Pregnancy and diabetes: Emerging insights from contemporary diabetes research

Abstract

This review summarizes the breakthrough studies on diabetes management in pregnancy presented at the 84^th American Diabetes Association Scientific Sessions, encompassing 31 presentations, categorized into basic science, clinical studies, therapeutic interventions, and maternal/neonatal outcomes. Basic science investigations reported the enduring impact of gestational diabetes mellitus on offspring adiposity, neurodevelopment, transgenerational metabolic risk, and key insights on β-cell functioning and islet dysfunctioning. Clinical studies explored novel diagnostic and monitoring approaches, highlighting the potential of continuous glucose monitoring for early detection, risk prediction, and personalized management. Therapeutic interventions demonstrated the efficacy of glucagon-like peptide 1 agonists in preventing cognitive deficits in offspring. Maternal and neonatal health studies emphasized the critical role of optimal glycemic control, early gestational diabetes mellitus intervention, and risk stratification utilizing HbA1c and electronic heart records.

Key Words: Gestational diabetes mellitus; Continuous glucose monitoring; Pregnancy outcomes; Insulin resistance; Maternal-fetal health

Core Tip: Emerging research from the 84^th American Diabetes Association Scientific Sessions emphasizes the importance of early detection, continuous glucose monitoring, and targeted interventions in managing gestational diabetes. Findings highlight improved maternal and neonatal outcomes through personalized care, with continuous glucose monitoring metrics and metabolic profiling offering promising tools for risk prediction and therapeutic optimization.

INTRODUCTION

The American Diabetes Association (ADA) Scientific Sessions have historically served as a central platform for presenting groundbreaking research in diabetes, including maternal and fetal outcomes in pregnancy-related diabetes. This review focuses on highlights from the 2024 meeting, which featured a breadth of translational and clinical findings. Managing diabetes in pregnancy presents unique challenges, necessitating tailored therapeutic approaches to ensure maternal and fetal health. Despite advancements, significant gaps remain in optimizing treatment strategies. Late-breaking research usually bridges this gap by providing crucial insights that can refine clinical guidelines and improve patient outcomes. The ADA Scientific Sessions serves as a crucial annual event, presenting the most recent advancements in diabetes research. Consequently, several late-breaking trials and clinical studies on diabetes during pregnancy management were presented at the 2024 edition of the ADA Scientific Sessions.

Multiple studies provided proof of an association between gestational diabetes mellitus (GDM) and developmental deficits in the child[1]. At the same time, a study demonstrated that prenatal use of glucagon-like peptide 1 (GLP-1) analog diminishes cognitive deficits[2]. In a 2024 ADA study, Thaker et al[3] reported metabolomic and transcriptomic profiles suggesting increased adiposity and inflammatory pathway activation among women with GDM. It was also proposed that the pathophysiology of diabetes in South Asian women following GDM was more likely due to insulin deficiency than insulin resistance[4]. Some therapeutic studies suggested continuous glucose monitoring (CGM) as a superior and more acceptable glucose monitoring method than the oral glucose tolerance test (OGTT)[5]. CGM at 13-14 weeks could be an alternative to OGTT at 24-28 weeks. A sleep study suggested that among women with a history of GDM, those with frequent snoring are at a significantly increased risk of developing overt diabetes[6]. This narrative review aims to identify emerging threads and discuss the implications of the latest groundbreaking studies for clinical practice.

BASIC SCIENCE/TRANSLATIONAL STUDIES

Neurodevelopmental effects of intrauterine exposure to gestational diabetes

Chakravartti et al[1] examined the impact of GDM exposure on children’s adiposity and brain development from childhood to adolescence. The study showed that GDM-exposed children had higher body mass index (BMI) (P = 0.058), body fat percentage (P < 0.049), waist circumference (P < 0.015), and increased growth in total cortex and gray matter volume, significantly if exposed before 26 weeks of gestation[1].

Metabolomic and transcriptomic profiles in gestational diabetes reveal nutritional and inflammatory mechanisms underlying intergenerational risk

Thaker et al[3] assessed the impact of GDM on the intergenerational transfer of metabolic risk. Relative to controls, participants with obesity or GDM showed increased activity in pathways involving intracellular protein movement, steroid signaling, cell cycle regulation, histone and DNA modifications, insulin receptor expression, and other metabolic processes.

Altered adipocyte expandability and function in gestational diabetes and preeclampsia compared with healthy pregnancies

Lees et al[7] investigated the impact of GDM and pre-eclampsia (PE) on adipose tissue (AT) morphology and function in the third trimester. Subcutaneous AT (SAT) and visceral AT (VAT) biopsies were obtained during cesarean sections. While SAT adipocyte size remained consistent across groups, GDM was associated with VAT adipocyte hypertrophy, fibrosis, elevated pericellular fibrosis, and increased hypoxia-inducible factor-1α mRNA expression[7].

Comparative assessment of postpartum β-cell function following gestational diabetes and normoglycemic pregnancy

In this prospective cohort study, when examined for islet cell function postpartum, at 3 months, the GDM cohort had significantly higher fasting glucose (P = 0.04) and fasting glucagon (P = 0.03) compared to the normal cohort. Furthermore, the study reported that both α- and β-cell dysfunction could contribute to the GDM, with residual dysfunctioning present up to 3 months post-partum[8].

Loss of β-cell insulin receptor substrate 1 increases susceptibility to gestational diabetes in female mice

Wang et al[9] explored how gestational diabetes develops and examined the role of insulin receptor substrate 1 (IRS1) in supporting β-cell adaptation during pregnancy. In islets lacking IRS1, transcriptomic data indicated suppressed GATA4 signaling and downregulation of its downstream effectors Reg1 and Reg3a, both important for β-cell replication. Conversely, pregnancy in wild-type mice was associated with enhanced IRS1 expression together with increased GATA4, Reg1, and Reg3a, reflecting the normal gestational rise in β-cell mass[9].

CLINICAL/EPIDEMIOLOGICAL STUDIES

Insulin deficiency as a determinant of early postpartum glucose intolerance in women

Gitlin et al[4] studied the development of postpartum type 2 diabetes mellitus (T2DM) in South Asian women with GDM. The study reported that 45% of participants developed prediabetes or T2DM. Furthermore, these women exhibited significantly lower insulinogenic index and oral disposition index at 6 weeks postpartum, indicating insulin deficiency[4].

Clinical insights from CGM during type 1 diabetic pregnancy

This retrospective study Fisher et al[10] used a linear mixed-effects model to assess third-trimester CGM metrics (Dexcom G6 CGM) and adverse pregnancy outcomes in singleton pregnancies with T2DM. At 28 weeks, pregnancies with hypertensive disorders (HDP) had higher time above range (TAR) (P < 0.01) and lower time in range (TIR) (P < 0.05) than those without HDP. HDP also significantly influenced TIR trends throughout the third trimester, particularly between 28 weeks and 31 weeks[10].

Predictive value of CGM in identifying gestational diabetes and poor pregnancy outcomes

Li et al[11] collected CGM data from 760 pregnant women. Logistic and elastic net regression models were developed, and their performance was evaluated using the area under the receiver operating characteristic curve. Time above 140 mg/dL (TA140) in the 2^nd trimester and weeks 13-14 predicted GDM with area under the receiver operating characteristic curves of 0.81 and 0.74, respectively. Furthermore, TA140 at weeks 12-14 showed similar sensitivity to the OGTT at 24-28 weeks for predicting HDP and large gestational age births (LGA)[11].

CGM among pregnant individuals with glucose intolerance

This single-blinded, prospective observational study Gordon et al[12] divided pregnant women (24-32 weeks) with varying glucose tolerance into four groups. The mean TIR for the normal glucose challenge test (GCT) was 96.65%, while the abnormal GCT/OGTT groups ranged from 91.8% to 92.6%. The normal GCT group had significantly higher TIR than the abnormal GCT/1 abnormal OGTT and GDM groups (P = 0.04)[12].

Association between CGM metrics and adverse pregnancy outcomes in gestational diabetes

This interventional study Kusinski et al[13] assessed the association of CGM metrics at 29 weeks and 36 weeks with adverse pregnancy outcomes in 432 women with BMI > 25 kg/m². Mean glucose, TIR, and TAR at 29 weeks were significantly associated with adverse outcomes, and time below range at 36 weeks was associated with neonatal hypoglycemia[13].

CGM as a tool to identify neonatal hypoglycemia in infants born to mothers with gestational diabetes

Jones et al[14] examined the role of CGM in detecting neonatal hypoglycemia in 13 mother-neonate pairs with GDM. CGM revealed instances of suspected neonatal hypoglycemia that routine clinical practices overlooked[14].

Characterization of postprandial glycemic patterns across uncomplicated pregnancies

This prospective observational study Carlson et al[15] examined CGM data from 157 uncomplicated pregnancies. The mean fasting glucose was 88 mg/dL, and the mean postprandial peak was 126 mg/dL. Glycemic excursion was significantly higher in women who developed HDP of pregnancy[15].

The risk of progression from gestational diabetes to T2DM

This study Yin et al[6] investigated the associations between sleep, T2DM risk, and metabolic biomarkers in 2999 women with a history of GDM from the Nurses’ Health Study II. A shorter sleep duration (≤ 6 hours) was associated with increased T2DM risk. Snoring also increased T2DM risk[6].

Associations between sleep duration and cardiometabolic biomarkers during pregnancy

Chen et al[16] examined the associations between sleep duration and cardiometabolic biomarkers during pregnancy using data from a case-control study nested in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singleton Cohort. The proportion of participants with ≤ 6 hours of sleep increased from 15.1% at visit 0 to 39.6% at visit 4. Furthermore, sleep duration ≥ 9 hours at visit one was positively associated with insulin levels[16].

Predicting late-onset gestational diabetes in women without early pregnancy GDM

In this prospective cohort study, pregnant women without early GDM (EGDM) but with GDM risk factors underwent HbA1c on entry and a 2-hour 75 g OGTT at 24-28 weeks’ gestation. Women with late GDM (LGDM) vs no GDM were older, more likely to be overweight/obese, non-European, and to have a family history of diabetes. Pregnant women who were older, overweight/obese, non-European, and with a family history of diabetes were found to have LGDM even if they did not have EGDM[17].

Pregnancy outcomes in women with one abnormal value on the Carpenter-Coustan OGTT

Scifres et al[18] controlled trial that comprised 827 participants, and among them, those with one abnormal value on a 100 g OGTT (1ABNL) on Carpenter-Coustan GDM were not treated and compared to (non-GDM) NGDM and GDM. Relative to the NGDM group, participants with 1 ABNL demonstrated higher glucose and insulin concentrations but showed diminished insulin sensitivity and impaired β-cell function. Similarly, LGA and maternal composite were higher, while neonatal composite and small for gestational age were lower[18].

Efficacy of real-time CGM in gestational diabetes

Ehrhardt et al[19] conducted to assess outcomes of real-time CGM (RT-CGM) compared with self-blood glucose monitoring (SMBG) in gestational diabetes. By 32 weeks gestational age, CGM metrics were similar for both groups, except for mean glucose and time below the range (TBR54). At 36 weeks, mean glucose decreased for RT-CGM but increased for SMBG, with a significantly lower TBR54 for RT-CGM (P = 0.03). A1c levels were similar between groups, while diabetes medication use was higher in the RT-CGM group (69% vs 32% for SMBG)[19].

RT-CGM improves TIR in pregnant individuals with gestational diabetes

This randomized, open-label trial compares RT-CGM for longer than 7 days to 4-times-daily SMBG (with blinded CGM). Two-sample t-tests were used, and glucose TIR (60-140 mg/dL) was the primary outcome. The CGM arm had more glucose TIR than the SMBG arm, especially during the daytime[20].

Reevaluating the role of the antenatal OGTT in diagnosing gestational diabetes

In this prospective cohort, Kusinski et al[21] examined the extent to which suboptimal specimen processing led to missed diagnoses of gestational diabetes and investigated the potential of a 28-week HbA1c measurement as an alternative to the OGTT for identifying hyperglycemic pregnancies. Among 1308 pregnant participants from nine United Kingdom centers, enhanced glucose processing led to 0.6 mmol/L higher glucose levels, increasing the gestational diabetes diagnosis rate from 9% to 22%[21].

THERAPEUTIC INTERVENTIONS AND OUTCOMES

Postpartum screening for glucose abnormalities using CGM

This prospective cohort study investigates the feasibility of postpartum CGM in detecting dysglycemia by assessing sensor return rates and participant experience. On OGTT, dysglycemia (7 impaired glucose tolerance, 1 diabetes) was accurately predicted when > 4% of time was spent above 180 mg/dL, yielding 86% sensitivity, 85% specificity, a positive predictive value of 60%, and a negative predictive value of 96%[5].

Prenatal GLP-1 agonist therapy ameliorates offspring cognitive deficits in maternal diabetes via ADGRL3-mediated placental modulation

This study Ito et al[2] tested the hypothesis that administering a GLP-1 agonist to mothers with diabetes could alleviate cognitive defects in offspring when given prenatally. To generate a pregestational diabetes model, 8-week-old female C57BL/6J mice were treated with streptozotocin. Cell-based studies using human trophoblast (HTR8/SVneo) and human embryonic kidney (HEK293) cell lines demonstrated that ADGRL3 transmits GLP-1 signals through Gαs and Gαq pathways, providing a mechanistic basis for the beneficial effects[2].

Association of fasting lactate concentrations with preeclampsia development among women with gestational glucose intolerance

This prospective cohort examined whether patients with GGI-defined as an abnormal screening GTT at 24-28 weeks of gestation-who later developed preeclampsia had higher blood lactate levels. 13% of the included patients developed PE, and in these patients, the median fasting lactate level was higher. After controlling for pre-pregnancy BMI, it was a significant predictor of PE (P = 0.047)[22].

MATERNAL AND NEONATAL HEALTH

Association between late-pregnancy HbA1c levels and adverse obstetric and perinatal outcomes

Wu et al[23] investigated the association between third-trimester HbA1c levels and obstetric and perinatal adverse outcomes. The study’s primary endpoint was defined as combined obstetric and perinatal adverse outcomes. Elevated HbA1c (> 5.8%) predicted increased likelihood of cesarean section (both overall and primary), macrosomia, neonatal hypoglycemia, and composite perinatal complications, independent of confounding factors.

Fasting vs postprandial glucose increments and overall hyperglycemia in pregnant women with type 1 diabetes

Ling et al[24] investigated and compared the relative contribution of fasting hyperglycemia and postprandial hyperglycemia across TIR and HbA1c in pregnant women with T1DM. 295 CGM-HbA1c profiles were analyzed in this study. As diabetes worsened, the postprandial hyperglycemia contribution rate steadily reduced, while the fasting hyperglycemia contribution rates went up gradually with decreasing TIR (P < 0.001) or increasing HbA1c (P < 0.001).

Impact of diagnostic timing of overt diabetes on maternal and neonatal outcomes

Reichelt et al[25] investigated the pregnancy outcomes in women with overt diabetes at the time of diagnosis. 217 of the total women developed overt diabetes (33.6%, 95%CI: 30.0%-37.0%). Women diagnosed before 13 weeks had lesser weight gain, lower third-trimester HbA1c levels, and fewer maternal hospital admissions than those diagnosed later. However, the pregnancy outcomes were similar in the groups and were unaffected by the diagnosis time.

Machine learning-based early prediction of gestational diabetes from electronic health records

Germaine et al[26] aimed to investigate the efficacy of machine learning models from data collected in the first trimester (8-14 weeks) of GDM patients using electronic health records (EHR) spanning from 2018-2022, excluding 2020. Four machine learning models-Random Forest, eXtreme Gradient Boosting, Logistic Regression, and Explainable Boosting Machine were tested, with Logistic Regression demonstrating the best performance.

Impact of maternal hyperglycemia and HDP of pregnancy on adverse outcomes across the coronavirus disease 2019 pandemic

Zhang et al[27] evaluated how the coronavirus disease 2019 pandemic influenced the association between maternal hyperglycemia, HDP, and adverse pregnancy outcomes. Findings showed that births occurring during both the early and late phases of the pandemic carried higher risks of complications-excluding preterm birth-than those delivered before the pandemic. The risk of LGA and macrosomia was higher among women with normal blood pressure in the early phase and among those with preeclampsia or eclampsia in the later phase[27].

Maternal weight and pregnancy outcomes following a reduced-energy dietary intervention

This randomized, controlled, double-blind trial included 423 women with gestational diabetes and BMI > 25 kg/m². Participants were randomized at 29 weeks of gestation into two arms: The control arm with women who received a standard-energy diet and the intervention arm with women who received weekly diet boxes of reduced-energy diet until delivery. The results showed no significant differences in maternal weight change or offspring birth weight between the groups. However, the group on the reduced-energy diet required less insulin therapy[28].

Influence of early therapeutic intervention on glycemic control and maternal–fetal outcomes in early GDM

Immanuel et al[29] examined the impact of early GDM treatment on glycemic control and pregnancy outcomes. Results showed that women achieving optimal glycemia had significantly fewer pregnancy complications. Additionally, lower mean fasting glucose levels were associated with reduced complications. Women who initiated treatment for early GDM earlier in their pregnancy demonstrated better overall glycemic control, including lower mean glucose and mean fasting glucose levels, compared to those who started treatment later[29].

Pregnancy outcomes in congenital generalized lipodystrophy due to homozygous AGPAT2 mutations

Santomauro Junior et al[30] reported two successful pregnancies in a woman with congenital generalized lipodystrophy managed without recombinant leptin. In pregnancy, the patient presented with characteristic congenital generalized lipodystrophy manifestations, including muscular pseudohypertrophy, diabetes, hepatic steatosis, polycystic ovary syndrome, and hypertriglyceridemia complicated by pancreatitis. Her condition was managed through a low-carbohydrate diet and metformin at 1500 mg per day. However, in her second pregnancy, insulin therapy was used in the third trimester to maintain optimal glycemic and lipid profiles[30].

Associations between fasting and postprandial triglycerides, mean glucose, and TIR in early pregnancy

This observational study in early pregnancy of 31 overweight/obese women found: Median fasting triglycerides were 126 mg/dL; median postprandial triglycerides were 153 mg/dL; 28-week mean glucose was 100 ± 9 mg/dL; 28-week TIR was 94% ± 6%. Early fasting triglycerides correlated positively with 28-week glucose and negatively with 28-week TIR. Early postprandial triglycerides also correlated positively with 28-week glucose. Table 1 summarizes the key findings of all the late-breaking studies[31].

Table 1 Key findings of late-breaking studies on diabetes management in pregnancy of the 84^th American Diabetes Association Scientific Sessions.

Study category	Study number	Study design and population	Sample size (n)	Primary outcome (s)	Key methods	Key findings	Clinical and research implications
Basic science/translational studies	1962-LB	Prospective cohort; children (7-11 years) exposed to GDM vs unexposed	204 (110 GDM exposed, 94 unexposed)	Adiposity and brain volumes	Brain MRI, adiposity measurements over 6 years, mixed-effects models	In utero GDM exposure was associated with increased adiposity (BMI, body fat percentage, waist circumference) and increased growth of total cortex and gray matter in offspring	Provides a mechanistic link between GDM exposure and adverse metabolic and neural outcomes in children. Population/setting: United States multiethnic cohort; IADPSG criteria. Risk-of-Bias Score: NOS = 7/9 (moderate)
	1965-LB	Prospective; mother-baby dyads (BMI < 25, obese, GDM)	39 dyads (13 control, 14 obese, 12 GDM)	Placental transcriptomic changes, cord blood metabolic profiles	RNA sequencing (placenta), metabolic profiling (cord blood)	GDM and obesity were associated with upregulation of genes involved in nutrient transport, inflammation, and methylation, as well as increased INSR expression	Suggests methylation and epigenetic changes may contribute to intergenerational transmission of metabolic risks. Population/setting: Japan (animal model); GLP-1 treatment. Risk-of-Bias Score: ARRIVE 2.0 = moderate
	260-OR	Observational; 3rd trimester biopsies (NT, GDM, PE)	30 (GDM), 7 (PE), 30 (NT)	Adipocyte size, AT fibrosis, mRNA expression, insulin signaling	Adipocyte size measurement, AT fibrosis assessment, mRNA expression analysis, insulin signaling (immunoblotting)	GDM was associated with increased visceral adipose tissue diameter, hypertrophy, and HIF1A mRNA expression. Both GDM and preeclampsia showed decreased insulin-stimulated Akt phosphorylation in subcutaneous adipose tissue. Preeclampsia did not affect visceral adipose tissue	Indicates that GDM and preeclampsia have distinct effects on adipose tissue signaling and function. Population/setting: Obese United States cohort; WHO 2013 GDM criteria. Risk-of-Bias Score: NOS = 6/9 (moderate)
	200-OR	Prospective cohort; women with/without GDM postpartum	20 (10 GDM, 10 control)	Islet-cell function (glucose, insulin, C-peptide, glucagon)	75 g OGTT at 3, 6, 12 months postpartum	Women with prior GDM showed increased fasting glucose, insulin, C-peptide, and glucagon at 3 months postpartum, but no differences were observed by 6 months	Early postpartum islet-cell dysfunction may increase long-term metabolic risk in women with a history of GDM. Population/setting: United Kingdom cohort; postpartum GDM analysis. Risk-of-Bias Score: NOS = 7/9 (moderate)
	199-OR	Interventional (mice); β-cell IRS1-knockout mice	Animal model	β-cell compensation, glucose levels	Islet RNA transcriptome analysis	IRS1 deficiency disrupted the IRS1-GATA4-Reg1/Reg3a pathway, impaired β-cell compensation, and led to GDM	Understanding this pathway may lead to new prevention and treatment strategies for GDM. Population/setting: Mouse model; IRS1 KO strain. Risk-of-Bias Score: ARRIVE 2.0 = low
Clinical/epidemiological studies	1969-LB	Prospective cohort; South Asian women postpartum	49	Insulin resistance and deficiency	75 g OGTT, insulin levels at 6 weeks and 6 months postpartum, HOMA-IR, IGI, oDI	Postpartum glucose intolerance was associated with insulin deficiency (decreased IGI, oDI) but not with changes in insulin resistance (HOMA-IR)	Postpartum insulin deficiency may be a better predictor of type 2 diabetes risk in South Asian women than insulin resistance. Population/setting: South Asian cohort; Chennai; postpartum glucose. Risk-of-Bias Score: NOS = 8/9 (low)
	62-OR	Retrospective cohort; T1DM pregnancies	86	Adverse pregnancy outcomes	CGM metrics (TIR, TAR, TBR, CV) from 28-39 weeks, linear mixed-effects model	HDP were associated with increased TAR and decreased TIR at 28 weeks	Early 3rd trimester CGM metrics are critical for preventing adverse pregnancy outcomes in T1DM pregnancies. Population/setting: United States T1DM pregnancies; Dexcom CGM. Risk-of-Bias Score: NOS = 7/9 (moderate)
	63-OR	Prospective observational; pregnant women	760	GDM, LGA, HDP	CGM data, logistic and elastic net regression	CGM-based models (TA140) predicted GDM, LGA, and HDP	CGM at 13-14 weeks could potentially serve as an alternative to the OGTT at 24-28 weeks for risk prediction. Population/setting: Multisite CGM trial; 760 pregnant women. Risk-of-Bias Score: NOS = 8/9 (low)
	64-OR	Prospective observational; pregnant women with glucose intolerance	Varies by group	TIR	Single-blinded CGM, GCT, OGTT	Abnormal GCT or OGTT results were associated with decreased TIR on CGM	Abnormal GCT/OGTT values should not be discounted, even if isolated findings. Population/setting: CGM data; abnormal GCT/OGTT cases. Risk-of-Bias Score: NOS = 7/9 (moderate)
	65-OR	Interventional; women with GDM (BMI > 25)	432	Adverse pregnancy outcomes	CGM, logistic regression	CGM metrics (mean glucose, TIR, TAR) at 29 weeks predicted adverse pregnancy outcomes	CGM metrics can predict adverse pregnancy outcomes in women with GDM. Population/setting: CGM metrics in overweight women with GDM. Risk-of-Bias Score: NOS = 7/9 (moderate)
	66-OR	Prospective observational; GDM mothers and neonates	13 mother-neonate dyads	Neonatal hypoglycemia	Masked CGM during labor and delivery, neonatal thigh CGM	CGM identified neonatal hypoglycemia that was missed by routine practices	CGM is potentially useful for identifying neonatal hypoglycemia. Population/setting: Neonatal CGM; 13 mother-infant dyads. Risk-of-Bias Score: NOS = 6/9 (moderate)
	67-OR	Prospective observational; uncomplicated pregnancies	157	Postprandial glucose patterns	Blinded CGM, smartphone app	HDP were associated with increased postprandial glucose excursions	Suggests an association between HDP and elevated postprandial glucose excursions. Population/setting: Uncomplicated pregnancies; CGM data. Risk-of-Bias Score: NOS = 8/9 (low)
	1976-LB	Prospective cohort; women with GDM history	2999	T2D risk	Cox regression, metabolic biomarkers	Shorter sleep duration (≤ 6 hours) and frequent snoring were associated with increased T2D risk	Sleep characteristics are important predictors of T2D risk in women with a history of GDM. Population/setting: NHS II cohort; sleep and T2D risk. Risk-of-Bias Score: NOS = 8/9 (low)
	1978-LB	Multiracial cohort; pregnant women	321	Cardiometabolic biomarkers	Sleep duration assessment, cardiometabolic biomarker measurements, linear mixed models	Shorter sleep duration was associated with increased glucose and HbA1c. Longer sleep duration was associated with increased insulin at the first visit. Shorter sleep duration at the second visit was associated with increased glucose, and longer sleep duration at the second visit was associated with decreased HbA1c	Adequate sleep is crucial for maintaining cardiometabolic health during pregnancy. Population/setting: United States NICHD cohort; sleep/cardiometabolic markers. Risk-of-Bias Score: NOS = 7/9 (moderate)
	202-OR	Prospective cohort; pregnant women without early GDM	2685	LGDM	HbA1c, OGTT, ROC assessment	1HBG level best predicted LGDM, but OGTT was still needed.	1HBG is a good predictor of LGDM, but OGTT remains essential for diagnosis. Population/setting: Prospective OGTT cohort; risk factors for LGDM. Risk-of-Bias Score: NOS = 8/9 (low)
	203-OR	Randomized controlled trial; pregnant women with 1 abnormal OGTT value	827	Metabolic and clinical outcomes	Propensity score models with IPTW	Women with 1 abnormal OGTT value had an increased risk of LGA compared to women with normal glucose tolerance and those with GDM	Women with 1 abnormal OGTT value have a metabolic profile closer to GDM and a higher risk of LGA. Population/setting: RCT; Carpenter-Coustan 1 abnormal OGTT. Risk-of-Bias Score: RoB-2 = moderate
	1975-LB	Randomized trial; GDM patients	107	Glycemic control	RT-CGM vs SMBG	RT-CGM was associated with decreased mean glucose and TBR54 at 36 weeks, but increased medication use	RT-CGM may offer benefits in lowering mean glucose and TBR54 in GDM, although it may be associated with increased medication use. Population/setting: RCT; CGM vs SMBG in GDM patients. Risk-of-Bias Score: RoB-2 = low
	259-OR	Randomized trial; pregnant women with GDM	111	TIR	Real-time CGM vs SMBG, two-sample t-tests	Real-time CGM was associated with higher TIR than SMBG, particularly during daytime	CGM is superior to SMBG in maintaining glucose range in women with GDM. Population/setting: RCT; CGM vs SMBG; TIR analysis. Risk-of-Bias Score: RoB-2 = low
	198-OR	Prospective cohort; pregnant women undergoing OGTT	1308	GDM diagnosis	Enhanced vs standard glucose processing	Enhanced glucose processing was associated with increased GDM diagnosis rates	Accurate glucose processing is crucial for the appropriate diagnosis of GDM. Population/setting: United Kingdom cohort; HbA1c vs OGTT. Risk-of-Bias Score: NOS = 7/9 (moderate)
Therapeutic interventions and outcomes	1973-LB	Prospective cohort; postpartum women with GDM	50	Postpartum dysglycemia	Postpartum CGM vs OGTT	Postpartum CGM was feasible and acceptable, and the percentage of time > 180 mg/dL predicted OGTT dysglycemia	CGM is a useful postpartum screening tool for dysglycemia. Population/setting: Prospective cohort; GGI and preeclampsia. Risk-of-Bias Score: NOS = 7/9 (moderate)
	1963-LB	Interventional (mice); diabetic mothers	Animal model	Cognitive deficits in offspring	GLP-1 agonist treatment, placental development assessment, behavioral testing of offspring, immunohistochemistry, single-cell RNA sequencing, qRT-PCR, in vitro studies	Prenatal GLP-1 agonist treatment mitigated cognitive deficits in offspring of diabetic mothers	GLP-1 agonists may have a role in preventing cognitive deficits in offspring of mothers with diabetes. Population/setting: HbA1c analysis in United States cohort. Risk-of-Bias Score: NOS = 8/9 (low)
	1964-LB	Prospective cohort; women with glucose intolerance	106	Preeclampsia development	Fasting lactate, insulin, glucose, HOMA-IR measurements	Increased fasting venous lactate was predictive of preeclampsia development in women with glucose intolerance	Fasting lactate may be a useful predictor of preeclampsia risk in women with glucose intolerance. Population/setting: T1DM women; CGM-HbA1c profiles. Risk-of-Bias Score: NOS = 8/9 (low)
Maternal and neonatal health	1970-LB	Prospective cohort; pregnant women at delivery	609	Adverse obstetric and perinatal outcomes	Third-trimester HbA1c measurement	HbA1c > 5.8% was associated with increased adverse obstetric and perinatal outcomes (C-section, hemorrhage, macrosomia, NICU admission, etc.)	HbA1c > 5.8% in the third trimester is a risk factor for pregnancy complications. Population/setting: Retrospective United States cohort; overt DM timing. Risk-of-Bias Score: NOS = 7/9 (moderate)
	1971-LB	Observational; T1DM pregnancies	112	Fasting and postprandial glucose contributions to hyperglycemia	CGM data analysis	Fasting hyperglycemia is a major contributor to overall hyperglycemia in T1DM pregnancies	Optimizing insulin regimens to reduce fasting hyperglycemia may improve outcomes in T1DM pregnancies. Population/setting: EHR + ML models for GDM; United States data. Risk-of-Bias Score: NOS = 8/9 (low)
	1972-LB	Retrospective cohort; women with overt diabetes	646	Pregnancy outcomes	Comparison of outcomes based on timing of diagnosis	Early diagnosis of overt diabetes was associated with better metabolic control (decreased weight gain, decreased 3rd-trimester HbA1c) but similar overall pregnancy outcomes compared to later diagnosis	Early screening for hyperglycemia in pregnancy is important for achieving better metabolic control. Population/setting: Louisiana cohort; Medicaid + COVID impact. Risk-of-Bias Score: NOS = 7/9 (moderate)
	1968-LB	Retrospective; pregnant women with GDM	About 27500	GDM prediction	EHR data, machine learning models (logistic regression, etc.)	Logistic regression models using EHR data can predict GDM in the first trimester	EHRs and machine learning can aid in early GDM prediction. Population/setting: RCT; energy diet in GDM (United Kingdom DiGest). Risk-of-Bias Score: RoB-2 = low
	1974-LB	Retrospective cohort; pregnant women in Louisiana	110447	Adverse pregnancy outcomes	Medicaid claims data, logistic regression	Maternal hyperglycemia and hypertensive disorders during the COVID-19 pandemic were associated with increased adverse pregnancy outcomes (LGA, macrosomia)	Tailored strategies are needed for managing high-risk pregnancies during crises such as the COVID-19 pandemic. Population/setting: Early GDM management; capillary glucose data. Risk-of-Bias Score: NOS = 8/9 (low)
	257-OR	Randomized controlled trial; women with GDM (BMI ≥ 25)	423	Maternal weight change, offspring birth weight	Dietary intervention (standard vs reduced-energy diet)	A reduced-energy diet was associated with decreased insulin needs, but had no significant effect on maternal weight change or offspring birth weight compared to a standard diet	Standard and reduced-energy diets have similar effects on maternal weight and offspring birth weight in women with GDM. Population/setting: Case study; congenital lipodystrophy, AGPAT2. Risk-of-Bias Score: ARRIVE 2.0 = moderate
	258-OR	Prospective cohort; women with early GDM	399	Glycemic control, pregnancy complications	Capillary blood glucose monitoring, comparison of early vs late treatment	Early treatment of early GDM was associated with better glycemic control (decreased mean glucose, increased optimal glycemia) and fewer pregnancy complications compared to late treatment	Early diagnosis and treatment of GDM are crucial for optimizing glycemic control and reducing complications. Population/setting: Obese pregnancy cohort; triglycerides, CGM. Risk-of-Bias Score: NOS = 7/9 (moderate)
	1977-LB	Case study; woman with CGL	1	Pregnancy outcomes	Clinical observation of two pregnancies	Successful pregnancies are possible in women with CGL without leptin therapy	CGL can present with varying degrees of metabolic severity, and successful pregnancy outcomes are possible. Population/setting: MRI + adiposity; LA-based United States cohort. Risk-of-Bias Score: NOS = 7/9 (moderate)
	201-OR	Observational cohort; overweight/obese pregnant women	31	Correlation between early pregnancy triglycerides and glucose metrics at 28 weeks	FTG and PPTG measurement, CGM at 28 weeks	Fasting and postprandial triglycerides in early pregnancy correlated with mean glucose and TIR at 28 weeks	Triglyceride levels in early pregnancy may help identify women at risk for later hyperglycemia. Population/setting: Placenta transcriptomics; obesity/GDM cohort. Risk-of-Bias Score: NOS = 7/9 (moderate)

GDM: Gestational diabetes mellitus; BMI: Body mass index; MRI: Magnetic resonance imaging; AT: Adipose tissue; SAT: Subcutaneous adipose tissue; VAT: Visceral adipose tissue; HIF1A: Hypoxia-inducible factor 1-alpha; OGTT: Oral glucose tolerance test; IGI: Insulinogenic index; oDI: Oral disposition index; HOMA-IR: Homeostatic model assessment of insulin resistance; T1DM: Type 1 diabetes mellitus; CGM: Continuous glucose monitoring; TIR: Time in range; TAR: Time above range; TBR/TBR54: Time below range (< 54 mg/dL); CV: Coefficient of variation; TA140: Time above 140 mg/dL; GCT: Glucose challenge test; LGA: Large for gestational age; HDP: Hypertensive disorders of pregnancy; PE: Preeclampsia; LGDM: Late gestational diabetes mellitus; 1HBG: One-hour blood glucose; SMBG: Self-monitored blood glucose; RT-CGM: Real-time continuous glucose monitoring; NICU: Neonatal intensive care unit; EHR: Electronic health records; FTG: Fasting triglycerides; PPTG: Postprandial triglycerides; GLP-1: Glucagon-like peptide 1; COVID-19: Coronavirus disease 2019.

Discussion and future directions

Recent findings at the ADA Scientific Sessions complement and, in some cases, expand upon prior research in gestational diabetes. Research on GDM’s impact should focus on uncovering the pathways linking maternal diabetes to brain development and cognitive outcomes in the children, particularly the role of MBH gliosis[32] and immune changes in obesity. Furthermore, investigations on how epigenetic modifications due to GDM contribute to intergenerational metabolic risk and understandings of the changes in VAT[33] and their distinct mechanisms in GDM vs PE are needed. Regarding early GDM screening, postprandial glucose patterns via CGM need to be studied to predict adverse pregnancy outcomes and optimize CGM protocols. Additionally, for GDM prevention/treatment, the IRS-1-GATA4-Reg1/Reg3a pathway in β-cells should be explored as a potential target.

Research on postpartum dysglycemia suggests that CGM may outperform OGTT, specifically in women with limited healthcare access, warranting further exploration. Compared to previous literature, which primarily emphasized OGTT for GDM screening, these CGM-based predictive models show improved early detection and patient acceptability, supporting a potential shift in clinical protocols.

Studies should also explore GLP-1 agonists as an alternative to insulin for diabetic mothers and investigate elevated fasting venous lactate levels in patients who develop PE. While prior trials have emphasized pharmacologic interventions in GDM, these ADA 2024 studies extend the evidence base by evaluating dietary modification and GLP-1 receptor agonists, suggesting a broader therapeutic landscape that includes both nutritional and neurodevelopmental endpoints.

Furthermore, optimizing early HbA1c screening and leveraging EHRs for GDM prediction could enhance early diagnosis and interventions. Additionally, the long-term benefits of early initiation of GDM management need to be further assessed. Together, these findings underscore the evolving landscape of GDM research, where integration of early screening, mechanistic insights, and population-specific data is critical to refine guidelines and improve maternal-fetal outcomes.

Limitations

This review summarizes studies presented at the June 2024 ADA Scientific Sessions and does not represent all current research on gestational diabetes. The heterogeneity in study populations, diagnostic criteria, and research designs may limit generalizability. Included studies drew from varied cohorts-such as South Asian, Japanese, and United States populations-with differing BMI classifications, screening protocols, and outcome measures. While structured bias assessments (NOS, RoB-2, ARRIVE 2.0) were performed, some assessments were limited by the level of detail available in abstracts rather than full-text articles. Additionally, abstract-based data often lacked information on treatment duration, comparator arms, and definitions of clinical endpoints, which constrained our ability to evaluate study rigor uniformly. As this review is based on scientific meeting abstracts, full peer-reviewed data and detailed methods were often unavailable, which limited the depth of reference formatting and methodological detail.

CONCLUSION

The 84^th ADA Scientific Sessions revealed key findings for future research and clinical guidelines in managing overweight or obese pregnant women with or without GDM. CGM can serve as a screening tool for hyperglycemia and predict adverse pregnancy outcomes. Earlier diagnosis and treatment of hyperglycemia, linked to poorer pregnancy and fetal outcomes, can help reduce complications for both mothers and babies.