Developmental Effects of (Pre-)Gestational Diabetes on Offspring: Systematic Screening Using Omics Approaches

Worldwide, gestational diabetes affects 2–25% of pregnancies. Due to related disturbances of the maternal metabolism during the periconceptional period and pregnancy, children bear an increased risk for future diseases. It is well known that an aberrant intrauterine environment caused by elevated maternal glucose levels is related to elevated risks for increased birth weights and metabolic disorders in later life, such as obesity or type 2 diabetes. The complexity of disturbances induced by maternal diabetes, with multiple underlying mechanisms, makes early diagnosis or prevention a challenging task. Omics technologies allowing holistic quantification of several classes of molecules from biological fluids, cells, or tissues are powerful tools to systematically investigate the effects of maternal diabetes on the offspring in an unbiased manner. Differentially abundant molecules or distinct molecular profiles may serve as diagnostic biomarkers, which may also support the development of preventive and therapeutic strategies. In this review, we summarize key findings from state-of-the-art Omics studies addressing the impact of maternal diabetes on offspring health.

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Gestational Diabetes Mellitus and Infant Adiposity at Birth: A Systematic Review and Meta-Analysis of Therapeutic Interventions

Journal of Clinical Medicine ◽

10.3390/jcm10040835 ◽

2021 ◽

Vol 10 (4) ◽

pp. 835

Author(s):

Manoja P. Herath ◽

Jeffrey M. Beckett ◽

Andrew P. Hills ◽

Nuala M. Byrne ◽

Kiran D. K. Ahuja

Keyword(s):

Diabetes Mellitus ◽

Adipose Tissue ◽

Gestational Diabetes ◽

Gestational Diabetes Mellitus ◽

Fat Mass ◽

Metabolic Disorders ◽

Later Life ◽

Therapeutic Interventions ◽

Increased Risk ◽

The Impact

Exposure to untreated gestational diabetes mellitus (GDM) in utero increases the risk of obesity and type 2 diabetes in adulthood, and increased adiposity in GDM-exposed infants is suggested as a plausible mediator of this increased risk of later-life metabolic disorders. Evidence is equivocal regarding the impact of good glycaemic control in GDM mothers on infant adiposity at birth. We systematically reviewed studies reporting fat mass (FM), percent fat mass (%FM) and skinfold thicknesses (SFT) at birth in infants of mothers with GDM controlled with therapeutic interventions (IGDMtr). While treating GDM lowered FM in newborns compared to no treatment, there was no difference in FM and SFT according to the type of treatment (insulin, metformin, glyburide). IGDMtr had higher overall adiposity (mean difference, 95% confidence interval) measured with FM (68.46 g, 29.91 to 107.01) and %FM (1.98%, 0.54 to 3.42) but similar subcutaneous adiposity measured with SFT, compared to infants exposed to normal glucose tolerance (INGT). This suggests that IGDMtr may be characterised by excess fat accrual in internal adipose tissue. Given that intra-abdominal adiposity is a major risk factor for metabolic disorders, future studies should distinguish adipose tissue distribution of IGDMtr and INGT.

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Advanced echocardiography in neonates of diabetic mothers: a large population study of newborns

European Heart Journal ◽

10.1093/ehjci/ehaa946.3197 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

S Paerregaard ◽

R.O.B Voegg ◽

C.A Pihl ◽

H Bundgaard ◽

K.K Iversen

Keyword(s):

Gestational Diabetes ◽

Cardiac Function ◽

Large Population ◽

Maternal Diabetes ◽

Doppler Imaging ◽

Funding Source ◽

Private Company ◽

Increased Risk ◽

The Impact ◽

Diabetic Mothers

Abstract Background Maternal diabetes is associated with increased risk of congenital heart defects in the newborn, but the impact on systolic and diastolic function is less well described and findings are conflicting. Purpose To assess subclinical cardiac abnormalities in newborns of diabetic mothers using advanced echocardiography. Methods Transthoracic echocardiography (TTE) was performed within 30 days after birth in unselected neonates consecutively included in a prospective, multicenter, population-based study (2016–2018 (n=25,750)). Cardiac function in newborns of mothers with pre-gestational (pre-GDM) or gestational diabetes (GDM) and a group of matched controls of newborns of non-diabetic mothers was assessed by Tissue Doppler Imaging (TDI) and Speckle Tracking Echocardiography (STE) to detect myocardial abnormalities. Controls were matched 1:1 by the following criteria; multiple pregnancy, sex, gestational age (± five days), age at TTE (± three days) and weight (± 200 g). Results TDI and STE was performed in 317 newborns exposed to maternal diabetes during pregnancy (98 newborns of mothers with pre-GDM (females; 45.7%) and 219 newborns of mothers with GDM (females; 50%)). The mean age at time of TTE in newborns of diabetic mothers was 12 days (± 7 days). Cardiac function assessed with TDI showed significantly lower mitral valve (MV) systolic annular velocity (MV S') (3.15 cm/sec ± 0.67 vs 3.41 cm/sec ± 0.68, p=0.001), MV early diastolic annular velocity (MV E') (−4.71 cm/sec ± 1.26 vs −5.07 cm/sec ± 1.10, p=0.009), MV late diastolic annular velocity (MV A') (−4.24 cm/sec ± 1.25 vs −4.67 cm/sec ± 1.34, p=0.007) and interventricular septum late diastolic velocity (IVS A') (−4.49 cm/sec ± 0.89 vs −4.84 cm/sec ± 1.01, p=0.005) in newborns of mothers with pre-GDM compared to newborns of non-diabetic mothers. Newborns of mothers with GDM showed significantly lower MV A' (−4.35 cm/sec ± 1.35 vs −4.67 cm/sec ± 1.34, p=0.008) compared to newborns of non-diabetic mothers. When comparing subtypes of diabetes, newborns of mothers with pre-GDM had significantly lower MV E' (−4.71 cm/sec ± 1.26 vs −5.02 cm/sec ± 1.22, p=0.046) and IVS A' (−4.49 cm/sec ± 0.89 vs −4.75 cm/sec ± 0.93, p=0.033) compared to newborns of mothers with GDM. STE analysis showed that end-systolic and peak longitudinal strain (LS) were significantly lower in both subtypes of diabetes when compared to newborns of non-diabetic mothers; pre-GDM: end-systolic LS −17.93% and peak LS −19.18%, GDM: end-systolic LS −18.39% and peak LS −19.56% vs −19.56% and −20.29% in children of non-diabetic mothers, p<0.001 for all. Standard echocardiographic parameters were similar when comparing each subtype of diabetes with the newborns of non-diabetic mothers. Conclusion Advanced echocardiography showed impaired systolic and diastolic cardiac function in newborns of diabetic mothers. The most severe impairment was seen in newborns of mothers with pre-gestational diabetes. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): PRIVATE COMPANY, Novo Nordisk Foundation: Pre-graduate Scholarhips 2019 - 6 months scholarship. Public Hospital, Herlev-Gentofte Internal Research Foundation 2019 - 6 months scholarship

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Pregnancy outcomes of early detected gestational diabetes: a retrospective comparison cohort study, Qatar

BMJ Open ◽

10.1136/bmjopen-2018-023612 ◽

2019 ◽

Vol 9 (2) ◽

pp. e023612 ◽

Cited By ~ 10

Author(s):

Mohammed Bashir ◽

Khaled Baagar ◽

Emad Naem ◽

Fadi Elkhatib ◽

Noor Alshaybani ◽

...

Keyword(s):

Cohort Study ◽

Gestational Diabetes ◽

Pregnancy Outcomes ◽

Optimal Time ◽

Early Screening ◽

Glucose Levels ◽

Retrospective Comparison ◽

Increased Risk ◽

Before And After ◽

The Impact

ObjectiveTo compare pregnancy outcomes in patients with early versus usual gestational diabetes mellitus (GDM).DesignA retrospective cohort study.SettingsThe Women’s Hospital, Hamad Medical Corporation, Qatar.ParticipantsGDM women who attended and delivered in the Women’s Hospital, between January and December 2016. GDM was diagnosed based on the 2013-WHO criteria. The study included 801 patients; of which, 273 E-GDM and 528 U-GDM. Early GDM (E-GDM) and usual GDM (U-GDM) were defined as GDM detected before and after 24 weeks’ gestation, respectively.OutcomesMaternal and neonatal outcomes and the impact of timing of GDM-diagnosis on pregnancy outcomes.ResultsAt conception, E-GDM women were older (mean age 33.5±5.4 vs 32.0±5.4 years, p<0.001) and had higher body mass index (33.0±6.3 vs 31.7±6.1 kg/m2, p=0.0059) compared with U-GDM. The mean fasting, and 1-hour blood glucose levels were significantly higher in E-GDM vs U-GDM, respectively (5.3±0.7 vs 4.0±0.7 mmol/L, p<0.001 and 10.6±1.7 vs 10.3±1.6 mmol/L, p<0.001). More patients in the U-GDM were managed on diet alone compared with E-GDM (53.6% vs 27.5%, p<0.001). E-GDM subjects gained less weight per week compared with U-GDM (0.02±0.03 vs 0.12±0.03 kg/week, p=0.0274). Maternal outcomes were similar between the two groups apart from a higher incidence of preterm labour (25.5% vs 14.4%; p<0.001) and caesarean section (52.4% vs 42.8%; p=0.01) in E-GDM vs U-GDM, respectively. After correction for covariates; gestational age at which GDM was diagnosed was associated with increased risk of macrosomia (OR 1.06, 95% CI 1.00 to 1.11; p<0.05) and neonatal hypoglycaemia (OR 1.05, 95% CI 1.00 to 1.11; p<0.05).ConclusionOur data support the concept of early screening and treatment of GDM in high-risk patients. More data are needed to examine the optimal time for screening.

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The Impact of Diabetes on Hippocampus

10.5772/intechopen.99895 ◽

2021 ◽

Author(s):

Saeed Vafaei-Nezhad ◽

Masood Vafaei-Nezhad ◽

Mehri Shadi ◽

Samira Ezi

Keyword(s):

Central Nervous System ◽

Developing Countries ◽

Nervous System ◽

Child Mortality ◽

Maternal Diabetes ◽

Mortality And Morbidity ◽

Increased Risk ◽

The Impact ◽

Diabetic Mothers ◽

Lines Of Evidence

Maternal Diabetes is one of the most common metabolic disorders resulting an increased risk of abnormalities in the developing fetus and offspring. It is estimated that the prevalence of diabetes during pregnancy among women in developing countries is approximately 4.5 percent and this range varies between 1 to 14 percent in different societies. According to earlier studies, diabetes during pregnancy is associated with an increased risk of maternal and child mortality and morbidity as well as major congenital anomalies including central nervous system (CNS) in their offspring. Multiple lines of evidence have suggested that infants of diabetic women are at risk of having neurodevelopmental sequelae. Previous studies reveal that the offspring of diabetic mothers exhibit disturbances in behavioral and intellectual functioning. In the examination of cognitive functioning, a poorer performance was observed in the children born to diabetic mothers when compared with the children of non-diabetic mothers. Therefore, it is important to study the possible effects of maternal diabetes on the hippocampus of these infants.

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Glucose levels during gestational diabetes pregnancy and the risk of developing postpartum diabetes or prediabetes

BMC Pregnancy and Childbirth ◽

10.1186/s12884-021-04352-w ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Chadakarn Phaloprakarn ◽

Siriwan Tangjitgamol

Keyword(s):

Diabetes Mellitus ◽

Blood Glucose ◽

Glycemic Control ◽

Gestational Diabetes ◽

Confidence Interval ◽

Control Group ◽

Oral Glucose ◽

Glucose Levels ◽

Blood Glucose Levels ◽

The Impact

Abstract Background Blood glucose levels during pregnancy may reflect the severity of insulin secretory defects and/or insulin resistance during gestational diabetes mellitus (GDM) pregnancy. We hypothesized that suboptimal glycemic control in women with GDM could increase the risk of postpartum type 2 diabetes mellitus (T2DM) or prediabetes. Our objective was to evaluate the impact of plasma glucose levels throughout GDM pregnancy on the risk of postpartum T2DM or prediabetes. Methods The medical records of 706 women with GDM who underwent a postpartum 75-g, 2-hour oral glucose tolerance test at our institution between January 2011 and December 2018 were reviewed. These women were classified into 2 groups according to glycemic control during pregnancy: ≤ 1 occasion of either fasting glucose ≥ 95 mg/dL or 2-hour postprandial glucose ≥ 120 mg/dL was defined as optimal glycemic control or else was classified as suboptimal glycemic control. Rates of postpartum T2DM and prediabetes were compared between women with optimal (n = 505) and suboptimal (n = 201) glycemic control. Results The rates of postpartum T2DM and prediabetes were significantly higher in the suboptimal glycemic control group than in the optimal glycemic control group: 22.4% vs. 3.0%, P < 0.001 for T2DM and 45.3% vs. 23.5%, P < 0.001 for prediabetes. In a multivariate analysis, suboptimal glucose control during pregnancy was an independent risk factor for developing either postpartum T2DM or prediabetes. The adjusted odds ratios were 8.4 (95% confidence interval, 3.5–20.3) for T2DM and 3.9 (95% confidence interval, 2.5–6.1) for prediabetes. Conclusion Our findings suggest that blood glucose levels during GDM pregnancy have an impact on the risk of postpartum T2DM and prediabetes.

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Television Viewing and Cognitive Dysfunction of Korean Older Adults

Healthcare ◽

10.3390/healthcare8040547 ◽

2020 ◽

Vol 8 (4) ◽

pp. 547

Author(s):

Mi Sook Jung ◽

Eunyoung Chung

Keyword(s):

Older Adults ◽

Cognitive Dysfunction ◽

Cognitive Aging ◽

Significant Risk ◽

Multivariate Logistic Regression Analysis ◽

Later Life ◽

Significant Risk Factor ◽

Tv Viewing ◽

Increased Risk ◽

The Impact

This study examined the association between television (TV) viewing and cognitive dysfunction in elderly Koreans. Among participants of the 2014 National Survey of Older Koreans, 9644 were considered in this study. To better identify the association between two factors, propensity score (PS) matching with exact method was used. Finally, 168 viewers and non-viewers each were selected based on estimated PS on key variables and eliminating double matches. Multivariate logistic regression analysis was performed when controlling for possible covariates. Viewers were more likely to have cognitive dysfunction than non-viewers, with significant differences in most covariates. After correcting confounding effects of these covariates with PS matching, TV viewing was found to be a significant risk factor of cognitive dysfunction, along with absence of diagnosed hypertension and non-participation in physical leisure activities. TV viewing might be associated with increased risk of cognitive dysfunction in later life. Appropriate education and strategies to minimize TV viewing among older adults should be established to contribute to attenuating cognitive aging. More interventional studies can help older adults, caregivers, and healthcare professionals explore the cognitively beneficial alternatives to TV use considering the impact of socioeconomic factors of selecting TV viewing as a preferred leisure activity.

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The Joint-Brain Axis: Insights From Rheumatoid Arthritis on the Crosstalk Between Chronic Peripheral Inflammation and the Brain

Frontiers in Immunology ◽

10.3389/fimmu.2020.612104 ◽

2020 ◽

Vol 11 ◽

Author(s):

Patrick Süß ◽

Tobias Rothe ◽

Alana Hoffmann ◽

Johannes C. M. Schlachetzki ◽

Jürgen Winkler

Keyword(s):

Rheumatoid Arthritis ◽

Current Knowledge ◽

Later Life ◽

Chronic Inflammatory Disease ◽

Peripheral Inflammation ◽

Cellular Mechanisms ◽

Increased Risk ◽

Neuropsychiatric Diseases ◽

Patients At Risk ◽

The Impact

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by erosive polyarthritis. Beyond joint pathology, RA is associated with neuropsychiatric comorbidity including depression, anxiety, and an increased risk to develop neurodegenerative diseases in later life. Studies investigating the central nervous system (CNS) in preclinical models of RA have leveraged the understanding of the intimate crosstalk between peripheral and central immune responses. This mini review summarizes the current knowledge of CNS comorbidity in RA patients and known underlying cellular mechanisms. We focus on the differential regulation of CNS myeloid and glial cells in different mouse models of RA reflecting different patterns of peripheral immune activation. Moreover, we address CNS responses to anti-inflammatory treatment in human RA patients and mice. Finally, to illustrate the bidirectional communication between the CNS and chronic peripheral inflammation, we present the current knowledge about the impact of the CNS on arthritis. A comprehensive understanding of the crosstalk between the CNS and chronic peripheral inflammation will help to identify RA patients at risk of developing CNS comorbidity, setting the path for future therapeutic approaches in both RA and neuropsychiatric diseases.

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Early growth and postprandial appetite regulatory hormone responses

British Journal Of Nutrition ◽

10.1017/s0007114513000950 ◽

2013 ◽

Vol 110 (9) ◽

pp. 1591-1600 ◽

Cited By ~ 10

Author(s):

Mia-Maria Perälä ◽

Eero Kajantie ◽

Liisa M. Valsta ◽

Jens J. Holst ◽

Jaana Leiviskä ◽

...

Keyword(s):

Test Meal ◽

Metabolic Diseases ◽

Hormone Secretion ◽

Later Life ◽

Early Growth ◽

Birth Cohort Study ◽

Slow Increase ◽

Increased Risk ◽

Hormone Responses ◽

The Impact

Strong epidemiological evidence suggests that slow prenatal or postnatal growth is associated with an increased risk of CVD and other metabolic diseases. However, little is known whether early growth affects postprandial metabolism and, especially, the appetite regulatory hormone system. Therefore, we investigated the impact of early growth on postprandial appetite regulatory hormone responses to two high-protein and two high-fat content meals. Healthy, 65–75-year-old volunteers from the Helsinki Birth Cohort Study were recruited; twelve with a slow increase in BMI during the first year of life (SGI group) and twelve controls. Subjects ate a test meal (whey meal, casein meal, SFA meal and PUFA meal) once in a random order. Plasma glucose, insulin, TAG, NEFA, ghrelin, peptide tyrosine-tyrosine (PYY), glucose-dependent insulinotropic peptide, glucagon-like peptide-1 and a satiety profile were measured in the fasting state and for 4 h after each test meal. Compared with the controls, the SGI group had about 1·5-fold higher insulin responses after the whey meal (P= 0·037), casein meal (P= 0·023) and PUFA meal (P= 0·002). TAG responses were 34–69 % higher for the SGI group, but only the PUFA-meal responses differed significantly between the groups. The PYY response of the SGI group was 44 % higher after the whey meal (P= 0·046) and 115 % higher after the casein meal (P= 0·025) compared with the controls. No other statistically significant differences were seen between the groups. In conclusion, early growth may have a role in programming appetite regulatory hormone secretion in later life. Slow early growth is also associated with higher postprandial insulin and TAG responses but not with incretin levels.

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A short review of machine learning methods for classifying the outcome of Gestational Diabetes

10.1101/643833 ◽

2019 ◽

Author(s):

Shreeya Banerji

Keyword(s):

Gestational Diabetes ◽

Classification Tree ◽

Probit Model ◽

Short Review ◽

Misclassification Rate ◽

Support Vector ◽

Pima Indians ◽

High Blood Glucose ◽

Glucose Levels ◽

Increased Risk

AbstractDiabetes mellitus is a growing problem, especially in developing countries. People suffering from diabetes have an increased risk of developing a number of serious health problems. Consistently high blood glucose levels can lead to serious diseases affecting the heart and blood vessels, eyes, kidney, etc. In addition, people with diabetes also have a higher risk of developing infections.This paper aims to use suitable data mining and classification techniques which include the Logit model, the Probit model, the Classification tree technique, Artificial Neural Networks, Support Vector Machines, Ridge Regression technique and the Least Absolute Shrinkage and Selection Operator(LASSO) in order to determine the best method which can be used to classify the patients as suffering from gestational diabetes or not. The misclassification rate is calculated for different methods and the method having the least misclassification rate is said to be the most suitable to be applied to the given data, which is the PIMA Indians diabetes dataset.

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Gestational Weight Gain Influences Neonatal Outcomes in Women With Obesity and Gestational Diabetes

10.21203/rs.3.rs-607107/v1 ◽

2021 ◽

Author(s):

Ana M Ramos-Levi ◽

Gemma Rodriguez-Carnero ◽

Cristina Garcia-Fontao ◽

Antia Fernandez-Pombo ◽

Paula Andújar-Plata ◽

...

Keyword(s):

Weight Gain ◽

Birth Weight ◽

Gestational Diabetes ◽

Gestational Weight Gain ◽

Gestational Age ◽

Perinatal Outcomes ◽

Large For Gestational Age ◽

Gestational Weight ◽

Increased Risk ◽

The Impact

Abstract Background. Obesity and gestational diabetes mellitus (GDM) are associated to increased risk of perinatal complications and obesity in the offspring. However, the impact of gestational weight gain (GWG) on maternal and fetal outcomes has led to controversial results. Research design and methods. Retrospective study of 220 women with GDM and pre-pregnancy body mass index (BMI) ≥ 30 kg/m2. Pregnant women were classified according to the Institute of Medicine (IOM) recommendations regarding prior BMI and GWG. We evaluated the impact of GWG on birth weight and perinatal outcomes. Results. Mean maternal age was 34.7±5.3 years. Pre-pregnancy obesity was classified as grade I in 55.3% of cases, grade II in 32.0%, and grade III in 12.7%. GWG was adequate (5-9kg) in 24.2%, insufficient (< 5kg) in 41.8% and excessive (> 9kg) in 34.2%. Birthweight was within normal range in 81.9%, 3.6% were small for gestational age (SGA) and 14.4% were large for gestational age (LGA). Insufficient GWG was associated to a higher rate of SGA offspring, excessive GWG was associated to LGA and adequate GWG to normal birth weight. Conclusion. GWG in women with pre-pregnancy obesity and GDM impacts neonatal birthweight. Insufficient GWG is associated to SGA and excessive GWG is associated to LGA. Women with adequate GWG according to IOM guidelines obtained better perinatal outcomes.

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