Inverse Association Between Serum Interleukin-40 and Glycemic Status in Postmenopausal Women: A Cross-Sectional Study

Background: The link between interleukin-40, a newly discovered cytokine, and the increased risk of type 2 diabetes after menopause has not been previously explored. Objectives: To assess the correlation between blood levels of IL-40 and glycemic status in post-menopausal women. Materials and Methods: In a cross-sectional study, HbA1c was employed to categorize 80 menopausal women into three groups: normoglycemic (n = 22), prediabetic (n = 22), and type 2 diabetes (n = 36). Serum IL-40 levels were measured by an enzyme-linked immunosorbent assay (ELISA) kit. Besides, hematologic tests, liver and kidney indicators, and the fundamental indices (glycemic, inflammatory, and atherogenic) were assessed. Statistical studies performed included receiver operating characteristic (ROC) analysis, group comparisons, correlation, and logistic regression. Results: IL-40 concentrations were significantly lower in prediabetic women (P-value = 0.031) than in normoglycemic individuals. Additionally, they demonstrated a negative connection with HbA1c (r = -0.264, P-value = 0.018) and hemoglobin (r = -0.227, P-value = 0.043). For every 1 ng/mL increase in IL-40, the risks of prediabetes reduce by 16% (OR = 0.84, 95% CI: 0.73–0.97, P-value = 0.015). Although C-reactive protein (CRP) had a higher overall (AUC) area under the curve (0.841), IL-40 demonstrated acceptable discrimination (AUC = 0.726) with higher specificity (86.4%) after recoding prediabetes as the positive state. When controls were classified as positive, ROC analysis showed an inverse effect (AUC = 0.274). Conclusion: IL-40 differentiates between normoglycemic and prediabetic women in postmenopausal women with higher specificity. It also has a negative correlation with glycemic status and hemoglobin levels. In this high-risk group, these results suggest that it may have clinical significance and diagnostic utility as a supplementary biomarker alongside CRP and fasting glucose, warranting confirmation in longer-term research.