Development and Clinical Application of ApoC3 Protein as a Predictive Biomarker for Insulin Resistance in Polycystic Ovary Syndrome

Polycystic Ovary Syndrome (PCOS) is the most common reproductive endocrine disorder causing infertility and miscarriage in women. The insulin resistance state in PCOS patients (PCOS with insulin resistance, PCOS-IR) not only affects their fertility but is also associated with a range of health issues, including type 2 diabetes mellitus, endometrial cancer, and spontaneous abortion during pregnancy. There is an urgent clinical need to explore sensitive serum biomarkers for the diagnosis of insulin resistance in PCOS. Our preliminary studies have demonstrated that apolipoprotein C-III (ApoC3) exhibits diagnostic efficacy for PCOS-IR and is positively correlated with HOMA-IR, for which we were granted a national invention patent in China in 2016. Building on our research foundation in PCOS insulin resistance, we have developed a rapid detection kit for the ApoC3 protein, enabling early screening of insulin resistance in PCOS. Furthermore, point-of-care testing (POCT) products can achieve rapid quantitative detection of biomarkers. This project has recently been funded by the Guangdong Provincial Department of Science and Technology under the 2024 Guangdong-Hong Kong-Macao Greater Bay Area International Innovation Center Construction Initiative (Guangdong-Hong Kong-Macao Joint Innovation Field).

I. Diagnostic Criteria The 2003 Rotterdam diagnostic criteria for PCOS jointly established by the European Society of Human Reproduction and Embryology (ESHRE) and the American Society for Reproductive Medicine (ASRM): Clinical and/or biochemical signs of hyperandrogenism; Oligo-ovulation or anovulation; Ultrasound findings: ovarian volume ≥ 10 mL, and/or \> 12 follicles with a diameter of 2-9 mm in a single section. A diagnosis of PCOS can be established when at least two of the following three criteria are met: ovarian dysfunction, hyperandrogenism, and polycystic ovarian morphology on ultrasound. II. Inclusion and Exclusion Criteria 1. PCOS with Insulin Resistance (PCOS-IR) Inclusion Criteria: Meets the 2003 Rotterdam diagnostic criteria for PCOS (at least 2 of the following 3 items): ① Oligo-ovulation or anovulation; ② Clinical or biochemical signs of hyperandrogenism; ③ Polycystic ovaries on ultrasound (unilateral or ovarian volume ≥ 10 mL). Insulin resistance (IR), meeting at least 1 of the following 3 criteria: ① HOMA-IR ≥ 2.5; ② Fasting insulin ≥ 15 μIU/mL; ③ Diagnosed impaired glucose tolerance (IGT) or type 2 diabetes mellitus (T2DM). Exclusion Criteria: Other endocrine disorders; Medication effects; Severe systemic diseases; Special physiological conditions (e.g., pregnancy, lactation); Poor sample quality. 2. PCOS without Insulin Resistance (PCOS-non-IR) Inclusion Criteria: Meets the PCOS diagnostic criteria (as above), with HOMA-IR \< 2.5 and no glucose metabolism abnormalities. Exclusion Criteria: Same as above.