Address for Correspondence: Bilal Natiq Nuaman, Al-Iraqia University-Medical College, IraqiaPhone: 009647702594485 E-mail: bilalnatiq@gmail.com Received: 15/10/2018 Accepted: 27/11/2018

®Copyright 2018 by Turkish Journal of Endocrinology and Metabolism AssociationTurkish Journal of Endocrinology and Metabolism published by Türkiye Klinikleri

Migraine is Strongly Associatedwith Central Obesity Than with General Obesity:

A Case-Control StudyMigren Genel Obeziteden Daha Fazla ve Güçlü Şekilde

Santral Obezite ile İlişkilidir: Bir Vaka-Kontrol Çalışması

Al-Iraqia University-Medical College, Iraqia*Al-Nuaman Teaching Hospital,Iraqia

Original ArticleTurk J Endocrinol Metab

IntroductionA migraine is a common disorder that man-ifests as recurrent episodes of a headacheaccompanied by features of sensitivity tolight, sound, and/or nausea, and has a life-time prevalence of 13-33% (1). Although amigraine is the second common cause of aheadache after a tension headache, it is the

most common form of a headache that pres-ents to physicians as it is more severe thana tension headache (2). About 67% of pa-tients with a migraine consult primary carephysicians, and only 16% of them consult aneurologist (3). Although presentations of atension headache and migraine are compa-rable, clinical features specific to a migraine

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Objective: Obesity and migraine are common diseasesworldwide, but their association is not confirmed. If an as-sociation is proved, weight loss can be made a managementobjective of a migraine. To assess the risk of migraines inIraqi patients with general obesity and central obesity.Material and Methods: A case-control, hospital-basedstudy was conducted at Al-Nuaman Teaching Hospital, Bagh-dad, Iraq from February 2017 to September 2017. One hun-dred - forty Iraqi patients were enrolled, including 50 patientswith migraines and 90 controls without any migraine. Gene-ral obesity and central obesity were assessed by examiningthe body mass index and waist-to-height ratio, respectively.Results: There is a significant association between migrai-nes and general obesity and between migraines and centralobesity (p<0.001, odds Ratio: general obesity 6.8, centralobesity 12.2).Conclusion: The risk of migraines in patients with centralobesity is double the risk in patients with general obesity.

Keywords: Central obesity; general obesity; migraine;case-control study; logistic regression

Amaç: Obezite ve migren dünya çapında yaygın hastalık-lardır, ancak birliktelikleri doğrulanmamıştır. Eğer birlikte-likleri kanıtlanırsa, kilo kaybı migren yönetiminde hedefhaline gelebilir. Burada, genel obezitesi ve santral obezi-tesi olan Irak’lı hastalarda migren riskini değerlendirmekamaçlanmıştır.Gereç ve Yöntemler: Şubat 2017-Eylül 2017 arasında,Al-Nuaman Eğitim Hastanesi’nde (Bağdat, Irak) vaka-kontrolü, hastane-tabanlı bir çalışma yürütülmüştür. Ça-lışmaya 50 tanesi migrenli, 90 tanesi migrensiz olan(kontrol) 140 Irak’lı hasta dahil edilmiştir. Genel obeziteve santral obezite sırasıyla vücut kitle indeksi ve bel-boyoranı incelenerek değerlendirilmiştir.Bulgular: Migren ile genel obezite ve santral obezite ara-sında anlamlı bir ilişki vardır (p <0,001, odds oranı: genelobezite 6,8; santral obezite 12,2).Sonuç: Santral obezitesi olan hastalarda migren riskigenel obezitesi olan hastalardan iki kat fazladır.

Anahtar kelimeler: Santral obezite; genel obezite; migren;vaka-kontrol çalışması; lojistik regresyon

Kaynaklar me�n içinde eksiksiz ve sıralı geçirilmeli.

than to a tension headache include photo-phobia, phonophobia, nausea, food triggers,and lack of physical activity (4-6).Many explanations have been proposed inthe pathophysiology of a migraine, includingdietary disorder, low physical activity, inflam-mation, and hypothalamic disorder (7-9).These possible mechanisms also contributeto the pathogenesis of obesity. Some evi-dence shows that obesity may promotecharacteristics of migraine episodes (10-12), but not a tension headache (13,14).Obesity can be classified as general obesity,measured by body mass index (BMI), andcentral obesity, measured by many parame-ters, and the best of these is termed as awaist-to-height ratio (WtHR) (15).Many studies have evaluated the associationbetween obesity and migraine; most ofthem were cross-sectional studies that couldnot document cause and effect. To the bestof our knowledge, there are limited case-control studies investigating such an associ-ation, at least in Iraq. Therefore, thiscase-control study aimed to assess the as-sociation between parameters of obesity andthe risk of a migraine, and to evaluatewhether a migraine is strongly associatedwith central obesity or general obesity.

Material and Methods

Study Design

A case-control study was conducted and ap-proved by the Internal Medicine and Neurol-ogy Departments of Iraqia Medical Collegeand AL-Nuaman Teaching Hospital.

Cases

All patients complaining from (undiagnosed)a headache or a migraine who visited med-ical and neurological outpatient departmentsof AL-Nuaman Teaching Hospital from Feb-ruary 2017 to September 2017 were eligiblefor enrollment. Magnetic Resonance Imag-ing of the brain was performed for selectedcases to exclude secondary causes. Overall,50 patients with a migraine were included.

Inclusion Criteria

Simplified diagnostic criteria for a migrainewere adapted from the InternationalHeadache Society Classification. These cri-teria include repeated episodes of a

headache persisting for 4-72 hs in otherwisenormal patients, plus two or more of thefollowing features: moderate-severe inten-sity, pulsating pain, one-sided pain, and ex-acerbation by motion, plus one of thefollowing features: photophobia, phonopho-bia, and nausea (16).

Exclusion Criteria

Any features indicating a life-threatening ill-ness, including:1-Onset after age 55 years; 2-Considerablefever, vomiting, or weight loss; 3-Importantpast medical history (malignancy or tuber-culosis); and 4-Abnormal neurologic exami-nation (including fundoscopic examination)(17). Additionally, pregnant women were ex-cluded.

Controls

Outpatients in addition to the medical andnon-medical staff of AL-Nuaman TeachingHospital with no history of a migraine orchronic diseases were randomly chosen ascontrols, and the same patient exclusion cri-teria were applied. Overall, 90 controls wereincluded.Patients and controls were categorized ac-cording to age as follows: <25, 25 - 35, 35- 45, and 45 - 55 years.All patients and controls supplied informedpermission for participation in the study.

Anthropometric Measurements

Weight (in kg), height (in m or cm), andwaist circumference (WC, in cm) weremeasured for patients and controls. Generalobesity assessed by calculating BMI throughdividing weight by height (in m2). A cutoffpoint of 30 was used to determine generalobesity, which was defined as having BMI≥30 kg/m2. Central obesity determined bycalculating WtHR by dividing WC by height.A WHtR cutoff point of 0.5 was used for as-sessing central obesity, which was definedas having WHtR >0.5.

Statistical Analysis

Data were analyzed using SPSS version20.0. Cross-tabulation analysis (Pearson‘sand Chi square) was performed to evaluatethe association between obesity (generaland central) and migraine. A logistic regres-sion was accomplished to establish the ef-

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* significant association.

(patients) Migraine (% of total) (control) No migraine (% of total) P Value

Gender .128

Male 15.7% 35.7%

Female 20% 28.6%

Age .715

<25 4.3% 5.7%

25 - 35 11.4% 25.7%

35 - 45 12.1% 22.1%

45 - 55 7.9% 10.7%

BMI categories .000*

<30 20.9% 58.6%

>30 15% 5.7%

WHtR categories .000*

<0.5 10% 53.6%

>0.5 25.7% 10.7%

Table 1. Basic characteristics of patients and controls.

fects of general obesity and central obesityon the possibility to have a migraine. Exp(B) and 95 % confidence intervals (95%CIs) were calculated to establish whethermigraine is strongly associated with generalobesity or central obesity. A P value of <0.05was indicated as the level of significance.

Results

Study Population

After the exclusion criteria were applied, 40patients were excluded (75% of them werewomen) and a total of 50 patients (with amigraine) were enrolled along with 90 per-sons (without a migraine).The mean (±standard deviation) age of participants was35.8±8.8 years, and 51.4% of participantswere men. Of the 50 patients, 28 werewomen (56%) and 22 were men (44%), andthe male-to-female ratio was 1:1.3. About75% of women with a migraine were be-tween 25 and 45 years of age, while 63% ofmen with migraine were between 35 and 55years of age. No significant gender-specificand age-specific differences were observedbetween patients and controls (P=0.128 andP=0.715, respectively). Characteristics ofpatients and controls are shown in Table 1.Characteristics of patients with a migraineare shown in Table 2. About two-thirds ofpersons with central obesity had a non-

obese pattern of BMI, and less than one-sixth of patients with general obesity had aWtHR <0.5 (Figure 1).

Association Between Obesity and Migraine

The frequency of general obesity in patientswith a migraine was 42%, which was aboutfour times more than that in controls, thus,there is a strong association between amigraine and general obesity (P<0.001)(Figure 2). The frequency of general obesity(BMI>30 kg/m2) in male and female mi-graineurs was 45.4% and 39.3%, respec-tively (P<0.0001)The frequency of central obesity in patientswith migraines was 72%, which was aboutfour times more than that in controls, thus,there is a strong association between amigraine and central obesity (P<0.001)(Figure 2). The frequency of central obesity(WHtR >0.5) in male and female mi-graineurs was 81.8% and 64.3%, respec-tively (P=0.00001).

Odds Ratio for a Migraine in Patients withGeneral Obesity Versus Central Obesity

Patients with general obesity (BMI>30kg/m2) were six times more likely to have amigraine than those with BMI <30 (oddsratio [OR] 6.8, 95% CI=2.3, 20) (Table 3).Patients with central obesity (WHtR >0.5)were 12 times more likely to have a mi-

graine than those with WHtR <0.5 (OR12.2, 95% CI=5, 29.8) (Table 3). Therefore,the likelihood of having a migraine was twicemore in patients with central obesity than inpatients with general obesity.

DiscussionA migraine and obesity are chronic prevalentdiseases in the world with undeterminedpathogenesis and associations. This study re-vealed that the frequency of general obesityand central obesity in patients with a migraine(42% vs. 72%, respectively) was muchhigher than the frequency in controls (9% vs.17%, respectively). Furthermore, the risk of amigraine in patients with general obesity wassix times more than controls (OR 6.8, 95%CI 2.3, to 20), while the risk in those withcentral obesity was 12 times more than thatin controls (OR 12.2, 95% CI=5, 29.8). Thesedata suggest that obesity is a risk factor for amigraine and it is strongly associated withcentral obesity than general obesity. This isthe first case-control study at least in Iraqthat examined the association and risk of amigraine in general obesity versus centralobesity using categorical variables.The large difference in the frequency of cen-tral obesity between male (82%) and female(64%) migraineurs may be explained bythe fact that central obesity in women, incontrast to adult men, is most pronouncedafter menopause, and most postmenopausalwomen were excluded from the study as weexcluded any patient ≥ 55 years (18-20).Obesity is associated with many pain-relatedmedical conditions including fibromyalgia(21,22), osteoarthritis (23,24), abdominalpain (25,26), and back pain (27). Severalstudies have proven the association be-tween obesity and headache, including mi-graine. Most of these studies examined theeffects of general obesity on migraine andconfirmed such significant association(39,43-45,60-62) and some of them foundthat a migraine is only associated with mor-bid obesity (28-30). However, some studieshave revealed no association between a mi-graine and general obesity (12,31-34), oreven showed an association between mi-graine and being underweight (12,35).Limited studies have considered the effectsof central obesity on migraines, except fora single category in a study by Lee Peterlinet al.(38), all of these studies confirmed astrong positive association (36-39). Lee Pe-terlin et al.(38), demonstrated a positive as-sociation between migraine prevalence withboth general obesity and central obesity inmen and women ≤55 years, however, in

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Variable Percentage

General obesity (BMI>30) 42%

Central obesity (WHtR>0.5) 72%

Hypertension 32%

Diabetes mellitus 14%

Smoking 23%

Table 2. Characteristics of patients with migraine.

Figure 1: Distrubition of central obesity among patientswith general obesity.

Figure 2: Frequency of general obesity and central obe-sity among patients and control.

men >55 years there was no significant as-sociation between a migraine and generalobesity or central obesity, while in women>55 years, migraine was not associated withgeneral obesity but was inversely associatedwith central obesity. Most of these studieswere cross-sectional, which unlike case-con-trol studies, cannot accord a connection be-tween a cause and an effect.Several studies have shown that WHtR is su-perior to other indices of central obesity (40-42), as it considers the stature of anindividual. Although Omid Sadeghi (37) wasthe first to use WHtR as an indicator of cen-tral obesity, he did not use it to define cen-tral obesity. In our study, we defined centralobesity as WHtR of ≥0.5.Although Miri et al. (OR 3.06, 95% CI 1.11-8.43) (43), Scher et al. (OR 5.28, 95% CI 1.3-21.1) (44), and Peres et al. (P< 0.0001) (45)established a strong positive association be-tween general obesity and migraine in case-control studies, our study compared bothgeneral and central types of obesity anddemonstrated a significant association of mi-graine with both types, but mainly with centralobesity. Many studies have proved that centralobesity is commonly an important risk factor ofa migraine than general obesity (46-48).The association between obesity and mi-graine can be elucidated by many factors: in-flammatory, hypothalamic, life-style-relatedlike lack of exercise, and psychological co-morbidities (49). Adipose tissue, especiallyvisceral adipose tissue, secrete many inflam-matory mediators like adipokines (50),tumor necrosis factor α (51), and calcitonin-related peptide (52-53), which can trigger amigraine, and this may explain the strongassociation between central obesity and mi-graine than general obesity.The hypothalamus is integral in the patho-physiology of obesity and migraine, as hy-pothalamic peptides and neurotransmitters,like serotonin (54), and orixen A(55), play arole in over eating in obese patients, andcan trigger a migraine attack.

Furthermore, some evidence suggests thatweight loss can improve symptoms of a mi-graine in obese patients whether behavioralsymptoms or after bariatric surgery (56-58),but the strongest evidence was a Women‘sHealth and Migraine randomized controlledtrial (59).This study had many limitations including asmall sample size, inequality between casesand controls, overweight persons were cat-egorized within the non obese category, andcharacteristics of a migraine were not as-sessed. Further studies are required toprove such an association, which is impor-tant in the management of a migraine.In conclusion, there is a strong association be-tween obesity and migraine and central obe-sity is an important risk factor for a migraine.Source of Finance: During this study, nofinancial or spiritual support was receivedneither from any pharmaceutical companythat has a direct connection with the re-search subject, nor from a company thatprovides or produces medical instrumentsand materials which may negatively affectthe evaluation process of this study.Conflict of Interest: No conflicts of inter-est between the authors and/or familymembers of the scientific and medical com-mittee members or members of the poten-tial conflicts of interest, counseling,expertise, working conditions, share holdingand similar situations in any firm.

Authorship ContributionsIdea/Concept: Bilal Natiq Nuaman, Asaad M.Sadik; Design: Bilal Natiq Nuaman, AsaadM.Sadik; Control/Supervision: Bilal Natiq Nua-man, Asaad M.Sadik; Data Collection and/orProcessing: Bilal Natiq Nuaman, AsaadM.Sadik; Analysis and/or Interpretation: BilalNatiq Nuaman, Asaad M.Sadik; Literature Re-view: Bilal Natiq Nuaman, Asaad M.Sadik;Writing the Article: Bilal Natiq Nuaman, AsaadM.Sadik; Critical Review: Bilal Natiq Nuaman;References and Fundings: Bilal Natiq Nuaman;Materials: Bilal Natiq Nuaman, Asaad M.Sadik.

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95%C.I.for EXP(B)

B S.E. Wald df Sig. Exp(B) Lower Upper

General obesity 1.9 .55 12.2 1 .000 6.8 2.3 20.0

Central obesity 2.5 .45 30.4 1 .000 12.2 5.0 29.8

Table 3. Odds ratio for migraines in patients with general obesity versus central obesity.

6

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