Letter to the Editor: Enhancing the predictive value of body composition and adipokine assessment for gestational diabetes mellitus risk

Abstract

In the recent issue of World Journal of Diabetes, Li et al report that elevated fat mass percentage and dysregulated adipokines (leptin and adiponectin) in early-to-mid-pregnancy are the key predictors for gestational diabetes mellitus (GDM). Beyond leptin and adiponectin, integrating a broader panel of adipokines like chemerin and resistin can capture the inflammatory signature of GDM. Precision can be further increased by measuring visceral fat area using nonionizing methods such as magnetic resonance imaging or validated ultrasonography to ensure maternal-fetal safety. This addresses the portal vein hypothesis, where visceral fat directly impairs hepatic insulin sensitivity via free fatty acid release. Tracking dynamic weight gain trajectories at 4-week intervals using latent class growth analysis and utilizing the Alternative Healthy Eating Index-Pregnancy, and Pregnancy Physical Activity Questionnaire would provide a more robust and complete model, substantially increasing the scientific impact of the study and guiding more precise early intervention strategies.

Key Words: Gestational diabetes mellitus; Body composition; Adipokines; Fat mass percentage; Visceral fat area; Dynamic gestational weight gain; Lifestyle factors; Risk prediction

Core Tip: Current risk assessment for gestational diabetes mellitus frequently overlooks the distinction between different fat compartments. While fat mass percentage is a vital marker, its predictive power is maximized when combined with visceral fat area and dynamic metabolic indicators. Establishing a comprehensive evaluation framework that includes lifestyle factors and longitudinal weight tracking will bridge existing gaps in prenatal care, allowing for more accurate identification of high-risk individuals and earlier clinical intervention.

TO THE EDITOR

We have carefully reviewed the insightful retrospective study by Li et al[1] published in the recent issue of World Journal of Diabetes, which investigated the complex relationship between maternal body composition, adipokine levels, and the risk of developing gestational diabetes mellitus (GDM). The authors provide robust evidence that early-pregnancy fat mass percentage (FMP) acts as a significant independent predictor of GDM, offering a more precise alternative to the traditional body mass index (BMI). This research is a vital contribution to prenatal metabolic screening, particularly in populations where adiposity-related risks are high, despite a normal BMI range. However, while the study establishes a strong foundation, we believe the predictive framework could be significantly optimized by addressing several physiological and behavioral dimensions not fully explored in the original analysis. We believe incorporating specific additional factors would significantly increase its clinical weightage and scientific impact.

Expanding the adipokine panel and molecular mechanisms: The study focuses on leptin and adiponectin; however, including a broader panel of proinflammatory adipokines such as chemerin and resistin would offer a more complete view of GDM pathogenesis[2,3]. High chemerin levels activate the nuclear factor-κB pathway, leading to serine phosphorylation of insulin receptor substrate-1, which blocks insulin signaling[2]. Additionally, resistin contributes to insulin resistance by suppressing AMP-activated protein kinase, a master regulator that typically promotes glucose uptake through GLUT4 translocation[4,5].

Precision measurement of visceral fat area

A primary consideration in metabolic research is the anatomical distribution of adipose tissue. While FMP provides a general view of total body fat, it does not distinguish between subcutaneous and visceral depots. Although total fat (FMP) is important, visceral fat is the primary driver of metabolic dysfunction. To ensure clinical safety during pregnancy, the gold standard for visceral fat area assessment should be magnetic resonance imaging at the L4-L5 level to avoid ionizing radiation[6]. For routine clinical screening, validated ultrasonography, measuring the distance between the internal abdominal muscle surface and the anterior wall of the aorta is a feasible, safe, and cost-effective alternative[7]. This is critical because, under the portal vein hypothesis, visceral fat releases free fatty acids directly into the liver, causing hepatic insulin resistance[5,7].

Dynamic weight monitoring and trajectory analysis

Rather than static weight checks, dynamic monitoring at every prenatal visit (typically 4-weeks intervals) is essential. Clinicians should use statistical methods like Latent Class Growth Analysis or Piecewise Growth Models[8]. These methods identify high-risk spikes in weight gain early in the second trimester, which have shown higher predictive value for GDM than total weight gain alone.

Validated lifestyle indices

To account for lifestyle confounders, we recommend using specific pregnancy-validated tools: The alternative healthy eating index-pregnancy, which focuses on pregnancy-specific nutrient weighting[9]; and the Pregnancy Physical Activity Questionnaire, which uniquely captures household and caregiving activities often missed by general scales[10].

We suggest that study of the parameters proposed in Table 1 could have achieved more valuable conclusions.

Table 1 Proposed enhancements for gestational diabetes mellitus risk stratification.

Dimension	Current metric[1]	Proposed enhancement	Clinical rationale	Refs
Adiposity	FMP	VFA	Stronger correlation with insulin resistance and cytokine release	Purnell[11], 2000
Kinetics	Pre-pregnancy BMI	Dynamic GWG trajectory	Reflects the body’s adaptive response to pregnancy demands	Hedderson et al[12], 2010
Behavioral	N/A	Validated lifestyle indices	Distinguishes between genetic predisposition and modifiable risk	Mijatovic-Vukas et al[13], 2018
Endocrine	Adiponectin/Leptin	Adiponectin-to-leptin ratio	Provides a more stable index of adipose health than individual markers	Davenport et al[14], 2018

FMP: Fat mass percentage; VFA: Visceral fat area; GWG: Gestational weight gain; BMI: Body mass index; N/A: Not available.

Conclusion

In summary, Li et al[1] have successfully identified FMP and specific adipokines as critical markers for GDM. We advocate for an expanded evaluation framework that moves beyond total fat mass to include visceral adiposity and dynamic weight tracking. Such a comprehensive approach will transition GDM screening from a generalized risk assessment to a targeted, precision-medicine strategy, ultimately improving clinical outcomes for both mother and child.

ACKNOWLEDGEMENTS

We wish to thank Dr. Arunkumar Rao and Dr. Basawaraj Warad for proofreading and English language, grammar, punctuation, spelling and overall style of the manuscript. We are also grateful to Mr. Vinod Jogdand and Mr. Dipak Badne for technical support.