Title: Diabetes mellitus management in the context of cranial tumors

Abstract

The study of the relationship between cancer and diabetes mellitus (DM) has been under investigation for many decades. Particularly in the field of neurology and neurosurgery, increasing emphasis has been put on the examination of comorbid DM in patients with cranial tumors. Namely, as the most common and invasive type of malignant adult brain tumor, glioblastoma (GBS) has been the focus of said research. Several mechanisms have been described in the attempt to elucidate the underlying association between DM and GBS, with the metabolic phenomenon known as the Warburg effect and its consequential downstream effects serving as the resounding culprits in recent literature. Since the effect seen in cancers like GBS exploits an upregulated form of aerobic glycolysis, the role of a sequela of DM, known as hyperglycemia, will be investigated. In particular, in the treatment of GBS, surgical resection and subsequent chemotherapy and/or radiotherapy are used in conjunction with corticosteroid therapy, the latter of which has been linked to hyperglycemia. Unsurprisingly, comorbid DM patients are significantly susceptible to this disposition. Further, this fact is reflected in recent literature that demonstrates the impact of hyperglycemia on cancer advancement and patient outcomes in several preclinical and clinical studies. Thus, this review will aim to underline the significance of diabetes and glycemic control via standard-of-care treatments such as metformin administration, as well as to describe emerging treatments such as the signaling modulation of insulin-like growth factor and the employment of the ketogenic diet.