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.