There is growing evidence that alterations in the insulin and glucose metabolism may be involved in the pathogenesis of migraine. Nitric oxide (NO) stress has been associated with migraine. However, the role of NO on the insulin and glucose metabolism in migraineurs has remained elusive to date. The aim of the present study was to investigate the insulin and glucose metabolism in migraineurs and to determine possible interactions with the NO pathway. One hundred and twenty non-obese probands participated in this study, including 48 migraineurs and 72 healthy volunteers. Various parameters of the NO pathway, glucose metabolism as well as body measurement parameters were determined. We found a highly significantly increased insulin and Homeostasis Model Assessment (HOMA)-index in migraine patients, whereas fasting glucose was decreased. Logistic regression revealed an odds ratio of 5.67 for migraine, when comparing the lowest with the highest quartile of HOMA. Multivariate analysis showed that HOMA, waist-to-length ratio and nitrite as parameters of NO stress were highly significantly correlated. We show here that hyperinsulinaemia is associated with migraine and, furthermore, is correlated with increased NO stress. These findings represent a new pathophysiological mechanism that may be of clinical relevance.