Taylor Robert M, Baca Justin T
Department of Emergency Medicine, The University of New Mexico, Albuquerque, NM 87131, USA.
Metabolites. 2022 May 10;12(5):424. doi: 10.3390/metabo12050424.
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 ( = 4.2 × 10), 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 ( = 0.3). This suggests ISF could possibly be useful as a surrogate for blood when determining ketone levels within a clinical setting.
糖尿病酮症酸中毒（DKA）是糖尿病最危险且代价高昂的并发症之一，约占24岁以下糖尿病患者死亡人数的50%。这导致每年超过13万例住院治疗，美国每年为此花费超过24亿美元。早期诊断、治疗和管理DKA对于实现更好的患者预后及防止长期住院至关重要。遭受疾病或损伤应激的糖尿病患者可能无法早期识别酮症，常表现为晚期酮症酸中毒，需要重症监护。我们最近开发了一种基于微针的技术，可从动物和人类身上提取真皮间质液（ISF），这能使可穿戴传感器快速检测酮症。ISF中的代谢物浓度可能与尿液和血液中的不同，可能代表周围组织的局部代谢状况。开发可穿戴酮检测器需要了解ISF中的酮浓度和动力学。在此，我们报告了关于大鼠真皮ISF中酮浓度、其与血液的相关性以及对开发可穿戴ISF“早期预警系统”以预防DKA发病可能产生的影响的首批此类数据。我们使用微创微针阵列从对照斯普拉格 - 道利大鼠和禁食17小时的大鼠中提取ISF。使用普通血糖仪和试纸测量ISF和血液中的酮水平。局部组织葡萄糖浓度与血液中的相似，血液与ISF葡萄糖的平均比值为0.99±0.15mg/dL。与血液酮（0.0±0.0mM）相比，ISF酮（0.4±0.3mM）显著更高（ = 4.2×10）。尽管禁食动物的ISF酮（1.3±1.1mM）略高于血液酮（1.0±1.0mM），但差异不显著（ = 0.3）。这表明在临床环境中测定酮水平时，ISF可能可作为血液的替代物。
