{"id":49641,"date":"2023-06-30T11:50:10","date_gmt":"2023-06-30T11:50:10","guid":{"rendered":"https:\/\/biomedpharmajournal.org\/?p=49641"},"modified":"2023-07-11T05:42:51","modified_gmt":"2023-07-11T05:42:51","slug":"gestational-diabetes-a-review","status":"publish","type":"post","link":"https:\/\/biomedpharmajournal.org\/staging\/vol16no2\/gestational-diabetes-a-review\/","title":{"rendered":"Gestational Diabetes: A Review"},"content":{"rendered":"\n

Introduction<\/strong><\/p>\n\n\n\n

Gestational diabetes (GD) is a\ndisorder of varying severity of glucose tolerance resulting in hyperglycemia\nthat either starts or is newly diagnosed during gestation, independent of\nrequisite interventions and postpartum evolution. Within this definition, the\nWorld Health Organization (WHO) encompasses both GD and pregnancy-diagnosed\ntype 2 diabetes (T2D) (1). GD is a common complication of pregnancy, and\ninadequate treatment may result in serious consequences for mother and child\nhealth conditions. Despite the large number of studies, the pathophysiology of\nGD is still unclear. Contemporary evidence substantiates a multifaceted interplay\namong diverse genetic, metabolic, and environmental factors in the pathogenesis\nof GD (2). The majority of the time, this hyperglycemia is brought on by poor\nglucose tolerance resulting from dysfunctional pancreatic beta-cell function\nagainst a background of ongoing insulin resistance (3).<\/p>\n\n\n\n

For decades, the debate regarding\nthe diagnosis of GD revolved around two questions: first, the necessity of\nscreening all parturient women versus selective screening limited to\nindividuals with identifiable risk factors; and second, the utilization of\ndiagnostic procedures in one or two steps. Screening only women with risk\nfactors may lead to GD going undiagnosed in 35\u201347% of pregnant women (4).<\/p>\n\n\n\n

In recent years, GD has gained\ngreat interest among researchers due to the multifactorial complexity of this\ndisease, which can have long-term consequences for maternal and child health.\nDespite progress made, research on GD is far from complete, and further studies\nare still necessary to uncover the underlying mechanisms of the disease, its\nconsequences, and effective prevention and treatment strategies. In this\nreview, we will focus on the diagnostic criteria, prevalence, risk factors,\nconsequences, and management of GD while drawing on recent literature data. <\/p>\n\n\n\n

Several electronic databases,\nincluding PubMed, Scopus, Google Scholar, Web of Science, ScienceDirect, etc.,\nalong with other sources of grey literature, were utilized to conduct this\nstudy. The search strategy encompassed the utilization of MESH terms and\nkeywords such as gestational diabetes, diabetes pregnancy-induced, diabetes\nmellitus gestational, pregnancy in diabetics, glucose intolerance, pregnancy,\nand pregnancy complications. Based on these keywords, a total of 91 articles\nwere included in this review.<\/p>\n\n\n\n

Diagnostic criteria for gestational diabetes<\/strong><\/p>\n\n\n\n

The diagnostic\ncriteria for GD are not new. In fact, the 1964 O’Sullivan and Mahan method\nrecommended a two-step screening process that involves administering 50 g of\noral glucose and measuring plasma glucose one hour later. If the glycemic level\nsurpasses or equals 1.40 g\/L (7.8 mmol\/L), anGD oral glucose tolerance test\n(OGTT) is conducted following the ingestion of 100 grams of glucose. The\ndiagnosis GD is confirmed when the glucose level reaches or exceeds 2 g\/L (11.1 mmol\/L) (5). The criteria\nmentioned above were challenged because they were based on data from the\ngeneral population and not on indicators of maternal and fetal morbidity (6). <\/p>\n\n\n\n

Subsequently, in\n1999, the World Health Organization (WHO) embraced alternative diagnostic\ncriteria for gestational diabetes (GD). It advocates conducting a 75-gram oral\nglucose tolerance test (OGTT) during the gestational period of 24 to 32 weeks, utilizing\nthe following thresholds: fasting glucose of 1.26 g\/L (7 mmol\/L) and\/or a\n2-hour glucose level of 1.40 g\/L  (7.8\nmmol\/L) following glucose ingestion (7). These screening criteria for GD do not\nadequately differentiate pregnant individuals who are at a heightened risk of\nadverse perinatal outcomes, instead focusing on those with an elevated\nsusceptibility to postpartum diabetes development (8).<\/p>\n\n\n\n

Following the dissemination of\nthe findings from the Hyperglycemia Adverse Pregnancy Outcome (HAPO) study in\n2008, involving 25,505 women, novel diagnostic parameters for GD have been\nadopted by the International Association of Diabetes and Pregnancy Study Groups\n(IADPSG). Thus, it recommends screening for pre-existing diabetes in patients\nearly in pregnancy through fasting blood glucose (FBG) or glycated hemoglobin\n(HbA1C) measurements. Patients with FBG > 1.26 g\/L or HbA1C > 6.5% are\nconsidered to have pre-existing diabetes. Patients with FBG > 2 g\/L must\nundergo a confirmation test with FBG measurement. If the patient’s FBG levels fall\nwithin the range of 0.92 g\/L (5.1 mmol\/L) and 1.26 g\/L, the diagnosis of GD is\nconfirmed, necessitating prompt initiation of treatment. Only patients with an\nFBG of 0.92 g\/L will undergo a 75-gram OGTT administered within the timeframe\nencompassing the 24th week to the 28th week of gestation. GD is diagnosed when\na single test value exceeds the predetermined thresholds: a glucose level of\n1.80 g\/L (10 mmol\/L) 1 hour after and\/or a glucose level of 1.53 g\/L (8.5\nmmol\/L) 2 hours after. <\/p>\n\n\n\n

The HAPO study is the first study\nto show an association between maternal blood glucose values and fetal-maternal\nmorbidity. Therefore, for each additional standard deviation (SD) of 0.07 g\/L\nof fasting glucose, the risk of macrosomia experienced a 1.38-fold increase (6).\nThe new IADPSG recommendations suggest a simultaneous modification of the\ndiagnostic strategy and diagnostic thresholds, which are revised downward based\non perinatal risks and are widely used worldwide (3). However, they have led to\na threefold increase in the diagnosis of GD, highlighting previous\nunderestimation (2).<\/p>\n\n\n\n

In the same vein, several studies\nhave confirmed the usefulness of using two-step screening tests, which may\nresult in a 3% increase in the prevalence of GDM and a significant reduction in\nadverse pregnancy outcomes. However, screening may cause anxiety in pregnant\nwomen, which may persist beyond the first trimester and have adverse\nconsequences for the health of both maternal and infant. It may also generate\nstress for physicians and lead to over-medicalization, an increase in the\nnumber of consultations, and even iatrogenic effects, such as high rates of\ncesarean sections, induction of labor, and repeated examinations during\npregnancy follow-up. In contrast, other studies have shown the beneficial\neffect of GDM screening in motivating pregnant women to modify their behavior,\nparticularly with adequate care. An Australian study involving 1000 women, on\nthe other hand, showed that there was no statistically significant difference\nin maternal anxiety levels between the intervention and control groups, as evaluated\nusing a 6-item self-evaluation scale of maternal anxiety, derived from a\nmodified version of the Spielberger State-Trait Anxiety Inventory (11).<\/p>\n\n\n\n

Currently, investigations are\nunderway to explore the prospective significance of protein biomarkers in the\ndiagnostic and predictive realms of GD. According to recent studies, a\ncompilation of evidence emphasizes 15 protein biomarkers. These can contribute\nto replacing the IADPSG diagnostic criteria (12). Certain biomarkers, such as\nleptin and adiponectin, which are hormones produced by adipose cells, can be\nused to predict GD. The adiponectin\/leptin  plasma ratio can be used to predict GD between\nthe 6th and 14th weeks of pregnancy. Other adipokines, such as visfatin,\nresistin, and omentin, can also be used to diagnose GD, but their effectiveness\nvaries. Placental\nfactors, including Fetuin-A and Sex Hormone-Binding Globulin (SHBG), may also\ninfluence the development of GD. Throughout the first trimester of gestation,\nthe decrease in maternal plasma SHBG levels can be utilized for the prediction\nof GD. Additionally, the use of molecular markers, including single nucleotide\npolymorphisms (SNPs), microRNAs, and DNA methylation, can enable the detection\nof GD. There are over 100 miRNAs currently being studied in relation to GD.\nMiRNAs, SNPs, and certain genetic mutations such as those in adiponectin,\nglucokinase, and insulin receptor substrate 1 have been correlated with an\nelevated likelihood of developing GD (13) (14).<\/p>\n\n\n\n

Currently, various organizations\nrecommend universal screening for the entire pregnant population to ensure\noptimal management of GD. However, the logistical aspect of implementing the\nHGPO test for all pregnant women constitutes a major obstacle. Precise\nbiomarkers could enable universal screening to become a reality. However, their\nuse in clinical practice is hindered by several challenges, including the need\nto evaluate their decision threshold, clinical usefulness, sensitivity, and\nspecificity, which still require further investigation (13).<\/p>\n\n\n\n

Prevalence of gestational diabetes<\/strong><\/p>\n\n\n\n

The prevalence of GD demonstrates\nvariability among different countries and regions. Different studies report\nvariable prevalence rates. In a 2019 meta-analysis and systematic review aiming\nto estimate the prevalence and determinants of gestational diabetes (GD) in\nAfrica, the combined prevalence of GD in the African population was found to be\n13.61%. Some studies included in this review reported a high prevalence of GD,\nsuch as in Cameroon (32.1%) and Uganda (30.3%). This result can be attributed\nto the expanded implementation of screening strategies for GD among pregnant\nwomen in these countries (15).<\/p>\n\n\n\n

The explanation for the\nheterogeneity of prevalence is the absence of consensus concerning the\ndiagnostic criteria for GD. According to studies, the prevalence of GD ranges\nfrom 1.3% to 19.9% (16). The observed variations may be related to a higher\nscreening rate and easier access to tests in recent years (15).<\/p>\n\n\n\n

In Morocco, reported figures show\na prevalence of close to 10%. This prevalence varies in some studies between\n7.7% and 24.2% (17). The potential for an increase in these figures exists due\nto limited awareness of the condition among a significant proportion of\nMoroccan women, leading to restricted\naccess to screening. Furthermore, the ongoing rise in the prevalence of obesity\nand overweight further contributes to this trend (18).<\/p>\n\n\n\n

In Europe, the prevalence of GD\nwas estimated at 10.9% in a systematic review including 15,572,847 pregnant\nwomen between 2014 and 2019 in 24 European countries. The highest prevalence of\nGD was in the Eastern region (31.5%), followed by Southern Europe (12.3%),\nWestern Europe (10.7%), and Northern Europe (8.9%) (19). The estimated\nprevalence reported in this study (10.9%) surpasses the findings of a prior\nmeta-analysis conducted in 2015, including 1,778,399 participants, with an\nestimated prevalence of 5.4% (20). Similarly, the 2019 report from the\nInternational Diabetes Federation (IDF) underscores substantial variability in\nthe prevalence of GD across seven regions globally, revealing an age-weighted\nprevalence estimated at 16.3% in Europe (21). Differences in population and\ncountry estimates could explain the variation between the reported prevalences.\nThe FID included data from women aged only 20 to 45 in 39 countries, while the\n2019 systematic review included data from 24 countries for all pregnant women\n(19). The 2015 meta-analysis included data from only 12 countries, which may\nexplain the difference in prevalence (20).<\/p>\n\n\n\n

The prevalence of GD in Latin\nAmerican and Caribbean populations obtained from a review of the literature\npublished between 2000 and 2019 reporting maternal and perinatal adverse\neffects of pregnancies was estimated at 8.5%, which is lower than that in\nEurope (10.9%) and Africa (13.61%) mentioned above. However, the validity of\nprevalence comparisons between world regions is limited by the absence of\nuniversally accepted diagnostic criteria and screening strategies, as well as\nby inter-regional variability. Indeed, prevalence in Latin American and\nCaribbean populations ranged from 2.1% to 15.8% (22). In Asia, this variation\ncan range from 1% to 25% depending on the region, showing that this\nheterogeneity affects different regions of the world (23).<\/p>\n\n\n\n

Within the 10th edition of the\nIDF Diabetes Atlas, a meta-analysis is conducted with the aim of standardizing\nthe assessment of GD prevalence across regions and national income levels,\nutilizing the diagnostic criteria of IADPSG. Based on data from studies\nconducted between January 1990 and December 2020, standardization of prevalence\nat 14.2% is obtained, with a slight decrease to 14% after age adjustment (24).<\/p>\n\n\n\n

To provide an overview of the\nvariability of prevalence between different regions, IDF generated comparable\nprevalence if IADPSG diagnostic criteria were uniformly used in different\nregions and pregnant women were aged 25 to 30. Table 1 shows the different prevalences\nobtained (24). <\/p>\n\n\n\n

Table 1: Comparable prevalence based on IADPSG criteria among women aged 25 to 30 years<\/strong><\/p>\n\n\n\n\n\n\n\n\n\n\n\n\n
\n

Region<\/strong><\/p>\n<\/td>\n

\n

Standardized* Prevalence<\/strong><\/p>\n<\/td>\n<\/tr>\n

\n

Middle East And North Africa<\/p>\n<\/td>\n

\n

27,6 %<\/p>\n<\/td>\n<\/tr>\n

\n

South-East Asia<\/p>\n<\/td>\n

\n

20,8 %<\/p>\n<\/td>\n<\/tr>\n

\n

Western Pacific<\/p>\n<\/td>\n

\n

14,7 %<\/p>\n<\/td>\n<\/tr>\n

\n

Afrique<\/p>\n<\/td>\n

\n

14,2 %<\/p>\n<\/td>\n<\/tr>\n

\n

South and Central America<\/p>\n<\/td>\n

\n

10,4 %<\/p>\n<\/td>\n<\/tr>\n

\n

Europe<\/p>\n<\/td>\n

\n

7,8%<\/p>\n<\/td>\n<\/tr>\n

\n

North America and Caribbean<\/p>\n<\/td>\n

\n

7,1%<\/p>\n<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n\n\n

* The standardization was conducted by considering the sample sizes in the studies included in the meta-analysis of the FID and utilizing Poisson regression analysis (24).<\/p>\n\n\n\n

The observed variation in\nprevalence across regions and countries can be attributed to differences in\npopulation characteristics, including but not limited to ethnicity, lifestyle,\nprevalence of T2D, and obesity. Moreover, the standardized prevalence was\nassessed based on income level per country, with low-income countries showing a\nprevalence of 12.7%, high-income countries exhibiting a prevalence of 14.2%,\nand middle-income countries having a prevalence of 9.2% (24).<\/p>\n\n\n\n

In conclusion, the prevalence of GD\nexhibits regional and inter-country variations. Reported GD prevalence estimates\nmay be underestimated due to the lack of awareness of the condition among a\nlarge proportion of women. The heterogeneity of prevalence according to the\naforementioned studies can be explained by the absence of consensus on GD\ndiagnostic criteria and screening strategies, as well as inter-regional\nvariability. It is important to harmonize diagnostic criteria and screening\nstrategies to improve the prevention and management of GD.<\/p>\n\n\n\n

Risk factors<\/strong><\/p>\n\n\n\n

Maternal obesity\nand overweight, Belonging to a population characterized by a high prevalence of\ndiabetes (non-white ethnicity: Caribbean black, Asian, or Middle Eastern), a\nhistory of prediabetes, familial diabetes, or antecedents of GD, are all recognized as predisposing\nfactors for the development of GD. In addition to these factors, a history of\nfetal death and the delivery of macrosomic newborns also contribute to the risk\nof GD. Increasing maternal age and polycystic ovary syndrome (PCOS) are also\nrisk factors for GD (25) (26).<\/p>\n\n\n\n

It is now\nestablished that obesity is associated with GD. In fact, the risk of developing\nGD can be four times higher in obese women and nine times higher in women with\nsevere obesity (27). Another systematic review, including 671,945 pregnant\nwomen, also confirms the association between obesity and GD. The unadjusted\nodds ratios for women classified as individuals with obesity (BMI > 29.9 kg\/m2<\/sup>),\nindividuals with moderate obesity (BMI 30-35 kg\/m2<\/sup>), and individuals\nwith severe obesity (BMI > 35 kg\/m2<\/sup>), in comparison to women of\naverage weight, were 3.76, 3.01, and 5.55, respectively (95% CI 3.31-4.28,\n2.34-3.87, and 4.27-7.21) (28). In 2021, a review reconfirmed the association\nbetween GD and obesity as a risk factor. This review analyzed data from 20\nstudies conducted between 1985 and 2020, and the risk increased two-fold and\nexceeded three-fold depending on the type of obesity (29).<\/p>\n\n\n\n

The risk of\ndeveloping GD is positively associated with maternal age. Women between the\nages of 35 and 39 exhibit an approximately twofold increase in the risk of\ndeveloping GD, whereas women aged over 40 have nearly a fourfold increase in\nrisk compared to their younger counterparts (30).<\/p>\n\n\n\n

 Furthermore, PCOS is a complex disorder\ncharacterized by disturbances in ovarian function, primarily marked by elevated\nandrogen levels and the presence of polycystic ovarian morphology (31). It is\naccompanied by insulin resistance and hyperandrogenemia, which may explain the\nincreased incidence of GD in this category of parturients. (32) GD can affect\nup to 40% of patients with PCOS. (33) The risk of developing GD can be\nincreased by 2.89 compared to women without this syndrome. However, the\nmajority of studies evaluating the risk of GD in patients with PCOS are mainly\nretrospective, which limits the availability of conclusive evidence regarding a\ndirect association between PCOS and GD (33).<\/p>\n\n\n\n

Furthermore,\nrecent scientific investigations have shed light on the potential role of\nvitamin D deficiency in the pathogenesis of GD (25). Inadequate levels of\nvitamin D can be associated with a 26% increased risk of developing GD,\nalthough this risk is lower in patients with a serum vitamin D concentration of\n40 to 90 nmol\/L (35). Iron supplementation may also be a potential factor in\nthe development of GD. The risk of adverse outcomes appears to be elevated in\npregnant women who receive iron supplementation. However, this hypothesis still\nrequires further in-depth studies (36). It is also noteworthy that a high\nconcentration of maternal folate combined with a vitamin B12 deficiency may\ncontribute to an increased risk of GD (37). This highlights the need for an\nevaluation of the status of different vitamins and micronutrients in women\nbefore prescribing any supplementation.<\/p>\n\n\n\n

Recent studies\nsuggest that epigenetics, changes in gene expression caused by factors like\ndiet, stress, and environment, can affect the development of GD. These\nmodifications can impact genes that regulate insulin and glucose, contributing\nto GD pathogenesis. Among the epigenetic mechanisms, DNA methylation has\ngarnered substantial attention as the foremost extensively studied mechanism,\ncharacterized by the addition of methyl groups to DNA (38).<\/p>\n\n\n\n

In recent years,\nnumerous studies have explored various likely risk factors associated with GD.\nAmong these factors, obstructive sleep apnea (OSA) is a frequent complication\nof pregnancy, affecting 3.6% to 22% of pregnant women, and evidence indicates\nan increased risk of GD in pregnant women with OSA. However, the mechanisms\nunderlying this association remain unclear. Intermittent hypoxemia (IH) and\nsleep arousals appear to be the most implicated factors (39). The association\nbetween thyroid dysfunction and GD also attracts researchers’ interest.\nPrevious studies have suggested that physiological changes during pregnancy\ncause dysfunction affecting thyroid function and glucose metabolism. The\nnecessary metabolic adaptations may contribute to the development of GD. Thyroid\nhormones have been implicated in the process of placental development, which\nconstitutes a pivotal determinant of insulin resistance during the gestational\nperiod Placental dysfunction can contribute to the development of gestational\ndiabetes (GD). Furthermore, in women with detectable anti-thyroperoxidase\nantibodies, a compromised thyroid response to human chorionic gonadotropin\n(hCG) can exacerbate insulin resistance and contribute to the pathogenesis of\nGD. The underlying pathophysiological mechanisms linking GD and thyroid\ndysfunction remain incompletely understood and warrant further investigation\n(40).<\/p>\n\n\n\n

Cytokines also\nreceive significant attention from researchers. Tumor necrosis factor (TNF),\nleptin, and interleukin-6 (IL) have garnered particular interest. A recent\nsystematic review of 24 studies suggests the possible involvement of these\ncytokines in the occurrence of GD (41). All the aforementioned risk factors are\nfar from exhaustive, and this section provides a general  overview of the risk factors that have been\nthe subject of numerous studies and others that are currently under\ninvestigation. This confirms the complexity of this multifactorial disease and\nnecessitates further research to better understand its pathophysiology and\nimprove its management.<\/p>\n\n\n\n

Consequences of gestational diabetes<\/strong><\/p>\n\n\n\n

Consequences for the mother<\/strong><\/p>\n\n\n\n

Hyperglycemia during pregnancy, even if it is mild, can have consequences for maternal health. It is correlated with an elevated predisposition to hypertensive disorders during the gestational period. There has also been an increase in preterm labor, cesarean delivery, metabolic disorders, and the later development of diabetes (42). <\/p>\n\n\n\n

Diabetes and subsequent metabolic syndrome<\/strong><\/p>\n\n\n\n

Studies have\nshown the involvement of GD in the occurrence of T2D and cardiovascular\ncomplications later on (42). According to studies, the risk was found to be\nsevenfold higher than that observed in women with normal blood glucose levels\nduring pregnancy. T2D can affect 30% to 50% of women with a history of GD\nwithin 10 years (43). This risk can be partially elucidated by the interplay of\nshared genetic and environmental predisposing factors underlying both GD and\nT2D (44). Furthermore, GD and T2D exhibit comparable pathophysiological\nmechanisms and display genetic architectural resemblances (45). However, this\nresult is controversial. On the one hand, this finding is supported by a\nmeta-analysis of 39 studies, encompassing a total of 95,750 women who were followed\nfor a period ranging from 6 months to 20 years. The meta-analysis revealed an\nestimated relative risk of 2.13 (95% CI 1.52, 3.56) associated with early\ndiagnosis of GD. On the other hand, a Canadian study of 90,000 women shows a\nvery slight increase in the risk of T2D among women with a previous history of\nGD (42).  <\/p>\n\n\n\n

The impact of GD on metabolic health has been extensively investigated, as demonstrated by a systematic review alongside a meta-analysis published in 2014. This study, encompassing 5,832 pregnant women, revealed a notable fourfold increase in metabolic risk among individuals with a history of GD (RR = 3.96, 95% CI: 3.99\u20135.26), with obesity and Caucasian origin being factors that increase the risk (46). Other studies confirm this result but with smaller samples. For example, a Danish cohort study including 481 women who had previously had GD and 1000 women of the same age without a history of GD revealed, after a follow-up of 9.8 years, a three-fold increase in the prevalence of metabolic syndrome in the previous GD group in comparison to the control group (47). It is worth noting that the risk of recurrent GD during pregnancy has been estimated at 48% in a meta-analysis combining data from 18 studies (48).      <\/strong><\/p>\n\n\n\n

Cardiovascular risk<\/strong><\/p>\n\n\n\n

Several studies confirm the increased cardiovascular risk in parturients with antecedents of GD. This may explain the subsequent development of T2D. (49). However, this link has not been demonstrated in a cohort of 8,191 women diagnosed with GD and 81,262 women without the condition were included in the study, followed for 11 years. This cohort exhibited an elevated risk of cardiovascular events, regardless of the presence of T2D and metabolic syndrome, as indicated by an adjusted odds ratio of 1.85 (95% CI: 1.21-2.82) (50). The results of a systematic literature review which encompassed data from 5,390,591 pregnant women, revealed that women diagnosed with GD exhibited a two-fold increased susceptibility to subsequent cardiovascular incidents (relative risk [RR] 1.98, 95% confidence interval [CI]: 1.57, 2.50). The T2D incidence rates observed in the studies did not exert any influence on this risk  (p = 0.34). This confirms that the risk of cardiovascular events remains independent of concurrent T2D and instead becomes evident within the initial decade following pregnancy (RR 2.31 [95% CI: 1.57, 3.39]) (51). Cardiovascular complications, according to a British study published in October 2022, including 13,094 women, are multiple and can include coronary conditions, ischemic strokes, myocardial infarctions, cardiac failures, peripheral artery disease, atrial fibrillations and mitral valve regurgitation (52).<\/p>\n\n\n\n

Other complications<\/strong><\/p>\n\n\n\n

The risk of pre-eclampsia and cesarean delivery is increased by GD. These risks demonstrate a positive linear association with the severity of initial hyperglycemia (53). Several maternal complications related to GD have been described in the literature. These complications may occur in the long term; renal insufficiency is one of them, and the risk can be multiplied by two in women who have a history of GD (54). Additionally, studies have demonstrated an elevated risk of long-term ocular morbidity among women with a prior history of GD, in whom the incidence of illnesses such as glaucoma, diabetic retinopathy, and retinal detachment was significantly higher compared to patients without a history of GD (55).<\/p>\n\n\n\n

Fetal consequences<\/strong><\/p>\n\n\n\n

Short-term consequences<\/strong><\/p>\n\n\n\n

Maternal\nhyperglycemia is linked to an augmented risk of fetal macrosomia, perinatal\nmortality, and delivering infants who are large for gestational age. Macrosomia\ncan affect 12% of newborns from non-diabetic women and 15\u201345% of newborns from\nwomen with GD (56). Indeed, GD alters placental physiology, inducing a\nmodification of the amount of glucose available to the fetus, which could be\nresponsible for abnormal fetal growth and perinatal complications (57). An\nassociation has also been established between macrosomia, shoulder dystocia,\nbirth trauma, and perinatal asphyxia (58) (59). <\/p>\n\n\n\n

Newborns from\nwomen with GD may be admitted to neonatal intensive care units during the\nimmediate postpartum period due to hypoglycemia explained by hyperinsulinemia\nin the newborn. The risk of respiratory distress is\nalso increased (60) (61). Evidence now exists that GD can serve as an\nindependent risk factor for respiratory distress in newborns. This risk is\nfurther heightened in women with GD who are obese (62).<\/p>\n\n\n\n

Regarding\nperinatal mortality, evidence is contradictory regarding the involvement of GD\nin its increase. Indeed, studies have shown that mortality can reach 30% with GD\ncompared to non-diabetic mothers (63). Conversely, other studies suggest that\nthe risk is only present in women with GD controlled by diet alone (64). Other\nstudies showed no difference in terms of perinatal mortality. However,\nparadoxically, other studies showed a reduction in risk in newborns from women\nwith GD. To reduce the risk of maternal and fetal morbidity, scheduled delivery\nis recommended for women with GD (63).<\/p>\n\n\n\n

Congenital\nabnormalities may have GD as a contributing factor. The link between maternal\ndiabetes and congenital heart disease has been proven over a lengthy period of\ntime by several investigations. Because there are so many diagnostic options\navailable and there is a chance that pregnant women may already have undetected\ndiabetes, the evidence of its role in infant congenital abnormalities is,\nhowever, minimal (65).<\/p>\n\n\n\n

Long-term consequences<\/strong><\/p>\n\n\n\n

Offspring from\npregnancies affected by GD are at an increased predisposition to childhood and\nadult obesity and increased cardiometabolic risk (63). This is evidenced by the\nHAPO study, which revealed an increase in neonatal cord C-peptide levels, a\nmarker of insulin resistance. Moreover, neonatal adiposity in newborns of women\nwith GD was positively correlated with maternal hyperglycemia (60). A\nsignificant increase in the risk of obesity at 10\u201314 years of age was confirmed\nby the HAPO follow-up study in children born to mothers with untreated GD\ncompared to those without GD (66).<\/p>\n\n\n\n

The mechanisms of\nGD’s effects on childhood and adult diseases are unclear. Metabolic\nabnormalities caused by GD in pregnant women create an in-utero environment for\nthe fetus. This environment programs the fetus to develop the disease later in\nlife. This “metabolic memory” may explain the obesity that can occur\nin children and persist into adulthood (16). In the same vein, a\npopulation-based study in Denmark including over 1.7 million births followed\nover a period of 30 years found that offspring born to mothers with GD had a\nhigh risk of circulatory system disease. A Finnish study also demonstrated that\nadults born to mothers with GD had higher levels of insulin resistance and an atherogenic\nlipid profile compared to those born to mothers without GD (63).<\/p>\n\n\n\n

Given the\nmultitude of adverse pregnancy outcomes in women with GD, including those\ndemonstrated by various studies and others still under investigation, optimal\nmanagement of this condition is crucial, and further studies are needed to\nclarify the various consequences and implement appropriate prevention measures.<\/p>\n\n\n\n

Therapeutic management of gestational diabetes<\/strong><\/p>\n\n\n\n

In most cases,\nnutritional therapy alone is sufficient to achieve normoglycemia objectives.\nHowever, additional treatment is sometimes necessary (67). Women are managed\nwith intensive regimens, based on dietary advice and insulin administration, to\nlimit potential pregnancy complications and improve maternal and infant\noutcomes, which may include decreased fetal and neonatal mortality,\nmacrosomia, shoulder dystocia, and preeclampsia. However, this same management can\nbe correlated with a high frequency of neonatal hospitalization in intensive\ncare units and induction of labor (68). To date, there is no consensus on the\nantidiabetic agents to prescribe for patients with GD. In the United States and\nCanada, insulin is the first-line pharmacological treatment. Conversely, oral\ntherapy is used as first-line therapy in the United Kingdom (69). Oral therapy\nis based on metformin and Glibenclamide. According to American recommendations,\ninsulin can be used in continuous subcutaneous infusion, and insulin analogs\ncan also be safe alternatives to human insulin in the treatment of GD (70).\nHowever, evidence is still weak to support a specific type of insulin (71).<\/p>\n\n\n\n

 In France, it is recommended to initiate\ninsulin therapy if glycemia is not adequately controlled following a duration\nof 7 to 10 days of adherence to hygienic-dietary rules. Oral antidiabetic\nmedications are not authorized for use during pregnancy, even if reassuring\ndata exist regarding their efficacy. They are not recommended for the treatment\nof GD in the absence of in-depth studies (72). For several years, it has been\nestablished that the use of insulin is safe as it does not cross the placenta\n(73). However, insulin can cause maternal disorders such as weight gain and\nhypoglycemia, requiring education of pregnant women in its use. Therefore, oral\nantidiabetic medications have received a lot of interest from researchers in recent\ntimes (63).<\/p>\n\n\n\n

Several trials\nhave been conducted to compare the effectiveness of GD treatments. A\nmeta-analysis published in 2018 included 41 clinical trials that compared the\nefficacy and safety of three treatments, namely metformin, Glibenclamide, and insulin,\nin the management of GD. The analysis evaluated outcomes such as the quality of\nglycemic control, premature delivery, neonatal hypoglycemia, gestational weight\ngain, macrosomia, low birth weight, gestational hypertension, and\npre-eclampsia. This meta-analysis shows that metformin could be a safe and\neffective treatment for GD. It is noteworthy that Glibenclamide is linked to a\nhigher incidence of neonatal hypoglycemia when compared to insulin (74). Other\nrecent studies show the effectiveness and safety of metformin utilization in\nmanaging GD (75). However, these results should be taken with caution due to\nhighly variable transplacental transfer, even though the concentrations found\nin newborns are generally very low (63). Further investigations are warranted\nto assess the long-term effects on offspring. The most effective treatment\nremains uncertain, given the evolving population characteristics and diagnostic\nthreshold (76).<\/p>\n\n\n\n

Nutritional management of gestational diabetes<\/strong><\/p>\n\n\n\n

Nutrition is part\nof the prevention and treatment strategy for GD, and a personalized nutrition\nprogram can be developed for women with GD. This program should provide the\nnecessary caloric intake to promote maternal and infant health, achieve\nappropriate gestational weight gain, and meet glycemic control objectives (70).\nAccording to recommended dietary allowances for pregnant women, a daily intake\nof 175 g of carbohydrates, 71 g of protein, 28 g of fiber, and 3 liters of\nwater is advised (77). It is recommended to have three main meals and 2-3\nsnacks per day, with a particular emphasis on a late evening snack around 9:30\np.m., which can help prevent morning ketosis and nocturnal hypoglycemia.\nNotably, a prospective observational study utilizing the “Myfood24\nGDM” online diet and glycemia tool demonstrated improved glycemic control\nwith more frequent meal consumption (78). Nonetheless, further research is required to\nthoroughly assess the long-term effects of these dietary interventions on both\nmaternal and offspring outcomes.<\/p>\n\n\n\n

To evaluate the effect of different nutritional advice in the context of GD, research was conducted in the Cochrane Trials Register and the WOMBAT Perinatal Trials Register in 2012, including 429 women (436 babies), comparing different diets. This comparison did not yield any statistically significant disparities (79). The diets compared in this study were:<\/p>\n\n\n\n

Low GI diet versus moderate GI, high-fiber diet<\/p>\n\n\n\n

Hypocaloric diet versus unrestricted energy diet<\/p>\n\n\n\n

Low-carbohydrate diet<\/p>\n\n\n\n

A diet rich in monounsaturated fats<\/p>\n\n\n\n

Standard fiber diet (20 grams of fiber per day) versus high fiber diet (80 grams of fiber per day)<\/p>\n\n\n\n

Overall, these\nfindings suggest that the individualized nutrition program for GD should focus\non providing adequate calories, proper nutrients, and appropriate dietary fiber\nand that more frequent meals may lead to better glycemic control. However, Additional\ninvestigations are warranted to ascertain the most favorable dietary strategy\nfor the management of GD.<\/p>\n\n\n\n

Due to\ninsufficient evidence regarding the role of nutrition in preventing GD, it\nappears that the Mediterranean diet can significantly reduce this risk. This\ndiet is primarily composed of fruits and vegetables, which possess numerous\nantioxidant properties and offer fiber along with micronutrients including\nmagnesium and vitamin C. Additionally, this dietary pattern is distinguished by\nreduced consumption of red and processed meats and increased intake of\nhigh-quality carbohydrates, thereby facilitating the attenuation of free radicals\nand enhancement of systemic oxidative stress (82).<\/p>\n\n\n\n

Low-carbohydrate dietary\nregimens have sparked much controversy as dietary interventions for patients\nwith GD. Such an intervention may be associated with an increase in fat\nconsumption, which can have a deleterious effect on maternal insulin\nresistance, ultimately contributing to excessive fetal fat accumulation (83). While\nlow-carbohydrate dietary patterns may attenuate excessive weight gain during\ngestation, caution must be exercised in their use, as the Institute of Medicine\n(IOM) suggests an optimal carbohydrate energy percentage (E%) between 46 and\n65% and advises a recommended daily intake of at least 175 g of carbohydrates to\nfacilitate brain function development and ensure appropriate fetal growth (84).<\/p>\n\n\n\n

The risk of GD\nonset is augmented with a preconception low-carbohydrate dietary pattern\ncharacterized by elevated levels of animal protein and fat. This risk is not\nobserved in a carbohydrate-restricted dietary regimen that is abundant in plant-based\nproteins and fats. According to the findings of a cohort study comprising\n21,457 participants, replacing just 5% of energy derived from animal proteins\nwith vegetable-based proteins was associated with a 51% reduction in the risk\nof GD. In contrast, replacing 5% of dietary energy derived via carbohydrates with\nanimal proteins led to a 29% increase in GD risk (84).<\/p>\n\n\n\n

Supplementation\nhas been associated with a reduction in the incidence of GD. Indeed, probiotics\nhave a protective effect against GD by modifying the intestinal microbiota, Which\nmodifies the breakdown of dietary polysaccharides through fermentation and\nenhances the integrity of the intestinal barrier, resulting\nin a decrease in the incidence of GD (85). According to studies, the occurrence\nrate was significantly lower at 13% in the diet\/probiotics group compared to\n36% in the diet\/placebo group and 34% in the control group (85). It has also\nbeen demonstrated that administration of myo-inositol supplements during\npregnancy significantly reduces the incidence of GD in gravid individuals by\nsensitizing them to insulin and reducing plasma glucose levels in situations\nthat generate an increase in insulin resistance, including PCOS and the\nadvanced phase of the third trimester of pregnancy (86). Additionally, supplementation\nwith vitamin D has been shown to potentially decrease the risk of premature\ndelivery, hyperalbuminemia, and neonatal hospitalizations. However, further\nstudies are required to elucidate the optimal duration and dosages required for\nsafe supplementation (87). Omega-3 and magnesium supplementation have\ndemonstrated positive effects on patients with GD. These interventions can\nmodulate lipid profile and alleviate insulin resistance in this population (88)\n(89).<\/p>\n\n\n\n

It is also\nimportant to highlight the role of physical activity in the context of GD.\nIndeed, physical exercise directly reduces the occurrence of GD and indirectly\nprevents weight gain during gestation (90). Multiple investigations have\nconfirmed that physical activity can reduce the risk of GD from 23 to 59% (91).\nThe integration of nutritional and physical exercise interventions has the\npotential to reduce the incidence and perinatal complications of GD, even\nthough the current level of evidence is moderate (91).<\/p>\n\n\n\n

Nutrition remains\na vast field to explore in the context of GD to define adequate dietary\ninterventions. Nutritional therapy for GD is crucial for the mother and fetus\nhealth. It should ensure adequate maternal and fetal nutrition while achieving\nglycemic goals with meals that include energy, vitamins, and macronutrient\nintake. It is important for women with GD to work closely with a nutrition\nspecialist to create a nutritional plan, as there is no ideal dietary model\ngiven the multiple dimensions of nutrition, such as biological, cultural,\nsocial, economic, and environmental. Therefore, the nutritional plan must take\ninto account these dimensions while meeting the needs of the woman and the\nglycemic control imposed by the management of GD.<\/p>\n\n\n\n

Conclusion<\/strong><\/p>\n\n\n\n

To conclude, GD is a complex\ndisease that requires a multidisciplinary approach combining dietary,\nbehavioral, and pharmacological adjustments to optimize maternal glycemia and\navoid pregnancy complications. Nonetheless, early identification of risk\nfactors and screening are crucial for effective management of the disease. It\nis important to educate pregnant women about the dangers of GD. Scientific\nadvances have improved the management of GD, However, additional research is\nrequired to gain a more comprehensive understanding of the disease and improve\nprevention and treatment.<\/p>\n\n\n\n

Recently, great interest has been\ngiven to research on GD, and several axes are currently the subject of in-depth\ninvestigations. These include, among others, the impact of epigenetics, the\nidentification of new biomarkers for diagnosis and screening, the exploration\nof underlying risk factors, experimentation with new drugs and nutritional\ntherapy, and the study of the long-term consequences of the disease.<\/p>\n\n\n\n

Acknowledgment<\/strong><\/p>\n\n\n\n

I would like to thank Mrs Kenza Hattoufi for her guidance during the editing of the review<\/p>\n\n\n\n

Conflict\nof Interest<\/strong><\/p>\n\n\n\n

The\nauthors declare no conflict of interest in this work.<\/p>\n\n\n\n

Funding Sources<\/strong><\/p>\n\n\n\n

There is no\nfunding source.<\/p>\n\n\n\n

References<\/strong><\/p>\n\n\n\n

  1. World Health Organization. Diagnostic Criteria and Classification of Hyperglycaemia First Detected in Pregnancy. 2013. WHO_NMH_MND_13.2_eng.pdf [Internet]. [consulted 14 janv 2023]. Available on: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/85975\/WHO_NMH_MND_13.2_eng.pdf<\/li>
  2. Modzelewski R, Stefanowicz-Rutkowska MM, Matuszewski W, Bandurska-Stankiewicz EM. Gestational Diabetes Mellitus\u2014Recent Literature Review. J Clin Med. 28 sept 2022;11(19):5736. <\/li>
  3. Plows JF, Stanley JL, Baker PN, Reynolds CM, Vickers MH. The Pathophysiology of Gestational Diabetes Mellitus. Int J Mol Sci. 26 oct 2018;19(11):3342. <\/li>
  4. Benhalima K, Hanssens M, Devlieger R, Verhaeghe J, Mathieu C. Analysis of Pregnancy Outcomes Using the New IADPSG Recommendation Compared with the Carpenter and Coustan Criteria in an Area with a Low Prevalence of Gestational Diabetes. Int J Endocrinol. 2013;2013:248121. <\/li>
  5. O\u2019sullivan JB, Mahan CM. CRITERIA FOR THE ORAL GLUCOSE TOLERANCE TEST IN PREGNANCY. Diabetes. 1964;13:278\u201185. <\/li>
  6. Legardeur H, Girard G, Mandelbrot L. D\u00e9pistage du diab\u00e8te gestationnel : vers un nouveau consensus ? Gyn\u00e9cologie Obst\u00e9trique Fertil. 1 mars 2011;39(3):174\u20119. <\/li>
  7. WHO_NCD_NCS_99.2.pdf [Internet]. [cit\u00e9 7 mai 2023]. Disponible sur: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/66040\/WHO_NCD_NCS_99.2.pdf?sequence=1&isAllowed=y<\/li>
  8. WHO Expert Committee on Diabetes Mellitus: second report. World Health Organ Tech Rep Ser. 1980;646:1\u201180. <\/li>
  9. Bartolo S, Vambergue A, Deruelle P. Le d\u00e9pistage du diab\u00e8te gestationnel\u202f: encore de nombreuses questions non r\u00e9solues. J Gyn\u00e9cologie Obst\u00e9trique Biol Reprod. f\u00e9vr 2016;45(2):105\u201111. <\/li>
  10. Mandelbrot L, Legardeur H, Girard G. D\u00e9pistage du diab\u00e8te gestationnel : le temps est-il venu de revoir les recommandations ? Gyn\u00e9cologie Obst\u00e9trique Fertil. 1 juin 2010;38(6):409\u201114. <\/li>
  11. Crowther CA, Hiller JE, Moss JR, McPhee AJ, Jeffries WS, Robinson JS. Effect of Treatment of Gestational Diabetes Mellitus on Pregnancy Outcomes. N Engl J Med. 16 juin 2005;352(24):2477\u201186. <\/li>
  12. Bogdanet D, Reddin C, Murphy D, Doheny HC, Halperin JA, Dunne F, et al. Emerging Protein Biomarkers for the Diagnosis or Prediction of Gestational Diabetes\u2014A Scoping Review. J Clin Med. 6 avr 2021;10(7):1533. <\/li>
  13. Karami M, Mousavi SH, Rafiee M, Heidari R, Shahrokhi SZ. Biochemical and molecular biomarkers: unraveling their role in gestational diabetes mellitus. Diabetol Metab Syndr. 11 janv 2023;15(1):5. <\/li>
  14. Dinesen S, El-Faitarouni A, Frisk NLS, S\u00f8rensen AE, Dalgaard LT. Circulating microRNA as Biomarkers for Gestational Diabetes Mellitus\u2014A Systematic Review and Meta-Analysis. Int J Mol Sci. 24 mars 2023;24(7):6186. <\/li>
  15. Muche AA, Olayemi OO, Gete YK. Prevalence and determinants of gestational diabetes mellitus in Africa based on the updated international diagnostic criteria: a systematic review and meta-analysis. Arch Public Health. d\u00e9c 2019;77(1):36. <\/li>
  16. Yessoufou A, Moutairou K. Maternal Diabetes in Pregnancy: Early and Long-Term Outcomes on the Offspring and the Concept of \u201cMetabolic Memory\u201d. Exp Diabetes Res. 2011;2011:1\u201112. <\/li>
  17. Chamlal H, Mziwira M, Ayachi ME, Belahsen R. Prevalence of gestational diabetes and associated risk factors in the population of Safi Province in Morocco. Pan Afr Med J. 26 nov 2020;37:281. <\/li>
  18. Utz B, Assarag B, Essolbi A, Barkat A, Benkaddour YA, De Brouwere V. Diagnosis a posteriori? Assessing gestational diabetes screening and management in Morocco. Glob Health Action. 1 d\u00e9c 2016;9(1):32511. <\/li>
  19. Paulo MS, Abdo NM, Bettencourt-Silva R, Al-Rifai RH. Gestational Diabetes Mellitus in Europe: A Systematic Review and Meta-Analysis of Prevalence Studies. Front Endocrinol. 9 d\u00e9c 2021;12:691033. <\/li>
  20. Eades CE, Cameron DM, Evans JMM. Prevalence of gestational diabetes mellitus in Europe: A meta-analysis. Diabetes Res Clin Pract. juill 2017;129:173\u201181. <\/li>
  21. 20200302_133352_2406-IDF-ATLAS-FRENCH-BOOK.pdf [Internet]. [cit\u00e9 14 janv 2023]. Available on : https:\/\/diabetesatlas.org\/upload\/resources\/material\/20200302_133352_2406-IDF-ATLAS-FRENCH-BOOK.pdf<\/li>
  22. Blanco E, Marin M, Nu\u00f1ez L, Retamal E, Ossa X, Woolley KE, et al. Adverse pregnancy and perinatal outcomes in Latin America and the Caribbean: systematic review and meta-analysis. Rev Panam Salud P\u00fablica. 14 avr 2023;46:e21. <\/li>
  23. Mohan D, Chandrasekaran S. Gestational Diabetes Mellitus in Asian Indian Population: Pathophysiology and Mechanism. J Indian Inst Sci [Internet]. 8 avr 2023; available on: https:\/\/doi.org\/10.1007\/s41745-023-00367-8<\/li>
  24. Wang H, Li N, Chivese T, Werfalli M, Sun H, Yuen L, et al. IDF Diabetes Atlas: Estimation of Global and Regional Gestational Diabetes Mellitus Prevalence for 2021 by International Association of Diabetes in Pregnancy Study Group\u2019s Criteria. Diabetes Res Clin Pract. 1 janv 2022;183:109050. <\/li>
  25. Chen P, Wang S, Ji J, Ge A, Chen C, Zhu Y, et al. Risk Factors and Management of Gestational Diabetes. Cell Biochem Biophys. mars 2015;71(2):689\u201194. <\/li>
  26. Farrar D, Simmonds M, Bryant M, Lawlor DA, Dunne F, Tuffnell D, et al. Risk factor screening to identify women requiring oral glucose tolerance testing to diagnose gestational diabetes: A systematic review and meta-analysis and analysis of two pregnancy cohorts. PloS One. 2017;12(4):e0175288. <\/li>
  27. Chu SY, Kim SY, Schmid CH, Dietz PM, Callaghan WM, Lau J, et al. Maternal obesity and risk of cesarean delivery: a meta-analysis. Obes Rev Off J Int Assoc Study Obes. sept 2007;8(5):385\u201194. <\/li>
  28. Torloni MR, Betr\u00e1n AP, Horta BL, Nakamura MU, Atallah AN, Moron AF, et al. Prepregnancy BMI and the risk of gestational diabetes: a systematic review of the literature with meta-analysis. Obes Rev Off J Int Assoc Study Obes. mars 2009;10(2):194\u2011203. <\/li>
  29. Alwash SM, McIntyre HD, Mamun A. The association of general obesity, central obesity and visceral body fat with the risk of gestational diabetes mellitus: Evidence from a systematic review and meta-analysis. Obes Res Clin Pract. 2021;15(5):425\u201130. <\/li>
  30. Frick AP. Advanced maternal age and adverse pregnancy outcomes. Best Pract Res Clin Obstet Gynaecol. janv 2021;70:92\u2011100. <\/li>
  31. Rotterdam ESHRE\/ASRM-Sponsored PCOS Consensus Workshop Group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome. Fertil Steril. janv 2004;81(1):19\u201125. <\/li>
  32. Diamanti-Kandarakis E, Dunaif A. Insulin resistance and the polycystic ovary syndrome revisited: an update on mechanisms and implications. Endocr Rev. d\u00e9c 2012;33(6):981\u20111030. <\/li>
  33. Choudhury AA, Rajeswari VD. Polycystic ovary syndrome (PCOS) increases the risk of subsequent gestational diabetes mellitus (GDM): A novel therapeutic perspective. Life Sci. 1 d\u00e9c 2022;310:121069. <\/li>
  34. Bahri Khomami M, Joham AE, Boyle JA, Piltonen T, Silagy M, Arora C, et al. Increased maternal pregnancy complications in polycystic ovary syndrome appear to be independent of obesity-A systematic review, meta-analysis, and meta-regression. Obes Rev Off J Int Assoc Study Obes. mai 2019;20(5):659\u201174. <\/li>
  35. Milajerdi A, Abbasi F, Mousavi SM, Esmaillzadeh A. Maternal vitamin D status and risk of gestational diabetes mellitus: A systematic review and meta-analysis of prospective cohort studies. Clin Nutr Edinb Scotl. mai 2021;40(5):2576\u201186. <\/li>
  36. Petry CJ. Iron Supplementation in Pregnancy and Risk of Gestational Diabetes: A Narrative Review. Nutrients. 12 nov 2022;14(22):4791. <\/li>
  37. Lai JS, Pang WW, Cai S, Lee YS, Chan JK, Shek LP, et al. High folate and low vitamin B12 status during pregnancy is associated with gestational diabetes mellitus. Clin Nutr Edinb Scotl. juin 2018;37(3):940\u20117. <\/li>
  38. Lowe WL. Genetics and Epigenetics: Implications for the Life Course of Gestational Diabetes. Int J Mol Sci. 23 mars 2023;24(7):6047. <\/li>
  39. Tong X, Yang L, Jiang C, Weng Z, Zu A, Hou Y, et al. A Review of the Associations Between Obstructive Sleep Apnea and Gestational Diabetes Mellitus and Possible Mechanisms of Disease. Reprod Sci. 7 mars 2022;30(1):81\u201192. <\/li>
  40. Pinto S, Croce L, Carlier L, Cosson E, Rotondi M. Thyroid dysfunction during gestation and gestational diabetes mellitus: a complex relationship. J Endocrinol Invest [Internet]. 7 avr 2023 [cit\u00e9 9 mai 2023]; Disponible sur: https:\/\/doi.org\/10.1007\/s40618-023-02079-3<\/li>
  41. Hosseini E, Mokhtari Z, Salehi Abargouei A, Mishra GD, Amani R. Maternal circulating leptin, tumor necrosis factor-alpha, and interleukine-6 in association with gestational diabetes mellitus: a systematic review and meta-analysis. Gynecol Endocrinol. 14 d\u00e9c 2023;39(1):2183049. <\/li>
  42. Reece EA. The fetal and maternal consequences of gestational diabetes mellitus. J Matern Fetal Neonatal Med. mars 2010;23(3):199\u2011203. <\/li>
  43. Bellamy L, Casas JP, Hingorani AD, Williams D. Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. The Lancet. 23 mai 2009;373(9677):1773\u20119. <\/li>
  44. Cosson E. Diab\u00e8te gestationnel\u202f: devenir des m\u00e8res apr\u00e8s la grossesse et de leurs enfants. M\u00e9decine Mal M\u00e9taboliques. oct 2017;11(6):518\u201124. <\/li>
  45. Lowe WL. Genetics and Epigenetics: Implications for the Life Course of Gestational Diabetes. Int J Mol Sci. 23 mars 2023;24(7):6047. <\/li>
  46. Xu Y, Shen S, Sun L, Yang H, Jin B, Cao X. Metabolic syndrome risk after gestational diabetes: a systematic review and meta-analysis. PloS One. 2014;9(1):e87863. <\/li>
  47. Lauenborg J, Mathiesen E, Hansen T, Gl\u00fcmer C, J\u00f8rgensen T, Borch-Johnsen K, et al. 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. juill 2005;90(7):4004\u201110. <\/li>
  48. Schwartz N, Nachum Z, Green MS. The prevalence of gestational diabetes mellitus recurrence\u2014effect of ethnicity and parity: a metaanalysis. Am J Obstet Gynecol. 1 sept 2015;213(3):310\u20117. <\/li>
  49. Shah BR, Retnakaran R, Booth GL. Increased risk of cardiovascular disease in young women following gestational diabetes mellitus. Diabetes Care. ao\u00fbt 2008;31(8):1668\u20119. <\/li>
  50. Db C, Km U, Rl H, J T, Tm W, K K, et al. Gestational diabetes mellitus increases the risk of cardiovascular disease in women with a family history of type 2 diabetes. Diabetes Care [Internet]. sept 2006 [cit\u00e9 13 d\u00e9c 2022];29(9). Available on: https:\/\/pubmed.ncbi.nlm.nih.gov\/16936156\/<\/li>
  51. Kramer CK, Campbell S, Retnakaran R. Gestational diabetes and the risk of cardiovascular disease in women: a systematic review and meta-analysis. Diabetologia. juin 2019;62(6):905\u201114. <\/li>
  52. Lee SM, Shivakumar M, Park JW, Jung YM, Choe EK, Kwak SH, et al. Long-term cardiovascular outcomes of gestational diabetes mellitus: a prospective UK Biobank study. Cardiovasc Diabetol. 29 oct 2022;21(1):221. <\/li>
  53. Expert consensus on gestational diabetes mellitus. Summary of expert consensus. Diabetes Metab. d\u00e9c 2010;36(6 Pt 2):695\u20119. <\/li>
  54. Beharier O, Shoham-Vardi I, Pariente G, Sergienko R, Kessous R, Baumfeld Y, et al. Gestational diabetes mellitus is a significant risk factor for long-term maternal renal disease. J Clin Endocrinol Metab. avr 2015;100(4):1412\u20116. <\/li>
  55. Beharier O, Sergienko R, Kessous R, Szaingurten-Solodkin I, Walfisch A, Shusterman E, et al. Gestational diabetes mellitus is a significant risk factor for long-term ophthalmic morbidity. Arch Gynecol Obstet. juin 2017;295(6):1477\u201182. <\/li>
  56. Kc K, Shakya S, Zhang H. Gestational diabetes mellitus and macrosomia: a literature review. Ann Nutr Metab. 2015;66 Suppl 2:14\u201120. <\/li>
  57. Leiva A, Pardo F, Ram\u00edrez MA, Far\u00edas M, Casanello P, Sobrevia L. Fetoplacental Vascular Endothelial Dysfunction as an Early Phenomenon in the Programming of Human Adult Diseases in Subjects Born from Gestational Diabetes Mellitus or Obesity in Pregnancy. Exp Diabetes Res. 2011;2011:349286. <\/li>
  58. Wendland EM, Torloni MR, Falavigna M, Trujillo J, Dode MA, Campos MA, et al. Gestational diabetes and pregnancy outcomes–a systematic review of the World Health Organization (WHO) and the International Association of Diabetes in Pregnancy Study Groups (IADPSG) diagnostic criteria. BMC Pregnancy Childbirth. 31 mars 2012;12:23. <\/li>
  59. Araujo J\u00fanior E, Peixoto AB, Zamarian ACP, Elito J\u00fanior J, Tonni G. Macrosomia. Best Pract Res Clin Obstet Gynaecol. janv 2017;38:83\u201196. <\/li>
  60. HAPO Study Cooperative Research Group, Metzger BE, Lowe LP, Dyer AR, Trimble ER, Chaovarindr U, et al. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 8 mai 2008;358(19):1991\u20112002. <\/li>
  61. Li Y, Wang W, Zhang D. Maternal diabetes mellitus and risk of neonatal respiratory distress syndrome: a meta-analysis. Acta Diabetol. juill 2019;56(7):729\u201140. <\/li>
  62. Mortier I, Blanc J, Tosello B, Gire C, Bretelle F, Carcopino X. Is gestational diabetes an independent risk factor of neonatal severe respiratory distress syndrome after 34 weeks of gestation? A prospective study. Arch Gynecol Obstet. d\u00e9c 2017;296(6):1071\u20117. <\/li>
  63. Murray SR, Reynolds RM. Short- and long-term outcomes of gestational diabetes and its treatment on fetal development. Prenat Diagn. ao\u00fbt 2020;40(9):1085\u201191. <\/li>
  64. Billionnet C, Mitanchez D, Weill A, Nizard J, Alla F, Hartemann A, et al. Gestational diabetes and adverse perinatal outcomes from 716,152 births in France in 2012. Diabetologia. avr 2017;60(4):636\u201144. <\/li>
  65. 65.       Zhang TN, Huang XM, Zhao XY, Wang W, Wen R, Gao SY. Risks of specific congenital anomalies in offspring of women with diabetes: A systematic review and meta-analysis of population-based studies including over 80 million births. PLoS Med. f\u00e9vr 2022;19(2):e1003900. <\/li>
  66. Scholtens DM, Kuang A, Lowe LP, Hamilton J, Lawrence JM, Lebenthal Y, et al. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Glycemia and Childhood Glucose Metabolism. Diabetes Care. 7 janv 2019;42(3):381\u201192. <\/li>
  67. Sandu C, Bica C, Salmen T, Stoica R, Bohiltea R, Gherghiceanu F, et al. Gestational diabetes – modern management and therapeutic approach (Review). Exp Ther Med. janv 2021;21(1):81. <\/li>
  68. Alwan N, Tuffnell DJ, West J. Treatments for gestational diabetes. Cochrane Database Syst Rev. 8 juill 2009;2009(3):CD003395. <\/li>
  69. Johns EC, Denison FC, Norman JE, Reynolds RM. Gestational Diabetes Mellitus: Mechanisms, Treatment, and Complications. Trends Endocrinol Metab TEM. nov 2018;29(11):743\u201154. <\/li>
  70. American Diabetes Association. 13. Management of Diabetes in Pregnancy: Standards of Medical Care in Diabetes\u20142018<\/em>. Diabetes Care. 1 janv 2018;41(Supplement_1):S137\u201143. <\/li>
  71. O\u2019Neill SM, Kenny LC, Khashan AS, West HM, Smyth RM, Kearney PM. Different insulin types and regimens for pregnant women with pre-existing diabetes. Cochrane Database Syst Rev. 3 f\u00e9vr 2017;2(2):CD011880. <\/li>
  72. PERINATAL NETWORK RECOMMENDATIONS : management of gestational diabetes, 08\/25\/2020. Available on: https:\/\/www.reseauperinatallorrain.fr\/app\/download\/33353841\/Diab%C3%A8te+pr%C3%A9existant+et+grossesse_10-09-20.pdf<\/li>
  73. Blum AK. Insulin Use in Pregnancy: An Update. Diabetes Spectr Publ Am Diabetes Assoc. mai 2016;29(2):92\u20117. <\/li>
  74. Guo L, Ma J, Tang J, Hu D, Zhang W, Zhao X. Comparative Efficacy and Safety of Metformin, Glyburide, and Insulin in Treating Gestational Diabetes Mellitus: A Meta-Analysis. J Diabetes Res. 2019;2019:9804708. <\/li>
  75. Liang HL, Ma SJ, Xiao YN, Tan HZ. Comparative efficacy and safety of oral antidiabetic drugs and insulin in treating gestational diabetes mellitus: An updated PRISMA-compliant network meta-analysis. Medicine (Baltimore). sept 2017;96(38):e7939. <\/li>
  76. Farrar D, Simmonds M, Bryant M, Sheldon TA, Tuffnell D, Golder S, et al. Treatments for gestational diabetes: a systematic review and meta-analysis. BMJ Open. 24 juin 2017;7(6):e015557. <\/li>
  77. national nutrition programme. Morocco. Available on:            https:\/\/www.sante.gov.ma\/Documents\/2019\/06\/Programme%20National%20de%20Nutrition.pdf <\/li>
  78. Morris MA, Hutchinson J, Gianfrancesco C, Alwan NA, Carter MC, Scott EM, et al. Relationship of the Frequency, Distribution, and Content of Meals\/Snacks to Glycaemic Control in Gestational Diabetes: The myfood24 GDM Pilot Study. Nutrients. 18 d\u00e9c 2019;12(1):3. <\/li>
  79. Han S, Crowther CA, Middleton P, Heatley E. Different types of dietary advice for women with gestational diabetes mellitus. Cochrane Database Syst Rev. 28 mars 2013;(3):CD009275. <\/li>
  80. Viana LV, Gross JL, Azevedo MJ. Dietary intervention in patients with gestational diabetes mellitus: a systematic review and meta-analysis of randomized clinical trials on maternal and newborn outcomes. Diabetes Care. d\u00e9c 2014;37(12):3345\u201155. <\/li>
  81. Plows JF, Reynolds CM, Vickers MH, Baker PN, Stanley JL. Nutritional Supplementation for the Prevention and\/or Treatment of Gestational Diabetes Mellitus. Curr Diab Rep. sept 2019;19(9):73. <\/li>
  82. Hamer M, Chida Y. Intake of fruit, vegetables, and antioxidants and risk of type 2 diabetes: systematic review and meta-analysis. J Hypertens. d\u00e9c 2007;25(12):2361\u20119. <\/li>
  83. Barbour LA. Unresolved controversies in gestational diabetes: implications on maternal and infant health. Curr Opin Endocrinol Diabetes Obes. ao\u00fbt 2014;21(4):264\u201170. <\/li>
  84. Mierzy\u0144ski R, Poniedzia\u0142ek-Czajkowska E, Sotowski M, Szyde\u0142ko-Gorzkowicz M. Nutrition as Prevention Factor of Gestational Diabetes Mellitus: A Narrative Review. Nutrients. 26 oct 2021;13(11):3787. <\/li>
  85. Luoto R, Laitinen K, Nermes M, Isolauri E. Impact of maternal probiotic-supplemented dietary counselling on pregnancy outcome and prenatal and postnatal growth: a double-blind, placebo-controlled study. Br J Nutr. juin 2010;103(12):1792\u20119. <\/li>
  86. Donazar-Ezcurra M, L\u00f3pez-Del Burgo C, Bes-Rastrollo M. Primary prevention of gestational diabetes mellitus through nutritional factors: a systematic review. BMC Pregnancy Childbirth. 13 janv 2017;17(1):30. <\/li>
  87. Wu C, Song Y, Wang X. Vitamin D Supplementation for the Outcomes of Patients with Gestational Diabetes Mellitus and Neonates: A Meta-Analysis and Systematic Review. Int J Clin Pract. 2023;2023:1907222. <\/li>
  88. Tan X, Huang Y. Magnesium supplementation for glycemic status in women with gestational diabetes: a systematic review and meta-analysis. Gynecol Endocrinol Off J Int Soc Gynecol Endocrinol. mars 2022;38(3):202\u20116. <\/li>
  89. Liu W, Gao M, Yang S, Sun C, Bi Y, Li Y, et al. Effects of omega-3 supplementation on glucose and lipid metabolism in patients with gestational diabetes: A meta-analysis of randomized controlled trials. J Diabetes Complications. avr 2023;37(4):108451. <\/li>
  90. Barakat R, Refoyo I, Coteron J, Franco E. Exercise during pregnancy has a preventative effect on excessive maternal weight gain and gestational diabetes. A randomized controlled trial. Braz J Phys Ther. 2019;23(2):148\u201155. <\/li>
  91. Zakaria H, Abusanana S, Mussa BM, Al Dhaheri AS, Stojanovska L, Mohamad MN, et al. The Role of Lifestyle Interventions in the Prevention and Treatment of Gestational Diabetes Mellitus. Medicina (Mex). 1 f\u00e9vr 2023;59(2):287. <\/li><\/ol>\n","protected":false},"excerpt":{"rendered":"

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