Understanding the Role of Metabolic Dysfunction in Migraine Pathogenesis

Background: Evidence suggests that metabolic dysfunction, specifically obesity and insulin resistance, influences the pathophysiology and chronification of migraine1,2. This progression is likely driven by inflammation, neuronal dysfunction, and vascular change2. Paradoxically, diagnosed diabetes is associated with a lower prevalence of migraines3. This inverse relationship may be attributed to medically stabilized blood glucose levels that prevent hypoglycemic triggers4, or to early autonomic neuropathy dulling pain perception5. In Hawaiʻi, Native Hawaiian and Pacific Islander (NHPI) populations experience disproportionately high rates of metabolic comorbidities. Utilizing local data provides an opportunity to investigate the relationship between metabolic dysfunction and migraine burden while addressing population-level health disparities.

Methods: A sample of 171 migraine patients (40 M, 131 F) was analyzed through the EClinicalWorks Hawaiʻi Pacific Neuroscience database. A registry search was run from January 1st, 1950, to July 7th, 2026, using the migraine ICD codes G43.0, G43.1, G43.7, G43.8, G43.9, and G43.E. A subset of patients with comprehensive metabolic panels from Diagnostic Laboratory Services was included. Lab values, such as HbA1c, fasting or non-fasting glucose, creatinine, and fasting insulin, were recorded. Additional biomarkers, such as body mass index (BMI) and blood pressure, were collected from physician visit records. For metabolic syndrome classification, complete lipid panels, blood pressure and pulse vitals, dyslipidemia drugs, and blood sugar medications were documented. Demographics, like insurance status, age, sex, and ethnicity, were also obtained. To account for possible confounding variables, information on comorbidities, such as substance use, hypertension, hyperlipidemia, depression, and diabetes, was gathered. Lastly, migraine data, including characterization (chronic or episodic), MIDAS migraine disability scores, or headache frequency (days per month), were collected from patients’ charts.

Results: Our patient population included 122 with chronic migraines, 26 with episodic migraines, and 23 with unknown characterizations. Patients with chronic migraines demonstrated higher HbA1c, BMI, and creatinine values compared to those with episodic migraines; however, no significant associations were identified through logistic regression and t-tests. Creatinine showed the strongest trend, with higher mean values in patients with chronic migraine compared to episodic migraine (0.931 vs. 0.808 mg/dL, p = 0.076). Among the biomarkers evaluated, only systolic blood pressure was found to have a significantly positive correlation with migraine frequency (p=0.046). MIDAS disability scores were positively associated with creatinine (p=0.003), systolic blood pressure (p=0.007), and diastolic blood pressure (0.006). However, these analyses were limited by a small sample size (n=12). Exploratory analyses examining race-based differences found that NHPI populations had higher creatinine and blood pressure levels, but lower HbA1c, glucose, and headache frequency compared to other races, all at non-significant differences. Interaction analyses revealed no significant effect modifications by NHPI status for glucose, HbA1c, BMI, or creatinine. However, significant interactions were observed for systolic (p=0.008) and diastolic (p=0.024) blood pressure, suggesting that the association between blood pressure and headache frequency differs between NHPI and non-NHPI patients.

Conclusion: Although metabolic biomarkers did not significantly predict chronic versus episodic migraine, systolic blood pressure was associated with monthly headache days, while blood pressure and creatinine were associated with MIDAS scores. These findings indicate that cardiovascular factors may be closely related to migraine frequency and disability rather than clinical classification. Some limitations in our study include a limited subset of patients with MIDAS scores and episodic migraine characterization. More comprehensive studies with larger sample sizes and improved clinical measurements are needed to further clarify these findings. Investigating these cardiovascular and renal values routinely may support individualized migraine treatment across Hawai’i’s diverse populations, especially among Native Hawaiian and Pacific Islander communities.