Objective — To examine the hormonal mechanisms underlying the variability in glycemic control during the different phases of the menstrual cycle in women with insulin-dependent diabetes mellitus (IDDM).

Research Design And Methods — Hyperglycemic (11.7 ± 0.1 mM), hyperinsulinemic (24 ± 3 mU/L) clamp studies were performed in 16 women with IDDM during the follicular (day 8 ± 1) and luteal (day 23 ± 1) phases of the menstrual cycle. Seven of the patients (group 1) experienced worsening glucose control during the luteal phase, whereas nine patients (group 2) did not.

Results — In group 1, glucose metabolism fell from 30.2 ± 3.8 μmol·kg⁻¹·min⁻¹ during the follicular phase to 24.5 ± 2.0 μmol·kg⁻¹·min⁻¹ during the luteal phase (P = 0.09), whereas in group 2 it increased from 18.5 ± 1.2 to 23.2 ± 2.3 μmol·kg⁻¹·min⁻¹ (P = 0.03). The decrease in glucose metabolism during the luteal phase in patients in group 1 was associated with a significant rise in the serum estradiol levels from the follicular to luteal phase (164 ± 39 vs. 352 ± 59 pM, P = 0.006), whereas this rise was not observed in group 2 (334 ± 156 vs. 423 ± 74 pM, NS). Changes in other reproductive hormones (progesterone, testosterone, dihydrotestosterone, androstenedione, luteinizing hormone, follicular-stimulating hormone, or prolactin) were not related to the differences in glucose uptake in the two groups.

Conclusions — 1) Marked heterogeneity in glucose metabolism is seen throughout the menstrual cycle in women with IDDM, 2) a subgroup of patients exhibits worsening premenstrual hyperglycemia and a decline in insulin sensitivity during the luteal phase, and 3) the deterioration in glucose uptake in this subgroup was associated with a greater increment in estradiol levels from the follicular to the luteal phase.