The metabolic syndrome in early pregnancy and risk of gestational diabetes mellitus

doi:10.1016/j.diabet.2009.07.003

Diabetes & Metabolism

Volume 35, Issue 6, December 2009, Pages 490-494

https://doi.org/10.1016/j.diabet.2009.07.003 Get rights and content

Abstract

Aim

The objective of the present study was to determine whether or not maternal metabolic syndrome in early pregnancy in women without previous diabetes is associated with the development of gestational diabetes mellitus (GDM).

Methods

A total of 508 women from the Rhea study—involving a pregnant cohort in Crete, Greece (2007–2009)—with singleton pregnancies were included in the present analysis. Maternal fasting serum samples were collected and blood pressure measured before gestational week 15. The metabolic syndrome in early pregnancy was defined according to NHLBI/AHA criteria. Pregnant women were screened for GDM between weeks 24 and 28 of gestation, as defined by Carpenter and Coustan criteria. Multivariable log-binomial regression models were used to estimate the effect of the metabolic syndrome in early pregnancy on the risk of GDM, after adjusting for confounding factors.

Results

Women with the metabolic syndrome were at high risk of GDM (RR = 3.17; 95% CI: 1.06–9.50). Among the components of the metabolic syndrome, the most significant risk factors were impaired fasting glucose (RR = 4.92; 95% CI: 1.41–17.23) and pre-pregnancy obesity (RR = 2.65; 95% CI: 1.23–5.70). A 10-mmHg rise in systolic and diastolic blood pressure increased the relative risk of GDM by 49% (RR = 1.49; 95% CI: 1.10–2.02) and 34% (RR = 1.34; 95% CI: 1.04–1.73), respectively, whereas a 1-unit increase in pre-pregnancy BMI increased the relative risk of GDM by 6% (RR = 1.06; 95% CI: 1.01–1.12).

Conclusion

These findings suggest that women with the metabolic syndrome in early pregnancy have a greater risk of developing GDM.

Résumé

Objectif

Déterminer si la présence d’un syndrome métabolique en début de grossesse, chez des femmes sans antécédent de diabète, est associée à l’apparition d’un diabète gestationnel (DG).

Méthodes

Cinq cent huit femmes participant à l’étude Rhea, étude de cohorte menée chez des femmes enceintes en Crète, Grèce (2007–2009) ayant une grossesse non gemellaire, ont été incluses dans l’analyse. Avant la 15^e semaine de gestation, des prélèvements de sang ont été réalisés à jeun et la pression artérielle a été mesurée. Le syndrome métabolique en début de grossesse a été défini selon les critères de l’AHA/NHLBI. Le dépistage du DG a été effectué entre la 24^e et la 28^e semaine de gestation et le DG a été défini selon les critères de Carpenter et Coustan. Des modèles de régression log-binomiale multivariés ont été utilisés pour estimer l’effet du syndrome métabolique en début de grossesse sur le risque de DG après ajustement sur les facteurs de confusion.

Résultats

Les femmes qui présentaient un syndrome métabolique avaient un risque élevé de DG (risque relatif [RR] = 3,17 ; IC à 95 % 1,06–9,50). Parmi les composants du syndrome métabolique, les facteurs de risque les plus importants étaient l’hyperglycémie modérée à jeun (RR = 4,92 ; IC à 95 % 1,41–17,23) et l’obésité avant la grossesse (RR = 2,65 ; IC à 95 % 1,23–5,70). Une augmentation de 10 mmHg de la pression artérielle systolique ou diastolique augmentait le RR de DG de 49 % (RR = 1,49, IC à 95 % 1,10–2,02) et de 34 % (RR = 1,34, IC à 95 % 1,04–1,73), respectivement, alors que l’augmentation par unité de l’IMC avant la grossesse augmentait le RR de DG de 6 % (RR = 1,06 ; IC à 95 1,01–1,12).

Conclusion

Ces résultats suggèrent que les femmes qui présentent un syndrome métabolique en début de grossesse ont un risque plus élevé de développer un DG.

Introduction

The metabolic syndrome (MetS) refers to a cluster of metabolic abnormalities that appear to promote the development of atherosclerotic cardiovascular disease and are associated with chronic low-grade systemic inflammation [1], [2], [3]. The main maternal effect of gestational diabetes is a higher long-term risk of developing MetS and type 2 diabetes [4]. Several studies have reported links between gestational diabetes mellitus (GDM) and the subsequent risk of type 2 diabetes and MetS [5], [6], [7], [8], but the association between metabolic alterations in early pregnancy and the development of GDM has been little explored.

For this reason, the objective of the present study was to examine the association between the MetS characteristics before and during early pregnancy in women with no previous diabetes, and the risk of developing GDM.

Section snippets

Mother–child cohort in Crete (the Rhea study)

The mother–child cohort study in Crete (the Rhea study) examined a sample population of women who became pregnant within one year, starting in February 2007, living in the prefecture of Heraklion. Over the study period, 1765 eligible women were approached, and 1610 (91%) agreed to participate; 1317 (82%) of these women were followed up to delivery. A total of 730 participants with singleton pregnancies provided fasting blood samples during their early pregnancy. Women who experienced

Results

Complete information was available for all main model variables for our 508 pregnant women. These data revealed that women with the MetS were more likely to be less educated and to smoke more during pregnancy, while women with GDM were more likely to have a family history of diabetes.

Table 1 shows the associations between the MetS in early pregnancy, and its components, and GDM. Women with the MetS were at high risk of GDM (RR = 3.17; 95% CI: 1.06–9.50) and, of the components of MetS, the most

Discussion

The present study provides novel evidence that women with singleton pregnancies who develop GDM were more likely to have the MetS before week 15 of gestation compared with women without GDM. The MetS refers to a cluster of cardiovascular risk factors that are thought to constitute a complete phenotype rather than separate conditions [11], [12]. This is supported by the present study results showing that the greater the number of MetS components, the greater the increase in risk of GDM. There

Conflicts of interest

The authors have not declared any conflicts of interest.

Acknowledgments

This study was supported in part by the EU NewGeneris integrated project, Sixth Framework Programme (contract no. FOOD-CT-2005-016320), and by the EU-funded project HiWATE, Sixth Framework Programme (contract no. Food-CT-2006-036224). The authors gratefully acknowledge Dr Eleni Fthenou for her handling of the biobank.

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Gestational diabetes mellitus (GDM) and metabolic syndrome (MetS) share common characteristics and risk factors. Both conditions increase the risk of chronic diseases and, thus, may share a common pathogenesis. This review begins with a clinical vignette, followed by evidence supporting the risk of MetS after GDM among women and their offspring and the risk of having GDM among pregnant women who have MetS before pregnancy.
Research studies published between 2010 and 2023 were identified via several databases, including PubMed, the Web of Science, MEDLINE, Science Direct, ERIC, and EBSCOhost. Search terms included gestational diabetes and metabolic syndrome. Reviews, books/e-books, patents, news, trade publications, reports, dissertations/theses, conference materials, and articles in non-English languages were all excluded.
MetS increases not only the incidence of GDM during pregnancy but also the risk of diabetes in women with a history of GDM. On the other hand, women with a history of GDM had an almost 4 times increased risk of developing MetS at minimum of 1 year after delivery, and the risk increases with longer time lapse since the index pregnancy. Prepregnancy body mass index appears to be the strongest factor predicting MetS. Children exposed to GDM in utero have at least a 2 times increased risk of MetS in later life.
Timely assessment and continuing surveillance of MetS before and after pregnancy followed by GDM are recommended. Weight management and nutrition counseling are of importance to reduce the risk of GDM and MetS among pregnant women.
Mediators of the association between maternal body mass index and breastfeeding duration in 3 international cohorts
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Maternal obesity has been associated with shorter breastfeeding duration, but little is known about mediating factors explaining this association. It is important to assess these relationships across diverse populations because breastfeeding is culturally patterned.
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We analyzed 5120 singleton pregnancies from mother–child cohorts in Spain (INfancia y Medio Ambiente), Greece (Rhea), and the United States (Project Viva). Outcome variables were duration of any and exclusive breastfeeding. A priori hypothesized mediators in the association of maternal prepregnancy BMI with breastfeeding were birthweight (BW), maternal prenatal C-reactive protein (CRP), cesarean delivery, maternal dietary inflammatory index (DII) during pregnancy, gestational age at delivery, and gestational diabetes mellitus (GDM). We estimated the association between BMI and breastfeeding duration using linear regression adjusting for confounders. Mediation analysis estimated direct and indirect effects of maternal overweight/obesity on breastfeeding for each mediator.
Women with overweight and obesity had shorter duration of any and exclusive breastfeeding compared with normal-weight women (any: overweight β = −0.79 mo, 95% CI: −1.17, −0.40; obese β = −1.75 mo 95% CI: −2.25, −1.25; exclusive: overweight β = −0.30 mo, 95% CI: −0.42, −0.16; obese β = −0.73 mo, 95% CI: −0.90, −0.55). Significant mediators (% change in effect estimate) of this association were higher CRP (exclusive: 5.12%), cesarean delivery (any: 6.54%; exclusive: 7.69%), and higher DII (any: 6.48%; exclusive: 7.69%). GDM, gestational age, and BW did not mediate the association of maternal weight status with breastfeeding.
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The relationship between pre-pregnancy metabolic syndrome and insulin use during pregnancy has not been investigated thus far. While Chatzi et al. [28] showed that the presence of metabolic syndrome in early pregnancy increased the risk of GDM, metabolic syndrome was confirmed in early pregnancy and not before conception. Moreover, the number of the subjects included in the study was relatively small (n = 508).
The present study aimed to evaluate whether mothers with obesity/central obesity and metabolic syndrome before gestation are at higher risk of insulin administration in gestational diabetes mellitus (GDM) to diminish the burden of insulin use during pregnancy.
This was a population-based retrospective cohort study conducted using data from the National Health Information Database of Korea. We identified all deliveries from January 1, 2011 to December 31, 2015 (N = 1,214,655). Among the deliveries, we identified mothers with pre-pregnancy health checkup records and without previous diabetes history (N = 325,208). Hazards of insulin use in GDM were calculated based on pre-pregnancy obesity/central obesity and metabolic syndrome.
Hazards of insulin use in GDM increased proportionately with an increase in the pre-pregnancy body mass index (BMI) and waist circumference (WC). After the adjustment for clinical factors, high BMI group (≥30 kg/m²) and high WC group (≥100 cm) were significantly associated with higher hazard ratios (HRs) (HR 4.161, 95% Confidence interval [CI] 3.381–5.121, P < 0.001 and HR 2.563, 95% CI 1.769–3.712, P < 0.001, respectively). The presence of pre-pregnancy metabolic syndrome significantly increased the hazard of insulin use in GDM (0.54% vs. 5.04%). In the presence of obesity (BMI ≥ 25 kg/m²) or central obesity (WC ≥ 85 cm), HRs of insulin use in GDM were 2.637 (95% CI 2.275–3.056) and 1.603 (95% CI 1.023–2.511), respectively, after adjustment for clinical factors.
The presence of pre-pregnancy obesity/central obesity and metabolic syndrome in Korean mothers is associated with increased risk of insulin use in GDM.
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Obesity during pregnancy increases the risk of gestational diabetes mellitus (GDM) and hypertension (HTN; Bartha et al., 2008; Grieger et al., 2018). Women with MetS are at a higher risk for preeclampsia and GDM (Grieger et al., 2018), and women with GDM are at a higher risk for T2DM and CVD later in life (Bartha et al., 2008; Chatzi et al., 2009; Kaufmann et al., 1995; Williams, 2003). Preeclampsia is an additional risk factor for T2DM and CVD (Bartha et al., 2008).
Sex hormones are involved in pathways of metabolic syndrome (MetS), an observation supported by animal studies. The relationships of sex hormones with components of MetS, such as insulin resistance and dyslipidemia, have been studied in pre- and postmenopausal women. High testosterone, low sex hormone-binding globulin, and low estrogen levels increase the risks of MetS and type 2 diabetes in women. Cutaneous diseases that are sex hormone mediated, such as polycystic ovary syndrome, acanthosis nigricans, acne vulgaris, and pattern alopecia, have been associated with insulin resistance and increased risk for MetS. Furthermore, inflammatory skin conditions, such as hidradenitis suppurativa and psoriasis, increase the risk for MetS. Patients with such skin conditions should be followed for metabolic complications, and early lifestyle interventions toward these populations may be warranted.
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Chatzi et al. used data of 508 pregnant women from the Rhea cohort study in Crete, Greece who screened for GDM between weeks 24 and 28 of gestation by Carpenter and Coustan criteria. They showed women with the metabolic syndrome in early weeks of pregnancy had higher risk of GDM (RR = 3.17; 95% CI: 1.06–9.50) [30]. Common pathogenesis pathway between metabolic syndrome and gestational diabetes (such as insulin resistance, endothelial dysfunction, glucose intolerance and hyperlipidemia) and some similar risk factors (such as older age, body mass index and history of diabetes) may explain association between metabolic syndrome in first visit of pregnancy and incidence of gestational diabetes [31,32].
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The prevalence of overweight and obesity were 40% and25.8% in the GMD group and in 35.8% and 16.2% in the control group respectively (p = 0.002). According to NCEP-ATP III criteria, 16.9% of women with GDM and 6.9% of mothers in the control group had metabolic syndrome in first visit of pregnancy (p < 0.001. Logistic regression showed that there is a significant relationship between maternal age[OR = 1.05(95% CI, 1.01–1.10)] (p = 0.01), previous GDM [OR = 5.60(95% CI, 2.21–14.18)] (p = 0.001), positive family history of diabetes[OR = 1.86(95% CI, 1.19–2.94)] (p = 0.006), pre-pregnancy BMI [OR = 1.05(95% CI, 1.007–1.11)] (p = 0.04) and metabolic syndrome in first visit of pregnancy[OR = 2.34 (95% CI, 1.038–5.30)] (p = 0.04) with GDM.
Factors including maternal age, previous GDM, family history of diabetes, pre-pregnancy BMI reported in previous studies around the world. A significant association between metabolic syndrome in the first visit of pregnancy and GDM is novel finding of this study. Therefore screening of pre-pregnancy metabolic syndrome in women at risk of gestational diabetes is recommended.
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Short reportThe metabolic syndrome in early pregnancy and risk of gestational diabetes mellitusSyndrome métabolique en début de grossesse et risque de diabète gestationnel

Abstract

Aim

Methods

Results

Conclusion

Résumé

Objectif

Méthodes

Résultats

Conclusion

Introduction

Section snippets

Mother–child cohort in Crete (the Rhea study)

Results

Discussion

Conflicts of interest

Acknowledgments

Lancet

Am J Obstet Gynecol

Diabetes Metab

Obstet Gynecol

Eur J Obstet Gynecol Reprod Biol

Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement

Circulation

The metabolic syndrome: inflammation, diabetes mellitus, and cardiovascular disease

Am J Cardiol

Inflammation and metabolic disorders

Nature

Gestational diabetes: the forerunner for the development of maternal and childhood obesity and metabolic syndrome?

J Matern Fetal Neonatal Med

Gestational diabetes: should it be added to the syndrome of insulin resistance?

Diabetes Care

The prevalence of the metabolic syndrome in a danish population of women with previous gestational diabetes mellitus is three-fold higher than in the general population

J Clin Endocrinol Metab

Short report
The metabolic syndrome in early pregnancy and risk of gestational diabetes mellitusSyndrome métabolique en début de grossesse et risque de diabète gestationnel