A method of calibrating a non-invasive blood glucose measurement instrument to a diabetic test subject employs targeted glycemic profiles in anti-correlated pairs. During calibration, reference blood glucose determinations are made using conventional invasive sampling methods. Concurrently, noninvasive spectral measurements are made using the noninvasive glucose monitor. Through controlled oral ingestion by the subject of calculated amounts of carbohydrate, the subject's blood glucose level is manipulated to mimic the patterns of the targeted profiles. During a first visit, a first profile of a pair is induced; during a second visit the inverse of the first profile is induced. The targeted profiles produce reference blood glucose values in which correlation to sampling factors is reduced or eliminated, thus the resulting calibration is correlated to glucose, and not to other analytes, sampling factors or environmental factors. A formula is provided for calculating the required amount of carbohydrate to ingest to induce a targeted glycemic profile in a test subject.