European Journal of Cardiovascular Medicine

Gestational Diabetes Mellitus (GDM), defined as glucose intolerance first recognized during pregnancy, affects approximately 5–15% of pregnant women globally, with a rising trend in South Asian populations due to increasing rates of obesity, sedentary lifestyle, and genetic predisposition [1]. GDM is associated with a spectrum of adverse perinatal outcomes including macrosomia, neonatal hypoglycemia, birth trauma, and increased risk of cesarean delivery [2]. Furthermore, it predisposes both mother and child to long-term metabolic complications such as type 2 diabetes mellitus and cardiovascular disorders [3].

Early detection of GDM remains a clinical priority to mitigate these adverse outcomes. Traditional screening methods, typically performed in the late second trimester (24–28 weeks gestation), may delay diagnosis and limit the window for effective preventive interventions. Hence, there is growing interest in identifying reliable first-trimester biomarkers that could predict GDM before clinical onset, facilitating early lifestyle and therapeutic modifications [4].

Adiponectin, an adipocyte-derived hormone, plays a central role in glucose regulation and lipid metabolism. Unlike other adipokines, adiponectin exhibits insulin-sensitizing, anti-inflammatory, and anti-atherogenic properties [5]. Low adiponectin levels have been strongly correlated with insulin resistance and metabolic syndrome, suggesting its potential utility in predicting disorders of glucose homeostasis including GDM [6].

Emerging evidence suggests that hypoadiponectinemia may precede hyperglycemia and insulin resistance observed in GDM. Longitudinal studies have demonstrated that women who subsequently develop GDM tend to have significantly lower levels of adiponectin as early as the first trimester, well before overt glycemic abnormalities become apparent [7]. This finding has prompted the exploration of adiponectin as a non-invasive, cost-effective screening tool that may complement existing GDM diagnostic protocols.

Despite increasing recognition of adiponectin’s relevance in pregnancy-related metabolic changes, there remains a paucity of data specific to the Indian population, particularly from resource-limited and rural healthcare settings. Given the unique genetic and environmental factors influencing metabolic disease in Indian women, region-specific studies are essential to validate the clinical applicability of adiponectin as a predictive biomarker [8].

The present study was undertaken to evaluate the association between first-trimester serum adiponectin levels and the subsequent development of GDM in a cohort of pregnant women attending antenatal clinics at a tertiary care hospital in Eastern India

Study Design and Setting

This retrospective observational study was conducted in the Department of General Medicine, Sardar Rajas Medical College Hospital and Research Centre, Bhawanipatna, Odisha. The study period extended from January 2010 to December 2010. Ethical clearance was obtained from the Institutional Ethics Committee prior to the initiation of the study.

Study Population

A total of 120 pregnant women attending the antenatal clinic during their first trimester (11–13 weeks of gestation) were recruited consecutively based on predefined inclusion and exclusion criteria. Inclusion criteria were: age between 18 and 35 years, singleton pregnancy, and no prior history of diabetes mellitus or major systemic illness. Exclusion criteria included women with pre-existing diabetes, hypertension, thyroid disorders, polycystic ovary syndrome, chronic kidney or liver disease, or those on medications affecting glucose metabolism.

Data Collection

After obtaining informed consent, baseline demographic and clinical data including age, body mass index (BMI), parity, family history of diabetes, and blood pressure were recorded. A fasting venous blood sample was collected between 8:00 and 10:00 AM for measurement of serum adiponectin. Samples were centrifuged and stored at –20°C until analysis. Serum adiponectin levels were estimated using a validated enzyme-linked immunosorbent assay (ELISA) kit following standard protocols.

At 24–28 weeks of gestation, all participants underwent a 75g oral glucose tolerance test (OGTT) as per the World Health Organization (WHO) 1999 criteria. GDM was diagnosed if the 2-hour plasma glucose was ≥140 mg/dL.

Statistical Analysis

Data were analyzed using SPSS version 16.0. Continuous variables were expressed as mean ± standard deviation (SD) and categorical variables as percentages. Independent t-tests were employed to compare continuous variables between GDM and non-GDM groups. Chi-square test was used for categorical comparisons. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cut-off level of adiponectin for predicting GDM. Multivariate logistic regression was used to assess the association between adiponectin levels and GDM risk, adjusting for potential confounders such as age, BMI, and family history of diabetes. A p-value <0.05 was considered statistically significant.

Study Design and Setting

This retrospective observational study was conducted in the Department of General Medicine, Sardar Rajas Medical College Hospital and Research Centre, Bhawanipatna, Odisha. The study period extended from January 2010 to December 2010. Ethical clearance was obtained from the Institutional Ethics Committee prior to the initiation of the study.

Study Population

A total of 120 pregnant women attending the antenatal clinic during their first trimester (11–13 weeks of gestation) were recruited consecutively based on predefined inclusion and exclusion criteria. Inclusion criteria were: age between 18 and 35 years, singleton pregnancy, and no prior history of diabetes mellitus or major systemic illness. Exclusion criteria included women with pre-existing diabetes, hypertension, thyroid disorders, polycystic ovary syndrome, chronic kidney or liver disease, or those on medications affecting glucose metabolism.

Data Collection

After obtaining informed consent, baseline demographic and clinical data including age, body mass index (BMI), parity, family history of diabetes, and blood pressure were recorded. A fasting venous blood sample was collected between 8:00 and 10:00 AM for measurement of serum adiponectin. Samples were centrifuged and stored at –20°C until analysis. Serum adiponectin levels were estimated using a validated enzyme-linked immunosorbent assay (ELISA) kit following standard protocols.

At 24–28 weeks of gestation, all participants underwent a 75g oral glucose tolerance test (OGTT) as per the World Health Organization (WHO) 1999 criteria. GDM was diagnosed if the 2-hour plasma glucose was ≥140 mg/dL.

Statistical Analysis

Data were analyzed using SPSS version 16.0. Continuous variables were expressed as mean ± standard deviation (SD) and categorical variables as percentages. Independent t-tests were employed to compare continuous variables between GDM and non-GDM groups. Chi-square test was used for categorical comparisons. Receiver operating characteristic (ROC) analysis was performed to determine the optimal cut-off level of adiponectin for predicting GDM. Multivariate logistic regression was used to assess the association between adiponectin levels and GDM risk, adjusting for potential confounders such as age, BMI, and family history of diabetes. A p-value <0.05 was considered statistically significant.

In this study of 120 pregnant women, 28 (23.3%) were diagnosed with Gestational Diabetes Mellitus (GDM) between 24 and 28 weeks of gestation. The baseline demographic and clinical characteristics (Table 1) revealed that while the mean age was slightly higher in the GDM group (27.8 ± 3.4 years) than in the non-GDM group (26.4 ± 3.6 years), the difference was not statistically significant (p = 0.08). However, BMI was significantly greater in the GDM group (26.7 ± 2.9 kg/m² vs 24.9 ± 2.5 kg/m², p = 0.002), and a positive family history of diabetes was more prevalent among women who developed GDM (35.7% vs 21.7%, p = 0.04), indicating that higher BMI and familial predisposition are important risk factors.

Table 2 demonstrates that first-trimester serum adiponectin levels were markedly lower in the GDM group (5.8 ± 1.4 µg/mL) compared to the non-GDM group (9.3 ± 2.1 µg/mL), with high statistical significance (p < 0.001). Receiver operating characteristic (ROC) analysis identified a serum adiponectin cut-off value of <7.0 µg/mL as optimal for predicting GDM. This threshold yielded a sensitivity of 85.7% and specificity of 78.3%, with an area under the curve (AUC) of 0.87 (95% CI: 0.80–0.94), indicating excellent diagnostic performance.

The accompanying bar graph visually reinforces the inverse association between adiponectin levels and GDM status, highlighting a substantial mean difference of 3.5 µg/mL between the two groups. These findings strongly suggest that low adiponectin levels measured during the first trimester are significantly associated with the subsequent development of GDM and may serve as a reliable early biomarker for risk stratification.

Gestational Diabetes Mellitus (GDM) is a significant metabolic complication of pregnancy, associated with short- and long-term risks for both mother and fetus. Identifying early, reliable biomarkers is essential to improving outcomes and minimizing complications through timely intervention.

The current study was undertaken to explore the predictive value of serum adiponectin levels measured in the first trimester as an early marker for GDM. While standard screening is typically performed in the second trimester, there is increasing evidence that metabolic dysfunction begins much earlier. Adiponectin, due to its insulin-sensitizing properties, has been hypothesized to play a role in the pathogenesis of GDM. Our goal was to determine whether reduced levels of adiponectin in early pregnancy could predict later development of GDM in an Indian population.

Our study demonstrated significantly lower adiponectin levels in women who developed GDM (5.8 ± 1.4 µg/mL) compared to those who did not (9.3 ± 2.1 µg/mL), with a strong level of statistical significance (p < 0.001). These findings are consistent with those reported by Retnakaran et al. [7], who observed that low first-trimester adiponectin levels were strongly predictive of GDM. Similarly, Lain and Catalano [8] highlighted adiponectin's role in early pregnancy metabolic adaptation, supporting its use as a screening biomarker. Bao et al. [9] further confirmed this association in a meta-analysis, demonstrating that hypoadiponectinemia was significantly associated with increased GDM risk across multiple populations. In our cohort, an adiponectin threshold of <7 µg/mL provided good diagnostic performance, with sensitivity of 85.7%, specificity of 78.3%, and an AUC of 0.87 (95% CI: 0.80–0.94), aligning well with published data.

Clinical Implications:

The implications of these findings are clinically significant. Incorporating adiponectin testing into first-trimester antenatal screening could identify high-risk women earlier than traditional glucose-based screening methods. This could allow for earlier lifestyle interventions, closer monitoring, and potential pharmacological strategies, ultimately reducing the incidence of GDM-related complications. As the assay is non-fasting and can be performed with routine antenatal blood work, its integration into clinical practice is feasible, especially in high-risk populations.

Study Limitations:

Despite promising results, the study had limitations. It was conducted at a single tertiary care center with a relatively small sample size, which may affect generalizability. The study design was observational, and potential confounders such as dietary intake and physical activity were not assessed. In addition, no post-partum follow-up was conducted to evaluate long-term maternal or neonatal outcomes.

This study highlights the clinical relevance of first-trimester serum adiponectin as a reliable early biomarker for predicting Gestational Diabetes Mellitus. Women who developed GDM exhibited significantly lower adiponectin levels early in pregnancy, and a cut-off value of <7 µg/mL demonstrated high sensitivity and specificity. These findings emphasize the importance of early metabolic screening in high-risk populations. Incorporating adiponectin testing into routine antenatal care could enhance early detection and guide timely preventive interventions, potentially reducing the burden of GDM-related complications. Further large-scale, multicenter studies are warranted to validate these findings and support its integration into standard prenatal screening protocols.

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