Long-term effects of diabetes during pregnancy on the offspring (original) (raw)
Pediatric Diabetes, 2007
In utero hyperglycemia has been associated with insulin resistance (IR) in children; however, there are limited data in low-risk populations. The purpose of this study was to describe the prevalence of metabolic markers of IR in a primarily Caucasian cohort of gestational diabetes mellitus (GDM) offspring aged 7-11 yr (mean 9.1) and to correlate offspring with maternal indexes. Sixty-eight children were recruited through a follow-up study of women who participated in a randomized controlled trial of minimal intervention vs. tight glycemic control for GDM. All participants had a fasting plasma glucose (FPG), insulin, total cholesterol, high-density lipoprotein cholesterol (HDLchol), triglyceride (TG) level, and a 2-h oral glucose tolerance test. We calculated homeostasis model assessment (HOMA) and recorded body mass index and waist circumference (WC). Criteria for metabolic syndrome for children included: FPG. 6.0 mmol/L, HDL-chol , 1.03 mmol/L, TG. 1.24 mmol/L, WC. 90% for age and gender, and 2-h glucose. 7.8 mmol/L. Among these children, 45 (66%), 17 (25%), 5 (7%), and 1 (1.5%) had zero, one, two, or three metabolic markers of IR, respectively. Hypertriglyceridemia (21%) was most prevalent, with no child having an elevated FPG. WC (p ¼ 0.018) and TG (p ¼ 0.005) were strong predictors of IR in the offspring after adjustment for age, gender, birthweight, family history, and maternal IR. Maternal and offspring HDL-chol, TG, WC, and HOMA but not fasting or 2-h glucose levels were significantly correlated. We conclude that metabolic markers of IR in children exposed to GDM may be present in the absence of abnormal fasting or 2-h glucose values. Screening strategies that focus on glucose levels may need to be reconsidered to institute early intervention with lifestyle changes for children at risk.
JAMA
The sequelae of gestational diabetes (GD) by contemporary criteria that diagnose approximately twice as many women as previously used criteria are unclear. OBJECTIVE To examine associations of GD with maternal glucose metabolism and childhood adiposity 10 to 14 years' postpartum. The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study established associations of glucose levels during pregnancy with perinatal outcomes and the follow-up study evaluated the long-term outcomes (4697 mothers and 4832 children; study visits occurred between February 13, 2013, and December 13, 2016). EXPOSURES Gestational diabetes was defined post hoc using criteria from the International Association of Diabetes and Pregnancy Study Groups consisting of 1 or more of the following 75-g oral glucose tolerance test results (fasting plasma glucose Ն92 mg/dL; 1-hour plasma glucose level Ն180 mg/dL; 2-hour plasma glucose level Ն153 mg/dL). Primary maternal outcome: a disorder of glucose metabolism (composite of type 2 diabetes or prediabetes). Primary outcome for children: being overweight or obese; secondary outcomes: obesity, body fat percentage, waist circumference, and sum of skinfolds (>85th percentile for latter 3 outcomes). The analytic cohort included 4697 mothers (mean [SD] age, 41.7 [5.7] years) and 4832 children (mean [SD] age, 11.4 [1.2] years; 51.0% male). The median duration of follow-up was 11.4 years. The criteria for GD were met by 14.3% (672/4697) of mothers overall and by 14.1% (683/4832) of mothers of participating children. Among mothers with GD, 52.2% (346/663) developed a disorder of glucose metabolism vs 20.1% (791/3946) of mothers without GD (odds ratio [OR], 3.44 [95% CI, 2.85 to 4.14]; risk difference [RD], 25.7% [95% CI, 21.7% to 29.7%]). Among children of mothers with GD, 39.5% (269/681) were overweight or obese and 19.1% (130/681) were obese vs 28.6% (1172/4094) and 9.9% (405/4094), respectively, for children of mothers without GD. Adjusted for maternal body mass index during pregnancy, the OR was 1.21 (95% CI, 1.00 to 1.46) for children who were overweight or obese and the RD was 3.7% (95% CI, -0.16% to 7.5%); the OR was 1.58 (95% CI, 1.24 to 2.01) for children who were obese and the RD was 5.0% (95% CI, 2.0% to 8.0%); the OR was 1.35 (95% CI, 1.08 to 1.68) for body fat percentage and the RD was 4.2% (95% CI, 0.9% to 7.4%); the OR was 1.34 (95% CI, 1.08 to 1.67) for waist circumference and the RD was 4.1% (95% CI, 0.8% to 7.3%); and the OR was 1.57 (95% CI, 1.27 to 1.95) for sum of skinfolds and the RD was 6.5% (95% CI, 3.1% to 9.9%). CONCLUSIONS AND RELEVANCE Among women with GD identified by contemporary criteria compared with those without it, GD was significantly associated with a higher maternal risk for a disorder of glucose metabolism during long-term follow-up after pregnancy. Among children of mothers with GD vs those without it, the difference in childhood overweight or obesity defined by body mass index cutoffs was not statistically significant; however, additional measures of childhood adiposity may be relevant in interpreting the study findings.
BioMed Research International, 2015
Objective. To examine the association of maternal glycemia during pregnancy and after delivery with anthropometry in the offspring of mothers with gestational diabetes mellitus (GDM).Methods. A total of 1,263 GDM mothers and their children finished the health survey at 1–5 years after delivery.Results. Offspring of GDM mothers who were diagnosed with diabetes during pregnancy had higher prevalence of overweight, higher mean weight for heightZscores, and higher mean BMI for ageZscores at 1–5 years old than the offspring of GDM mothers who were diagnosed with impaired glucose tolerance (IGT) during pregnancy. Offspring of GDM mothers who developed diabetes 1–5 years after delivery had higher mean values ofZscores for weight for height and BMI for age at 1–5 years old than the offspring of GDM mothers who had normal glucose or prediabetes after delivery.Conclusions. Offspring of GDM mothers who were diagnosed with diabetes during pregnancy or after delivery had an increased risk of chi...
Maternal Gestational Diabetes and Different Indicators of Childhood Obesity – A Large Study
Endocrine Connections
Previous studies found conflicting results about the associations between the exposure to hyperglycemia in utero and the later risks of childhood overweight and obesity. The aim of the present study is to compare the children’s body mass index (BMI) growth between offspring exposed to maternal gestational diabetes mellitus (GDM) and those not exposed, and assess the associations between maternal GDM and their offspring’s overweight and obesity risk. We performed a large observational study in 1156 women and their offspring (578 GDM and 578 non-GDM mother-child pairs, matched by their offspring’s gender and age). Maternal GDM was diagnosed according to the World Health Organization criteria. Childhood height, weight, waist circumference, body fat and skinfold were measured using standardized methods. After adjustment for maternal and children’s characteristics, children born to mothers with GDM during pregnancy had higher mean values of Z scores for BMI-for-age, Z-scores for weight-f...
Frontiers in Endocrinology
Previous studies showed the association between maternal GDM and long-term effects of overweight in offspring. However, the nature of this association in the early postnatal period is still undetermined. The aim of this prospective cohort study was to evaluate whether maternal GDM is associated with overweight and obesity status in offspring at age 1 year. We studied 1167 infants born at a large obstetrical care hospital including 778 normal glucose tolerance (NGT) and 389 GDM pregnancies, matched in a 1:2 ratio according to offspring’s gender, during the years 2016–2017. Overweight and obesity status in offspring of both groups were evaluated at 1 year of age through questionnaires. Infant outcomes were defined according to the WHO Child Growth Standards based on the length-based BMI-for-age. Female offspring from the GDM group exhibited a higher mean BMI (17.2 vs. 16.6, p < 0.01), a higher rate of obesity (13.9% vs. 7.7%; p < 0.05), and overweight (33.1% vs. 23.5%; p < 0....
Diabetic Medicine, 2009
Aims To determine effects on mothers and daughters of gestational diabetes mellitus ⁄ gestational impaired glucose tolerance (GDM ⁄ GIGT) on their future metabolic and cardiovascular risks. Methods Case mothers who had GDM ⁄ GIGT in pregnancy (cases; n = 90) and normoglycaemic control women (n = 99) and their daughters underwent lifestyle assessment and metabolic tests 15-years post-partum. Results Prevalence of glucose intolerance (GI) in daughters was 1.1%. Maternal prevalence was 44.4% in cases compared to 13.1% in controls, with conversion best predicted by weight gain. Case daughters had higher insulin resistance (IR) and greater waist circumference (WC) (51.2%) relative to control daughters (36.4%, p < 0.05) made worse if case mothers became GI at follow-up (65%) (relative risk =1.8; 95% confidence interval 1.2-2.9). In multivariable linear regression analyses adjusting for daughters' birthweight, maternal obesity (> 30.0 kg ⁄ m 2) at 15years and mothers' case-control status were strong predictors of daughters' WC (p < 0.01; P < 0.01, respectively). For daughters' body mass index (BMI) percentile and percentage of body fat, maternal obesity was a stronger predictor (p < 0.01; p < 0.001)) than mothers' case-control status (p < 0.01; P = 0.09). Conclusions GDM ⁄ GIGT pregnancies led to increased conversion to GI in mothers, minimal in daughters. Case daughters have increased risk of central adiposity and insulin resistance, whereas maternal obesity strongly predicted daughters' BMI percentile and per cent of body fat. Controlling hyperglycaemia in pregnancy and family weight management may provide the key to preventing offspring obesity and glucose intolerance post GDM ⁄ GIGT.
Diabetes, 2018
While overt diabetes during pregnancy is associated with a higher childhood risk of altered glucose metabolism, the contribution of GDM to this disorder is less clear. Using data from HAPO FUS, we examined associations of maternal GDM not confounded by treatment with childhood glucose metabolism. Maternal glycemic status was based on a 75 g oral glucose tolerance test (OGTT) at ∼28 weeks gestation. Offspring disorders of glucose metabolism (impaired glucose tolerance or type 2 diabetes using American Diabetes Association criteria) were assessed at the HAPO FUS visit using an OGTT in 41children at mean age 11.4 (range 7.9-15.5) years. Insulin sensitivity (IS) was calculated using the Matsuda index and insulin secretion using the insulinogenic index. GDM was defined by International Association of Diabetes in Pregnancy Study Groups criteria. Among offspring of mothers with and without GDM, 10.6% and 5.2%, respectively, had a disorder of glucose metabolism. After adjusting for field ce...
BMC public health, 2016
Maternal overweight, obesity, and gestational diabetes (GD) have been negatively associated with offspring development. Further knowledge regarding metabolic and nutritional alterations in these mother and their offspring are warranted. In an observational cohort study we included 331 pregnant women from Granada, Spain. The mothers were categorized into four groups according to BMI and their GD status; overweight (n:56), obese (n:64), GD (n:79), and healthy normal weight controls (n:132). We assessed maternal growth and nutritional biomarkers at 24 weeks (n = 269), 34 weeks (n = 310) and at delivery (n = 310) and the perinatal characteristics including cord blood biomarkers. Obese and GD mothers had significantly lower weight gain during pregnancy and infant birth weight, waist circumference, and placental weight were higher in the obese group, including a significantly increased prevalence of macrosomia. Except for differences in markers of glucose metabolism (glucose, HbA1c, insul...
The Journal of Clinical Endocrinology & Metabolism, 2009
In animal studies, exposure to intrauterine hyperglycemia increases the risk of cardiovascular disease through only partly understood epigenetic mechanisms. Human long-term follow-up studies on the same topic are few. The aim was to study the risk of overweight and the metabolic syndrome in adult offspring of women with diet-treated gestational diabetes mellitus (GDM) or type 1 diabetes, and additionally to study associations between estimates of maternal hyperglycemia and outcome in the offspring. We conducted a follow-up study of 1066 primarily Caucasian women aged 18 -27 yr in the Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark. Participants: Offspring of women with diet-treated GDM (n ϭ 168) and an unexposed reference group (n ϭ 141) participated, as well as offspring of women with type 1 diabetes (n ϭ 160) and offspring from the background population representing an unexposed reference group (n ϭ 128). The follow-up rate was 56% (597 of 1066). Women with body mass index of at least 25 kg/m 2 were considered overweight. The metabolic syndrome was determined by the International Diabetes Federation 2006 criteria. The risk of overweight was doubled in offspring of women with diet-treated GDM or type 1 diabetes compared with offspring from the background population, whereas the risk of the metabolic syndrome was 4-and 2.5-fold increased, respectively. Offspring risk of the metabolic syndrome increased significantly with increasing maternal fasting blood glucose as well as 2-h blood glucose (during oral glucose tolerance test). Conclusions: Adult offspring of women with diet-treated GDM or type 1 diabetes are risk groups for overweight and the metabolic syndrome. Intrauterine hyperglycemia may in addition to genetics and other factors contribute to the pathogenesis of overweight and the metabolic syndrome. (
Diabetologia, 1993
Maternal diabetes mellitus is complicated by fetal macrosomia and predisposes the offspring to diabetes, but recent evidence indicates that a low, not high, birthweight is associated with a higher incidence of Type 2 (non-insulin dependent) diabetes in adult life. To clarify the relationships between maternal glucose and insulin levels and birthweight, we measured oral glucose tolerance and neonatal weight in a large group (n = 529) of women during the 26th week of pregnancy. Women with gestational diabetes (n = 17) had more familial diabetes, higher pre-pregnancy body weight, and tended to have large-for-gestational-age babies. In contrast, women with essential hypertension (n = 10) gave birth to significantly (p < 0.01) smaller babies. In the normal group (without gestational diabetes or hypertension, n --503), maternal body weight before pregnancy and at term, maternal height, week of delivery, gender of the newborn, and parity were all significant, independent predictors of birthweight, together explaining 23 % of the variability of neonatal weight. In addition, both fasting (p < 0.006) and 2-h post-glucose (p = 0.03) maternal plasma glucose concentrations were positively associated with birthweight independent of the other physiological determi-nants, accounting, however, for only 10% of the explained variability. In a subgroup of 134 normal mothers with prepregnancy body mass index of less than 25 kg. m 2, in whom plasma insulin measurements were available, the insulin area-under-curve was inversely related to birthweight (p < 0.02) after simultaneously adjusting for physiological factors and glucose area. When glucose and insulin measurements were combined in the I/G ratio (ratio of insulin to glucose area), this was still inversely related to birthweight. Furthermore, maternal insulinaemia was directly related to blood pressure levels (p <0.001) independently of body weight. We conclude that in normal pregnancy, whereas physiological factors account for most of the explainable variability of infant weight, the influence of the maternal metabolic milieu is dual, positive for glucose levels but negative for insulin concentrations. Maternal hyperinsulinaemia during pregnancy may be one trait linking low birthweight with predisposition to diabetes in adult life.
Gestational diabetes and childhood obesity
Current Opinion in Obstetrics & Gynecology, 2012
Purpose of review-To review recently published studies examining the role of prepregnancy obesity in the relationship between gestational diabetes mellitus and childhood obesity. Recent findings-Seven epidemiologic studies published from January 2011 to February 2012 differentiate between preexisting diabetes mellitus and gestational diabetes mellitus, and six of them examine the role of maternal obesity. In studies that account for maternal obesity as a covariate, the association between gestational diabetes mellitus and childhood obesity is attenuated significantly after adjustment for prepregnancy BMI. In the one study that does not adjust for maternal obesity, maternal glucose level during pregnancy is associated with greater offspring adiposity, independent of the child's diet and lifestyle. Summary-This review shows a positive association between maternal gestational diabetes mellitus and offspring overweight and obesity that is attenuated significantly after adjustment for prepregnancy BMI. The relationship between maternal gestational diabetes mellitus and offspring overweight and obesity could reflect fetal programming, shared genes and/or shared environments, such as postnatal diet and physical activity. Maternal gestational hyperglycemia and subsequent fetal hyperinsulinemia may predispose offspring to increased adiposity, impaired glucose tolerance, hyperinsulinemia, and insulin resistance. Because maternal obesity is a more prevalent condition than gestational diabetes mellitus and strongly associated with offspring obesity, effective interventions addressing prepregnancy obesity need to be further explored as they may have a greater public health impact on childhood overweight and obesity than those targeting women with gestational diabetes mellitus.
Archives of Biological Sciences, 2015
An increase in prevalence of gestational diabetes mellitus (GDM) was observed using new diagnostic criteria. We evaluated the prevalence of GDM in a population of pregnant women (109 women with gestational age of 24-28 weeks) and risk factors for GDM, such as maternal obesity and weight gain. The evaluation of each patient included an oral glucose tolerance test (OGTT) using the new diagnostic criteria of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) for GDM, 2D ultrasounds and the registration of risk factors. The prevalence of GDM in the age group ?30 years was 11.9%, which is comparable to the results of other studies. The relative risk (RR) for GDM was 1.738 (95% CI 0.630-4.795) in women over 30 years and 3.782 (95% CI 1.127-12.686) in women over 35. Weight gain in the group with GDM was significantly higher than in the group that included pregnant women without GDM (p <0.01). Considering the high risk of GDM with excessive gestational weight g...
Obesity (Silver Spring, Md.), 2018
This study aimed to determine the relationship between different forms of, and potential pathways between, maternal diabetes and childhood obesity at different ages. Prospective cohort data from The Environmental Determinants of Diabetes in the Young (TEDDY) study, which was composed of 5,324 children examined from 0.25 to 6 years of age, were analyzed. Cross-sectional and longitudinal analyses taking into account potential confounders and effect modifiers such as maternal prepregnancy BMI and birth weight z scores were performed. Offspring of mothers with gestational diabetes mellitus (GDM) or type 1 diabetes mellitus (T1DM) showed a higher BMI standard deviation score and increased risk for overweight and obesity at 5.5 years of age than offspring of mothers without diabetes. While these associations could be substantially explained by maternal prepregnancy BMI in offspring of mothers with GDM, significant associations disappeared after adjustment for birth weight z scores in offs...
The interplay between maternal obesity and gestational diabetes mellitus
Journal of Perinatal Medicine, 2014
There is a strong epidemiological association between maternal obesity and gestational diabetes mellitus (GDM). Since the publication of the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study on women with mild hyperglycemia in 2008, new criteria have been introduced in maternity services internationally for the diagnosis of GDM. As a result, the diagnosis of GDM may be made in one-third of obese women (n=68). The aim of this review was to examine the interplay between maternal obesity and GDM in light of the HAPO study and the subsequent revised diagnostic criteria. Obesity and GDM are important obstetric risk factors because they both are potentially modifiable. However, the new international criteria for the diagnosis of GDM have serious resource implications for maternity services provided to the large number of women attending for care in developed countries. Further consideration needs to be given as to whether obese women with mild hyperglycemia need to be referred to a...
Glucose Intolerance and Cardiometabolic Risk in Adolescents Exposed to Maternal Gestational Diabetes
Diabetes Care, 2010
OBJECTIVE Adolescent offspring of women with a history of gestational diabetes (GD) were evaluated for their cardiometabolic risks at a mean age of 15 years. RESEARCH DESIGN AND METHODS One hundred and twenty-nine adolescents who were assessed for their cardiometabolic risks at 8 years of age were reassessed at 15 years of age. RESULTS Adolescent offspring of mothers with GD had similar blood pressure, plasma lipid profile, and a rate of abnormal glucose tolerance as control subjects. In utero hyperinsulinemia was associated with a 17-fold increase in metabolic syndrome and a 10-fold increase in overweight at adolescence, independent of birth weight, Tanner stage, maternal GD status, and mother's BMI. CONCLUSIONS In utero environment of hyperinsulinemia, irrespective of the degree of maternal GD, was associated with increased risk of overweight and metabolic syndrome during early adolescence in the offspring.
Associations of Maternal Diabetes and Body Mass Index With Offspring Birth Weight and Prematurity
JAMA Pediatrics, 2019
IMPORTANCE Maternal obesity, pregestational type 1 diabetes, and gestational diabetes have been reported to increase the risks for large birth weight and preterm birth in offspring. However, the associations for insulin-treated diabetes and non-insulin-treated type 2 diabetes, as well as the associations for joint diabetes disorders and maternal body mass index, with these outcomes are less well documented. OBJECTIVE To examine associations of maternal diabetes disorders, separately and together with maternal underweight or obesity, with the offspring being large for gestational age and/or preterm at birth.
Gestational Diabetes – Metabolic Risks of Adult Women With Respect to Birth Weight
Physiological Research, 2015
Metabolic disorders such as obesity, insulin resistance and other components of metabolic syndrome (MetS) are connected with birth weight. Low and high birth weight is associated with a higher risk of developing type 2 diabetes mellitus, the mechanism is not clear. In this study, we evaluated the association between birth weight and anthropometric as well as biochemical components of MetS in women with a history of gestational diabetes mellitus (GDM) in comparison with control women. In part of the GDM group, we re-evaluated metabolic changes over 5-8 years. Anthropometry, blood pressure, glucose metabolism during the 3-h oGTT, lipid profile, uric acid, thyroid hormones, and liver enzymes were assessed. From the analyzed components of MetS in adult women we proved the association of low birth weight (birth weight <25th percentile) with glucose processing, in particular among women with a history of GDM. Low birth weight GDM women revealed significantly higher postchallenge insuli...