Impact of IL-6 receptor inhibitors on cerebrospinal fluid metabolites in type 2 diabetes patients.

Type 2 diabetes mellitus (T2DM) is a major global public health concern. According to the World Health Organization, the estimated prevalence of diabetes among adults aged ≥ 18 years was 14.0% worldwide as of 2022 []. Although T2DM accounts for over 90% of all diabetes cases and is largely preventable, its prevalence continues to rise []. Hypoglycemia, the most common acute complication of diabetes treatment, has significant short- and long-term consequences. The short-term consequences include fatal arrhythmia, brain damage, and severe physical injury [], whereas the long-term effects involve neurocognitive impairment []. Hypoglycemia also exerts multifaceted effects, such as reduced cognitive function, increased cardiovascular risks, diminished quality of life, higher hospitalization rates, and elevated healthcare costs [-]. When hypoglycemia-induced symptoms are absent or insufficiently recognized, the condition may progress to life-threatening conditions, such as seizures, loss of consciousness, myocardial infarction, or even death [,]. The American Diabetes Association emphasized individualized glycemic targets and proactive hypoglycemia prevention strategies in its clinical guidelines []. Repeated episodes of hypoglycemia in individuals with diabetes can lead to an impaired awareness of hypoglycemia (IAH) []. Normally, a drop in the blood glucose level < 70 mg/dL triggers the activation of the sympathetic nervous system, producing warning symptoms, such as sweating and tremors that alert the individual to take corrective action []. However, in patients with IAH, this autonomic response becomes blunted, and the hypoglycemia often goes unrecognized until the blood glucose reaches dangerously low levels []. Consequently, IAH is associated with a markedly increased risk of severe hypoglycemia, with some studies reporting a 17-fold higher risk among affected individuals [].