmokinghasnotbeenstud- iedextensively.However,diabeticpatientswithautonomicneuropathyhavebeenshownto
havemoreprofoundvasoconstrictorresponsestocigarettesmokingthandiabeticpatients withoutneuropathyorhealthycontrols
[263] ,assumingthatthemeasuredreductionsin
skintemperatureareacceptablecorrelatesofbloodlow.
Table 7.5
Dataontherelativeriskforthedevelopmentofnon-insulin-dependentdiabetesmellitus asfunctionofpack-yearsofsmoking
[261] Pack-years
Total person-years
Casesoftype 2diabetes
Age-adjusted relativerisk
95CI Relativerisk,
multi-variate
a
95CI
13,266 79
1.00 1.00
0.1–20.0 15,132
93 1.120.82–1.69
1.220.89–1.67 20.1–30.0
12,980 120
1.561.17–1.81 1.571.16–2.11
30.1–40.0 5,332
47 1.441.00–2.64
1.551.06–2.26 40.0
3,854 42
1.691.15–2.49 1.731.15–2.60
pfortrend
0.0007
0.001
a
Covariates:age,bodymassindex,alcoholconsumption,physicalactivity,familyhistoryofdiabe- tes,fastingglucoselevel,totalcholesterol,triglycerides,HDLcholesterolandhaematocrit
Arterioscleroticchangesinthemajorvesselsoccuratanearlystageintype1diabetic patients who die early from smoking
[264] . Levels of circulating adhesion molecules
cAMareincreased,andtheseultimatelyinluenceendothelialfunctionandhencepro- motetheriskofcardiovasculardisease
[265–267] .Astudyofthelevelsofcirculating
intercellularadhesionmoleculecICAMintype1diabeticpatientswithoutclinicalmac- roangiopathy,incomparisonwithhealthycontrols,revealedraisedplasmacICAMcon-
centrations in type 1 diabetic smokers, with the highest plasma levels +25 being recordedinindividualssmokingmorethan10cigarettesday
[268] .
7.4.2.1 Insulin Resistance
Accordingtorecentlypublishedindings,smokingmayhaveadeleteriouseffectoninsulin activitybothinhealthysubjects
[269,270] andinnon-insulin-dependentdiabeticNIDDM
patients [271]
.Inaddition,comparedwithnon-smokers,non-diabeticsmokersareinsulin- resistantandexhibithyperinsulinaemia
[272–275] .Furthermore,smokersdisplaytypical
signs of an insulin resistance syndrome. The deviations from normal metabolism are relatedtosmokinghabits
[272] .Theprogressionofarteriosclerosisisdirectlyandindi-
rectly fostered by compensatory hyperinsulinaemia [276]
. In a study of 28 non-obese NIDDMsmokerscomparedwith12otherwisesimilarnon-smokers,plasmainsulinand
C-peptideresponsestooralglucoseloadafterfastingweresigniicantlyhigherinsmokers thannon-smokers,whereasglucoselevelswerenotsubstantiallydifferentseeFig.
7.1 .In
addition,therateoftotalinsulin-mediatedglucosedisposaldependsonthenumberof cigarettessmokedFig.
7.2 .FastingglucoselevelsandHbA
1c
werealsohigherinsmokers thaninnon-smokers
[276] ,asrelectedinthepropensityofthesepatientstodevelopdia-
beticcomplicationsmoreoften [277]
.
7.4.2.2 Diabetic Nephropathy
Theeffectofsmokinginacceleratingtheprogressionofdiabeticnephropathyhasbeen demonstrated in numerous studies
[278–284] . As illustrated by the data presented in
Fig. 7.3
,theeffectonshorteningsurvivalisparticularlyevidentindiabeticpatientsin end-stagenephropathywherethepatientrequireshaemodialysis
[285] .
Diabetic nephropathy is characterised primarily by a decline in excretory function becauseofvasculardamagecausedbydiabetes.Inpatientswithtype2diabetes,renal
damageadditionallyacceleratestheprogressionofarteriosclerosis,asassessedintermsof carotidarteryintima-mediathicknessIMT
[286] .Whereasageandimpairedcreatinine
clearanceleadtothickeningofthecarotidarterywallp£0.001,thedurationofdiabetes andsmokingstatuswerefoundtoaffectthefemoralarteryp0.0001
[286] .
Anearlysignofnephropathyistheonsetofmicroalbuminuria [287–289]
,accompa- niedinadditionbyincreasednumbersoffreeradicalsinplasma.Ininsulin-treateddia-
betic patients, albumin excretion is already triggered by smoking-related glomerular