Studying Phenotypes of Gestational Diabetes Mellitus in an Asian Pregnant Cohort

Gestational diabetes mellitus (GDM) is a transient hyperglycemic condition identified during pregnancy in women without a history of chronic diabetes. Evidence indicates that GDM can lead to various adverse health outcomes, including preterm birth, progression to pre-diabetes, and type 2 diabetes after delivery in mothers. Notably, GDM is becoming increasingly prevalent among Asian pregnant women due to rising rates of overweight and obesity, as well as genetic susceptibility. Despite growing recognition of GDM, its treatment efficiency and efficacy remain poor, primarily due to its heterogeneity, which is underpinned by various pathophysiological mechanisms.

Therefore, a better understanding of GDM heterogeneity can aid clinicians in providing more targeted treatment and follow-up strategies for GDM mothers. This study aims to define GDM phenotypes based on in vivo cardio-metabolic profiles and treatment response during pregnancy, utilizing advanced technologies such as continuous glucose profiling and untargeted metabolite profiling. In this proposed 3-year pregnancy cohort study, the investigators will recruit 800 overweight or obese Asian pregnant women in early pregnancy, without a history of diabetes, and follow them through to delivery. The goal of the study is to develop systematic antenatal and postnatal screening, treatment, and intervention guidelines for mothers with GDM.

The transient hyperglycemia first identified during pregnancy is known as gestational diabetes mellitus (GDM). GDM increases the risks of adverse pregnancy and neonatal outcomes, such as pre-eclampsia and macrosomia. Due to the widespread prevalence of overweight, obesity, and genetic susceptibility, GDM is more common among Asian pregnant women-occurring 2- to 3-fold more frequently compared to European pregnant women, with rates ranging from 15% to 30% in individuals of Chinese and Indian descent.

Emerging evidence suggests that variations in insulin sensitivity, fat deposition, and β-cell activity may contribute to the heterogeneous phenotypes of GDM, leading to different pregnancy outcomes and maternal diabetic progression. However, current clinical treatment and follow-up strategies for GDM typically adopt a "one-size-fits-all" approach, ignoring the underlying pathophysiological variations among patients. As a result, the efficiency and efficacy of the current clinical approach during pregnancy and postpartum are suboptimal.

In this study, the investigators aim to define the heterogeneity of GDM in terms of in vivo cardio-metabolic profiling and treatment response during pregnancy, using advanced technologies such as continuous glucose profiling and untargeted metabolite profiling. The investigators hypothesize that a better clinical and molecular understanding of GDM phenotypes will enable tailored, effective treatment strategies for individuals and aid in predicting and preventing postnatal abnormal glucose metabolism.

This proposed 3-year longitudinal study will involve a cohort of 800 overweight (23-24.9 kg/m²) or obese (≥25 kg/m²) singleton pregnant women, recruited no later than 12 weeks of gestation. These women, who are of Chinese, Malay, and Indian ethnicities, will be recruited from the National University Hospital (NUH) in Singapore and will not have a history of diabetes. All participants will be screened for GDM at 24-28 weeks of gestation and followed until delivery.

The primary outcome will be the identification of GDM phenotype-specific continuous glycemic profiles and alterations in cardio-metabolic biomarkers. The secondary outcome will focus on the treatment responses specific to different GDM phenotypes.

Eligibility Criteria:
Inclusion Criteria:

* Gestational age of ≤ 13 weeks 6 days
* Overweight and obese subjects with BMI of 23kg/m² - 24.9kg/m² and ≥ 25.0kg/m², respectively
* Aged 21-45 years with singleton pregnancy
* Plan to be followed up during the whole pregnancy and deliver at NUH
* Chinese, Malay or Indian ethnicity for pregnant subject
* Can complete questionnaires in English language
* Willing to wear continuous glucose monitoring device at least for 7 days at each required clinic visit

Exclusion Criteria:

* Participants who are not Singapore citizens or Singapore Permanent Residents, not intending to eventually deliver in Singapore National University Hospital and to reside in Singapore for the next 2 years
* Have serious skin conditions (eg. eczema) that precludes wearing the sensor for 14 days
* With history of Type 1 diabetes or Type 2 diabetes
* With chronic preexisting life-threatening conditions including pancreatic cancer, end-stage kidney dysfunction, and psychosis
* Unable to read or speak English