Embodiments of the present system and methods measure a concentration of a substance, such as glucose, in a body. The present embodiments measure a first amount of infrared (IR) radiation absorbed or emitted from the body in a first wavelength band, and a second amount of IR radiation absorbed or emitted from the body in a second wavelength band. The present embodiments also measure a temperature at a surface of the body and an ambient temperature. A normalized ratio parameter is calculated from the four measurements, and the concentration of the substance in the body is calculated by correlating the normalized ratio parameter with the body surface temperature and the ambient temperature using an empirically derived lookup table. Also disclosed are methods for creating the empirically derived lookup table.