COMMENTARY

Type 2 Diabetes Risk May Be Lower in Women With Migraine

Laurie Barclay, MD

Disclosures

January 17, 2019

Associations Between Migraine and Type 2 Diabetes in Women: Findings From the E3N Cohort Study

Fagherazzi G, El Fatouhi D, Fournier A, et al
JAMA Neurol. 2018 Dec 17. [Epub ahead of print]

Study Summary

Migraine, particularly migraine with aura, is known to be associated with hyperlipidemia, hypertension, and increased Framingham Risk Score for coronary heart disease, as well as with increased risk for overall and specific cardiovascular disease events. Although migraine has been linked to factors connected with insulin resistance and type 2 diabetes, the particulars of this association and its temporality remain unclear.

This analysis examined the association between migraine and type 2 diabetes incidence and changes in the prevalence of active migraine before and after type 2 diabetes diagnosis, using data from the E3N (cohort study. This prospective, population-based study began in 1990 on a cohort of 98,995 French women born between 1925 and 1950 who had a health insurance plan that mostly insured teachers. For the present analysis, the investigators considered 76,403 eligible E3N participants who completed the 2002 follow-up questionnaire with information available on migraine, and then excluded 2156 prevalent cases of type 2 diabetes.

The final analysis included 74,247 women with a mean age of 61 + 6 years at baseline who were predominantly white. During 10 years of follow-up between 2004 and 2014, there were 2372 incident cases of pharmacologically treated type 2 diabetes identified through a drug-reimbursement database. Compared with women with no migraine history, those with active migraine had a 30% lower risk for type 2 diabetes (multivariable-adjusted hazard ratio, 0.70; 95% confidence interval [CI], 0.58-0.85).

After adjustment for potential type 2 diabetes risk factors, active migraine prevalence decreased linearly during the 24 years prior to diabetes diagnosis, from 22% (95% CI, 16%-27%) to 11% (95% CI, 10%-12%), followed by a plateau of migraine prevalence of approximately 11% for 22 years after diagnosis.

Viewpoint

Limitations to the current study include the potential lack of generalizability of the findings to men and other populations with migraine, reliance on self-report for migraine history, a lack of data on the presence of migraine aura or on self-medication for migraine, a failure to capture type 2 diabetes cases who did not receive pharmacotherapy, and an observational design with potential residual and unmeasurable confounding.

Nonetheless, the inverse association between active migraine and type 2 diabetes incidence may suggest a potential role of both hyperglycemia and hyperinsulinism on reducing migraine occurrence. Plasma glucose concentration continues to increase over time until type 2 diabetes ultimately occurs. Monitoring the decrease of migraine frequency in persons with obesity or other risk factors for diabetes may herald an emerging increase in blood glucose levels, prediabetes, or type 2 diabetes.

Future studies should aim to clarify mechanisms underlying the observed associations between migraine and type 2 diabetes, which may further elucidate the pathophysiology of each of these highly prevalent diseases. Nutritional, hormonal, or metabolic factors, such as an elevation in free fatty acid plasma concentration and ketone bodies, may trigger migraine in some individuals. Previous research also suggests an association between polymorphisms in the insulin receptor gene and migraine.

Another potential mechanism may involve calcitonin gene-related peptide (CGRP), which is a neuropeptide expressed in sensory nerves and implicated in migraine pathophysiology as well as in glucose metabolism. Development of insulin resistance and hyperglycemia may damage sensory neurons that produce CGRP, and their reduced activity could potential alleviate migraine.

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