Original Article
The association between obesity and migraine in a population of Iranian adults: a case-control study
Ali Miri
a, Morteza Nasiri
b, Sahar Zonoori
c, Fatemeh Yarahmad
c,
Arasb Dabbagh-Moghadam
d, Gholamreza Askari
e, Omid Sadeghi
f,*, Masoumeh Asadi
gaDepartmentofNutrition,SchoolofHealth,ZabolUniversityofMedicalSciences,Zabol,Iran
bDepartmentofOperationRoomTechnology,SchoolofParamedicine,QomUniversityofMedicalSciences,Qom,Iran
cDepartmentofNursing,BrojerdSchoolofNursing,LorestanUniversityofMedicalSciences,Lorestan,Iran
dDepartmentofHealth,SchoolofHealth,AJAUniversityofMedicalSciences,Tehran,Iran
eFoodSecurityResearchCenterandDepartmentofCommunityNutrition,SchoolofNutritionandFoodSciences,IsfahanUniversityofMedicalSciences, Isfahan,Iran
fDepartmentofCommunityNutrition,SchoolofNutritionalSciencesandDietetics,TehranUniversityofMedicalSciences,Tehran,Iran
gDepartmentofNursingandMidwifery,AbadanSchoolofMedicalSciences,Abadan,Iran
ARTICLE INFO
Keywords:
Adult
Bodymassindex Obesity
Migrainewithaura
ABSTRACT
Aim:Toassesstheassociationbetweenobesityandriskofmigrainewithauraandfeaturesofmigraine attacksamongapopulationofIranianadults.
Methods:Inthiscase-controlstudy,102confirmedcasesofmigrainewithaurawerematchedbasedon ageandgenderwith102healthysubjects.Dataondemographiccharacteristicsandanthropometric measurementswerecollectedfromallcasesandcontrolsbythesamemethods.Overweightandobesity wereconsideredasbodymassindex25–30kg/m2and30kg/m2,respectively.Featuresofmigraine attacksincludingfrequency,durationandheadachedailyresultweredeterminedforpatientsbasedon internationalheadachesocietycriteria.
Results:Meanageofsubjectswas 34.57.4yearsand77.9%ofthemwerefemale.Comparedwith subjectswithnormalbodymassindex,thosewithobesityhadgreateroddsforhavingmigrainewithaura (OR:3.06,95%CI:1.11–8.43).Suchfindingwasalsoseenevenafteradjustingforconfoundingvariables;in awaythatsubjectswithobesitywere2.92timesmorelikelyforhavingmigrainewithauracompared withthosewithnormalweight(OR:2.92,95%CI:1.03-8.33).Amongmigrainewithaurapatients,we foundthatthosewithobesityhadhigherheadachedailyresultcomparedwithsubjectswithnormal weight.However,obesitywasnotassociatedwithfrequencyanddurationofmigraineattacks.
Conclusions:Wefoundthatobesitywaspositivelyassociatedwithriskofmigrainewithaura.Inaddition, subjectswithobesityhadhigherheadachedailyresultcomparedwiththosewithnormalweight.
©2018DiabetesIndia.PublishedbyElsevierLtd.Allrightsreserved.
1.Introduction
Migraineisachronicneurovasculardisorderwhichismostly prevalentinmiddle-agedindividuals[1,2].InIslamicRepublicof Iranasadevelopingcountry,areviewofstudiesbetween1998and 2014hasshownthat7.14%–18.11%ofadultsexperiencedmigraine headache [3]. Aquarter of migrainepatientsperceive migraine with aura (MA), a transient disturbance in visual, sensory, language,ormotorfunctionbeforeattackoccurrence[4,5].
Itseemsthatgeneticandenvironmentalfactorsareinvolvedin etiology of migraine.Investigations have indicated that genetic
polymorphisms [6], alcohol and coffee consumption [7], low physicalactivity [8], nutritionaldeficiencies[9,10], and psycho- logical difficulties[11] affectadversely migraine riskand symp- toms.Recentlyithasbeenshownthatobesitymightcontributeto riskofmigraine[12–15],butfindingsinthisregardareconflicting andsomestudieshavefailedtoreachanysignificantassociations orhaveshownan inverseassociation[16–18]. So,it seemsthat furtherstudiesfromdifferentpartsoftheworldarerequiredto shedlightonthisissue.
Moststudiesontheassociationbetweenobesityand risk of migrainecarriedoutinWesterncountries,whereasthepatternof obesityismarkedlydifferentfromMiddleEastcountries.InMiddle East, a pattern of obesity, named Middle Eastern pattern, is prevalent particularly amongwomen and it ischaracterized by abdominal fat accumulation and enlarged waist circumference
* Correspondingauthor.
E-mailaddress:[email protected](O.Sadeghi).
https://doi.org/10.1016/j.dsx.2018.04.020
1871-4021/©2018DiabetesIndia.PublishedbyElsevierLtd.Allrightsreserved.
Diabetes&MetabolicSyndrome:ClinicalResearch&Reviews12(2018)733–736
ContentslistsavailableatScienceDirect
Diabetes & Metabolic Syndrome: Clinical Research &
Reviews
j o u r n a lh o m e p ag e : w w w . e l s e vi e r . c o m / l o c a t e / d s x
(WC)[19].Inaddition,thereisadearthofknowledgeaboutthe associationbetweenobesityandMA,andmostpreviousstudies haveassessedmigrainewithoutaura(MOA)orunderminedkinds ofmigraine[13,17,20].Giventolimitedandconflictingevidences, andhighprevalenceofmigraineand obesityin Iranian,current studyaimedtoassesstheassociationbetweenobesityandriskof MAaswellasfeaturesofmigraineattacksamongapopulationof Iranianadults.Wehypothesizedthatobesitymightincreasethe riskofMAandfeaturesofmigraineattacks.
2.Materialandmethods
Thiscase-controlstudywasdone,basedonSROBEstatement,in Isfahan,IslamicRepublicofIran,betweenJanuary2014andJuly 2016. Patients with MA were selected from Khorshidand and EmamMosaSadrclinicsofIsfahanUniversityofMedicalSciences, Isfahan,Iran.
The study was ethically approved by Isfahan University of Medical Sciences, Isfahan, Iran, and AJA University of Medical Sciences,Tehran,Iran,andallproceduresperformedinthisstudy wereinaccordancewiththeethicalstandardsoftheinstitutional and/or national research committee and with the Helsinki declaration.Priortostudyenrolment,awritteninformedconsent wasobtainedfromallsubjects.Patientswereincludedifhad:1) 18–50 yearsold, 2) history of migraine for 5years, 3)1-year historyofsevere,recurrent,andlong-lastingmigraineattacks(at leastoneattackpermonthlasting4h),and4)acurrentdiagnosis of MA approved by an experienced neurologist according to InternationalHeadacheSociety (IHS)(third revision)beta diag- nosticcriteria[5].Patientswithtension-typeheadacheandMOA wereexcluded.Healthysubjectslivinginthesameareacompared with MA patients were selected as control group. They were between 18–50 years old and with no history of migraine headache.Bothcases andcontrols wereselectedbytheconve- nience non-random sampling method.Totally,102MA patients and 102 healthy subjects participated in this study. Cases and controlswerematchedintermsofageandgender.Wegathered completedataaboutdemographiccharacteristicsandanthropo- metricmeasurementsfor allcasesandcontrols usingthesame methods.
Features of migraine attacks including attacks frequency, duration and headache daily result(HDR) were determinedby anexperiencedneurologist.Attacksfrequencywasconsideredas thenumberofmigraineattacksduringamonth.Attacksduration wasdefinedasmeanofhoursthatattackslast.Wealsodetermined themeandurationofmigraineattacksperday,namedHDR,using thefollowingformula:frequencyof attacksduration ofhead- ache[21,22].
Aquestionnairewasusedtocollectdataonage(year),gender, weight(Kg)andheight(cm).Weightwasmeasuredbya digital scalewithminimumclothingandwithoutshoeswithaprecision of100g.Inaddition,heightwasmeasuredinastandingposition without shoes by a tape measure with the nearest 0.5cm. To calculatebodymassindex(BMI)inbothcaseandcontrolgroups, weusedfollowingformula:weight(Kg)/height(metersquare).We classifiedtotalsubjectsintothreecategoriesbasedontheirBMIas follows:normal(BMI<25),overweight(BMI25–30),andobese (BMI30).
AllstatisticalanalysesweredoneusingSPSSsoftwareversion 19.0(SPSSInc,ChicagoIL).Independentsamplet-testwasusedto examinesignificantdifferencesincontinuousvariablesbetween casesandcontrols.Toexaminesignificantdifferencesincontinu- ous variables across categories of BMI, we applied one-way analysis of variance (ANOVA). In addition, to examine the distributionof categoricalvariables acrosscategories ofBMI or between cases and controls, we used Chi-square test. The
associationbetween obesityand risk of migrainewas assessed usingbinarylogisticregressionincrudeandtwoadjustedmodels.
Genderwasadjustedascontinuousvariableinthefirstmodel.Age wasadditionallyadjustedinthesecondmodel.Intheseanalyses, normal category based on BMI (< 25) was considered as the reference category. The overall trend of OR across increasing categoriesofBMIwasexaminedbyconsideringthesecategoriesas a continuous variable. P values were considered significant at<0.05.
3.Results
Meanageofsubjectswas34.57.4yearsand77.9%ofthem werefemale.Overall,theprevalence ofoverweightand obesity amongstudypopulationwere43.6%and11.8%,respectively.
Generalcharacteristicsofsubjectsbasedoncaseand control groupsareshowninTable1.PatientswithMAhadlowerheight, andweremorelikelytobeobesecomparedwithhealthysubjects.
Nosignificantdifferencewasfoundintermsofage,genderandBMI betweenMApatientsandhealthysubjects.Themeanfrequency and duration of migraine attacks among MA patients was 10.29.2and2017.3,respectively.
GeneralcharacteristicsofsubjectsacrosscategoriesofBMIare presentedinTable2.ComparedwithsubjectswithnormalBMI, those with obesitywere older with greater weight and lower height. In MA patients, HDR was significantly different across categoriesofBMI.However,nosignificantdifferencewasfoundin termsofattacksfrequencyandduration.
Adjustedoddsratiosand95%confidenceintervalsforMAacross categoriesofBMIareindicatedinTable3.Comparedwithsubjects withnormalBMI,thosewithobesityhadgreateroddsforhaving MA(OR:3.06,95%CI:1.11-8.43).Suchfindingwasalsoseeneven afteradjustingforconfoundingvariables;inawaythatsubjects withobesitywere2.92timesmorelikelyforhavingMAcompared with those with normal weight (OR: 2.92, 95% CI: 1.03-8.33).
However, such findings were not observed for subjects with overweight(OR:0.76,95%CI:0.42-1.40).
4.Discussion
Migraineisknownasthe19thcauseofdisabilityaroundthe world [23]. It has been shown that patients with migraine, especially MA, have increased odds of cardiovascular diseases (CVDs)andstroke[24,25].Giventhatobesityisamainriskfactor forincidenceofCVDsandstroke[26,27],itmightbeareasonfor the association between migraine and mentioned diseases.
However,dataontheassociationbetweenobesityandmigraine areconflicting.
Table1
Generalcharacteristicsofsubjectsincaseandcontrolgroups.
Variables Casegroup Controlgroup P-value*
(n=102) (n=102)
Age(year) 34.98.4 34.16.3 0.43
Gender(female)(%) 78.4 77.5 0.86
Weight(Kg) 68.112.2 69.310.6 0.46
Height(cm) 162.29.2 165.68.6 0.007
BMI(Kg/m2) 25.94.6 25.23.1 0.18
Obesity(%) 17.6 5.9 0.02
Attacksfrequency(permonth) 10.29.2 – Attacksduration(hour) 2017.3 –
HDRa 163.3175.4 –
Dataarepresentedasmeanstandarddeviationorpercent.
Abbreviation:BMIbodymassindex,HDRheadachedailyresult.
a Determinedasattacksfrequencyattacksduration.
* Obtainedfromindependentsamplet-testorChi-squaretest,whereappropriate.
734 A.Mirietal./Diabetes&MetabolicSyndrome:ClinicalResearch&Reviews12(2018)733–736
Inthecurrentstudy,obesitywaspositivelyassociatedwithrisk ofMA.Suchfindingwasalsoseenevenafteradjustmentforage andgender;inawaythatsubjectswithobesitywere2.92times more likely for having MA compared with those with normal weight.Tothebestofourknowledge,presentstudyisthefirst case-controlstudyintheMiddleEasttoexaminetheassociation betweenobesityandriskofMA.Inlinewithourfindings,Yuetal., ingeneralpopulationofChinesecohortreportedthatincidenceof migraine inpeoplewith generalobesity (BMI30)was higher thanthosewithnormalweight[12]. InanationalsampleofUS adults, Fordet al., indicated that BMI was associated with the prevalence of severe headaches or migraines in a non-linear manner[15].Inanothergeneralpopulationsurvey,Peterlinetal., reportedasignificantpositiveassociationbetweengeneralobesity andmigraineamongpeoplelessthan55yearsbutnointhoseover 55 years [17]. In contrast, Mattsson et al., showed that the prevalenceofgeneralobesitywasnotdifferentbetweenwomen withandwithoutmigraine[18].Althoughitseemsthatresultsof mentionedstudywereinoppositetoourfindings,butitwasdone onfemalesandweassessedtheassociationbetweenobesityand migraine in both genders. In addition, conflicting results in previousstudiescould beattributedtodifferent methodsused fordiagnosisofmigraine.Insomestudies,migrainewasassessed by a self-reported questionnaire, while in this study it was diagnosed byanexperienced neurologistbased onIHScriteria.
Furthermore, MOA or non-determined kind of migraine was assessed in relation to obesity in earlier studies, while we consideredjustMA.
In the current study, HDR was significantly higher in MA patients with overweight or obesity than those with normal
weight.However,wedidnotfindsuchassociationforfrequency anddurationofmigraineattacks.Tothebestofourknowledge,no studywas foundtoassesstheassociationbetweenobesityand HDR. However,in previous studieson thecurrent MApatients [28,29],resultsoflinearregressionfortheassociationofBMIand WC with mentioned features showed a significant positive association of BMI and WC with frequency and duration of migraine attacks. When potential confounding variables were taken into account, suchfindings werealso seen. However,no significantassociationwasfoundbetweenBMI,WCandduration ofmigraineattacks.
Themechanismsthatmightberesponsiblefortherelationship betweenobesityandmigrainearestillunknown.Thisrelationship mightbeexplainedbytheeffectsofobesity-relatedinflammation [30,31].Earlierstudieshaveshownthatindividualswithobesity haveincreasedlevelofinflammatorycytokines[31].Also,ithas beenshown that inflammationis involvedin developmentand progression of migraine [32,33]. In addition, hypertension contributes toincidence of migraine,and obesityis considered asoneofthemostimportantriskfactorforhypertension[34,35].
Furthermore, obesity is known as a pro-thrombotic state that associatedwithincreasedriskofmigraine[14,36].
Somelimitationsshouldbetakenintoaccountwheninterpret- ingpresentfindings.Basedoncase-controldesignofthestudy,we cannot confer a causal link between obesity and migraine.
Therefore, prospective studies are required to confirm these findings.Inaddition,studieswithcase-controldesign arehighly susceptibletoseveralbiasesincludingselection.Totalnumberof subjectsincurrentstudywasrelativelylow,whichmightdecrease statisticalpower.Finally, despiteadjustmentof ageand gender, furthercontrolforotherresidualconfoundersincludingphysical activity,health statusand psychologicalfactorsarerequiredfor obtainingindependentassociationbetweenobesityandMA.
5.Conclusions
Wefoundthatobesitywaspositivelyassociatedwithrisk of migrainewithaura.Inaddition,subjectswithobesityhadhigher headachedailyresultcomparedwiththosewithnormalweight.
Authorship
OScontributedindesign,concept,datacollection,analysis,and interpretation and draft extration. AM and MN analysed and interpreteddataanddraftedthemanuscript.GAandADMassisted Table2
GeneralcharacteristicsofsubjectsbasedoncategoriesofBMI.
Variables Normal Overweight Obesity P-value*
(BMI<25) (BMI25–30) (BMI30)
Total(Caseandcontrol)
Number 91 89 24
Age(year) 32.46.9 35.77 37.78.8 0.001
Gender(female)(%) 75.8 75.3 95.8 0.07
Weight(Kg) 60.98.2 72.99.2 82.48 <0.001
Height(cm) 165.28.8 1649.2 158.58.3 0.006
BMI(Kg/m2) 22.22 271.3 32.82.9 <0.001
MApatients(Case)
Number 43 38 15
Attacksfrequency(permonth) 8.16.9 11.610.1 12.611.5 0.1
Attacksduration(hour) 18.717.4 19.816.7 24.219.2 0.5
HDRa 114.9104.3 208.5214 187.4204.6 0.04
Dataarepresentedasmeanstandarddeviationorpercent.
Abbreviation:MA:migrainewithaura,BMI:bodymassindex,HDR:headachedailyresult.
aDeterminedasattacksfrequencyattacksduration.
* Obtainedfromone-wayANOVAorChi-squaretest,whereappropriate.
Table3
Oddsratiosand95%confidenceintervalsforMAacrosscategoriesofBMI.
Variables Normal Overweight Obesity P-trend
(BMI<25) (BMI25–30) (BMI30)
Totalnumber 91 89 24
Numberofcases 43 38 15
Crude 1 0.79(0.44-1.43) 3.06(1.11-8.43) 0.17 Model1 1 0.79(0.44-1.43) 3.12(1.12-8.65) 0.18 Model2 1 0.76(0.42-1.40) 2.92(1.03-8.33) 0.25 DataarepresentedasORand95%CI.
Abbreviation:MA:migrainewithaura,BMI:bodymassindex.
Model1:adjustedforgender.
Model2:furtheradjustmentforage.
A.Mirietal./Diabetes&MetabolicSyndrome:ClinicalResearch&Reviews12(2018)733–736 735
indesign,concept,interpretationofdataandcriticalreviewofthe draft.SZ,FYandMAanalysedandinterpreteddataandeditedthe finaldraft.Allauthorswereapprovedthefinalversionsubmitted forpublication.
Funding
This study was supported by Isfahan University of Medical Sciences, Isfahan, Iran, and AJA Universityof Medical Sciences, Tehran,Iran.
Conflictsofinterest
Authorsdeclarednopersonalorfinancialconflictsofinterest.
Acknowledgments
Authorsappreciatethevaluableassistanceofallsubjects.We also would like to thank the authorities of AJA University of MedicalSciences,Tehran,Iran,andSchoolofNutritionandFood Sciences,IsfahanUniversityofMedicalSciences,Isfahan,Iran,for theircooperation.
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