Different gestational diabetes phenotypes: which relationship with maternal hemodynamics?

GDM is one of the most common complications of pregnancy affecting around 14% of pregnancies worldwide. GDM is increasingly recognized as a heterogeneous metabolic disorder rather than a uniform clinical entity. We hypothesize that different phenotypes of GDM can exhibit different clinical features and longitudinal maternal hemodynamic adaptation profiles. Thus, the aim of our study was to investigate the relationship between maternal hemodynamic pathways and GDM phenotype.

A prospective, observational cohort study was conducted on GDM singleton pregnancies referred to the our Maternal-Fetal Medicine Unit between December 2022 and August 2023. GDM phenotypes were categorized based on the timing of clinical diagnosis: "early-onset GDM" (eGDM; diagnosed at 16-18 weeks of gestation) or "standard GDM" (sGDM; diagnosed at 24-28 weeks of gestation). eGDM cases were further stratified according to the presence/absence of insulin resistance (IR). IR was identified in presence of: BMI > 30 kg/m2 and/or HOMA-IR (Homeostatic Model Assessment of Insulin Resistance) > 2.5 and/or fasting glucose at OGTT > 100 mg/dl. Maternal hemodynamic assessment was performed using an UltraSonic Cardiac Output Monitor (USCOM Ltd. Coffs Harbour, Australia); we evaluated cardiac output (CO), total vascular resistance (TVR) and inotropy index (INO) at 24-28 and 36-39 weeks. We defined as delta (△) the difference in the value of the considered hemodynamic parameter between 24 and 28 weeks and 36-39 weeks. eGDM group also received an early hemodynamic assessment at 18-20 weeks.

During the study period 180 women affected by GDM with singleton pregnancy participated. The diagnosis of GDM was performed early in 44 cases and at the standard time in 136 cases. 23 women were affected by early GDM with IR (eGDM-IR), 21 women were affected by early GDM without IR (eGDM-noIR) and 136 women were affected by "standard" GDM (sGDM). No significant differences in CO, TVR, or INO were seen among the three GDM phenotypes at 24-28 and 36-39 weeks. The early assessment of maternal hemodynamic parameters showed significantly higher cardiac output in eGDM-IR group than in eGDM-noIR group (p < 0.05) at 18-20 weeks of gestation. Comparing longitudinal adaptation from mid-to-late gestation, the eGDM-IR cohort exhibited significantly blunted changes in CO and INO accompanied by a significantly restricted trajectory of TVR reduction compared to both the eGDM-noIR and sGDM groups. This pattern is highly suggestive of a more restricted, less compliant cardiovascular adaptive trajectory in this metabolically compromised phenotype.

Our findings suggest that an insulin-resistant state combined with early-onset GDM may affect maternal hemodynamic adaptation during pregnancy. Identifying these distinct phenotypic trajectories could help clinicians develop targeted cardiovascular surveillance strategies and personalized postpartum follow-up protocols to optimize long-term maternal cardiovascular health.