The present invention comprises one or more microprocessors programmed to execute methods for improving the performance of an analyte monitoring device including prediction of glucose levels in a subject by utilizing a predicted slower-time constant (1/k.sub.2). In another aspect of the invention, pre-exponential terms (1/c.sub.2) can be used to provide a correction for signal decay (e.g., a Gain Factor). In other aspects, the present invention relates to one or more microprocessors comprising programming to control execution of (i) methods for conditional screening of data points to reduce skipped measurements, (ii) methods for qualifying interpolated/extrapolated analyte measurement values, (iii) various integration methods to obtain maximum integrals of analyte-related signals, as well as analyte monitoring devices comprising such microprocessors. Further, the present invention relates to algorithms for improved optimization of parameters for use in prediction models that require optimization of adjustable parameters.