OBJECTIVES/SPECIFIC AIMS: The objective of this study is to identify and categorize non-invasive measurement methods for autonomic nervous system (ANS) symptoms that develop in hypoglycemic episodes. METHODS/STUDY POPULATION: We first reviewed literature for hypoglycemia symptomology. We then performed a selective literature review of Google Scholar, PubMed and Scopus for an ANS symptom and/or synonyms and the words ‘sensor’ or ‘detection’, e.g. ‘sweat sensor’ and ‘tremor detection’, studies utilizing non-invasive measurements in DM, and datasets of non-invasive measurements in DM. Measurement methods were then organized based on the ANS symptoms and existing metadata models for harmonizing sensors and surveys. RESULTS/ANTICIPATED RESULTS: We identified several measurement methods to for ANS symptoms during hypoglycemic events: thermometer, accelerometer, electrocardiogram (ECG), galvanic skin response (GSR), image processing, infrared imaging, thermal actuator, and ecological momentary assessment (EMA). The stage of implementation varied across the measurement methods from under development, to use in research and clinical settings, and even commercially available consumer products. Measurement methods that could be worn as wrist-band wearables or as film-based epidermal sensors would be capable of automatically gathering data with little to no effort required of the person wearing the device. Image-based methods would require the individual to actively engage in generating a photograph for analysis. In the case of EMA’s, a message containing a question is sent to the individual, often via text message, soliciting short and immediate responses. It is anticipated that one sensor alone would not be sufficient to measure ANS responses to hypoglycemia, but rather several data points would be required. For example, if the GSR was the only signal, sweat in response to vigorous exercise or a warm environment would inject noise into the signal. Including the accelerometer data would allow for the identification of body movement which would indicate exercise, while an ECG signal could confirm the exercise. DISCUSSION/SIGNIFICANCE OF IMPACT: Impaired awareness of hypoglycemia (IAH) is a complication that develops in about 30% of type 1 DM and 10% type 2 DM populations. In individuals with intact awareness of hypoglycemia, the ANS leads to symptoms which includes: shaking, trembling, anxiety, nervousness, palpitation (i.e. change in heart rate and/or function), clamminess, sweating, dry mouth, hunger, pallor (i.e. drop in blood flow and/or skin-surface temperature), and pupil dilation. IAH is defined as the onset of hypoglycemia before the appearance of autonomic warning symptoms. IAH is caused by repeated exposures to low blood glucose levels, which reduces the body’s ability to sense hypoglycemia, and therefore it is difficult for patients to recognize and self-treat. Individuals with IAH are six times more likely to experience severe hypoglycemia, an emergent condition which can lead to unconsciousness, seizure, coma, and death. Clinical investigators are developing interventions that aim to improve awareness of hypoglycemia. Surveys, observations by clinicians, and laboratory tests, often carried out in highly controlled in-patient settings, are currently used to assess the severity of IAH and the ANS’s ability to respond to hypoglycemia. In other disease states, for example heart disease and Parkinson’s disease, electrocardiograms and accelerometers have been used to assess heart function and tremor, respectively. However, there is currently a barrier to examining the efficacy of IAH interventions in real world settings as there are no established objective and non-invasive means to measure ANS symptoms due to hypoglycemia. This work encompasses the first important step necessary to direct translational researchers interested in testing the efficacy of IAH interventions and developing diagnostic tools for IAH in real-world studies outside the clinic. Next steps include evaluating these sensors and specifying EMA surveys, designing studies, and integration and assimilation of these data streams to identify true events of IAH by leveraging informatics platform such as the Utah PRISMS Informatics Ecosystem. Investigators would then be able to conduct studies that aim to develop and validate models that take sensor and EMA data as the input to detect and assess the severity of IAH.