A method of determining a measure of a tissue state (e.g.,
glycation end-product or
disease state) in an individual is disclosed. A portion of the
skin of the individual is illuminated with excitation light, then light emitted by the tissue due to
fluorescence of a chemical with the tissue responsive to the excitation light is detected. The detected light can be combined with a model relating
fluorescence with a measure of tissue state to determine a tissue state. The invention can illuminate the
skin and detect responsive light over a time that spans a plurality of cardiac cycles of the individual, which can, as an example, help mitigate the effects of time-varying signals such as those due to
hemoglobin. The invention can also determine the amount of light to be directed to the
skin, for example by controlling the time that a
light source is energized. The amount of illumination light can be determined from a skin reflectance characteristic such as pigmentation or
melanin in the skin. Controlling the amount of light directed to the tissue can reduce the
dynamic range required of a corresponding optical
system, for example by allowing a single
system to accurately measure individuals with very
light skin and individuals with very
dark skin.