Introduction
About one in five patients with type 1 diabetes (T1D) have impaired awareness of hypoglycemia (IAH).1 IAH represents a risk factor for severe and recurrent hypoglycemic events, which can lead to brain damage.2 3 As no effective treatment has been clearly established,4 biomarkers capable of detecting and quantifying cerebral damage in this population are needed for the design of novel preventive or therapeutic strategies.
On the one hand, cerebral atrophy or functional impairment can be assessed using neuroimaging techniques. In fact, a structural and functional brain compromise has been described in patients with T1D-IAH.5 However, neuroimaging techniques have important limitations in terms of specificity, logistics, standardization, scalability, and cost-efficiency. On the other hand, while cerebrospinal fluid biomarkers of cerebral damage overcome some of these limitations, they require an invasive lumbar puncture procedure.
In recent years, research has focused on the detection of blood biomarkers of neural damage. Clearly, cost-efficient blood biomarkers would represent an accessible and centralizable alternative. However, the main challenge for the development of an adequate technology in this context has been the low blood concentration of proteins derived from the central nervous system (CNS). Importantly, in the last few years, the Single Molecule Array (Simoa) technology has shown unprecedented precision and sensitivity (ie, femtomolar range) for the quantification of blood biomarkers of brain damage.6 In particular, increased levels of neurofilament light chain (NfL) in blood have shown a great potential for the detection of neurodegeneration (neuronal loss and axonal damage), traumatic brain injury, and cerebrovascular accidents.7
In this brief report, we investigate whether patients with T1D with hypoglycemia unawareness show increased levels of plasma NfL compared with patients with normal awareness of hypoglycemia (NAH) and healthy controls (HC). Additionally, we explore whether abnormally increased NfL levels in this population correlate with IAH severity and reduced cerebral gray matter volume (GMV).