Feasibility of Interstitial Fluid Ketone Monitoring with Microneedles

Diabetic ketoacidosis (DKA) is one of the most dangerous and costly complications of diabetes, accounting for approximately 50% of deaths in diabetic individuals under 24 years. This results in over 130,000 hospital admissions yearly and costs the USA over USD 2.4 billion annually. Earlier diagnosis, treatment, and management of DKA are of critical importance to achieving better patient outcomes and preventing prolonged hospital admissions. Diabetic patients undergoing stress from illness or injury may not recognize early ketosis and often present advanced ketoacidosis, requiring intensive care admission. We have recently developed a microneedle-based technology to extract dermal interstitial fluid (ISF) from both animals and humans, which could enable wearable sensors to rapidly detect ketosis. Metabolite concentrations in ISF may differ in urine and blood and could likely represent local metabolic conditions in the surrounding tissue. Development of a wearable ketone detector will require an understanding of ketone concentrations and kinetics in ISF. Here, we report data that is first of its kind, with regard to the ketone concentrations present in the dermal ISF of rats, their correlation to blood, and the possible impact on the development of a wearable ISF "early warning system" to prevent morbidity from DKA. We extracted ISF, using minimally invasive microneedle arrays, from control Sprague Dawley rats and 17 h fasted rats. ISF and blood ketone levels were measured using a common glucose/ketone meter and strips. Local tissue concentrations of glucose were similar to those of blood, with an average blood to ISF glucose ratio of 0.99 ± 0.15 mg/dL. ISF ketones (0.4 ± 0.3 mM) were significantly higher (p = 4.2 × 10^-9), compared with blood ketones (0.0 ± 0.0 mM). Although the fasted animals had slightly higher ISF ketones (1.3 ± 1.1 mM) compared with blood ketones (1.0 ± 1.0 mM), the difference was not significant (p = 0.3). This suggests ISF could possibly be useful as a surrogate for blood when determining ketone levels within a clinical setting.