Metabolic heterogeneity of gestational diabetes mellitus: BMI-dependent divergence of insulin resistance and β-cell dysfunction in Bangladeshi women

Abstract

Background: Gestational diabetes mellitus (GDM) is metabolically heterogeneous, reflecting varying contributions of insulin resistance and β-cell dysfunction.

Objectives: To characterize the metabolic phenotypes of GDM based on insulin resistance and β-cell function and to examine their distribution according to body mass index (BMI) among Bangladeshi women.

Methods: This cross-sectional study included 262 women with GDM and 469 with normal glucose tolerance (NGT), classified using WHO 2013 criteria following a 75-g oral glucose tolerance test. Fasting insulin and C-peptide were measured by chemiluminescent immunoassay, and HOMA-derived indices were calculated. Exploratory metabolic phenotypes were defined using NGT-derived thresholds for HOMA-IR and HOMA-B.

Results: Compared with women with NGT, those with GDM had higher fasting insulin (11.5 ± 4.7 vs. 9.2 ± 3.9 µU/mL), HOMA-IR (2.7 ± 1.4 vs. 1.8 ± 0.8), and C-peptide (2.8 ± 0.9 vs. 2.2 ± 0.8 ng/mL), and lower HOMA-%S (40.5 [27.9–56.2] vs. 57.8 [43.5–78.9]; all p<0.001). Among women with GDM, 36.6% had an insulin resistance-dominant phenotype, 29% a secretion defect-dominant phenotype, 20.2% a mixed phenotype, and 14.1% no predominant HOMA abnormality. Phenotype distribution differed significantly by BMI (p<0.001). Among women with BMI <23 kg/m², 70.0% had a secretion defect-dominant phenotype, whereas among those with BMI ≥23 kg/m², insulin resistance was most frequent (39.7%).

Conclusion: GDM in Bangladeshi women demonstrated heterogeneous metabolic phenotypes that varied by BMI. Secretion defect-dominant GDM was more common among lean women, whereas insulin resistance-dominant phenotypes predominated at higher BMI. These findings warrant validation in larger, independent prospective cohorts.

[J Assoc Clin Endocrinol Diabetol Bangladesh, 2026;5(Suppl 1): S40]