Attempts were made to non-invasively detect glucose-specific spectral signals in the skin by ATR-FTIR spectroscopy. In vivo spectra were collected from the inner wrists of healthy, prediabetes and diabetes subjects in the 750-4000 cm-1 region, with a closer assessment of the glucose-related region between 1000 and 1180 cm-1. Spectra in vivo showed glucose-specific peaks at 1030, 1080, 1118 and 1151 cm-1, as a variety of glucose solutions are found in vitro. Based on the differences of intensities at 1030 and 1118 cm-1 two spectral patterns were seen: I1118 > I1030 for a diabetes and I1030 > I1118 for non-diabetes subjects. The peak at 1030 cm-1 was used to assess glucose concentrations in the skin due to its good correlation with glucose concentrations in vitro. Calculated mean values of the peak at 1030 cm-1 showed evidence of correlation with blood glucose levels when grouped as = 140, 140-200 and = 200 mg/dL, though there was no constant correlation between them when compared before/after OGTT or at the fasting/postprandial states. Absorbances at 1030 cm-1 were not only increased in a dose-dependent manner in a diabetes patient, but were also generally higher than in non-diabetes subjects at 30 min OGTT assessment. Also we could monitor absorbances at 1030 cm-1 and determine their changes in the skin tissue at different times of OGTT. We assume that our approach to in vivo measurement and monitoring of glucose concentrations at 1030 cm-1 may be one of the indicators to assess glucose activity level and its changes in the skin tissue, and has further implications in the study of clinical and pathophysiological aspects of hyperglycemia in diabetes and non-diabetes subjects by ATR-FTIR spectroscopy.