Obese Gestational Diabetes Mellitus Research Articles

Association Between Apolipoprotein C-3 SstⅠ Polymorphism and Serum Lipids in Patients With Gestational Diabetes Mellitus

To investigate the apolipoprotein C-3 (APOC3) gene Sst Ⅰ polymorphism and its relationship with changes in serum lipids in patients with gestational diabetes mellitus (GDM). A total of 630 pregnant women with GDM and 1027 normal pregnant controls were covered in the study. The genotype and allele frequencies of APOC3 Sst Ⅰ polymorphism were analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). Total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose (Glu) were measured by enzymatic methods. Plasma insulin (INS) was measured by chemiluminescence. Apolipoproteins A 1 (apoA1) and B (apoB) levels were measured by turbidimetric immunoassay. The allele frequencies of S1 and S2 of the APOC3 polymorphism at the SstⅠ locus were 0.704 and 0.296 in the GDM group and 0.721 and 0.279 in the control group, respectively. There was no significant difference in genotype frequency and allele frequency of APOC3 Sst Ⅰ polymorphism between the GDM and the control groups ( P>0.05). In the GDM group, those with S2S2 and S1S2 genotypes had higher plasma HDL-C levels and lower atherogenic index (AI) values than those with S1S1 genotype did, with the differences being statistically significant (all P<0.05). GDM patients were then divided into obesity and non-obesity subgroups. Further subgroup analysis showed that the association of APOC3 genotype with changes in HDL-C levels was observed only in obese GDM patients, while the association of APOC3 genotype with changes in AI values was observed in both obese and nonobese patients. In addition, in obese GDM patients, those with S2S2 genotype had significantly higher plasma TG levels than those with S1S1 and S1S2 genotypes did ( P<0.05 and P<0.01, respectively). In non-obese GDM patients, those with S2S2 genotype had significantly lower apoB/apoA1 ratio than S2S2 carriers did ( P<0.05). No genotype-related effect on lipid and apolipoprotein variations was evident in the normal controls. APOC3 Sst Ⅰ polymorphism in GDM patients is associated with HDL-C and TG levels as well as AI value and apoB/apoA1 ratio. The changes in lipid levels and apolipoprotein ratio showed BMI-dependent features. However, association between polymorphism at the locus and the development of GDM was not observed.

Metabolomic Profiles of Nonobese and Obese Women With Gestational Diabetes.

To examine whether nonobese (BMI<30 kg/m2) and obese (BMI≥30 kg/m2) women with gestational diabetes mellitus (GDM) and obese non-GDM women differ in metabolomic profiles from nonobese non-GDM controls. Levels of 66 metabolic measures were assessed in early (median 13, IQR 12.4-13.7 gestation weeks), and across early, mid (20, 19.3-23.0) and late (28, 27.0-35.0) -pregnancy blood samples in 755 pregnant women of the PREDO and RADIEL studies. The independent replication cohort comprised 490 pregnant women. Nonobese and obese GDM, and obese non-GDM women differed similarly from the controls across early, mid, and late pregnancy in 13 measures, including VLDL-related measures, and fatty acids. In 6 measures, including fatty acid ratios, glycolysis-related measures, valine and 3-hydroxybutyrate, the differences between obese GDM women and controls were more pronounced than the differences between nonobese GDM or obese non-GDM women and controls. In 16 measures, including HDL-related measures, fatty acid ratios, amino acids and inflammation, differences between obese GDM or obese non-GDM women and controls were more pronounced than the differences between nonobese GDM women and controls. Most differences were evident in early pregnancy, and in the replication cohort were more often in the same direction than would be expected by chance alone. Differences between nonobese and obese GDM, or obese non-GDM women and controls in metabolomic profiles may allow detection of high-risk women for timely targeted preventive interventions.

GESTASYONEL DİYABETES MELLİTUS İLE D VİTAMİNİ, KALSİTONİN VE PARATHORMON İLİŞKİSİ

ABSTRACT: Objective: There is growing evidence that Vitamin D has important role in glucose metabolism. Calcitonin and parathyroid hormone were not fully investigated in gestational diabetes mellitus (GDM). The aim of our study was to investigate the effects of vitamin D, calcitonin (Cal) and parathormone in GDM. Material and Methods: We evaluated retrospectively demographic and anthropometric parameters, vitamin D, active vitamin D, calcitonin and parathormone levels of 100 pregnant women including 50 with normal glucose metabolism and 50 with GDM whose ages and body mass indices (BMI) were similar in summer season. We classified the women according to age, parity, being veiled, BMI and vitamin D levels, and compared all parameters, then searched the correlation of all the parameters in groups and subgroups. Results: 25 hydroxy vitamin D (VitD) levels were non-significantly low in GDM and also in older, multiparous, veiled and obese GDM subgroups. Calcitonin and parathormone levels were not different in two groups. Vitamin D-deficient and obese GDM subgroups had significantly higher calcitonin levels than their opposite subgroups. There was a positive correlation between Cal and BMI in GDM, in Vit D deficient, older, or veiled GDM subgroups. Positive correlation between vitamin D and C peptide was found in only obese GDM. In logistic regression analysis including GDM subgroups and calcium metabolism hormones, except younger age (OR=0.116 (95% CI=0.04-0.338, p=&amp;lt;0.001)), VitD, active VitD, Cal, and PTH had no effect on GDM prediction. Conclusion: Although we could not find a significant difference in VitD, Cal and PTH levels of our GDM patients in summer season, we thought that VitD could play a role in obese GDM patients.We also concluded that Cal and PTH did not have roles in gestational diabetes mellitus. Larger, carefully designed studies including throughout pregnancy and postpartum periods and seasonal variations are required.

Atlantic DIP: is weight gain less than that recommended by IOM safe in obese women with gestational diabetes mellitus?

The Institute of Medicine (IOM) recommends gestational weight gain (GWG) of 5-9 kg in women with a body mass index (BMI) ≥ 30 kg/m2. Debate continues as to whether GWG less than that recommended is safe in women with gestational diabetes mellitus (GDM). The study objective was to examine maternal and infant outcomes for obese women with GDM who lost weight or gained 0-5 kg during pregnancy. A 7-year retrospective cohort study of pregnancy outcomes for obese women with GDM recorded in the Atlantic Diabetes in Pregnancy database was conducted. We examined pregnancy outcomes for mothers with GDM and a BMI ≥ 30 who either lost weight or gained 0-5 kg (Group 1, n = 237) and women who gained 5-9 kg (Group 2, n = 77). We further divided groups 1 and 2 into women treated by diet only (GDM-D) (n = 120) and those requiring additional treatment with insulin (GDM-I) (n = 194). GDM-D women in Group 1 were more likely to deliver earlier (38.9 vs 39.8 weeks, p < 0.01), to develop pregnancy induced hypertension (PIH) (15.4% v 0%; p = 0.02) or have a post-partum haemorrhage (PPH) (13.2% vs 0, p = 0.03) compared to women in Group 2. Rates of prematurity were higher in group 1 vs 2 (14.3% vs 0%, p = 0.03). However, further logistic regression analysis adjusted for smoking status, family history of diabetes, ethnicity and age determined no significant difference in maternal or infant outcomes for women in Group 1 compared to those in Group 2. In our population, weight gain less than IOM guideline appears safe and is not associated with any further increase in adverse outcomes. However, validation through a prospective study with a larger obese GDM cohort is required before the findings presented here could be recommended for routine clinical use.

Effect of glucose on Akt2 mRNA and methylation level and the association between early-pregnancy Akt2 mRNA level in peripheral blood and pre-pregnancy BMI and GDM

Objective: To explore the effect of glucose on Akt2 gene methylation and mRNA level in the trophoblast cell line HTR8/SVneo and the association between first-trimester Akt2 mRNA level in peripheral blood and pre-pregnancy body mass index (BMI) and gestational diabetes mellitus (GDM). Methods: The cell model of intrauterine hyperglycemia in pregnant women with GDM was established, and divided into 5 groups based on the different glucose concentrations (2.5, 5.0, 10.0, 25.0, and 40.0 mmol/L). The mRNA levels of Akt2 gene were detected by real-time quantitative PCR, and the methylation levels of Akt2 gene promoter region were detected by mass spectrometry. According to pre-pregnancy BMI and diagnosis of GDM, 60 pregnant women who had given birth at Peking University First Hospital during December 2014 to July 2016 were classified into overweight non-GDM group, overweight GDM group, obese non-GDM group and obese GDM group. Real-time quantitative PCR analyses were used to detect the levels of Akt2 mRNA in first-trimester peripheral blood of the 4 groups. Results: (1) Level of Akt2 mRNA significantly rose with the glucose concentration of medium increased, showing concentration dependency (all P<0.05). Compared with the 25.0 mmol/L group, the following methylation levels changed significantly (all P<0.05): cytosine-phosphate-guanine (CpG) 10, CpG23, and CpG24.5 of Akt2 gene promoter region in the 5.0 mmol/L group, CpG23 and CpG24.5 in the 2.5 mmol/L group, and CpG10 in the 10.0 mmol/L group. Compared with the 5.0 mmol/L group, CpG10 in the 40.0 mmol/L group showed methylation change (P<0.05). (2) Compared with the overweight non-GDM group [1.04(0.90~1.26)], overweight GDM group [2.10(1.85~2.28)] and obese GDM group [1.68(0.82~2.43)] all had higher Akt2 mRNA levels and the differences were statistically significant (all P<0.05). Compared to obese GDM group [1.68(0.82~2.43)], the level of Akt2 mRNA was higher in overweight GDM group [2.10(1.85~2.28)] and lower in obese non-GDM group [1.00(0.71~2.17)], but the differences were not statistically significant (all P>0.05). Conclusions: Glucose might affect Akt2 mRNA level by changing the methylation of Akt2 gene promoter region, and the change might appear in the first trimester of pregnant women with GDM, especially for women with lower pre-pregnancy BMI.

Obesity in patients with gestational diabetes: Impact on newborn outcomes

ObjectiveTo compare the perinatal adverse outcomes of obese and non-obese pregnant women with Gestational Diabetes Mellitus (GDM). Materials and methodsThis is a Cross-sectional study. Data were collected from the medical records of patients diagnosed with GDM at Unimed Hospital Center in the city of Joinville, from 2011 to 2017. Maternal-fetal characteristics, therapies and complications of pregnant women diagnosed with GDM were analyzed. The subjects of the study were separated into two groups: obese and non-obese GDM patients. Statistical analysis was performed by calculating multinomial logistic regression, adjusted using the 95% confidence interval (CI). ResultsA total of 442 patients were described as having gestational diabetes, of which 260 (58.8%) were diagnosed with obesity and 182 (41.1%) were non-obese. Maternal characteristics diverged regarding the Body Mass Index (BMI) (30.0vs22.5 P = 0.000), Gestational Age (GA) from GDM diagnosis (26.95vs29.07 P = 0.002), cesarean section (c-section) (86.2%vs75.9% P = 0.003), the incidence of chronic Hypertension (10.3%vs4.2% P = 0.011), treatment by dieting (29.0%vs48.1% P = 0.000) and metformin (44.5%vs34.7% P = 0.027) of obese and non-obese pregnant women, respectively. As for newborns, there was a reduction in weight (3185.8vs3,217.4 P = 0.045) and in the number of newborns of normal weight (13.8%vs23.6% P = 0.005), of newborns from obese and non-obese mothers, respectively. After ratio calculation, it was noticed that obese pregnant women had a higher chance of undergoing a c-section (OR 2.137 CI 95%, 1257-3.631). There was no significance found in other pregnancy outcomes. ConclusionPregnant women diagnosed with GDM and obesity are approximately twice as likely to undergo Cesarean Surgery, compared to non-obese women. As a result, newborns will have a greater influence on the outcomes and occasional events of cesarean section.

Adipose Tissue Insulin Resistance in Gestational Diabetes.

Gestational diabetes mellitus (GDM) is a metabolic disorder characterized by insulin resistance (IR) and altered glucose-lipid metabolism. We propose that ectonucleotide pyrophosphate phosphodiesterase-1 (ENPP1), a protein known to induce adipocyte IR, is a determinant of GDM. Our objective was to study ENPP1 expression in adipose tissue (AT) of obese pregnant women with or without GDM, as well as glucose tolerance in pregnant transgenic (Tg) mice with AT-specific overexpression of human ENPP1. AT biopsies and blood were collected from body mass index-matched obese pregnant women non-GDM (n = 6), GDM (n = 7), and nonpregnant controls (n = 6) undergoing cesarian section or elective surgeries, respectively. We measured the following: (1) Expression of key molecules involved in insulin signaling and glucose-lipid metabolism in AT; (2) Plasma glucose and insulin levels and calculation of homeostasis model assessment of IR (HOMA-IR); (3) Intraperitoneal glucose tolerance test in AtENPP1 Tg pregnant mice. We found that: (1) Obese GDM patients have higher AT ENPP1 expression than obese non-GDM patients, or controls (P = 0.01-ANOVA). (2) ENPP1 expression level correlated negatively with glucose transporter 4 (GLUT4) and positively with insulin receptor substrate-1 (IRS-1) serine phosphorylation, and to other adipocyte functional proteins involved in glucose and lipid metabolism (P < 0.05 each), (3) AT ENPP1 expression levels were positively correlated with HOMA-IR (P = 0.01-ANOVA). (4) Pregnant AT ENPP1 Tg mice showed higher plasma glucose than wild type animals (P = 0.046-t test on area under curve [AUC]glucose). Our results provide evidence of a causative link between ENPP1 and alterations in insulin signaling, glucose uptake, and lipid metabolism in subcutaneous abdominal AT of GDM, which may mediate IR and hyperglycemia in GDM.

Endocan expression is increased in the placenta from obese women with gestational diabetes mellitus

IntroductionEndocan, a member of the proteoglycan family, is involved in a wide range of diseases including obesity and diabetes. The aim of this study was to determine the effect of (i) maternal obesity and gestational diabetes mellitus (GDM) on placental endocan expression; and (ii) endocan knockdown on markers of inflammation. MethodsEndocan mRNA and protein expression was determined in human placenta from (i) lean and obese and normal glucose tolerant (NGT) pregnant women (n = 10 patients per group); and (ii) women with GDM and BMI-matched NGT women (n = 40 patients per group). Primary villous trophoblast cells and HUVECs were used to assess the effect of endocan siRNA knockdown on pro-inflammatory cytokines. ResultsThere was no effect of maternal obesity on placental endocan expression. Further, endocan expression was not different between lean NGT and BMI-matched women with GDM. However, endocan mRNA and protein expression was significantly higher in placenta from obese women with GDM when compared to BMI-matched NGT women. Knockdown of endocan in villous trophoblast cells and HUVECs had no effect on infection- or inflammation-induced expression and secretion of IL-6, IL-8 and MCP-1. DiscussionEndocan expression is increased in the human placenta from obese women with GDM, and in response to pro-inflammatory stimuli. Loss-of-function studies in villous trophoblast cells and HUVECs revealed that endocan is not directly involved in the genesis or in the expression of pro-inflammatory cytokines induced by LPS or IL-1β. Further studies are required to elucidate the functional consequences of increased placental endocan expression in obese GDM pregnancies.

First-trimester multimarker prediction of gestational diabetes mellitus using targeted mass spectrometry.

Gestational diabetes mellitus (GDM) is associated with an increased risk of pre-eclampsia, macrosomia and the future development of type 2 diabetes mellitus in both mother and child. Although an early and accurate prediction of GDM is needed to allow intervention and improve perinatal outcome, no single protein biomarker has yet proven useful for this purpose. In the present study, we hypothesised that multimarker panels of serum proteins can improve first-trimester prediction of GDM among obese and non-obese women compared with single markers. A nested case-control study was performed on first-trimester serum samples from 199 GDM cases and 208 controls, each divided into an obese group (BMI ≥27kg/m(2)) and a non-obese group (BMI <27kg/m(2)). Based on their biological relevance to GDM or type 2 diabetes mellitus or on their previously reported potential as biomarkers for these diseases, a number of proteins were selected for targeted nano-flow liquid chromatography (LC) MS analysis. This resulted in the development and validation of a 25-plex multiple reaction monitoring (MRM) MS assay. After false discovery rate correction, six proteins remained significantly different (p<0.05) between obese GDM patients (n=135) and BMI-matched controls (n=139). These included adiponectin, apolipoprotein M and apolipoprotein D. Multimarker models combining protein levels and clinical data were then constructed and evaluated by receiver operating characteristic (ROC) analysis. For the obese, non-obese and all GDM groups, these models achieved marginally higher AUCs compared with adiponectin alone. Multimarker models combining protein markers and clinical data have the potential to predict women at a high risk of developing GDM.

Maternal Obesity, Maternal Gestational Diabetes Mellitus, and Maternal and Neonatal Outcomes

We aimed to investigate the co-morbid effects of maternal obesity, Gestational Diabetes Mellitus (GDM), and GDM treatment options on maternal and neonatal outcomes in an inner-city population. This is a retrospective chart review study of singleton mothers with new diagnosis of GDM and their infants during a 3-year period. During the study period, 356 women ages 13-48 years with GDM gave birth to 180 males and 175 females. Majority of mothers were African American (50.8%) and had Medicaid insurance (75.8%). Obese mothers constituted 48.3% of the study population, had a higher prevalence of pregnancy induced hypertension/preeclampsia, more commonly were managed with medication and delivered by C-section than non-obese mothers. Infants of obese GDM mothers had significantly higher mean birth weight, lower mean blood glucose, and were less at risk for Small for Gestational Age (SGA). In obese mothers, heaviest mothers had infants with higher bilirubin levels than less heavy mothers. We also observed a high rate of feeding difficulty in infants of GDM mothers (12.4%). Our study emphasizes the burden of maternal obesity as a major risk factor for both maternal and neonatal poor outcomes in the context of GDM and calls for further prospective and interventional research.

A retrospective study of maternal and neonatal outcomes in overweight and obese women with gestational diabetes mellitus

In pregnant women, obesity is a risk factor for multiple adverse pregnancy outcomes, including gestational diabetes mellitus (GDM), preeclampsia, and preterm birth. The aim of this study was to determine the effects of pre-pregnancy body mass index (BMI) on maternal and neonatal outcomes in women with GDM. A retrospective study of 5010 patients with GDM in 11 provinces in China was performed in 2011. Participants were divided into three groups based on BMI as follows: a normal weight group (BMI 18.5–23.9 kg/m2), an overweight group (BMI 24–27.9 kg/m2), and an obese group (BMI ≥28.0 kg/m2). Maternal baseline characteristics and pregnancy and neonatal outcomes were compared between the groups. Multiple logistic regression analysis was used to explore the relationships between BMI and the risk of adverse outcomes. Of the 5010 GDM patients, 2879 subjects were from north China and 2131 were from south China. Women in the normal weight group gained more weight during pregnancy compared with the overweight and obese GDM patients. Women in the overweight and obese groups had increased odds of hypertension during pregnancy (adjusted odds ratio (AOR) = 1.50, 95 % confidence interval (CI) = 1.31–1.76 and AOR = 2.12, 95 % CI = 1.84–3.16). The AORs for macrosomia in the overweight and obese groups were 1.46 (95 % CI = 1.16–1.69) and 1.94 (95 % CI = 1.31–2.98), respectively. The relative risk of delivering a baby with an Apgar score <7 at 5 min was significantly higher in women who were obese (AOR = 2.11, 95 % CI = 1.26–2.85) before pregnancy compared with normal weight women. Compared with the normal weight subjects, the incidence of cesarean section and emergency cesarean section among overweight and obese women with GDM was significantly higher (P < 0.001). Overall, overweight and obese women with GDM have an increased risk of adverse outcomes, including hypertension during pregnancy, macrosomic infants, infants with low Apgar scores, and the need for an emergency cesarean section. More attention should be paid to GDM women who are obese because they are at risk for multiple adverse outcomes.

Association of gestational diabetes mellitus (GDM) with subclinical atherosclerosis: a systemic review and meta-analysis.

BackgroundGestational diabetes mellitus (GDM) is associated with an elevated risk of adverse health outcomes such as type 2 diabetes and cardiovascular diseases. Carotid intima-media thickness (cIMT) is increasingly used as a noninvasive marker for subclinical atherosclerosis. Whether there is a direct correlation between GDM and elevated cIMT is still controversial.MethodsPubMed, Embase and reference lists of relevant papers were reviewed. Studies assessing the relationship between GDM and cIMT were included. Weighted Mean Difference (WMD) of cIMT was calculated using random-effect models.ResultsFifteen studies with a total of 2247 subjects were included in our analysis, giving a pooled WMD of 0.05 (95% confidence interval [CI] 0.03 –0.07). Furthermore, meta regression and subgroup analysis found that the association between GDM and larger cIMT already existed during pregnancy, and this relation was stronger in obese GDM patients.ConclusionsGDM in and after pregnancy is associated with subclinical atherosclerosis. Weight control may be helpful to prevent cardiovascular diseases for GDM patients.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2261-14-132) contains supplementary material, which is available to authorized users.

Gestational weight gain is an important risk factor for excessive fetal growth.

ObjectiveTo estimate the odds ratio of prepregnant body mass index (BMI), gestational weight gain (GWG), and gestational diabetes mellitus (GDM) for excessive fetal growth, which we define as large for gestational age (LGA).MethodsWe included 16,297 women who delivered a live-born singleton baby at term. We fit logistic regressions to estimate the odds ratios of variables, including maternal age, parity, prepregnant BMI ≥23, GWG ≥15 kg, and GDM, for LGA. We classified GWG into four categories (<10, 10-14.9, 15-19.9, and ≥20 kg) and BMI into four categories (underweight, normal, overweight, and obese). After adjusting for age and parity, we analyzed the odds ratios of prepregnant BMI according to GWG between non-GDM and GDM women for LGA.ResultsThe odds ratios of GWG ≥15 kg and prepregnancy BMI ≥23 for LGA were 2.40 (95% confidence interval [CI], 2.16-2.67) and 2.24 (95% CI, 1.99-2.51), respectively. The odd ratio of GDM was 1.37 (95% CI, 1.09-1.71). The risk of GDM women with normal/-overweight BMI and GWG <15 kg for LGA was not significantly greater than those of the reference group. The odd ratios of GDM women with overweight/obese BMI and GWG 15 to 19.9 kg were 3.95 (95% CI, 1.26-12.38) and 9.70 (95% CI, 3.79-24.87), respectively.ConclusionGWG ≥15 kg might be a more important risk factor for LGA than either prepregnancy BMI ≥23 or GDM. Risk for LGA was highest in obese GDM women with GWG ≥15 kg.

Omentin-1 Is Decreased in Maternal Plasma, Placenta and Adipose Tissue of Women with Pre-Existing Obesity

ObjectiveThe aim of this study was to determine (i) the effect of maternal obesity and gestational diabetes mellitus (GDM) on (i) the circulating levels of omentin-1 in cord and maternal plasma, and (ii) gene expression and release of omentin-1 from human placenta and adipose tissue. The effect of pregnancy on circulating omentin-1 levels was also determined.DesignOmentin-1 levels were measured in maternal and cord plasma from obese and non-obese normal glucose tolerant women (NGT; n = 44) and women with GDM (n = 39) at the time of term elective Caesarean section. Placenta and adipose tissue expression and release of omentin-1 was measured from 22 NGT and 22 GDM women collected at the time of term elective Caesarean section. Omentin-1 levels were also measured in maternal plasma from 13 NGT women at 11 and 28 weeks gestation and 7 weeks postpartum.ResultsMaternal obesity was associated with significantly lower omentin-1 levels in maternal plasma; however, there was no effect of maternal obesity on cord omentin levels. Omentin-1 gene expression was lower in placenta and adipose tissue obtained from women with pre-existing obesity. In addition to this, adipose tissue release of omentin-1 was significantly lower from obese pregnant women. Omentin-1 levels were significantly lower in non-obese GDM compared to non-obese NGT women. However, there was no difference in omentin-1 levels between obese NGT and obese GDM women. There was no effect of GDM on cord omentin levels, and placental and adipose tissue omentin-1 expression. Maternal omentin-1 levels were negatively correlated with fetal birthweight and fetal ponderal index.ConclusionsThe data presented in this study demonstrate that pre-existing maternal obesity is associated with lower omentin-1 expression in placenta, adipose tissue and maternal plasma. Alteration in omentin-1 in pregnancy may influence the development of metabolic disorders in offspring later in life.

The hyperglycemia and adverse pregnancy outcome study: associations of GDM and obesity with pregnancy outcomes.

OBJECTIVETo determine associations of gestational diabetes mellitus (GDM) and obesity with adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study.RESEARCH DESIGN AND METHODSParticipants underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 32 weeks. GDM was diagnosed post hoc using International Association of Diabetes and Pregnancy Study Groups criteria. Neonatal anthropometrics and cord serum C-peptide were measured. Adverse pregnancy outcomes included birth weight, newborn percent body fat, and cord C-peptide >90th percentiles, primary cesarean delivery, preeclampsia, and shoulder dystocia/birth injury. BMI was determined at the OGTT. Multiple logistic regression was used to examine associations of GDM and obesity with outcomes.RESULTSMean maternal BMI was 27.7, 13.7% were obese (BMI ≥33.0 kg/m2), and GDM was diagnosed in 16.1%. Relative to non-GDM and nonobese women, odds ratio for birth weight >90th percentile for GDM alone was 2.19 (1.93–2.47), for obesity alone 1.73 (1.50–2.00), and for both GDM and obesity 3.62 (3.04–4.32). Results for primary cesarean delivery and preeclampsia and for cord C-peptide and newborn percent body fat >90th percentiles were similar. Odds for birth weight >90th percentile were progressively greater with both higher OGTT glucose and higher maternal BMI. There was a 339-g difference in birth weight for babies of obese GDM women, compared with babies of normal/underweight women (64.2% of all women) with normal glucose based on a composite OGTT measure of fasting plasma glucose and 1- and 2-h plasma glucose values (61.8% of all women).CONCLUSIONSBoth maternal GDM and obesity are independently associated with adverse pregnancy outcomes. Their combination has a greater impact than either one alone.

Gestational Diabetes, Obesity, and Metabolic Syndrome Diagnosed During Pregnancy

The aim was to analyze the impact of obesity on women with gestational diabetes mellitus (GDM) and the association of obesity and GDM with the metabolic syndrome. In a retrospective study, the data of 233 obese women with GDM were compared with the data of 96 women with GDM and normal weight. Significantly higher fasting glycemia before the oral glucose tolerance test (5.2±1.1 mmol/L vs. 4.5±0.8 mmol/L, P<0.00001) and higher frequency of hypertensive disorders of pregnancy (26.2% vs. 9.4%, P=0.0003) were found in obese women with GDM than in GDM women of normal weight. These women needed insulin therapy more often (18.9% vs. 8.3%, P=0.007). Also 31 (13.3 %) of them had chronic hypertension as compared with 3.1% in women of normal weight (P=0.003). These 31 women had three components necessary for diagnosing of metabolic syndrome according to the World Health Organization-impaired glucose tolerance, obesity, and hypertension. No difference in gestational age and mean weight of their newborns was found, but newborns of obese GDM women with metabolic syndrome components more often were significantly macrosomic with features of diabetic fetopathy and had more often symptoms of hypoglycemia after birth. The presence of obesity and GDM has a significant impact on both maternal and fetal complications. The metabolic syndrome can be diagnosed not only after pregnancy but also during pregnancy.

Chronically Increased S6K1 Is Associated with Impaired IRS1 Signaling in Skeletal Muscle of GDM Women with Impaired Glucose Tolerance Postpartum

The rapidly increasing prevalence of gestational diabetes mellitus (GDM) globally places a growing population at risk for developing type 2 diabetes mellitus (T2DM), particularly those with persistent impaired glucose tolerance (IGT) postpartum. We sought to 1) identify dynamic insulin signaling abnormalities in vivo in a prospective, longitudinal study of GDM women compared to weight-matched pregnant controls both antepartum and postpartum; and 2) determine abnormalities that might distinguish GDM women who normalize their glucose tolerance postpartum from those with persistent IGT. Skeletal muscle biopsies were obtained before and after a 75-g glucose load in nine overweight to obese GDM women and 10 weight-matched pregnant controls antepartum and postpartum. Postpartum biopsies were collected in five weight-matched GDM women with IGT (GDM/IGT). GDM women had decreased skeletal muscle insulin-stimulated insulin receptor and insulin receptor substrate 1 (IRS1) tyrosine activation and reduced IRS1, concomitant with increased basal IRS1 serine phosphorylation and basal p70 S6-kinase (S6K1) activation, which resolved postpartum. However, GDM/IGT subjects had a persistent impairment in IRS1 activation and increased S6K1 phosphorylation compared to GDM subjects with normal glucose tolerance. This study reveals that women with GDM demonstrate impaired IRS1 signaling associated with increased S6K1 activation in skeletal muscle in vivo. This defect is maintained postpartum in GDM/IGT subjects, despite similar body weights and cytokine levels. Given that GDM women with persistent IGT are at a high risk of developing T2DM, understanding how the nutrient-sensitive mammalian target of rapamycin/S6K1 pathway is chronically activated in GDM may lead to important therapies that could prevent the progression to T2DM.

Low gestational weight gain improves infant and maternal pregnancy outcomes in overweight and obese Korean women with gestational diabetes mellitus

Objective. The aim of the study was to retrospectively assess what was the optimal gestational weight gain to have better maternal and neonatal outcomes in overweight and obese Korean women with gestational diabetes mellitus (GDM) who maintained normoglycemia throughout pregnancy by dietary modification, exercise, and/or insulin treatment.Study design. We performed a hospital-based study of 215 GDM women with prepregnancy BMI ≥ 25 kg/m2. Body weight, glucose homeostasis, lipid profiles, insulin treatment, and maternal outcomes were collected as predictors of neonatal birth weight. We divided the subjects into three groups according to modified Institute of Medicine (IOM) guidelines for weight gain during pregnancy: inadequate (n = 42), normal (n = 96), and excessive (n = 77) groups.Results. Excessive weight gain resulted in increased macrosomia, HbA1c at delivery, and postprandial blood glucose levels, but fasting blood glucose levels were not significantly different among the groups. The inadequate weight gain group (2.4 kg weight gain during pregnancy) had better neonatal outcomes and better maternal glycemic control with fewer requiring insulin treatment.Conclusion. Minimal weight gain, well below IOM recommendations, and tight control of blood glucose levels during pregnancy with proper medical management and dietary modification may eliminate most of the adverse pregnancy outcomes experienced by obese GDM Asian women.

Lifestyle Intervention of Diet and Exercise Limits Weight Gain and Complications in Obese GDM Women

Evidence-based obstetrics indicate that exercise is an important component of a healthy pregnancy. In addition to exercise, weight gain restriction in obese women also may be beneficial in decreasing maternal and neonatal complications in pregnancy. PURPOSE: To determine the impact of diet and exercise on pregnancy outcomes and weight gain restriction in obese women with gestational diabetes mellitus (GDM) compared to diet alone. METHODS: 174 women diagnosed with GDM met inclusion criteria, 49 in the structured exercise group, 17 in the self-initiated exercise group, and 108 in the diet only group by choosing not to exercise or having contraindications to exercise. All women were provided an isocaloric meal plan and recorded blood glucose, daily food intake, and daily amount of physical activity achieved. The structured exercise program participants performed an exercise test to maximal effort and received an exercise prescription of 60% of maximal oxygen uptake. RESULTS: The exercise and diet only groups had similar maternal Body Mass Index (BMI) (33.2± 6.9 vs. 35.4 ± 8.7 kg/m2) at study entry as well as gestational age at study entry (29.1 ± 5.2 vs. 28.2 ± 6.2 weeks). Of those participating in exercise, 62% in the structured exercise group recorded weekly exercise while only 18% of those in the self-initiated exercise group reported weekly exercise compared to the diet only group (p<0.001). Weight gain per week was significantly lower in the exercise groups (0.2 ± 0.9 lb. vs. 0.7 ± 1.0 lb., p<0.01). Women who gained weight compared to those who had no weight change or loss were 2.6 times as likely to have a c-section (95% CI: 1.1-6.1, p<0.05). Obese pregnant women with BMI >35 kg/m2 at study entry were 4.7 times as likely to have a c-section (95% CI: 1.5-15.3, p<0.01) than normal/overweight women (BMI 18.5-29.9 kg/m2). A trend towards macrosomia was observed in women who gained weight (Odds Ratio: 1.6, 95% CI: 0.4-5.7, p=0.49) and women with BMI >35 kg/m2 (Odds Ratio: 3.2, 95% CI: 0.3-31.3, p=0.37), although not statistically significant perhaps due to small sample size. CONCLUSIONS: Lifestyle intervention of exercise and diet in obese women with GDM may diminish the burden of obesity and possibly reduce maternal and neonatal complications. Since women are often more motivated to make healthy lifestyle changes in pregnancy, this is an opportune time for healthcare providers to impact future lifestyle behaviors.

Downregulated IRS-1 and PPARgamma in obese women with gestational diabetes: relationship to FFA during pregnancy.

Gestational diabetes mellitus (GDM) is associated with elevated postprandial free fatty acids (FFA) and insulin resistance; however, little is known about the cellular mechanisms underlying insulin resistance to suppress lipolysis during gestation. We evaluated the longitudinal changes in insulin suppression of FFA before pregnancy and in early (12-14 wk) and late (34-36 wk) gestation in obese subjects with normal glucose tolerance and in obese GDM subjects. Abdominal subcutaneous adipose tissue biopsies were also obtained during cesarean delivery from normal obese pregnant (Preg-Con), GDM, and nonpregnant obese control (Non-Preg-Con) subjects during gynecological surgery. GDM subjects had higher basal plasma FFA before pregnancy (P = 0.055). Insulin's ability to suppress FFA levels declined from early to late gestation in both GDM and Preg-Con subjects and was significantly less in GDM subjects compared with Preg-Con subjects over time (P = 0.025). Adipose tissue insulin receptor substrate (IRS)-1 protein levels were 43% lower (P = 0.02) and p85alpha subunit of phosphatidylinositol 3-kinase was twofold higher (P = 0.03) in GDM compared with Preg-Con subjects. The levels of peroxisome proliferator-activated receptor-gamma (PPARgamma) mRNA and protein were lower by 38% in Preg-Con (P = 0.006) and by 48% in GDM subjects (P = 0.005) compared with Non-Preg controls. Lipoprotein lipase and fatty acid-binding protein-2 mRNA levels were 73 and 52% lower in GDM compared with Preg-Con subjects (P < 0.002). Thus GDM women have decreased IRS-1, which may contribute to reduced insulin suppression of lipolysis with advancing gestation. Decreased PPARgamma and its target genes may be part of the molecular mechanism to accelerate fat catabolism to meet fetal nutrient demand in late gestation.