Biological sex influences whole-body glucose metabolism, with females generally displaying greater insulin sensitivity than males, yet paradoxically similar or poorer glucose tolerance when assessed with oral glucose tolerance tests (OGTTs). This discrepancy suggests that plasma glucose concentrations alone may not capture sex-specific differences in postprandial glucose metabolism. Measuring exogenous glucose oxidation during a U-¹³C₆glucose-enriched OGTT may offer a non-invasive approach to detect such differences, but this method has not yet been applied to examine sex differences. Forty adults (18-65 yrs; n=20 per sex) classified as normal-weight (NW; n=10 per sex) or obese (OB; n=10 per sex) based on body mass index completed a virtually monitored metabolic trial. After a 10-h overnight fast, participants ingested a 75-g glucose beverage enriched with 75-mg (0.1%) U-¹³C₆ D-glucose. Capillary glucose concentration, salivary insulin and exogenous glucose oxidation were measured fasted and across the 3-h postprandial period. Compared to NW, participants with OB had higher 3-h mean blood glucose ( p0.05). A sex × obesity interaction was observed for exogenous glucose oxidation, such that it was higher in females than males in NW (69.1±5.4 vs 48.2±7.5; p<0.0001) but not in OB (40.9±8.4 vs. 36.0±9.3mg/kg/hr; p=0.53). OB participants also exhibited lower overall exogenous glucose oxidation compared with NW (38.4±8.8 vs. 58.7±6.4mg/kg/h; p<0.001). These findings suggest that despite no sex differences in glucose or insulin responses during the OGTT, females exhibit higher exogenous glucose oxidation than males, but this elevated metabolic response is attenuated in obesity.
Estafanos et al. (Thu,) studied this question.