Exploring Insulin Resistance and Glucose Dysregulation in PCOS: Current Diagnostics and Emerging Therapies.

Abstract

The common endocrine disorder known as polycystic ovary syndrome (PCOS), which increases the risk of type 2 diabetes and cardiovascular disease, is characterized by insulin resistance and glucose intolerance. Accurate diagnosis is still challenging since gold standard procedures, such as the hyperinsulinemic-euglycemic clamp, are not practical for daily use. Surrogate markers such as HOMA-IR and oral glucose tolerance tests (OGTT) have limitations while being often used. The primary therapeutic options are lifestyle changes and insulin-sensitizing drugs, however treatment is hampered by patient variability and adherence issues. By describing current diagnostic techniques and underlining treatment challenges in managing metabolic dysfunction in PCOS, this review highlights the need for improved screening and tailored care.

Introduction

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age, affecting 6–18% globally depending on diagnostic criteria. It is characterized by reproductive abnormalities such as hyperandrogenism, menstrual irregularities, and polycystic ovarian morphology, alongside significant metabolic disturbances. Insulin resistance (IR) and glucose intolerance are central metabolic features, increasing the risk of type 2 diabetes, cardiovascular disease, and other long-term complications. IR occurs in most women with PCOS regardless of body weight, though it is worsened by abdominal obesity, and leads to compensatory hyperinsulinemia that aggravates hyperandrogenism by increasing ovarian androgen production and reducing sex hormone–binding globulin levels. Many glucose abnormalities remain undetected by fasting glucose alone, making the oral glucose tolerance test (OGTT) the preferred diagnostic tool, despite practical limitations.

The pathophysiology of PCOS involves a complex interaction between reproductive and metabolic dysfunctions. Up to 80% of affected women exhibit selective insulin resistance, where glucose metabolism is impaired while ovarian steroidogenic pathways remain insulin-sensitive. Genetic, epigenetic, inflammatory, and adipose tissue factors contribute to the heterogeneity of clinical presentation and metabolic risk. Although obesity exacerbates metabolic dysfunction, lean women with PCOS can also develop significant IR and glucose intolerance.

Diagnosing insulin resistance relies on several tools. The hyperinsulinemic–euglycemic clamp remains the gold standard but is impractical for routine use. Surrogate indices such as HOMA-IR and QUICKI, based on fasting glucose and insulin, are commonly used, while OGTT-derived measures like the Matsuda Index and Insulin Sensitivity Index provide dynamic assessment. Despite these tools, variability in diagnostic thresholds, limited practicality of gold-standard methods, and challenges in treatment—including inconsistent response to medications and lifestyle modification barriers—highlight ongoing difficulties in managing PCOS-related metabolic risk.

Conclusion

Polycystic ovary syndrome is a complex condition that affects many aspects of women’s health, form metabolism to reproduction. While we have made significant progress in understanding its causes and finding ways to diagnose it, treating PCOS remains a challenge. Insulin resistance and glucose intolerance are key problem that complicate the condition and increase the risk of diabetes and heart disease. Treatments like lifestyle changes and medications such as metformin help many women but don’t work equally well for everyone. Newer therapies show promise, but more research is needed to confirm their safety and effectiveness over time. Moving Forword, a personalized approach that considers each women’s unique symptoms and risks, along with continued scientific advancement, will be essential to improve care and quality of life for those living with PCOS.

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Copyright

Copyright © 2026 Satish Mendake, Mayur Kudale, Vaibhav Kudale, Shraddha Kulkarni, Snehal Kute, Snehal Lanjewar. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.