Menstrual cyclicity has a profound effect on glucose homeostasis

Results from oral glucose tolerance tests have frequently demonstrated a deterioration in glucose metabolism during the luteal phase of the menstrual cycle. To examine this issue further, eight women underwent both midfollicular (days 3 to 10) and midluteal (days 20 to 25) phase hyperglycemic clamp studies (+125 mg glucose/dl) after an overnight fast. Glucose levels rose from 83 ± 1 to 207 ± 2 and 87 ± 1 to 207 ± 2 mg/dl, respectively, during the follicular and luteal phases. The basal (6 ± 1 versus 7 ± 1 μU/ml) and glucose-stimulated (42 ± 5 versus 43 ± 6 μU/ml) insulin responses were similar in the follicular and luteal studies. However, glucose uptake was significantly higher during the follicular versus the luteal phase (10.99 ± 0.97 versus 6.93 ± 0.37 mg/kg-min; P < 0.01), as was the ratio of glucose uptake to insulin concentration (30.0 ± 5.5 versus 19.7 ± 3.7, P < 0.01). The authors conclude that: (1) Glucose metabolism is impaired in the luteal phase of the menstrual cycle; (2) This defect cannot be explained by differences in the plasma insulin response; and (3) This impairment in the ability to promote glucose uptake under hyperglycemic conditions suggests a defect in the mass action effect of glucose per se.