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 Full Text Journal Information Journal ID (nlm-ta): J Headache Pain Journal ID (iso-abbrev): J Headache Pain ISSN: 1129-2369 ISSN: 1129-2377 Publisher: Springer Milan, Milan Article Information Download PDF © The Author(s) 2012 Received Day: 2 Month: 11 Year: 2011 Accepted Day: 16 Month: 1 Year: 2012 Electronic publication date: Day: 26 Month: 1 Year: 2012 pmc-release publication date: Day: 26 Month: 1 Year: 2012 Print publication date: Month: 6 Year: 2012 Volume: 13 Issue: 4 First Page: 321 Last Page: 326 ID: 3356472 PubMed Id: 22278639 Publisher Id: 416 DOI: 10.1007/s10194-012-0416-y
 Metabolic syndrome and insulin resistance in migraine Sanjeev K. BhoiAff1 Jayantee KalitaAff1 Address: jkalita@yahoo.com Usha K. MisraAff1 Address: +91-522-2494167 +91-522-2668811 drukmisra@rediffmail.com ukmisra@sgpgi.ac.in Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareily Road, Lucknow, 226014 India

Introduction

Migraine is a common disorder with overall prevalence of 5–15% [13].The prevalence of migraine in females is higher (6–22%) compared to males (3–7%) [46]. The pathogenesis of migraine is multifactorial and a number of genetic and environmental factors have been suggested. Recently, association of migraine with metabolic syndrome and insulin resistance has been reported [7, 8]. The prevalence of migraine was estimated as 11.9% in males and 22.5% in females with metabolic syndrome. Of the components of metabolic syndrome diabetes mellitus, increased waist circumference and body mass index (BMI) were more frequent in migraine patients compared to those without migraine. The frequency of hypertension and dyslipidemia, however, was not significantly different [9]. In a population-based study on obesity and migraine evaluating 30,215 participants whose mean age was 38.4 years including 65% females, revealed lack of association of BMI with the prevalence of migraine but was associated with the frequency of headache attacks. In the normal weight group, 4.4% had 10–15 headache days per month increasing to 5.8% in the overweight and 20.7% in the morbidly obese [10]. Majority of these studies are from the western countries where obesity is common. In a population-based study, 685 women aged 40–74 years were evaluated for relationship of BMI and migraine. The proportion of obesity (BMI >30) did not differ in the women with active migraine, inactive migraine and those who never experienced migraine. The frequency, duration and severity of migraine attacks also did not differ between obese and non-obese migraine patients [11].

On PubMed search using Keywords “Migraine” and “Metabolic syndrome/insulin resistance/insulin metabolism” revealed six articles; two on metabolic syndrome and four on insulin metabolism in migraine [8, 9, 1215]. The incidence of obesity is lower in Asian countries and we could not find any study from Southeast Asia evaluating the role of metabolic syndrome in migraine. In the present study, we report the frequency of metabolic syndrome in migraine patients and compare the clinical characteristics of migraine in patients with and without metabolic syndrome as well as insulin resistance.

Patients and methods

Diagnosis of metabolic syndrome was based on National Cholesterol Education Programme (NCEP): Adult Treatment Panel (ATP) III 2001 [17] and International Diabetic Federation (IDF) criteria [18], according to which three of the following criteria were needed including central obesity.

1. Central obesity: waist circumference >90 cm in males and 80 cm in females.
2. Hypertriglyceridemia >150 mg/dl or on specific medication.
3. Low HDL cholesterol <40 mg/dl in males and <50 mg/dl in females.
4. Hypertension: blood pressure >130 systolic or >85 mm Hg diastolic or specific medication.
5. Fasting plasma glucose >100 mg/dl or on specific medication or previously diagnosed type 2 diabetes.

Insulin resistance and β cell function were calculated in 90 patients by HOMA model [19].

[Formula ID: Equa]
[\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{HOMA-IR}}\,\left( {\text{insulin resistance}} \right) \, = \, \frac{{{\text{Fasting\, blood\, sugar }} \times {\text{ fasting\,insulin}}}}{ 40 5}$$\end{document}]
[Formula ID: Equb]
[\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$${\text{HOMA-B}}\,\left( {\beta {\text{ cell function}}} \right){\text{ was calculated as follows}}:\, = \frac{{ 3 60 \, \times {\text{ insulin}}}}{\text{Fasting blood sugar}} \, - { 63}$$\end{document}]

The cut-off value of insulin resistance was taken as >1.77 for the diagnosis of metabolic syndrome [20].

Blood counts, haemoglobin, ESR, platelet count, blood urea nitrogen, serum creatinine, bilirubin, transaminases and TSH were carried out. Fasting and 2-h post prandial blood sugar, lipid profile and insulin level were estimated. The blood sugar was assayed by autoanalyzer using oxidase–peroxidase method. The insulin was estimated by immunoradiometric assay using Siemens Medical Solutions Diagnostic, LA, USA. Patients with high thyroid stimulating hormone, renal and hepatic failure were excluded.

Statistical analysis

The migraine patients were categorized into those with metabolic syndrome and those without. The patients were also categorized into insulin resistant and those without based on HOMA-IR. The demographic, severity and frequency of migraine, presence of allodynia, aura and triggers were compared in those with and without metabolic syndrome as well as with and without insulin resistance using X2 and independent t’ test. The variables were considered significant if 2-tailed p value was <0.05. The statistical analysis was done using SPSS 15 version software.

Results

There were 135 patients with migraine whose mean age was 31.4 (SD 10.5) years; 108 of whom were females. Family history of migraine was present in 58 patients. The mean duration of headache was 8.5 (SD 6.7) years. Only seven patients had migraine with aura. The frequency of migraine ranged between 2 and 30 attacks per month; 54 of them had headache frequency of more than 15 attacks per month. Mechanical (static and dynamic) allodynia was present in 116 (85.9%) and 27 (20%) of them also had thermal allodynia. The allodynia was cephalic in 43 (37.1%) and extended to extracephalic region in 73 (62.9%) patients. The majority of patients [134 (99.3%)] had moderate to severe headache. The general characteristics of the patients are provided in Table 1.

Metabolic syndrome

The BMI was above 30 in 13 (9.6%) patients and between 25 and 30 in 26 (19.3%). Female patients were more overweight compared to males (34 vs. 5) and 2 females were morbidly obese (BMI >35). Waist circumference was abnormal in 78 (57.8%) patients. HDL was reduced in 108 (80%) and triglyceride was increased in 28 (20.7%) patients. Fasting blood sugar was high in 13 (9.6%) patients. The systolic blood pressure was raised in 15 and diastolic in 33 (24.5%) patients. Insulin resistance (HOMA-IR) was present in 10 (11.1%) patients. β cell function (HOMA-B) was 179.3 ± 552.4. Based on ATP-III and IDF criteria, 43 (31.9%) patients had metabolic syndrome. Out of 5 components of metabolic syndromes, all 5 were present in 3, 4 in 14 and 3 in 26 patients. Only 2 components of metabolic syndrome were present in 40 patients, however they were not diagnosed as metabolic syndrome.

Correlation

The patients with metabolic syndrome were older (p = 0.0001), more frequently females (p = 0.01), had longer duration of illness (10.3 ± 7.5 vs. 7.6 ± 6.2, p = 0.03), higher number of triggers (11.6 ± 2.5 vs. 10.5 ± 2.8, p = 0.03) and longer duration of attack (2.0 ± 0.8 vs. 1.7 ± 0.8, p = 0.05) compared to those without metabolic syndrome. The majority of patients had multiple triggers; commonest being noise in 129 (95.6%) followed by stress in 128 (94.8%), sunlight in 121 (89.6%) and fasting in 100 (74.1%) patients. On comparing the triggers, head wash was more frequent in those with metabolic syndrome compared to without (65.1% vs. 44.6%; p = 0.03). The details of triggers are given in Table 2. The presence of aura (3 vs. 4, p = 0.68), frequency of headache (15.1 ± 11.1 vs. 15.5 ± 10.6, p = 0.82), severity of migraine (p = 0.66), migraine index (MI) (30.8 ± 22.6 vs. 37.0 ± 28.0, p = 0.20), corrected migraine index (MIc) (55.8 ± 39.4 vs. 54.6 ± 40.0, p = 0.87), functional impairment (p = 0.19), presence of allodynia (p = 0.79) and extent of allodynia (p = 0.84) were not significantly different between the two groups (Table 3). Insulin resistance (HOMA-IR >1.77) was present in 10 (11.1%) patients. There was no difference in demography, duration of migraine, migraine index, corrected migraine index, number of triggers, and fasting and hunger as triggers between the two groups (Table 4). The duration of migraine attack was more in the patients with insulin resistance (p = 0.04).

Discussion

In the present study, 31.9% of the migraine patients had metabolic syndrome but only 9.6% were obese. The diagnosis of metabolic syndrome was based on increased waist circumference (57.8%), hypertriglyceridemia (20.7%), hypertension (27.4%), low HDL (80.0%) and increased fasting blood sugar (9.6%). Moreover, insulin resistance was present in 11.1% patients. These observations are in agreement with the reports from the western countries in which metabolic syndrome has been associated with migraine [7, 9, 21]. In our study, only 2 patients were morbidly obese and remaining 11 patients were obese. In a study from USA, the effect of BMI on the prevalence of severe headache or migraine revealed significant association of headache or migraine with low (<18.5 kg/m2) and high BMI (>30 kg/m2) [22]. In Asians, central obesity is common and was present in 57.8% of our patients. Central obesity, high triglyceride and low HDL are reported to be the main component of metabolic syndrome in the Asians [23], whereas in the western countries high BMI is more common [13, 24].

Metabolic syndrome is associated with insulin resistance. The patients with migraine have significantly higher level of fasting glucose and insulin; both of which remain elevated after glucose loading suggesting insulin resistance [14]. Similar observations have also been reported in a smaller study in which oral glucose tolerance test and plasma glucose were significantly higher in migraine patients compared to controls. Insulin sensitivity is significantly altered in migraine patients as measured by ISI-Stumvoll and OGIS-180 index [8]. Insulin resistance is a state in which normal amount of insulin produces a subnormal physiological response. Insulin resistant state may increase free fatty acids and blood lipids which may induce migraine attack [25]. Low HDL is an important component of metabolic syndrome and HDL has anti-inflammatory property. Reduced LDL may reduce pain perception [26].

In our study, metabolic syndrome was significantly related to age. The mean age in the patients with metabolic syndrome was 37.8 (SD 7.7) years, whereas it was 28.4 (SD 10.3) years in those without. Age may be directly related to various components of metabolic syndrome such as obesity, hypertension, glucose intolerance and hyperlipidemia which may be an association rather than underlying mechanism. In our study, metabolic syndrome and migraine both were more common in females than males. Whether it is merely an association or it has a biological basis needs further study. Migraine is precipitated by a number of endogenous and exogenous triggers. Fasting and hunger are important triggers and have been reported in Indian subjects in 46.3% [27]. Fasting is common in both Hindus and Muslims as a religious practice. In the present study, the most common trigger was noise (95.6%) followed by stress (94.8%), sun exposure (89.6%) and fasting (74.1%). Fasting results in activation of insulin receptors which may trigger a migraine attack [28]. Low sucrose diets may reduce the frequency of migraine attack [29]. In migraineurs, the onset of diabetes mellitus increases the average yearly number of headache days [30]. In our study, fasting was neither associated with metabolic syndrome nor with insulin resistance but the duration of migraine attack (days) was significantly related to insulin resistance. Our results are limited by absence of a control group, absence of children, disproportionately large number of females and unequal number of patients with and without metabolic syndrome. In a population-based study from North India, the prevalence of metabolic syndrome is 67.2% (male 75.9% and female 58.4%) and obesity in 79.3% (male 74.5% and female 84.0%) [31]. The lower frequency of metabolic syndrome and obesity in our study compared to the above-mentioned study may be due to the referral bias. The study by Yadav et al. [31] was based on urban affluent population. We have studied migraine patients from different regions of North India including both urban and rural population comprising diverse socioeconomic classes.

Based on our results, it can be concluded that migraine is associated with metabolic syndrome in 31.9% and insulin resistance in 11.1% patients. The patients with metabolic syndrome are older, have multiple triggers, longer history of migraine as well as duration of migraine attack. A larger controlled study is needed to confirm these results.

We thank Rupali Mishra for secretarial help.

Conflict of interest

There is no conflict of interest.

Ethics approval

The research has been approved by the Institutional Ethics Committee, SGPGIMS, Lucknow.

Open Access

References

Tables
[TableWrap ID: Tab1] Table 1

Demography and clinical characteristics of migraine patients

Parameters Number of patients (n = 135)
Age (years) 31.41 ± 10.5 (range 14–61)
Female 108 (80%)
Urban/rural 81/54
Education (years) 10.36 ± 5.02
Family history of headache 58 (43%)
Total family members affected 1.66 ± 0.9 (range 1–6)
Only patients 77 (57%)
1st generation 33 (24.4%)
2nd generation 23 (17%)
3rd generation 2 (1.5%)
Migraine with aura 7 (5.2%)
Duration (years) 8.48 ± 6.7 (range 0.5–40)
Frequency/months 15.4 ± 10.7 (range 2–30)
Duration attack (days) 1.8 ± 0.8 (range 0.5–4)
Total no. of triggers 10.84 ± 2.78 (range 2–15)
Allodynia 116 (85.9%)
Mechanical 116 (85.9%)
Static 116 (85.9%)
Dynamic 115 (85.2%)
Thermal 27 (20%)
Cephalic 43 (37.1%)
Extracephalic 73 (62.9%)
Number of metabolic parameters abnormality (0–5)
0 11 (8.1%)
1 41 (30.4%)
2 40 (29.6%)
3 26 (19.3%)
4 14 (10.4%)
5 3 (2.2%)

[TableWrap ID: Tab2] Table 2

Frequency of different triggers migraine and its comparison in the patients with and without metabolic syndrome

Triggers Total number of patients (%) Metabolic syndrome Metabolic syndrome p value
Present Absent
N = 43 (31.9%) N = 92 (68.1%)
Physical stress 128 (94.8) 41 87 1.00
Mental stress 128 (94.8) 40 88 0.70
Fasting 100 (74.1) 36 64 0.09
Hunger 100 (74.1) 36 64 0.09
Sunlight 121 (89.6) 41 80 0.22
Noise 129 (95.6) 43 86 0.18
Cold exposure 81 (60) 23 58 0.35
Hot exposure 100 (74.1) 34 66 0.41
Weather change 104 (77) 35 69 0.51
Menstruation 35 (30.7) 12 23 1.00
Sleep deprivation 119 (88.1) 40 79 0.27
Food 6 (4.4) 3 3 0.38
Travel 116 (85.9) 40 76 0.12
Perfume 33 (24.4) 11 22 0.83
Hair oil 3 (2.2) 1 2 1.00
Head wash 69 (51.1) 28 41 0.03
Dry hair 88 (65.2) 33 55 0.08

[TableWrap ID: Tab3] Table 3

Comparison of clinical characteristics in patients with and without metabolic syndrome

Parameters Metabolic syndrome Metabolic syndrome p value
Present Absent
N = 43 (31.9%) N = 92 (68.1%)
Age (years) 37.8 ± 7.7 28.4 ± 10.3 <0.0001
Female 40 (93%) 68 (73.9%) 0.01
Urban/rural 26/17 55/37 1.00
Education (years) 9.35 ± 4.76 10.84 ± 5.09 0.11
Family history of headache 22 (51.2%) 36 (39.1) 0.20
Total family members affected 1.86 ± 1.15 1.57 ± 0.79 0.08
Migraine with aura 3 (7%) 4 (4.4%) 0.68
Duration (years) 10.28 ± 7.5 7.64 ± 6.21 0.03
Total no. of triggers 11.58 ± 2.53 10.49 ± 2.84 0.03
Fasting 36 (83.7%) 64 (69.6%) 0.09
Hunger 36 (83.7%) 64 (69.6%) 0.09
Onset to peak time (min) 32.09 ± 32.68 27.61 ± 20.17 0.33
Frequency/months 15.07 ± 11.05 15.52 ± 10.58 0.82
Duration attack (days) 2.0 ± 0.75 1.72 ± 0.78 0.05
Severity of headache 2.98 ± 0.15 2.93 ± 0.29 0.37
Functional impairment 3.28 ± 0.7 3.2 ± 0.62 0.48
Rescue analgesics/mo 13.07 ± 9.82 14.03 ± 11.58 0.64
Allodynia 38 (88.4%) 78 (84.8%) 0.79
Migraine index (MI) 30.75 ± 22.59 37.03 ± 27.97 0.20
Corrected MI (MIc) 55.83 ± 39.43 54.6 ± 40.04 0.87

[TableWrap ID: Tab4] Table 4

Comparison of clinical characteristics in patients with and without insulin resistance (HOMA-IR >1.775)

Parameters Insulin resistance Insulin resistance p value
Present Absent
N = 10 (11.1%) N = 80 (88.9%)
Age (years) 33.0 ± 9.04 31.39 ± 10.98 0.66
Female 8 (80%) 62 (77.5%) 1.00
Urban/rural 6/4 45/35 0.81
Education (years) 11.0 ± 3.86 10.05 ± 5.06 0.57
Migraine with aura 0(%) 6 (7.5%) 0.37
Duration (years) 9.98 ± 6.30 8.40 ± 7.48 0.52
Total no. of triggers 10.9 ± 3.45 11.15 ± 2.54 0.78
Fasting 7 (70%) 59 (73.8%) 0.72
Hunger 7 (70%) 59 (73.8%) 0.72
Onset to peak 28.0 ± 13.78 27.00 ± 17.73 0.86
Severity of headache 3.00 ± 00 2.95 ± 0.27 0.56
Severity of functional impairment 3.10 ± 0.88 3.16 ± 0.63 0.78
Frequency/months 16.00 ± 12.27 13.53 ± 10.7 0.50
Duration attack (days) 2.42 ± 0.66 1.90 ± 0.78 0.04
Rescue analgesics/months 17.10 ± 14.43 12.39 ± 9.77 0.18
Allodynia 9 (90%) 69 (86.3%) 1.00
Family history of headache 6 (60%) 31 (38.6%) 0.31
Migraine index (MI) 35.40 ± 25.97 31.46 ± 25.98 0.65
Corrected MI (MIc) 75.26 ± 42.07 52.65 ± 43.01 0.12
No. of metabolic parameters abnormality (metabolic syndrome) 3.70 ± 1.16 1.48 ± 0.98 <0.0001

 Article Categories:Original Keywords: Keywords Migraine, Obesity, Metabolic syndrome, Insulin resistance, HOMA.

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