Serum Isthmin-1 in Gestational Diabetes Mellitus: A Case-Control Study Providing Preliminary Evidence of Elevated Levels and Association With Insulin Resistance.

BACKGROUND This study aimed to evaluate serum Isthmin-1 (ISM1) levels in pregnant women with and without gestational diabetes mellitus (GDM) and to assess its diagnostic value in comparison with established metabolic parameters. MATERIAL AND METHODS A case-control design was employed for this study, which enrolled 60 pregnant women between the ages of 20 and 40 years. Data collection took place over a 6-month period, from September 2023 through February 2024, at a tertiary-level hospital. Thirty women with GDM and 30 healthy pregnant controls were enrolled. Fasting and postprandial glucose, insulin, HOMA-IR, HbA1c, C-peptide, and ISM1 levels were measured. No multivariable adjustment was performed. ISM1 and C-peptide concentrations were analyzed using ELISA. RESULTS When compared to the control group, serum ISM1 concentrations were notably elevated in women with GDM, with median values of 7.67 (6.7-10.8) ng/mL versus 6.96 (6.4-7.6) ng/mL, respectively, a difference that reached statistical significance (P=0.020). ISM1 showed weak positive correlations with insulin (r=0.289, 95% CI: 0.038-0.506, P=0.025) and HOMA-IR (r=0.281, 95% CI: 0.029-0.500, P=0.029), although neither association survived correction for multiple comparisons. The diagnostic performance of ISM1 for GDM yielded an AUC of 0.674, with high specificity (93.3%) but low sensitivity (40%). Insulin and HOMA-IR demonstrated superior predictive values. CONCLUSIONS Serum ISM1 is modestly elevated in GDM and shows weak associations with insulin resistance parameters; its diagnostic performance is characterized by low sensitivity (40%) and an AUC of 0.674 (95% CI: 0.54-0.79) and is insufficient for independent clinical use. Any supportive role as part of a multi-marker panel requires confirmation in adequately powered, prospective studies.