The invention relates to statistical methods for fitting a mathematical model of the interaction of signals, such as optical signals, with tissue to detected signals or data related to the interaction. In particular it relates to statistical methods for fitting a mathematical model of the interaction of optical signals with tissue to actual signals, such as interferometric signals related to data optical scattering in tissue and their relationship to glucose concentration. It also relates to statistical methods for fitting a mathematical model of the interaction of optical signals with tissue to data such as the spectral distribution values of optical signals absorbed or scattered by tissue and their relationship to glucose concentration. The invention provides a practical non-invasive glucose measurement method and system. The invention also provides a measurement method and system that performs well in low signal-to-noise environments.