This case-control study evaluated serum Isthmin-1 (ISM1) concentrations in pregnant women with gestational diabetes mellitus (GDM) compared with healthy pregnant controls, and assessed relationships with metabolic parameters and diagnostic performance. The investigation enrolled 60 participants (30 with GDM, 30 controls) at a tertiary-level hospital during a 6-month period from September 2023 through February 2024.
The study used a case-control design including women aged 20–40 years. Thirty women diagnosed with GDM were matched against 30 healthy pregnant controls. Clinical and laboratory data collected included fasting and postprandial glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), C-peptide, and serum ISM1.
Serum ISM1 and C-peptide concentrations were quantified by enzyme-linked immunosorbent assay (ELISA). The authors report that no multivariable adjustment was performed in analyses. Details such as diagnostic criteria for GDM, exact matching variables, or timing of sample collection within pregnancy were not reported in the abstract.
Median serum ISM1 was reported to be higher in the GDM group compared with controls. Specifically, median ISM1 in women with GDM was 7.67 ng/mL (interquartile range 6.7–10.8) versus 6.96 ng/mL (IQR 6.4–7.6) in healthy pregnant controls. This difference reached statistical significance (P = 0.020) according to the abstract.
The reported increase is modest in magnitude and presented as group medians and IQRs; no multivariable analysis was performed to account for potential confounders in the abstract information provided.
The authors examined correlations between serum ISM1 and markers of insulin resistance. ISM1 showed weak positive correlations with insulin (correlation coefficient r = 0.289; 95% CI 0.038–0.506; P = 0.025) and with HOMA-IR (r = 0.281; 95% CI 0.029–0.500; P = 0.029).
However, the abstract states these associations did not remain statistically significant after correction for multiple comparisons. No additional adjusted correlation or regression analyses were reported in the abstract, and the extent to which other metabolic variables (for example, glucose, HbA1c, or C-peptide) related to ISM1 was not detailed beyond the items cited.
Receiver operating characteristic (ROC) analysis of ISM1 for detecting GDM produced an area under the curve (AUC) of 0.674 (95% CI 0.54–0.79). At the reported operating point, ISM1 had high specificity (93.3%) but low sensitivity (40%).
By contrast, conventional metabolic markers such as insulin and HOMA-IR demonstrated superior predictive values for GDM, although specific comparative AUCs or thresholds for those markers are not provided in the abstract.
The combination of high specificity and low sensitivity indicates ISM1 would miss a substantial proportion of GDM cases if used alone, limiting its value as a standalone diagnostic test.
The authors conclude that serum ISM1 is modestly elevated in women with GDM and shows weak associations with insulin resistance measures. Given the AUC of 0.674 and low sensitivity (40%), ISM1 alone is not sufficient for clinical diagnosis of GDM.
They suggest that ISM1 could be considered as a component of a multi-marker panel but emphasize the need for confirmation in adequately powered, prospective studies before any clinical application. The abstract does not present recommendations for changes to current diagnostic pathways or immediate clinical use.
Key limitations reported or implied by the abstract include the small sample size (n=60), case-control design, the absence of multivariable adjustment, and lack of prospective validation. The correlations with insulin and HOMA-IR did not survive correction for multiple comparisons, reducing confidence in those associations.
The authors note that supportive evidence for ISM1 as part of a multi-marker approach will require larger, prospective studies with appropriate statistical adjustments and external validation. The abstract does not provide details on assay variability, inter-assay reproducibility, or predefined diagnostic cutoffs for ISM1, which would be important for translation into clinical practice.
Overall, the study provides preliminary evidence that serum Isthmin-1 is modestly higher in GDM and may relate to insulin resistance, but current data do not support its use as an independent diagnostic biomarker. Further research with larger cohorts and prospective designs is needed to clarify the role of ISM1 in GDM screening or risk stratification.