Fractalkine as a Biomarker of Metabolic Dysregulation in Reproductive-Age Women with Impaired Glucose Metabolism and Comorbid Conditions

Abstract

Disturbances of metabolic homeostasis are important determinants of reduced female fertility, as they negatively affect reproductive outcomes, hormonal balance, adipose tissue status, and carbohydrate metabolism, and contribute to a more severe course of comorbid diseases. Today, one of the most promising biomarkers of metabolic dysfunction and progression of comorbid pathology is considered to be fractalkine, a highly selective adipose tissue ligand. Objective. To assess fractalkine levels in reproductive-age women with prediabetes or type 2 diabetes mellitus (T2DM) and comorbid conditions, as well as to analyze the relationships between its concentration and clinical and laboratory parameters of metabolic disorders.

Materials and Methods A total of 56 reproductive-age women were examined and divided into three groups according to carbohydrate metabolism status: control group (n=12) – apparently healthy individuals; group II (n=20) – women with prediabetes; group III (n=24) – patients with T2DM. Serum levels of fractalkine, leptin, and insulin were measured using enzyme-linked immunosorbent assay (ELISA). Associations between fractalkine levels and key anthropometric indicators (body mass index (BMI), visceral adiposity index (VAI), total and visceral fat content), clinical parameters (metabolic age), and laboratory markers of metabolic status (leptin resistance index, insulin resistance index (HOMA-IR), and vitamin D status) were analyzed.

Results Fractalkine levels were significantly higher in patients with T2DM (3.88±0.48 ng/mL) compared with women with prediabetes (2.45±0.26 ng/mL) and the control group (0.42±0.09 ng/mL) (p<0.001). Fractalkine demonstrated strong associations with key metabolic parameters: a strong positive correlation was observed with fasting capillary blood glucose (r=0.846; p=0.0001), glycated hemoglobin (HbA1c) (r=0.813; p=0.0001), metabolic age (r=0.709; p=0.0001), waist circumference (r=0.716; p=0.0001), and hip circumference (r=0.716; p=0.0001). Moderate positive correlations were found with BMI (r= 0.668; p=0.0001), visceral fat (r=0.544; p=0.0001), total fat content (r=0.433; p=0.0001), HOMA-IR (r=0.502; p=0.0001), and VAI (r=0.389; p=0.004). A moderate inverse correlation was also identified between fractalkine levels and serum 25-hydroxyvitamin D [25(OH)D] concentration (r=−0.453; p=0.001). Thus, elevated fractalkine levels are associated with activation of the main mechanisms of metabolic dysfunction.

Conclusions Reproductive-age women with impaired carbohydrate metabolism combined with insulin resistance, obesity, and vitamin D deficiency exhibit a statistically significant increase in serum fractalkine levels. Hyperfractalkinemia shows significant correlations with key clinical and laboratory indicators of metabolic disorders. Fractalkine is an early and informative prognostic biomarker of metabolic dysfunction in reproductive-age women with prediabetes and T2DM especially in the presence of comorbid metabolic diseases.