ORIGINAL RESEARCH article
Front. Neurol.
Sec. Headache and Neurogenic Pain
Glucose Dysregulation and Glycemic Phenotyping in Chronic Migraine
Provisionally accepted
- Noorda College of Osteopathic Medicine, Provo, United States
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Background: Emerging evidence suggests that a metabolic mismatch between cerebral energy demand and supply may be a contributing factor to the onset of migraine(Amery, 1982; Gross et al, 2019). Studies have drawn connections between migraine and conditions such as hypoglycemia, fasting, GLUT1 transporter deficiency, insulin resistance, and diabetes, highlighting the role of metabolic dysregulation in migraine susceptibility(Del Moro et al, 2022; Horckmans & Van Paesschen, 2024; Hufnagl & Peroutka, 2002; Scoppola et al, 2021; Wang et al, 2008). Understanding these metabolic patterns could pave the way for personalized migraine treatments targeting glucose regulation. Methods: We conducted a retrospective cohort analysis from chronic migraine subjects (>15 headache days/month) using continuous glucose monitoring (CGM) (n=131) and oral glucose tolerance tests (GTT) (n=247). Continuous glucose monitoring data was analyzed from a prospective cohort of 24 healthy controls using metrics such as Inter/Intraday standard deviation (SD), Average Daily Risk Range (ADRR), mean amplitude of glycemic excursion (MAGE), mean glucose excursion (MGE), mean of daily differences (MODD), Continuous Overall Net Glycemic Action (CONGA24), post-prandial glucose recovery time (PGRT), post-prandial area under the curve (PP-AUC). Subjects were clustered into three groups based on OGTT responses using K-means clustering to identify possible postprandial phenotypes. Results: Compared to age and gender-matched standards of normal GTT response those with chronic migraine had significantly lower values at fasting and two hours. CGM data also showed that migraine subjects had greater glucose variability, including greater day-to-day (MODD) and within-day (CONGA24) glycemic variability, and inter and intraday standard deviation during waking hours. Post-prandial dysregulation was also shown in measures of MAGE, MGE, PGRT, and PPAUC each showing significant differences (except PGRT) from control during waking hours. Clustering of glucose tolerance tests showed three distinct phenotypes in response varying in profiles of glucose and insulin responses. Discussion: Chronic migraine subjects displayed postprandial glucose dysregulation, greater glycemic variability than healthy controls. The identified GTT phenotypes highlight distinct glucose regulation patterns, suggesting different migraine-associated metabolic profiles. Further research will explore factors contributing to these phenotypes and their implications for migraine pathogenesis. These findings support the potential for targeted migraine treatments informed by glucose dysregulation patterns.
Keywords: chronic migraine, glucose metabolism, glucosetolerance test, Hyperglycemia, Hypoglycemia, Insulin, phenotype
Received: 06 Oct 2025; Accepted: 11 Dec 2025.
Copyright: © 2025 Nelson, Reaveley, Jennings, Burger, Kim, Sant and Bills. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Kyle B Bills
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