METABOLIC PROFILE CHANGES IN SERUM OF MIGRAINE PATIENTS DETECTED USING 1H-NMR SPECTROSCOPY 37 2 for all 22 signals. The regression showed support for association between the signal data and active migraine status (OR = 2.72; 95% CI 2.09 - 3.54; p = 1.35 x 10-13) explaining 8.5% of the variance, this association remained after correction for sex, age, BMI and current smoking status (OR = 1.84; 95% CI 1.34 - 2.53; p = 1.64 x 10-4) with a total explained variance of 12.3% (Nagelkerke R2). Hosmer and Lemeshow shows a good fit of the final model (p = 0.688). The outcome of our ANOVA analysis (p = 7.1 x 10-5) added to the evidence for involvement of these metabolites in active migraine patients. The majority of the 22 signals have been annotated to metabolites, but four remained unknown (Table 2). The known metabolites that were relevant to distinguish metabolic profile of migraine patients from controls were cholesterol, isoleucine, leucine, lipids (CH2 and CH*2CH=CH), acetate, pyruvate, methionine, dimethylglycine, 1,5-anhydrosorbitol, valine, myoinositol, glucose, serine, creatinine, and proline. Our data suggests that there is a metabolic profile for active migraine that distinguishes them from controls even after correcting for age, sex, BMI and smoking status. Remarkable is that five of the six signals predictive for lifetime migraine status are also predictive for active migraine status (Table 2). Table 2 1H-NMR signals associated with lifetime migraine patients and active migraine patients Life time migraine patients Active migraine patients Metabolite Chemical shift (ppm) Metabolite Chemical shift (ppm) Isoleucine 0.92847 Cholesterol 0.89006 Isoleucine 0.99919 Isoleucine 0.92847 Unknown 1.40660 Unknown 0.95118 Methionine 2.63742 Leucine 0.95702 1,5-Anhydrosorbitol 3.58832 Isoleucine 0.99919 Creatine 3.92001 Lipids (CH2)† 1.26482 Unknown 1.40660 Acetate 1.90859 Lipids (CH*2CH=CH)† 2.22215 Pyruvic acid 2.36196 Methionine 2.63742 Dimethylglycine 2.91618 Unknown 3.35396 1,5-Anhydrosorbitol 3.58832 Valine 3.59782 Myoinositol 3.62232 Glucose 3.72103 Serine 3.95567 Creatinine 4.04386 Proline 4.12106 Unknown 4.50117 Glucose 5.22921 Ppm: parts per million. †The term in parenthesis indicates the structural feature of the lipids measured by 1H-NMR spectroscopy
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