Gestational diabetes mellitus and long-term consequences for mother and offspring: a view from Denmark

Predictive factors for the development of diabetes in women with previous gestational diabetes mellitus

Introduction: Adrenal glands are a common site for cancer metastases. However, massive adrenal haemorrhage secondary to adrenal metastasis is rare. We report an unusual case of spontaneous massive retroperitoneal haemorrhage from an adrenal gland metastasis. Case report: A 74-year-old man was admitted with sudden onset of right upper quadrant abdominal pain. He had a 20 pack per year history of cigarette smoking. On examination he was distressed with blood pressure of 85/59mmHg and regular pulse of 90 beats /min. Abdominal examination revealed tenderness and guarding in the right hypochondrium and the right flank. Initial laboratory investigations revealed haemoglobin of 14.4g/dl and haematocrit of 41%. His haemoglobin and haematocrit subsequently dropped to 8.9g/dl and 25.9%, respectively. Computed tomography (CT) scan of the abdomen revealed bilateral adrenal masses (right 5.6cm and left 2.4cm) with right adrenal and extensive retroperitoneal haemorrhage. No signs and symptoms of hypoadrenalism developed and his response to short synacthen test was satisfactory. Phaeochromocytoma was ruled out by normal urinary catecholamine levels (6 samples). Subsequent CT of the chest showed an abnormal lesion in the right upper lobe and 4cm soft subcarinal mass, the histology of which showed squamous cell carcinoma of the lung. Discussion: Clinically significant adrenal haemorrhage secondary to metastases from lung cancer is extremely rare. To the best of our knowledge, there are only 10 reports (15 patients) in the English literature of adrenal haemorrhage secondary to metastases of lung carcinoma. Of the 15 patients, only 7 patients were known to have lung cancer before their presentation with adrenal haemorrhage.

Childhood obesity has contributed to an increased incidence of type 2 diabetes mellitus and metabolic syndrome (MS) among children. Intrauterine exposure to diabetes and size at birth are risk factors for type 2 diabetes mellitus, but their association with MS in childhood has not been demonstrated. We examined the development of MS among large-for-gestational-age (LGA) and appropriate-for-gestational age (AGA) children. The major components of MS (obesity, hypertension, dyslipidemia, and glucose intolerance) were evaluated in a longitudinal cohort study of children at age 6, 7, 9, and 11 years who were LGA (n = 84) or AGA (n = 95) offspring of mothers with or without gestational diabetes mellitus (GDM). The cohort consisted of 4 groups, ie, LGA offspring of control mothers, LGA offspring of mothers with GDM, AGA offspring of control mothers, and AGA offspring of mothers with GDM. Biometric and anthropometric measurements were obtained at 6, 7, 9, and 11 years. Biochemical testing included measurements of postprandial glucose and insulin levels and high-density lipoprotein (HDL) cholesterol levels at 6 and 7 years and of fasting glucose, insulin, triglyceride, and HDL cholesterol levels at 9 and 11 years. We defined the components of MS as (1) obesity (BMI >85th percentile for age), (2) diastolic or systolic blood pressure >95th percentile for age, (3) postprandial glucose level >140 mg/dL or fasting glucose level >110 mg/dL, (4) triglyceride level >95th percentile for age, and (5) HDL level <5th percentile for age. There were no differences in baseline characteristics (gender, race, socioeconomic status, and maternal weight gain during pregnancy) for the 4 groups except for birth weight, but there was a trend toward a higher prevalence of maternal obesity before pregnancy in the LGA/GDM group. Obesity (BMI >85th percentile) at 11 years was present in 25% to 35% of the children, but rates were not different between LGA and AGA offspring. There was a trend toward a higher incidence of insulin resistance, defined as a fasting glucose/insulin ratio of <7, in the LGA/GDM group at 11 years. Analysis of insulin resistance at 11 years in a multivariate logistic regression revealed that childhood obesity and the combination of LGA status and maternal GDM were associated with insulin resistance, with odds ratios of 4.3 (95% confidence interval [CI]: 1.5-11.9) and 10.4 (95% CI: 1.5-74.4), respectively. The prevalence at any time of > or =2 components of MS was 50% for the LGA/GDM group, which was significantly higher than values for the LGA/control group (29%), AGA/GDM group (21%), and AGA/control group (18%). The prevalence of > or =3 components of MS at age 11 was 15% for the LGA/GDM group, compared with 3.0% to 5.3% for the other groups. Cox regression analysis was performed to determine the independent hazard (risk) of developing MS attributable to birth weight, gender, maternal prepregnancy obesity, and GDM. For Cox analyses, we defined MS as > or =2 of the following 4 components: obesity, hypertension (systolic or diastolic), glucose intolerance, and dyslipidemia (elevated triglyceride levels or low HDL levels). LGA status and maternal obesity increased the risk of MS approximately twofold, with hazard ratios of 2.19 (95% CI: 1.25-3.82) and 1.81 (95% CI: 1.03-3.19), respectively. GDM and gender were not independently significant. To determine the cumulative hazard of developing MS with time, we plotted the risk according to LGA or AGA category for the control and GDM groups from 6 years to 11 years, with Cox regression analyses. The risk of developing MS with time was not significantly different between LGA and AGA offspring in the control group but was significantly different between LGA and AGA offspring in the GDM group, with a 3.6-fold greater risk among LGA children by 11 years. We showed that LGA offspring of diabetic mothers were at significant risk of developing MS in childhood. The prevalence of MS in the other groups was similar to the prevalence (4.8%) among white adolescents in the 1988-1994 National Health and Nutrition Examination Survey. This effect of LGA with maternal GDM on childhood MS was previously demonstrated for Pima Indian children but not the general population. We also found that children exposed to maternal obesity were at increased risk of developing MS, which suggests that obese mothers who do not fulfill the clinical criteria for GDM may still have metabolic factors that affect fetal growth and postnatal outcomes. Children who are LGA at birth and exposed to an intrauterine environment of either diabetes or maternal obesity are at increased risk of developing MS. Given the increased obesity prevalence, these findings have implications for perpetuating the cycle of obesity, insulin resistance, and their consequences in subsequent generations.

Does recurrent gestational diabetes mellitus increase the risk of preterm birth? A population-based cohort study

OBJECTIVETo examine the associations of maternal gestational glucose tolerance with offspring body composition in late childhood.RESEARCH DESIGN AND METHODSAmong 958 women in the prebirth cohort Project Viva, glucose tolerance was assessed in the second trimester by nonfasting 50-g 1-h glucose challenge test (GCT), followed if abnormal by fasting 100-g 3-h oral glucose tolerance test (OGTT). We categorized women as normoglycemic (83.3%) if GCT was ≤140 mg/dL, isolated hyperglycemia (9.1%) if GCT was abnormal but OGTT normal, intermediate glucose intolerance (IGI) (3.3%) if there was one abnormal value on OGTT, or gestational diabetes mellitus (GDM) (4.5%) if there were two or more abnormal OGTT values. Using multivariable linear regression, we examined adjusted associations of glucose tolerance with offspring overall (N = 958) and central (N = 760) adiposity and body composition using dual X-ray absorptiometry (DXA) measured at the school-age visit (95 ± 10 months).RESULTSCompared with that in the male offspring of normoglycemic mothers, DXA fat mass was higher in male offspring of GDM mothers (1.89 kg [95% CI 0.33–3.45]) but not in male offspring of mothers with IGI (0.06 kg [−1.45 to 1.57]). DXA trunk-to-peripheral fat mass, a measure of central adiposity, was also somewhat higher in male offspring of GDM mothers (0.04 [−0.01 to 0.09]). In girls, DXA fat mass was higher in offspring of mothers with IGI (2.23 kg [0.12–4.34]) but not GDM (−1.25 kg [−3.13 to 0.63]). We showed no association of gestational glucose tolerance with DXA lean mass.CONCLUSIONSIn this study, only male offspring of GDM mothers manifested increased adiposity, whereas only female offspring of mothers with IGI did so. Sex differences in glycemic sensitivity may explain these findings.

Women with previous preeclampsia (PE), gestational hypertension (GH), or gestational diabetes mellitus (GDM) have increased cardiovascular disease (CVD) risk. Physical activity (PA) is an important CVD risk modifier. We aimed to assess PA levels, using a validated objective method, and other modifiable CVD risk factors in women with these previous pregnancy complications. One year postpartum we assessed PA levels for 1week in women with previous PE (n=68), GH (n=26), GDM (n=23), and normotensive pregnancies (n=65), using the ActiGraph-wGT3X-BT™ accelerometer. We assessed adherence to American PA guidelines (≥150min/week of moderate or ≥75min/week of vigorous intensity PA), and time spent in moderate and vigorous PA. We also assessed steps/day, blood pressure and anthropometric indices. Recommended PA levels were achieved in only 50%, 39%, and 35% following PE, GH, and GDM, respectively, not significantly different from controls (52%). Differences in moderate and vigorous PA levels and steps/day between the groups were non-significant, except from lower vigorous PA in women with previous GDM. Elevated blood pressure (systolic BP≥120mmHg and/or diastolic BP≥80mmHg) was more common after PE and GH. Overweight rates were significantly higher in PE, GH, and GDM groups compared to controls. Less than half of women achieved recommended PA levels 1year postpartum. This did not differ significantly between women with previous PE, GH, or GDM compared to controls. Measures to increase PA in postpartum women are warranted, especially in women with pregnancy complications associated with high risk of premature CVD.

Randomized controlled trial of prepregnancy lifestyle intervention to reduce recurrence of gestational diabetes mellitus

Since the implementation of China's new birth policy, the incidence of large for gestational age (LGA) and macrosomia associated with gestational diabetes mellitus (GDM) has increased. It remains unclear whether a history of GDM in a previous pregnancy raises the risk of LGA or macrosomia in Chinese women planning two or more pregnancies. To analyze the association between previous GDM and the risk of LGA and macrosomia in second pregnancy. A retrospective study was conducted on a cohort of 3,131 women who had experienced two consecutive singleton births. The incidences of LGA and macrosomia in the second pregnancy were compared between women with and without previous GDM. The relationship between previous GDM and the occurrence of LGA and macrosomia was analyzed using multivariate logistic regression and stratified analysis. The incidence of LGA and macrosomia during the second pregnancy was significantly higher in women with previous GDM (22.67% and 10.25%, respectively) compared to those without prior GDM (15.34% and 5.06%, respectively) (P < 0.05). After adjusting for potential confounders, previous GDM was significantly associated with LGA (aOR: 1.511, 95% CI: 1.066-2.143) and macrosomia (aOR: 1.854, 95% CI: 1.118-3.076) in the second pregnancy. Stratified analysis revealed that these associations were present only in women without previous LGA, those with GDM, appropriate gestational weight gain (AGWG), non-advanced maternal age, and male newborns during the second pregnancy (P < 0.05). Compared to excessive GWG (EGWG), AGWG correlated with lower risks for LGA and macrosomia during the second pregnancy in women without prior GDM, an association not observed in those with previous GDM. Among women without previous GDM, if the pre-pregnancy BMI is normal, the risk of LGA and macrosomia is significant lower in AGWG compared with EGWG (P< 0.001), while this difference was no significant among women with prior GDM (P>0.05). Previous GDM is strongly linked to LGA and macrosomia in subsequent pregnancies. However, this relationship is influenced by GWG, prior LGA history, fetal sex, and maternal age. Managing weight alone may not sufficiently reduce the risk of LGA or macrosomia for women with a history of GDM.

To estimate the incidence of gestational diabetes mellitus (GDM) according to The International Association of the Diabetes and Pregnancy Study Groups (IADPSG) criteria and the pregnancy complications in women fulfilling these criteria but who are not considered diabetic according to the Canadian Diabetes Association criteria. We estimated the rate of GDM according to the IADPSG criteria from November 2008 to October 2010. Then, we conducted a chart review to compare maternal and neonatal outcomes between women classified as GDM according to the IADPSG criteria but not by the Canadian Diabetes Association criteria (group 1; n=186) and nondiabetic women according to both criteria (group 2; n=372). Results were expressed as crude (odds ratio [OR]) or adjusted OR and 95% confidence interval (CI). The study has a statistical power of 80% to detect a difference between 16% and 8% in large for gestational age newborns (α level of 0.05; two-tailed). The rate of GDM using the IADPSG criteria was 27.51% (95% CI 25.92-29.11). Group 1 presented similar rates of large-for-gestational-age newborns (9.1% compared with 5.9%, adjusted OR 1.58, 95% CI 0.79-3.13; P=.19), delivery complications (37.1% compared with 30.1%, OR 1.37, 95% CI 0.95-1.98; P=.10), preeclampsia (6.5% compared with 2.7%, adjusted OR 2.40, 95% CI 0.92-6.27; P=.07), prematurity (6.5% compared with 2.7%, OR 1.10, 95% CI 0.53-2.27; P=.85), neonatal complications at delivery (13.4% compared with 9.7%, OR 1.45, 95% CI 0.84-2.49; P=.20), and metabolic complications (10.8% compared with 14.2%, OR 0.73, 95% CI 0.42-1.26; P=.29) compared with group 2. Women classified as nondiabetic by the Canadian Diabetes Association Criteria but considered GDM according to the IADPSG criteria have similar pregnancy outcomes as women without GDM. More randomized studies with cost-effectiveness analyses are needed before implementation of these criteria. II.

IntroductionThe incidence of gestational diabetes mellitus (GDM) is increasing in Australia, influenced by changed diagnostic criteria. We aimed to identify whether the diagnostic change was associated with improved outcomes and/or...

To determine cord blood angiotensin II (Ang II) concentration and assess its relationship to fetal insulin sensitivity in the offspring of mothers with gestational diabetes mellitus (GDM) at birth. Thirty women with GDM and 30 healthy women were evaluated at elective cesarean delivery. Cord blood was obtained for measurement of Ang II, glucose and insulin. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated and used to estimate fetal insulin sensitivity. The offspring of mothers with GDM had higher ponderal index (PI), HOMA-IR and cord Ang II and insulin concentrations than the offspring of healthy mothers. Cord insulin concentration and HOMA-IR were positively associated with PI in all the offspring. Cord Ang II concentration was positively associated with HOMA-IR in the offspring of mothers with GDM. Increased cord Ang II concentration is associated with decreased insulin sensitivity in the offspring of mothers with GDM.

Offspring of pregnancies affected by gestational diabetes mellitus (GDM) are at increased risk of the development of type 2 diabetes. However, the extent to which these dysmetabolic traits may be due to offspring and/or maternal adiposity is unknown. We examined body composition and associated cardiometabolic traits in 561 9- to 16-year-old offspring of mothers with GDM and 597 control offspring. We measured anthropometric characteristics; puberty status; blood pressure; and fasting glucose, insulin, C-peptide, and lipid levels; and conducted a DEXA scan in a subset of the cohort. Differences in the outcomes between offspring of mothers with GDM and control subjects were examined using linear and logistic regression models. After adjustment for age and sex, offspring of mothers with GDM displayed higher weight, BMI, waist-to-hip ratio (WHR), systolic blood pressure, and resting heart rate and lower height. Offspring of mothers with GDM had higher total and abdominal fat percentages and lower muscle mass percentages, but these differences disappeared after correction for offspring BMI. The offspring of mothers with GDM displayed higher fasting plasma glucose, insulin, C-peptide, HOMA-insulin resistance (IR), and plasma triglyceride levels, whereas fasting plasma HDL cholesterol levels were decreased. Female offspring of mothers with GDM had an earlier onset of puberty than control offspring. Offspring of mothers with GDM had significantly higher BMI, WHR, fasting glucose, and HOMA-IR levels after adjustment for maternal prepregnancy BMI, and glucose and HOMA-IR remained elevated in the offspring of mothers with GDM after correction for both maternal and offspring BMIs. In summary, adolescent offspring of women with GDM show increased adiposity, an adverse cardiometabolic profile, and earlier onset of puberty among girls. Increased fasting glucose and HOMA-IR levels among the offspring of mothers with GDM may be explained by the programming effects of hyperglycemia in pregnancy.

Gestational diabetes mellitus (GDM) is a common complication of pregnancy associated with a higher risk of developing type 2 diabetes (T2DM) in the future. Postpartum diabetes screening is important to identify glucose intolerance and introduce diabetes prevention support. However, screening uptake is suboptimal, including in China where the prevalence of GDM is high. There is limited evidence on the barriers and facilitators to screening uptake among Chinese women. To explore the barriers and facilitators of postpartum diabetes screening uptake among Chinese women with GDM to inform the development of an intervention to increase screening attendance. Women with current or previous GDM were recruited from social network platforms and pregnancy groups in China. Data were collected using semi-structured interviews and analysed using Framework Analysis to identify themes related to the barriers and facilitators for screening uptake. Twenty-four women with current (n = 4) or previous (n = 20) GDM participated. The postpartum glucose screening attendance rate was 35% among those with previous GDM. Screening uptake was influenced by: risk awareness of T2DM and its complications, interactions with healthcare providers (HCPs), screening-related factors (understanding and beliefs, accessibility and acceptability of the test) and motivation to maintain personal health, which was influenced by fear of T2DM, lack of symptoms, confidence in self management without support, and prioritisation of the child's needs. Postpartum screening uptake after GDM could be boosted through raising risk awareness, more constructive communication from HCPs, increasing the acceptability and accessibility of screening procedures, and addressing psychological factors related to attendance.

![][1] The old adage that pregnant women eat for two might be more true than ever before in the light of recent research into diet and the control of gene expression. The link between the diet of pregnant women—and, to some extent, men—during pre‐conception and the health of the fetus has been viewed mostly in terms of major risk factors such as smoking or substance abuse. However, epidemiological and molecular research is revealing a more complex and subtle picture of how a pregnant woman's eating behaviour influences the expression of her own—and possibly her fetus's—genes, and thus the long‐term health of her children. “Type II diabetes, heart disease due to obesity, insulin resistance, and hypertension are the diseases most strongly associated with maternal diet during pregnancy,” said Karen Lillycrop, who specializes in perinatal nutrition at the University of Southampton in the UK. In addition, there is growing evidence that dietary effects, which can alter the expression and control of genes, might even have been a driving force for human evolution. A recent study revealed that the greatest divergence between the genomes of humans and chimpanzees is found among genes that control metabolism and are closely associated with diet (Somel et al , 2008). The mechanisms that allow the genome to interact with environmental factors, such as diet, are epigenetic changes—a concept first proposed by the British biologist Conrad Waddington (1905–1975) in 1942 to describe the interplay between genes and the environment in determining the phenotype of an organism. Further research since Waddington's time has shown that epigenetic changes not only take place during embryonic development, but also throughout the lifetime of an organism. The same mechanisms—notably DNA methylation and histone modification—have a role in the acquisition and maintenance of epigenetic changes induced by dietary or other environmental factors. In fact, they … [1]: /embed/graphic-1.gif

BackgroundPregnant women with a history of gestational diabetes mellitus (GDM) are at high risk of GDM. It is unclear whether this population has pregnancy characteristics different from the general population. Whether these features affect the perinatal outcome has not yet been elucidated.MethodsA retrospective study was conducted, including baseline characteristics, laboratory data, gestational weight gain (GWG), and pregnancy outcomes of 441 pregnant women with prior GDM. Besides, 1637 women without a history of GDM treated in the same period were randomly selected as the control group. The above indicators of the two groups were compared. Multivariable logistic regression analysis was performed to investigate how GWG was associated with perinatal outcomes for previous GDM women.ResultsAmong women with GDM history, triglycerides (TG) and fasting plasma glucose (FPG) in the 1st trimester were higher than those without GDM history. GWG was lower in women with prior GDM relative to the control group at various pregnancy stages. However, women with GDM history had a higher risk of developing GDM (OR 3.25, 95% CI 2.26–4.68) and pregnancy-induced hypertension (OR 1.50, 95% CI 1.05–2.45). In women with previous GDM, excessive GWG before OGTT exhibited a positive correlation with pregnancy-induced hypertension (OR 1.47, 95% CI 1.05–3.32), while inadequate GWG was not a protective factor for GDM and pregnancy-induced hypertension.ConclusionWomen with prior GDM have glucose and lipid metabolism disorders in the 1st trimester. Limited reduction of GWG before oral glucose tolerance test (OGTT) was insufficient to offset the adverse effects of glucose and lipid metabolism disorders in women with previous GDM. Relevant interventions may be required at early stage or even before pregnancy.