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 microU/ml) and glucose-stimulated (42 +/- 5 versus 43 +/- 6 microU/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 less than 0.01), as was the ratio of glucose uptake to insulin concentration (30.0 +/- 5.5 versus 19.7 +/- 3.7, P less than 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.