Women with migraine had a lower risk of developing type 2 diabetes, French researchers reported.
In a prospective longitudinal study, women with active migraine had a 20% reduction in the risk of developing pharmacologically-treated type 2 diabetes — which rose to a 30% reduction in multivariate modeling — than women without a history of migraine, according to Guy Fagherazzi, PhD, of the Center for Research in Epidemiology and Population Health in Villejuif, France, and coauthors.
And, among women who developed incident diabetes during the study, the prevalence of active migraine declined in the years leading up to a diabetes diagnosis and plateaued after, they wrote in JAMA Neurology.
“Our results may suggest a potential role of both hyperglycemia and hyperinsulinism on migraine occurrence,” Fagherazzi said. “Because plasma glucose concentration rises with time up to type 2 diabetes occurrence, the prevalence of migraine symptoms may decrease. Consequently, tracking the evolution — and especially the decrease — of migraine frequency in migraineurs at high risk of diabetes, such as obese individuals, irrespective of age, could be the sign of an emerging increased blood glucose levels, prediabetes, or type 2 diabetes,” he told MedPage Today.
“The linear decrease of migraine prevalence long before and the plateau long after type 2 diabetes diagnosis is novel,” he added. “The association deserves to be studied in other populations, and in men, as well.”
These findings are in line with observations from clinical practice, observed Amy Gelfand, MD, MAS, of the University of California San Francisco, and Elizabeth Loder, MD, MPH, of Brigham and Women’s Hospital in Boston and Harvard Medical School, in an accompanying editorial. “Headache practitioners have long discussed the rarity of patients with type 2 diabetes in headache clinics,” they wrote.
But the reason for the link is uncertain: “One plausible biological explanation involves calcitonin gene related peptide, which is involved in energy metabolism in animal models,” Gelfand and Loder wrote. “Calcitonin gene-related peptide is also clearly involved in the pathophysiology of migraine. It is possible that the development of insulin resistance and hyperglycemia result in damage to sensory neurons that produce this peptide.”
It’s also possible that a migraine trigger could be nutritional, hormonal, or metabolic in some people, Fagherazzi and co-authors noted.
In this study, Fagherazzi and his group analyzed data from the E3N-EPIC cohort, a French prospective study of women born between 1925 and 1950 who are insured by a health insurance plan that covers mostly teachers.
In this study, participants completed self-administered biennial questionnaires since 1990, and the health insurance plan provided information about all outpatient reimbursements for health expenditures since 2004, including dosages and dates of drug purchases.
Based on the questionnaire data, the researchers classified women into three main categories: no migraine history, active migraine (women who self-reported migraine on the current questionnaire), and prior migraine (women who reported migraine in at least one past questionnaire but not currently). They defined type 2 diabetes as a patient who was treated pharmacologically with type 2 diabetes–specific medications at least twice, with diagnosis date as the date of the first drug reimbursement.
At baseline, the 74,247 women in the analysis had mean age of 61 years and no diagnoses of diabetes. From 2004 to 2014, a total of 2,372 women had incident cases of type 2 diabetes: 1,562 of these women had no migraine history; 681 had prior migraine, and 129 had active migraine.
In univariate models, women with active migraine had a lower risk of incident type 2 diabetes than women with no migraine history (HR 0.80, 95% CI 0.60-0.96); in multivariable-adjusted models, this magnitude increased (HR 0.70, 95% CI 0.58-0.85). Prior migraine was not associated with the risk of type 2 diabetes in both univariate models (HR 1.16, 95% CI 1.06-1.27) and multivariable-adjusted models (HR 1.07, 95% CI 0.98-1.17).
The 2-year prevalence of active migraine decreased linearly from 24 months before the type 2 diabetes diagnosis (22%, 95% CI 16%-27%) to the date of diagnosis (11%, 95% CI 10%-12%). After type 2 diabetes diagnosis, prevalence of active migraine stabilized at rates of 10% to 11% that persisted up to 22 years after diagnosis.
This study has several limitations, the authors noted. Migraine status was based on self-reports, and no information about self-medication was available. The E3N sample consisted of women who mainly were white, not obese, post-menopausal, and teachers; these results may not apply to men or other women. Because the study is observational, potential residual and unmeasured confounding may exist, they added.
The E3N cohort is supported by the Mutuelle Générale de l’Education Nationale, European Community, French League against Cancer, Gustave Roussy, and the French Institute of Health and Medical Research. The current study was also supported by the French Research Agency.
Study authors reported relationships with CoLucid, Amgen, Lilly, Novartis, and Daiichi Sankyo.
Editorialist Gelfand reported relationships with Eli Lilly, Impax, Zosano, Biohaven, Amgen, and eNeura. Loder had no disclosures.