Plasma Glucose Levels Increase During Spontaneous Attacks of Migraine With and Without Aura

Ditte Georgina Zhang, BSc; Faisal Mohammad Amin, MD, PhD; Song Guo, MD, PhD; Mark B. Vestergaard, MSc, PhD; Anders Hougaard, MD, PhD; Messoud Ashina, MD, DMSc


Headache. 2020;60(4):655-664. 

In This Article

Abstract and Introduction


Objective: To investigate plasma glucose changes during the ictal state of migraine compared to the interictal state.

Background: Previous studies suggest abnormal glucose metabolism in migraine patients during and outside of attacks. It is not known if plasma glucose levels change during spontaneous migraine attacks.

Methods: Plasma glucose levels were measured during and outside of spontaneous migraine attacks with and without aura. Plasma glucose values were corrected for diurnal variation of plasma glucose by subtracting the difference between the moving average (intervals of 2 hours) and overall mean from the plasma glucose values.

Results: This was a sub-study of a larger study conducted at Rigshospitalet Glostrup in the Capital Region of Denmark. Thirty-one patients (24 F, 7 M, 13 with aura, 18 without aura) were included in the study. Mean time from attack onset to blood sampling was 7.6 hours. Mean pain at the time of investigation was 6 on a 0–10 verbal rating scale. Plasma glucose was higher ictally compared to the interictal phase (interictal mean: 88.63 mg/dL, SD 11.70 mg/dL; ictal mean: 98.83 mg/dL, SD 13.16 mg/dL, difference 10.20 mg/dL, 95% CI = [4.30; 16.10]), P = .0014). The ictal increase was highest in patients investigated early during attacks and decreased linearly with time from onset of migraine (−1.57 mg/dL/hour from onset of attack, P = .020). The attack-related increase in blood glucose was not affected by pain intensity or presence of aura symptoms.

Conclusions: We demonstrated higher plasma glucose values during spontaneous migraine attacks, independent of the presence of aura symptoms and not related to pain intensity, peaking in the early phase of attacks. Additional studies are necessary to confirm our findings and explore the possible underlying mechanisms.


A well-known feature of migraine is that attacks can be triggered by various stimuli.[1] Fasting is one of the most frequent patient-reported triggers of migraine[1,2] and food craving is a common premonitory symptom.[3] Based on these clinical observations, fluctuations of blood glucose have been proposed to be able to initiate migraine attacks.[4]

During the interictal phase, migraineurs have an impaired insulin sensitivity and higher fasting plasma insulin levels compared to controls.[5–7] A decrease of insulin release has been reported during the ictal phase of migraine[8] and a polymorphism in the insulin receptor gene is associated with migraine.[9] Furthermore, susceptibility to cortical spreading depression, the presumed underlying electrophysiological phenomenon of the migraine aura, may be affected by blood glucose levels.[10–12]

To date, changes in blood glucose levels during migraine attacks have not been specifically studied. The aim of this study was to (1) investigate changes in blood glucose levels during spontaneous migraine attacks; (2) to correlate changes in blood glucose to the perceived pain intensity and time since attack onset; (3) to determine if blood glucose changes differ between migraine patients with and without aura. Based on the previous observations mentioned above, we hypothesized that plasma glucose levels would be increased during migraine attacks compared to the interictal state.