Heterogeneity of pregnancy outcomes and risk of LGA neonates in Caucasian females according to IADPSG criteria for gestational diabetes mellitus

doi:10.1016/j.diabet.2012.09.006

Diabetes & Metabolism

Volume 39, Issue 2, April 2013, Pages 132-138

https://doi.org/10.1016/j.diabet.2012.09.006 Get rights and content

Abstract

Objective

The International Association of Diabetes and Pregnancy Study Group (IADPSG) guidelines for gestational diabetes mellitus (GDM) diagnosis determines that fasting, 1-h and 2-h glucose values may contribute independently to adverse outcomes. However, given the different physiological bases of impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), differences in pregnancy outcomes are to be expected. This study aimed to determine whether classification of GDM women according to glucose homoeostasis results in heterogeneity in maternal and/or fetal outcomes.

Material and methods

Of the 75 pregnant women included after a 75-g 2-h OGTT performed between weeks 24–32 of gestation as per WHO criteria, 55 were classified as GDM (16 with IFG and 39 with IGT) according to IADSPG criteria. Their anthropometric and metabolic characteristics were compared with those of non-GDM women with IFG or IGT. Maternal and neonatal outcomes were prospectively recorded for each group.

Results

GDM women with IFG, including isolated IFG and combined IFG + IGT, were significantly heavier, had higher leptin values and were more frequently multiparous than GDM women with isolated IGT. HOMA-IR was significantly higher when fasting glucose was impaired. There were no significant differences in maternal outcomes according to metabolic status. In addition, large for gestational age (LGA) neonates were significantly seen more often in the IFG group. Fasting glucose was significantly associated with LGA independently of BMI and 2-h OGTT glucose. The > 5.1 mmol/L cut-off value for fasting glucose was highly predictive of delivery of LGA infants.

Conclusion

IFG in GDM women was associated with increases in BMI, fat mass and hepatic insulin resistance. Delivery of LGA neonates was more frequent when fasting glycaemia was increased during the third trimester of pregnancy, and was independent of BMI and 2-h OGTT glucose values.

Résumé

Objectif

Les recommandations du Groupe international d’étude diabète et grossesse (IADPSG) indiquent que le diabète gestationnel peut se définir par une seule anomalie de la glycémie soit à jeun soit à une ou deux heures après une charge orale de 75 g de glucose. Nous avons cherché à déterminer dans quelle mesure cette classification induisait une hétérogénéité du pronostic maternel et/ou fœtal en fonction du type d’anomalie métabolique sous-jacente.

Patientes et méthodes

Soixante-quinze femmes enceintes ont été incluses après une HGPO de 75 de glucose entre 24 et 32 semaines d’aménorrhée. Parmi elles, 55 avaient les critères du diabète gestationnel (DG) en fonction des critères du IADPSG dont 16 avec une anomalie de la glycémie à jeun (IFG) et 39 avec une intolérance au glucose (IGT) soit isolée soit combinée avec une hyperglycémie à jeun. Les données anthropométriques et métaboliques ont été comparées entre les groupes et les données maternelles et fœtales analysées.

Résultats

Les femmes du groupe IFG avaient un poids, des concentrations plasmatiques de leptine plus élevés et étaient plus fréquemment multipares que les femmes du groupe IGT. Les indices HOMA-IR étaient plus importants dans le groupe IFG. Nous n’avons pas observé de différences dans le pronostic maternel entre les groupes. En revanche, la proportion d’enfants nés avec un poids au-delà des normes pour l’âge gestationnel était plus élevée dans le groupe IFG. La glycémie à jeun était significativement associée à l’augmentation du poids fœtal de façon indépendante de l’IMC et de la glycémie deux heures après l’HGPO. Une valeur de glycémie à jeun supérieure à 5,1 mmol/L était fortement prédictive d’une anomalie pondérale fœtale.

Conclusions

Une augmentation de la glycémie à jeun au cours de la grossesse est associée avec un IMC plus élevé, une masse grasse plus importante et une insulinorésistance hépatique. Le risque d’augmentation du poids de l’enfant à la naissance est plus fréquent lors d’une élévation de la glycémie au-delà de 5,1 mmol/L au troisième trimestre de grossesse, et cela de façon indépendante de l’IMC et des valeurs de glycémie à deux heures lors de l’HGPO.

Introduction

Gestational diabetes mellitus (GDM) represents a healthcare burden that is expected to rise as the frequency of obesity increases worldwide [1], [2]. This means that GDM is the subject of considerable clinical interest. The International Association of Diabetes and Pregnancy Study Group (IADPSG) has recently revisited the criteria for diagnosis [3] established more than 40 years ago [4]. Beyond the utility for detecting women at high risk of developing diabetes in later life, current strategies of GDM screening [5] were defined to improve pregnancy outcomes and reduce fetal complications. GDM and maternal obesity are independently associated with adverse effects [1]. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study demonstrated a positive linear relationship between glucose values and adverse perinatal outcomes, and argued for new screening values that would better identify pregnancies at risk of perinatal complications [6], [7]. One characteristic of the new IADPSG criteria is that only one single value above defined fasting or post-load glucose thresholds is now sufficient for a diagnosis of GDM.

However, the metabolic roots underlying impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) with elevated 1- or 2-h oral glucose tolerance test (OGTT) plasma glucose levels are different. Isolated IFG is a common feature of insulin resistance [8], while subjects with isolated IGT exhibit more severe deficits in beta-cell function with defects in early- and late-phases of insulin secretion [9]. Given the different physiological bases of IFG and IGT, differences in pregnancy outcomes and fetal complications are to be expected. Delivery of infants large for gestational age (LGA) in terms of body weight is the most common complication of GDM, and is linearly related to maternal plasma glucose levels [6]. Birth weight above the 90th percentile for gestational age is associated with serious birth complications, including neonatal hyperinsulinaemia and adiposity resulting from insulin resistance during fetal life [10], and later health risks with a greater prevalence of the metabolic syndrome in childhood [11]. In a recent meta-analysis of several interventional trials [12], it was reported that the detection and treatment of mild GDM was associated with reductions in birth weight. Thus, an important rationale for GDM screening is to identify women at higher risk of LGA neonates to allow intensive targeted interventions. It was also hypothesized that women screened according to the IADPSG criteria for GDM were heterogeneous from a metabolic point of view, thereby resulting in different possible outcomes. The present study was performed to determine whether the type of glucose abnormalities in GDM presages maternal and fetal outcomes.

Section snippets

Participants

All pregnant women at a single institution were eligible to participate unless they had one or more of the following exclusion criteria: age < 18 years; type 1 or type 2 diabetes mellitus before pregnancy; gestational age > 32 weeks; and multiple pregnancies. The study cohort was initially selected to determine the predictive value of proinflammatory cytokines during GDM, as diagnosed by World Health Organization (WHO) criteria, for maternal and fetal outcomes. The local Institutional Review Board

Demographic and anthropometric characteristics

The demographics of the study population are shown in Table 1. Women in the GDM group (n = 55) had comparable age, personal history of GDM, history of type 2 diabetes in first-degree relatives and smoking status to those of the control group (n = 20). Women in the IFG group (isolated IFG or combined with IGT) had a higher prevalence of multiparity compared with the IGT group (P < 0.05). In addition, women in the IFG group had significantly higher antepartum weights than either the IGT group (BMI 30.1 ±

Discussion

Pregnant women with IADPSG criteria for GDM are heterogeneous in their underlying metabolic alterations and thus have potentially different fetal outcomes. Indeed, it was observed that our GDM women with IFG were heavier and fatter, and had greater fasting insulin levels and hepatic insulin resistance compared with GDM women with normal fasting glucose. Our study also demonstrated that GDM women with IFG were at higher risk of delivering LGA neonates than were GDM women with normal fasting

Disclosure of interest

The authors declare that they have no conflicts of interest concerning this article.

Acknowledgements

We thank Dr D. Maucort-Boulch from the biostatistics department of Hospices Civils de Lyon for statistical advice.

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Prognosis of treated hyperglycemia in pregnancy (HIP) may differ according to whether diagnosis following an oral glucose tolerance test (OGTT) is based on high fasting and/or high post-load glucose values.
From a multiethnic prospective study, we included 8,339 women screened for HIP after 22 weeks of gestation. We evaluated the risk of large-for-gestational-age (LGA) infant (primary endpoint) and other adverse pregnancy outcomes according to HIP status in four groups defined as follows: no HIP (n = 6,832, reference); isolated fasting HIP (n = 465), isolated post-load HIP (n = 646), and fasting and post-load HIP (n = 396).
After adjusting for age, body mass index, ethnicity, smoking during pregnancy and parity, compared with no HIP, the adjusted odds ratios [95% confidence interval] for LGA infant were higher in the isolated fasting HIP (1.47 [1.11–1.96]) and fasting and post-load HIP (1.65 [1.23–2.21]) groups, but not in the isolated post-load HIP (1.13 [0.86–1.48]) group. The adjusted odds ratios for preterm delivery and neonatal intensive care unit were higher in the post-load HIP group (1.44 [1.03–2.03] and 1.28 [1.04–1.57], respectively), the fasting and post-load HIP group (1.81 [1.23–2.68] and 1.42 [1.10–1.81], respectively) but not in the isolated fasting HIP group (1.34 [0.90–2.00] and 1.20 [0.94–1.52], respectively).
Despite glucose-lowering care and adjustment for confounders, compared with no HIP, fasting HIP was associated with a higher rate of LGA infant, whereas post-load HIP was associated with higher preterm delivery and neonatal intensive care unit admission rates.
Gestational diabetes mellitus screening according to Carpenter–Coustan and IADPSG criteria: A 7-year follow-up of prevalence, treatment and neonatal complications at a Belgian general hospital
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In the initial period of type 2 diabetes mellitus (T2DM) known as prediabetes, blood glucose levels are above normal but below diabetes thresholds. Impaired glucose tolerance (IGT) and impaired fasting glycaemia (IFG) are two forms of prediabetes (Disse et al., 2013). Over 80% of prediabetic patients have IGT.
Oroxylum indicum (L.) Kurz (Bignoniaceae) has been widely used for the treatment of respiratory infections and gastrointestinal disorders. Our previous study showed that an ethanol–water O. indicum seed extract (OISE), when combined with acarbose, reduced the risk of diabetes by 75% and effectively prevented the associated complications. Oroxin A, a major component of OISE, can activate PPARγ and inhibit α-glucosidase and it represents a promising candidate for diabetes intervention.
The aim of this study is to investigate the effect of oroxin A from O. indicum on the progression of prediabetes to diabetes and the underlying mechanisms in streptozotocin and high-fat-diet induced prediabetic mice.
Oroxin A was purified from OISE and its PPARγ transcriptional activation was determined in vitro and in vivo. The prediabetic mice were established by high-fat diet and streptozotocin, which was followed by treatment with oroxin A. The effect of oroxin A was determined by analysis of the lipid profiles, oxidative stress, hepatic function and histology. The mechanism of oroxin A was also investigated.
Oroxin A is a compound with low toxicity that has reduced the relative risk of progression from prediabetes to diabetes by 66.7% without inducing weight gain or hepatotoxicity. Oroxin A also improved the complications of prediabetes, such as lipid metabolism dysfunction and liver injury. Results of mechanism studies suggested that oroxin A is a partial PPARγ agonist that can activate PPARγ transcriptional activation in vitro and in vivo. Oroxin A also exhibited an inhibitory activity against α-glucosidase and an antioxidant capacity.
Oroxin A prevents the progression from prediabetes to diabetes through a multi-pathway intervention mechanism.
Single Fasting Plasma Glucose Versus 75-g Oral Glucose-Tolerance Test in Prediction of Adverse Perinatal Outcomes: A Cohort Study
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Fasting plasma glucose (FPG) provides a cheap, acceptable reliable, reproducible alternative GDM screening method to the OGTT for the last three decades (Mortensen et al., 1985; Zhu et al., 2013), with renewed attention following introduction of the IADPSG criteria. Early studies suggested that FPG had significantly higher predictive value for LGA in comparison to post-load glucose, independent of maternal BMI and 2 h glucose value (Disse et al., 2013; Legardeur et al., 2014). A recent systematic review also found that fasting glucose concentration has stronger associations with LGA than post-load glucose concentration (Farrar et al., 2016).
There remains uncertainty regarding whether a single fasting glucose measurement is sufficient to predict risk of adverse perinatal outcomes.
We included 12,594 pregnant women who underwent a 75-g oral glucose-tolerance test (OGTT) at 22–28 weeks' gestation in the Born in Guangzhou Cohort Study, China. Outcomes were large for gestational age (LGA) baby, cesarean section, and spontaneous preterm birth. We calculated the area under the receiver operator characteristic curves (AUCs) to assess the capacity of OGTT glucose values to predict adverse outcomes, and compared the AUCs of different components of OGTT.
1325 women had a LGA baby (10.5%). Glucose measurements were linearly associated with LGA, with strongest associations for fasting glucose (odds ratio 1.37, 95% confidence interval 1.30–1.45). Weaker associations were observed for cesarean section and spontaneous preterm birth. Fasting glucose have a comparable discriminative power for prediction of LGA to the combination of fasting, 1 h, and 2 h glucose values during OGTT (AUCs, 0.611 vs. 0.614, P = 0.166). The LGA risk was consistently increased in women with abnormal fasting glucose (≥ 5.1 mmol/l), irrespective of 1 h or 2 h glucose levels.
A single fasting glucose measurement performs comparably to 75-g OGTT in predicting risk of having a LGA baby.
Are third-trimester adipokines associated with higher metabolic risk among women with gestational diabetes?
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The disease involves several aspects of the metabolic syndrome, including obesity, insulin resistance and dyslipidaemia. Considerable metabolic heterogeneity has previously also been demonstrated in women with GDM according to IADPSG criteria, depending on either impaired fasting or post-OGTT glucose values [10]. Post-delivery counselling and behavioural modification are key features for reducing the future risk of diabetes, but they may be difficult to organize in light of the increase in newly diagnosed women with GDM according to the new screening strategy.
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Abstract

Objective

Material and methods

Results

Conclusion

Résumé

Objectif

Patientes et méthodes

Résultats

Conclusions

Introduction

Section snippets

Participants

Demographic and anthropometric characteristics

Discussion

Disclosure of interest

Acknowledgements

Obstet Gynecol

ATLANTIC DIP: the impact of obesity on pregnancy outcome in glucose-tolerant women

Diabetes Care

The short and long-term implications of maternal obesity on the mother and her offspring

BJOG

International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy

Diabetes Care

Criteria for the oral glucose tolerance test in pregnancy

Diabetes

Atlantic Diabetes in Pregnancy (DIP). The prevalence and outcomes of gestational diabetes mellitus using new diagnostic criteria

Diabetologia

Hyperglycemia and adverse pregnancy outcomes

N Engl J Med

Insulin secretion and insulin sensitivity in relation to glucose tolerance: lessons from the Botnia Study

Diabetes

Insulin secretion and insulin sensitivity pattern is different in isolated impaired glucose tolerance and impaired fasting glucose: the risk factor in impaired glucose tolerance for atherosclerosis and diabetes study

Diabetes Care

Fetuses of obese mothers develop insulin resistance in utero

Diabetes Care