Clinical heterogeneity of gestational diabetes defined by insulin physiology; a systematic review and meta-analysis — ASN Events
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Clinical heterogeneity of gestational diabetes defined by insulin physiology; a systematic review and meta-analysis (#363)

Tait Mason 1 , Daniella Audish 1 , Xinyi Ji 1 , Devni Nagodavithana 1 , Yitayeh Mengistu 1 , Mahnaz Bahri Khomami 1 , Helena Teede 1 , Aya Mousa 1
  1. Monash Centre for Health Research & Implementation, Monash University, Melbourne, VIC, AU

Gestational diabetes mellitus (GDM) is a heterogeneous disorder underpinned by diverse insulin actions, yet underlying insulin physiology is not routinely considered when assessing pregnancy risk. We conducted a systematic review and meta-analysis to determine whether subtyping by insulin resistance (GDM-IR), insulin secretory defect (GDM-ISD), or mixed pathophysiology (GDM-Mixed) identifies distinct maternal or neonatal risk profiles.

We searched Ovid MEDLINE, EMBASE, EBM-Reviews and grey literature from 2005 to April 2026, for studies classifying GDM (by any diagnostic criteria) by insulin resistance/ secretion indices. Two independent reviewers conducted screening, extraction and appraisal (Newcastle-Ottawa Scale). Random-effects meta-analyses were conducted for maternal and neonatal outcomes.

Forty-nine studies comprising 622670 pregnancies were included, of which 11 studies (n=22676) contributed to the insulin physiology meta-analysis. Compared with normoglycaemic pregnancies (NGT), GDM-IR was associated with higher odds of caesarean section (OR 1.71; 95%CI 1.50, 1.94), preterm birth (OR 1.68; 95%CI 1.32, 2.13), large-for-gestational-age (LGA) infants (OR 2.12; 95%CI 1.30, 3.45), small-for-gestational-age (SGA) infants (OR 1.10; 95%CI 1.01, 1.20) and earlier gestational age at delivery (MD -0.64 weeks; 95%CI -0.82, -0.11). Compared with GDM-ISD, GDM-IR had higher odds of gestational hypertension (OR 4.03; 95%CI 1.32, 12.28) and macrosomia (OR 2.39; 95%CI .04, 2.79). GDM-Mixed showed a similar risk profile, including higher odds of caesarean section (OR 1.50; 95%CI 1.04, 2.16) and LGA (OR 2.23; 95%CI 1.56, 3.17) compared with NGT and higher LGA compared with GDM-ISD. GDM-ISD was associated with higher LGA (OR 1.51; 95%CI 1.19, 1.91) and preterm birth (OR 1.56; 95%CI 1.13, 2.17), but lower gestational hypertension (OR 0.65; 95%CI 0.57, 0.74) compared with NGT.

Insulin physiology identifies clinically distinct GDM phenotypes with differing maternal and neonatal outcome patterns. GDM-IR and -mixed phenotypes were associated with a more adverse risk profile than -ISD, supporting further evaluation of insulin physiology in delineating GDM heterogeneity and risk stratification.