Accumulation of advanced glycation end products (AGEs) is accelerated during glycemic and oxidative stress and is an important predictor of complications in diabetes mellitus (DM).Here we both review and present original data on the relationship between skin autofluorescence (SAF), a noninvasive measure of AGEs, and short- and intermediate-term glycemic variations.Acute changes in glucose levels during an oral glucose tolerance test in 56 persons with varying degrees of glucose tolerance did not influence SAF. AGE-rich meals result in a transient postprandial rise in SAF of 10% 2-4 h later. This could not be attributed to meal-induced glycemic changes and is probably caused by the AGE content of the meal. In type 1 DM major intermediate-term improvements of glycemic control as depicted by multiple hemoglobin A1c (HbA1c) measurements were associated with lower skin AGE levels. In a well-controlled, stable type 2 DM cohort, only a weak correlation was found between SAF and HbA1c. In both studies skin AGE/SAF levels predicted complications of diabetes with an accuracy superior to that of HbA1c. SAF has also been proposed as a new tool in diagnosing impaired glucose tolerance (IGT) and DM. It proved to be more sensitive than either fasting glucose or HbA1c.SAF is not influenced by short-term glycemic variations. AGE-rich meals may, however, cause a transient rise postprandially. There is a weak correlation between SAF or skin AGEs and current or time-integrated HbA1c levels. SAF has strong added value in risk prediction of complications of diabetes and is a promising tool for early detection of diabetes and IGT.