β-cell secretory defect and reduced hepatic insulin extraction in women with polyendocrine metabolic ovarian syndrome

Abstract

Background: Compensatory hyperinsulinemia promotes ovarian androgen production in women with polyendocrine metabolic ovarian syndrome (PMOS). The extent to which this hyperinsulinemia results from pancreatic oversecretion versus impaired hepatic insulin extraction remains unclear.

Aim: To assess the utility of the connecting peptide (C-peptide)/insulin ratio as an indicator of β-cell secretory defect and hepatic insulin extraction in women with PMOS

Methods: In this case-control study, 150 women with PMOS and 101 age-matched control women [23 (20, 26) vs. 24 (20, 29), median (Q1, Q3), P=0.118] were consecutively recruited from a university hospital over two years. PMOS diagnosis was based on the Rotterdam criteria, while controls exhibited none of the diagnostic features. Fasting and post-oral glucose tolerance test (OGTT) blood samples were collected to measure insulin and C-peptide concentrations. Molar ratios of C-peptide to insulin at fasting and 2 hours post-OGTT were calculated after conversion to pmol/L. Insulin and C-peptide levels were determined using a chemiluminescence microparticle immunoassay.

Results: Fasting insulin levels were higher, while C-peptide levels were lower in women with PMOS compared to controls. Both 2-hour OGTT insulin and C-peptide concentrations were elevated in the PMOS group. The PMOS group exhibited a 35.5% lower fasting (β=-0.44, P<0.001) and a 14.6% lower 2-hour OGTT (β=-0.16, P<0.001) C-peptide/insulin molar ratio relative to controls, after adjustment for age and BMI and logarithmic transformation in linear regression.

Conclusions: Women with PMOS demonstrated a β-cell secretory defect, particularly in the basal state. Reduced hepatic insulin extraction may contribute to compensatory hyperinsulinemia in this population compared with controls.

[J Assoc Clin Endocrinol Diabetol Bangladesh, 2026;5(Suppl 1): S46]