Evaluation of folliculogenesis and oxidative stress parameters in type 1 diabetes mellitus women with different glycemic profiles.

Background: Despite enormous advances in diabetes treatment, women with type 1 diabetes mellitus (DM) still experience delayed menarche, menstrual irregularities, fewer pregnancies, and a higher rate of stillbirths compared to women without the disease. Due to the fact that type 1 DM occurs at a young age, the preservation of reproductive health is one of the most important goals of treatment.

Aims: The aim of this study was to evaluate the relationship between different glycemic profiles and changes in the pro-oxidant-antioxidant balance and ovarian follicular apparatus in reproductive-age patients with type 1 DM.

Methods: We examined 50 reproductive-age (19-38 years) women with type 1 DM with a disease duration of at least ten years. Carbohydrate metabolism was assessed with the continuous glucose monitoring (CGM) system and glycated hemoglobin (HbA1c) concentration measurement. CGM was performed using the FreeStyle Libre flash glucose monitoring system (Abbott Diabetes Care, Witney, UK). In each patient, malondialdehyde level, catalase activity and 3-nitrotyrosine level in the blood serum were determined. To assess the ovarian function, we measured the ovarian volume, the antral follicle count, and the serum levels of anti-Müllerian hormone and follicle-stimulating hormone. All patients were divided into four groups (glucotypes) based on the CGM results. Group 1 included type 1 DM patients with satisfactory compensation of carbohydrate metabolism; group 2 consisted of patients with frequent hypoglycemic conditions and pathological glucose variability; group 3 included individuals with prolonged hyperglycemic conditions and maximum HbA1c levels; and group 4 comprised patients with the glycemic profile characterized by all the presented types of dysglycemia (intermittent glycemia).

Results: We revealed a negative correlation between serum catalase activity and time of hypoglycemic conditions in patients with type 1 DM based on the CGM results (r_s = -0.47, p < 0.01). In group 4 (intermittent glycemia), patients demonstrated the lowest serum catalase activity and increased serum 3-nitrotyrosine level, while in group 3, women with chronic hyperglycemia (HbA1c 8.4 [8.1; 9.9]%; 68 [65; 85] mmol/mol) had a moderate change in antioxidant defense and oxidative stress parameters. Correlation analysis of ovarian volume, the antral follicle count, and the serum anti-Müllerian hormone level in type 1 DM women with different glycemic profiles established a negative relationship (r_s = -0.82, p < 0.05) between the antral follicle count and glucose variability in group 1, a positive relationship (r_s = 0.68, p < 0.05) between ovarian volume and glucose variability in group 2, and a positive relationship (r_s = 0.88, p < 0.05) between ovarian volume and time of hypoglycemic conditions, which, according to the CGM results, amounted to a critical value of 57.5 [40.0; 82.0]%.

Conclusions: The data obtained indicate the relationship between the ovarian volume, serum anti-Müllerian hormone level, the antral follicle count and oxidative stress parameters not only in patients with hyperglycemia, but also in those with hypoglycemic conditions, as well as with pathological glucose variability.