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Filardi T, Bleve E, Gorini S, Caprio M, Morano S. Is Breastfeeding an Effective Approach to Reduce Metabolic Risk After GDM in Mothers and Infants? J Clin Med 2025; 14:3065. [PMID: 40364095 PMCID: PMC12072720 DOI: 10.3390/jcm14093065] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2025] [Revised: 04/21/2025] [Accepted: 04/25/2025] [Indexed: 05/15/2025] Open
Abstract
Gestational diabetes mellitus (GDM) leads to increased lifelong cardiometabolic risk in both mothers and their offspring. The identification of effective strategies to contain the future risk of type 2 diabetes (T2D) and cardiovascular disease (CVD) is of utmost importance to reduce the burden of the disease. Breastfeeding (BF) is effective in reducing short- and long-term child morbidity. In recent years, BF has emerged as a candidate low-cost intervention to prevent future cardiometabolic complications both in mothers and infants exposed to GDM. The aim of this review is to provide an overview of the evidence about the possible metabolic benefits of BF for both mothers with a history of GDM and their offspring. Increasing evidence supports the positive effects of exclusive BF over formula feeding (FF) or mixed feeding on glucose homeostasis and the lipid profile in women with previous GDM in the early postpartum period. Studies with a longer observation suggest clear benefits of intensive and longer BF on the risk of diabetes and prediabetes in mothers after adjustment for confounders. In regards to infants, in most studies, the intensity and duration of BF are positively associated with slower infant growth curves compared with FF, indicating that the positive effect of BF on growth trends might contrast the increased risk of obesity and metabolic diseases observed in infants exposed to GDM. Considering these findings, a global effort should be made to support BF practice to possibly reduce cardiometabolic morbidity after GDM.
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Affiliation(s)
- Tiziana Filardi
- Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta, 247, 00166 Rome, Italy; (S.G.); (M.C.)
- Department of Experimental Medicine, “Sapienza” University, Viale Regina Elena 324, 00161 Rome, Italy; (E.B.); (S.M.)
| | - Enrico Bleve
- Department of Experimental Medicine, “Sapienza” University, Viale Regina Elena 324, 00161 Rome, Italy; (E.B.); (S.M.)
| | - Stefania Gorini
- Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta, 247, 00166 Rome, Italy; (S.G.); (M.C.)
- Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, Via di Val Cannuta, 247, 00166 Rome, Italy
| | - Massimiliano Caprio
- Department for the Promotion of Human Sciences and Quality of Life, San Raffaele Roma Open University, Via di Val Cannuta, 247, 00166 Rome, Italy; (S.G.); (M.C.)
- Laboratory of Cardiovascular Endocrinology, IRCCS San Raffaele, Via di Val Cannuta, 247, 00166 Rome, Italy
| | - Susanna Morano
- Department of Experimental Medicine, “Sapienza” University, Viale Regina Elena 324, 00161 Rome, Italy; (E.B.); (S.M.)
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Massalha M, Iskander R, Hassan H, Spiegel E, Erez O, Nachum Z. Gestational diabetes mellitus - more than the eye can see - a warning sign for future maternal health with transgenerational impact. FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2025; 6:1527076. [PMID: 40235646 PMCID: PMC11997571 DOI: 10.3389/fcdhc.2025.1527076] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/12/2024] [Accepted: 02/06/2025] [Indexed: 04/17/2025]
Abstract
Gestational diabetes mellitus (GDM) is regarded by many as maternal maladaptation to physiological insulin resistance during the second half of pregnancy. However, recent evidence indicates that alterations in carbohydrate metabolism can already be detected in early pregnancy. This observation, the increasing prevalence of GDM, and the significant short and long-term implications for the mother and offspring call for reevaluation of the conceptual paradigm of GDM as a syndrome. This review will present evidence for the syndromic nature of GDM and the controversies regarding screening, diagnosis, management, and treatment.
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Affiliation(s)
- Manal Massalha
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
- Rappaport Faculty of Medicine, Technion, Institute of technology, Haifa, Israel
| | - Rula Iskander
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
| | - Haya Hassan
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
| | - Etty Spiegel
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
| | - Offer Erez
- Department of Obstetrics and Gynecology, Soroka University Medical Center, Beer Sheva, Israel
- Faculty of Medicine, Ben Gurion University of the Negev, Beer Sheva, Israel
- Department of Obstetrics and Gynecology, Hutzel Women’s Hospital, Wayne State University, Detroit, MI, United States
| | - Zohar Nachum
- Department of Obstetrics and Gynecology, Emek Medical Center, Afula, Israel
- Rappaport Faculty of Medicine, Technion, Institute of technology, Haifa, Israel
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O'Reilly SL, McAuliffe FM, Geraghty AA, Burden C, Davies A. Implementing weight management during and after pregnancy to reduce diabetes and CVD risk in maternal and child populations. Proc Nutr Soc 2025; 84:24-35. [PMID: 38037711 DOI: 10.1017/s0029665123004883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/02/2023]
Abstract
Maintaining a healthy weight during pregnancy is critical for both women's and children's health. Excessive gestational weight gain (GWG) can lead to complications such as gestational diabetes, hypertension and caesarean delivery. Insufficient GWG can cause fetal growth restriction and increase infant mortality risk. Additionally, postpartum weight retention raises risk of obesity, type 2 diabetes and other chronic diseases for both mother and child. This review seeks to identify current obstacles in weight management research during and after pregnancy and explore evidence-based strategies to overcome them. Pregnancy offers a window of opportunity for health behaviour changes as women are more receptive to education and have regular contact with health services. Staying within Institute of Medicine's recommended GWG ranges is associated with better maternal and fetal outcomes. Systematic review evidence supports structured diet and physical activity pregnancy interventions, leading to reduced GWG and fewer complications. Health economic evaluation indicates significant returns from implementation, surpassing investment costs due to decreased perinatal morbidity and adverse events. However, the most effective way to implement interventions within routine antenatal care remains unclear. Challenges increase in the postpartum period due to competing demands on women physically, mentally and socially, hindering intervention reach and retention. Flexible, technology-supported interventions are needed, requiring frameworks such as penetration-implementation-participation-effectiveness and template-for-intervention-description-and-replication for successful implementation. Greater research efforts are necessary to inform practice and investigate fidelity aspects through pragmatic implementation trials during the pregnancy and postpartum periods. Understanding the best ways to deliver interventions will empower women to maintain a healthy weight during their reproductive years.
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Affiliation(s)
- Sharleen L O'Reilly
- School of Agriculture and Food Science, University College Dublin College of Health Sciences, Dublin, Ireland
- UCD Perinatal Research Centre, National Maternity Hospital, University College Dublin School of Medicine, Dublin 2, Ireland
| | - Fionnuala M McAuliffe
- UCD Perinatal Research Centre, National Maternity Hospital, University College Dublin School of Medicine, Dublin 2, Ireland
| | - Aisling A Geraghty
- School of Agriculture and Food Science, University College Dublin College of Health Sciences, Dublin, Ireland
- UCD Perinatal Research Centre, National Maternity Hospital, University College Dublin School of Medicine, Dublin 2, Ireland
| | - Christy Burden
- Academic Women's Health Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
| | - Anna Davies
- Academic Women's Health Unit, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK
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Žutić M, Matijaš M, Štefulj J, Brekalo M, Nakić Radoš S. Gestational diabetes mellitus and peripartum depression: a longitudinal study of a bidirectional relationship. BMC Pregnancy Childbirth 2024; 24:821. [PMID: 39702041 DOI: 10.1186/s12884-024-07046-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/24/2024] [Accepted: 12/05/2024] [Indexed: 12/21/2024] Open
Abstract
BACKGROUND Gestational diabetes mellitus (GDM) and peripartum depression (PPD) are increasing global health issues with potentially long-lasting adverse outcomes. While limited studies suggest a bidirectional relationship between GDM and PPD, most research has been cross-sectional and focused on one direction of the relationship, primarily if GDM predicts postpartum depression. The interplay between antenatal depression and GDM is less explored, with a critical lack of prospective bidirectional studies. This longitudinal study aimed to investigate the bidirectional relationship between GDM and PPD in a total sample and according to different pre-pregnancy body mass index (BMI) categories. Specifically, we examined whether antenatal depression symptoms predict a subsequent GDM diagnosis and whether GDM predicts subsequent postpartum depression symptoms. METHODS A three-wave online longitudinal study included 360 women who were followed from the second trimester (20-28 weeks, T1) through the third trimester (32-42 weeks, T2), and into the postpartum period (6-20 weeks after birth, T3). Participants completed the General Data Questionnaire, one item about the diagnosis of GDM, and the Edinburgh Postnatal Depression Scale (EPDS). The sample was stratified according to pre-pregnancy BMI into normal-weight (N = 247) and overweight/obese (N = 113) subgroups. Women with type I and II diabetes, GDM at T1, and underweight BMI were excluded. RESULTS In the total sample, antenatal depression symptoms predicted GDM, whereas GDM did not predict postpartum depression symptoms. A bidirectional relationship was observed in normal-weight women, where antenatal depression symptoms predicted subsequent GDM diagnosis, and GDM diagnosis predicted postpartum depression symptoms. In contrast, no associations were found in either direction in the overweight/obese subgroup. CONCLUSIONS This study provides evidence of a bidirectional relationship between GDM and PPD only in women with normal body weight before pregnancy. The results highlight the complexity of the relationship between peripartum mental and metabolic health, that is dependent on pre-pregnancy BMI. Clinicians should be aware that normal-weight women may have a unique sensitivity to the bidirectional interplay between GDM and PPD. Pregnant women should be closely monitored for both mental and metabolic health issues and targeted for prevention programs to reduce the risks and burdens associated with both conditions.
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Affiliation(s)
- Maja Žutić
- University Department of Psychology, Catholic University of Croatia, Ilica 244, Zagreb, 10000, Croatia
| | - Marijana Matijaš
- University Department of Psychology, Catholic University of Croatia, Ilica 244, Zagreb, 10000, Croatia
- University of Amsterdam, Amsterdam Business School, Amsterdam, Netherlands
| | - Jasminka Štefulj
- University Department of Psychology, Catholic University of Croatia, Ilica 244, Zagreb, 10000, Croatia
- Division of Molecular Biology, Ruđer Bošković Institute, Zagreb, Croatia
| | - Maja Brekalo
- University Department of Psychology, Catholic University of Croatia, Ilica 244, Zagreb, 10000, Croatia
| | - Sandra Nakić Radoš
- University Department of Psychology, Catholic University of Croatia, Ilica 244, Zagreb, 10000, Croatia.
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Miller MG, Terebuh P, Kaelber DC, Xu R, Davis PB. SARS-CoV-2 Infection and New-Onset Type 2 Diabetes Among Pediatric Patients, 2020 to 2022. JAMA Netw Open 2024; 7:e2439444. [PMID: 39401034 PMCID: PMC11581647 DOI: 10.1001/jamanetworkopen.2024.39444] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2024] [Accepted: 08/22/2024] [Indexed: 10/15/2024] Open
Abstract
Importance In adults, diagnoses of new-onset type 2 diabetes (T2D) have increased following diagnosis with COVID-19, but whether this occurs in children is unclear. Objective To determine whether risk of incident T2D diagnosis is increased during the 6 months after SARS-CoV-2 infection among children. Design, Setting, and Participants This retrospective cohort study used electronic health records from the TriNetX analytics platforms between January 1, 2020, and December 31, 2022. Pediatric patients aged 10 to 19 years without preexisting diabetes were eligible for inclusion. Data were analyzed from August 15 to September 15, 2023, with supplemental analyses January 20 and August 8 to 13, 2024. Exposures Diagnosis of COVID-19 or a non-COVID-19 respiratory infection. Main Outcomes and Measures New diagnosis of T2D compared by risk ratios (RRs) and 95% CIs at 1, 3, and 6 months after index infection. Results The main study population included 613 602 patients, consisting of 306 801 with COVID-19 (mean [SD] age at index, 14.9 [2.9] years; 52.8% female) and 306 801 with other respiratory infections (ORIs) but no documented COVID-19 (mean [SD] age at index, 14.9 [2.9] years; 52.6% female) after propensity score matching. Risk of a new diagnosis of T2D was significantly increased from day of infection to 1, 3, and 6 months after COVID-19 diagnosis compared with the matched cohort with ORIs (RR at 1 month, 1.55 [95% CI, 1.28-1.89]; RR at 3 months: 1.48 [95% CI, 1.24-1.76]; RR at 6 months: 1.58 [95% CI, 1.35-1.85]). Similar results were found in the subpopulation classified as having overweight or obesity (RR at 1 month: 2.07 [95% CI, 1.12-3.83]; RR at 3 months: 2.00 [95% CI, 1.15-3.47]; RR at 6 months: 2.27 [95% CI, 1.38-3.75]) and the hospitalized subpopulation (RR at 1 month: 3.10 [95% CI, 2.04-4.71]; RR at 3 months: 2.74 [95% CI, 1.90-3.96]; RR at 6 months: 2.62 [95% CI, 1.87-3.66]). Similar elevation in risk was found at 3 and 6 months when excluding patients diagnosed during the interval from the index date to 1 month after infection. Conclusions and Relevance In this retrospective cohort study of children and adolescents aged 10 to 19 years, the risk of an incident diagnosis of T2D was greater following a COVID-19 diagnosis than in children diagnosed with ORIs. Further study is required to determine whether diabetes persists or reverses later in life.
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Affiliation(s)
- Margaret G. Miller
- Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Pauline Terebuh
- Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - David C. Kaelber
- Center for Clinical Informatics Research and Education, The MetroHealth System and Departments of Medicine, Pediatrics, and Population and Quantitative Health Sciences, Case Western Reserve University, Cleveland, Ohio
| | - Rong Xu
- Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University School of Medicine, Cleveland, Ohio
| | - Pamela B. Davis
- Center for Community Health Integration, Case Western Reserve University School of Medicine, Cleveland, Ohio
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Brito Nunes C, Borges MC, Freathy RM, Lawlor DA, Qvigstad E, Evans DM, Moen GH. Understanding the Genetic Landscape of Gestational Diabetes: Insights into the Causes and Consequences of Elevated Glucose Levels in Pregnancy. Metabolites 2024; 14:508. [PMID: 39330515 PMCID: PMC11434570 DOI: 10.3390/metabo14090508] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2024] [Revised: 09/16/2024] [Accepted: 09/17/2024] [Indexed: 09/28/2024] Open
Abstract
Background/Objectives: During pregnancy, physiological changes in maternal circulating glucose levels and its metabolism are essential to meet maternal and fetal energy demands. Major changes in glucose metabolism occur throughout pregnancy and consist of higher insulin resistance and a compensatory increase in insulin secretion to maintain glucose homeostasis. For some women, this change is insufficient to maintain normoglycemia, leading to gestational diabetes mellitus (GDM), a condition characterized by maternal glucose intolerance and hyperglycaemia first diagnosed during the second or third trimester of pregnancy. GDM is diagnosed in approximately 14.0% of pregnancies globally, and it is often associated with short- and long-term adverse health outcomes in both mothers and offspring. Although recent studies have highlighted the role of genetic determinants in the development of GDM, research in this area is still lacking, hindering the development of prevention and treatment strategies. Methods: In this paper, we review recent advances in the understanding of genetic determinants of GDM and glycaemic traits during pregnancy. Results/Conclusions: Our review highlights the need for further collaborative efforts as well as larger and more diverse genotyped pregnancy cohorts to deepen our understanding of the genetic aetiology of GDM, address research gaps, and further improve diagnostic and treatment strategies.
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Affiliation(s)
- Caroline Brito Nunes
- Institute for Molecular Bioscience, The University of Queensland, Brisbane 4067, Australia
| | - Maria Carolina Borges
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 1QU, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2PS, UK
| | - Rachel M. Freathy
- Department of Clinical and Biomedical Sciences, Faculty of Health and Life Sciences, University of Exeter, Exeter EX4 4PY, UK;
| | - Deborah A. Lawlor
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 1QU, UK
- Population Health Sciences, Bristol Medical School, University of Bristol, Bristol BS8 2PS, UK
| | - Elisabeth Qvigstad
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway
- Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, 0424 Oslo, Norway
| | - David M. Evans
- Institute for Molecular Bioscience, The University of Queensland, Brisbane 4067, Australia
- MRC Integrative Epidemiology Unit, University of Bristol, Bristol BS8 1QU, UK
- Frazer Institute, University of Queensland, Brisbane 4102, Australia
| | - Gunn-Helen Moen
- Institute for Molecular Bioscience, The University of Queensland, Brisbane 4067, Australia
- Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, 0372 Oslo, Norway
- Frazer Institute, University of Queensland, Brisbane 4102, Australia
- K.G. Jebsen Center for Genetic Epidemiology, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, 7491 Trondheim, Norway
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Guo M, Fang Y, Peng M, He C, Chen J, Sun B, Liu C, Zhou Y, Zhang H, Zhao K. Prenatal exposure to polycyclic aromatic hydrocarbons and phthalate acid esters and gestational diabetes mellitus: A prospective cohort study. Int J Hyg Environ Health 2024; 261:114419. [PMID: 38968840 DOI: 10.1016/j.ijheh.2024.114419] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 06/25/2024] [Accepted: 06/30/2024] [Indexed: 07/07/2024]
Abstract
BACKGROUND Polycyclic aromatic hydrocarbons and phthalate acid esters (PAHs & PAEs), known as endocrine disrupting chemicals (EDCs), widely exist in daily life and industrial production. Previous studies have suggested that PAHs & PAEs may modify the intrauterine homeostasis and have adverse effects on fetal development. However, epidemiological evidence on the associations between PAHs & PAEs and gestational diabetes mellitus (GDM) is still limited. OBJECTIVE To investigate the effects of prenatal PAHs &PAEs exposure on the risk of GDM and hyperglycemia in pregnant women. METHODS The study population was a total of 725 pregnant women from a prospective birth cohort study conducted from December 2019 to December 2021. Blood glucose levels were collected by the hospital information system. Urinary PAHs & PAEs concentrations were determined by gas chromatography tandem mass spectrometry. The Poisson regression in a generalized linear model (GLM), multiple linear regression, quantile-based g-computation method (qgcomp), and Bayesian kernel machine regression (BKMR) were applied to explore and verify the individual and overall effects of PAHs & PAEs on glucose homeostasis. Potential confounders were adjusted in all statistical models. RESULTS A total of 179 (24.69%) women were diagnosed with GDM. The Poisson regression suggested that a ln-unit increment of 4-OHPHE (4-hydroxyphenanthrene) (adjusted Risk Ratio (aRR) = 1.13; 1.02-1.26) was associated with the increased GDM risk. Mixed-exposure models showed similar results. We additionally found that MBZP (mono-benzyl phthalate) (aRR = 1.19; 1.02-1.39) was positively related to GDM risk in qgcomp model. Although neither model demonstrated that 2-OHNAP (2-hydroxynaphthalene) and 9-OHFLU (9-hydroxyfluorene) increased the risk of GDM, 2-OHNAP and 9-OHFLU exposure significantly increased blood glucose levels. BKMR model further confirmed that overall effects of PAHs & PAEs were significantly associated with the gestational hyperglycemia and GDM risk. CONCLUSIONS Our study presents that environmental exposure to PAHs & PAEs was positively associated with gestational glucose levels and the risks of developing GDM. In particular, 2-OHNAP, 9-OHFLU, 4-OHPHE and MBZP may serve as important surveillance markers to prevent the development of GDM.
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Affiliation(s)
- Minghao Guo
- Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China
| | - Yiwei Fang
- Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Peking University Third Hospital, No. 49, North Garden Road, Haidian District, Beijing, 100191, PR China; National Clinical Research Center for Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, PR China; State Key Laboratory of Female Fertility Promotion, Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, 100191, PR China; Key Laboratory of Assisted Reproduction, Ministry of Education, Peking University, Beijing, 100191, PR China; Beijing Key Laboratory of Reproductive Endocrinology and Assisted Reproductive Technology, Beijing, 100191, PR China.
| | - Meilin Peng
- Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China
| | - Chao He
- Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China
| | - Jin Chen
- Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China
| | - Borui Sun
- Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China
| | - Chunyan Liu
- Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China
| | - Yuanzhong Zhou
- School of Public Health, Zunyi Medical University, Zunyi, Guizhou, 563060, PR China
| | - Huiping Zhang
- Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
| | - Kai Zhao
- Institute of Reproductive Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, PR China.
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Titmuss A, Korula S, Wicklow B, Nadeau KJ. Youth-onset Type 2 Diabetes: An Overview of Pathophysiology, Prognosis, Prevention and Management. Curr Diab Rep 2024; 24:183-195. [PMID: 38958831 PMCID: PMC11269415 DOI: 10.1007/s11892-024-01546-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/19/2024] [Indexed: 07/04/2024]
Abstract
PURPOSE OF REVIEW This review explores the emerging evidence regarding pathogenesis, future trajectories, treatment options, and phenotypes of youth-onset type 2 diabetes (T2D). RECENT FINDINGS Youth-onset T2D is increasing in incidence and prevalence worldwide, disproportionately affecting First Nations communities, socioeconomically disadvantaged youth, and people of colour. Youth-onset T2D differs in pathogenesis to later-onset T2D and progresses more rapidly. It is associated with more complications, and these occur earlier. While there are limited licensed treatment options available, the available medications also appear to have a poorer response in youth with T2D. Multiple interacting factors likely contribute to this rising prevalence, as well as the increased severity of the condition, including structural inequities, increasing obesity and sedentary lifestyles, and intergenerational transmission from in-utero exposure to maternal hyperglycemia and obesity. Youth-onset T2D is also associated with stigma and poorer mental health, and these impact clinical management. There is an urgent need to develop effective interventions to prevent youth-onset T2D and enhance engagement of affected youth. It is also critical to better understand the differing phenotypes of youth-onset T2D, to effectively target treatments, and to address intergenerational transmission in high-risk populations.
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Affiliation(s)
- Angela Titmuss
- Wellbeing and Preventable Chronic Diseases Division, Menzies School of Health Research, Charles Darwin University, Casuarina, PO Box 41096, Darwin, Northern Territory, Australia.
- Department of Paediatrics, Division of Women, Child and Youth, Royal Darwin Hospital, Darwin, Northern Territory, Australia.
| | - Sophy Korula
- Paediatric Endocrinology and Metabolism Division, Paediatric Unit-1, Christian Medical College Hospital, Vellore, India
- Department of Paediatrics, Latrobe Regional Hospital, Traralgon, Victoria, Australia
| | - Brandy Wicklow
- Department of Paediatrics and Child Health, University of Manitoba, Winnipeg, Canada
- Children's Hospital Research Institute of Manitoba, Winnipeg, Manitoba, Canada
| | - Kristen J Nadeau
- Children's Hospital Colorado, Aurora, Colorado, USA
- School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA
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Foo RX, Ma JJ, Du R, Goh GBB, Chong YS, Zhang C, Li LJ. Gestational diabetes mellitus and development of intergenerational non-alcoholic fatty liver disease (NAFLD) after delivery: a systematic review and meta-analysis. EClinicalMedicine 2024; 72:102609. [PMID: 38707911 PMCID: PMC11067479 DOI: 10.1016/j.eclinm.2024.102609] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 03/30/2024] [Accepted: 04/05/2024] [Indexed: 05/07/2024] Open
Abstract
Background It is known that gestational diabetes mellitus (GDM)-complicated pregnancies could affect maternal cardiometabolic health after delivery, resulting in hepatic dysfunction and a heightened risk of developing non-alcoholic fatty liver disease (NAFLD). Hence, this study aims to summarise existing literature on the impact of GDM on NAFLD in mothers and investigate the intergenerational impact on NAFLD in offspring. Methods Using 4 databases (PubMed, Embase, Web of Science and Scopus) between January 1980 and December 2023, randomized controlled trials and observational studies that assessed the effect of maternal GDM on intergenerational liver outcomes were extracted and analysed using random-effects meta-analysis to investigate the effect of GDM on NAFLD in mothers and offspring. Pooled odds ratio (OR) was calculated using hazards ratio (HR), relative risk (RR), or OR reported from each study, with corresponding 95% confidence intervals (CI), and statistical heterogeneity was assessed with the Cochran Q-test and I2 statistic, with two-sided p values. The study protocol was pre-registered on PROSPERO (CRD42023392428). Findings Twenty studies pertaining to mothers and offspring met the inclusion criteria and 12 papers were included further for meta-analysis on intergenerational NAFLD development. Compared with mothers without a history of GDM, mothers with a history of GDM had a 50% increased risk of developing NAFLD (OR 1.50; 95% CI: 1.21-1.87, over a follow-up period of 16 months-25 years. Similarly, compared with offspring born to non-GDM-complicated pregnancies, offspring born to GDM-complicated pregnancies displayed an approximately two-fold elevated risk of NAFLD development (2.14; 1.57-2.92), over a follow-up period of 1-17.8 years. Interpretation This systematic review and meta-analysis suggests that both mothers and offspring from GDM-complicated pregnancies exhibit a greater risk to develop NAFLD. These findings underline the importance of early monitoring of liver function and prompt intervention of NAFLD in both generations from GDM-complicated pregnancies. Funding No funding was available for this research.
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Affiliation(s)
- Ru Xun Foo
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Jenny Junyi Ma
- Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Ruochen Du
- Statistics Unit, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - George Boon Bee Goh
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
- Medicine Academic Clinical Program, Duke-NUS Medical School, Singapore
| | - Yap Seng Chong
- Department of O&G, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Cuilin Zhang
- Department of O&G, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Global Centre for Asian Women's Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- NUS Bia-Echo Asia Centre for Reproductive Longevity and Equality (ACRLE), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Ling-Jun Li
- Department of O&G, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- Global Centre for Asian Women's Health, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
- NUS Bia-Echo Asia Centre for Reproductive Longevity and Equality (ACRLE), Yong Loo Lin School of Medicine, National University of Singapore, Singapore
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10
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Nyen SL, Stunes AK, Evensen K, Børsting T, Syversen U, Salvesen KÅ, Mørkved S, Stafne SN. Associations between maternal and offspring glucose metabolism: a 9-year follow-up of a randomised controlled trial. Front Endocrinol (Lausanne) 2024; 14:1324925. [PMID: 38269252 PMCID: PMC10806570 DOI: 10.3389/fendo.2023.1324925] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2023] [Accepted: 12/18/2023] [Indexed: 01/26/2024] Open
Abstract
Introduction There is increasing evidence that the in utero environment affects the health and disease risk of offspring throughout their lives. The long-term effect of maternal hyperglycaemia on offspring glucose metabolism is of interest in a public health perspective. The aim of this study was to examine the association between in utero exposure to maternal glycaemia and offspring glucose metabolism. Methods Mother-child pairs were recruited from an RCT to prevent gestational diabetes mellitus where 855 healthy pregnant women were randomised to exercise or standard antenatal care. The original RCT detected no group differences in gestational diabetes mellitus prevalence or insulin resistance. The two groups were analysed as one group in the present study. Maternal glucose levels were assessed after 2-hour 75-gram oral glucose tolerance tests in pregnancy week ~34. Offspring outcomes were evaluated at ~9 years of age and included fasting glucose and homeostatic model assessment of insulin resistance. Multivariable regression models were performed, controlling for potential hereditary and lifestyle confounding factors. Results Complete data were available for 105 mother-child pairs. The regression analysis showed a positive association between maternal and offspring fasting glucose that was borderline significant (beta=0.18, 95% CI [-0.00027, 0.37], p=0.050). We did not find significant associations between maternal fasting glucose and offspring insulin resistance (beta=0.080, 95% CI [-0.087, 0.25], p=0.34), or between maternal 2-hour glucose and offspring fasting glucose (beta=0.016, 95% CI [-0.038, 0.070], p=0.56) or insulin resistance (beta=0.017, 95% CI [-0.032, 0.065], p=0.49). Conclusions Assessing a homogeneous group of healthy mother-child pairs, we found a borderline significant positive association between maternal and offspring fasting glucose, which persisted after adjustment for potential hereditary and lifestyle confounding factors. Our findings support other similar studies and highlight that improving the metabolic health of pregnant women, and women in childbearing age, should remain a key public health priority. Clinical trial registration ClinicalTrials.gov, identifier NCT00476567.
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Affiliation(s)
- Sigrid L. Nyen
- Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Astrid Kamilla Stunes
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Center for Oral Health Services and Research, Mid-Norway (TkMidt), Trondheim, Norway
| | - Kari Anne I. Evensen
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Children’s Clinic, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
- Department of Rehabilitation Science and Health Technology, Faculty of Health Sciences, Oslo Metropolitan University, Oslo, Norway
| | - Torunn Børsting
- Center for Oral Health Services and Research, Mid-Norway (TkMidt), Trondheim, Norway
- Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Unni Syversen
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Endocrinology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Kjell Å. Salvesen
- Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Obstetrics and Gynecology, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Siv Mørkved
- Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Clinic of Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
| | - Signe N. Stafne
- Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Clinic of Rehabilitation, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway
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11
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Moore BA, Callahan ML, Martin SL, Everett A, Garvey WT, Chandler-Laney P. Associations Among Physical Activity, Adiposity, and Insulin Resistance in Children Exposed In Utero to Maternal Obesity With and Without Gestational Diabetes. Pediatr Exerc Sci 2023; 35:165-173. [PMID: 36543176 PMCID: PMC10874230 DOI: 10.1123/pes.2021-0222] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Revised: 08/13/2022] [Accepted: 10/27/2022] [Indexed: 12/24/2022]
Abstract
PURPOSE Investigate whether obesity risk and current weight status are independently associated with physical activity (PA) and whether PA is associated with adiposity and insulin resistance (homeostatic model assessment of insulin resistance) among children with high versus low obesity risk based on in utero exposure to maternal overweight/obesity with gestational diabetes mellitus (GDM; high risk) or without GDM (overweight/obesity; high risk) or maternal normal weight without GDM (low risk). METHOD Secondary analysis of data from children born to women with overweight/obesity and GDM, overweight/obesity without GDM, or normal weight without GDM. PA was assessed with accelerometry, percentage of body fat derived from anthropometrics, and homeostatic model assessment of insulin resistance calculated from glucose and insulin. RESULTS Among 4- to 10-year-old children (N = 163), analyses of covariance showed that children with a current BMI ≥85th percentile had less vigorous PA than those with BMI <85th percentile, but in utero exposure was not an independent predictor of PA. In linear regression modeling, moderate to vigorous PA was inversely associated with percentage of body fat and homeostatic model assessment of insulin resistance independent of age, Tanner stage, and accelerometer wear time, with stronger associations in high-risk groups. CONCLUSIONS Children's PA is related to current weight status but not underlying risk for obesity but may be especially important to reduce obesity and insulin resistance in high-risk children.
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Affiliation(s)
- Bethany A Moore
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL,USA
| | - Makenzie L Callahan
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL,USA
| | - Samantha L Martin
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL,USA
| | - Alysha Everett
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL,USA
| | - W Timothy Garvey
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL,USA
| | - Paula Chandler-Laney
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, AL,USA
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12
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Hassan S, Gujral UP, Quarells RC, Rhodes EC, Shah MK, Obi J, Lee WH, Shamambo L, Weber MB, Narayan KMV. Disparities in diabetes prevalence and management by race and ethnicity in the USA: defining a path forward. Lancet Diabetes Endocrinol 2023; 11:509-524. [PMID: 37356445 PMCID: PMC11070656 DOI: 10.1016/s2213-8587(23)00129-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2022] [Revised: 05/01/2023] [Accepted: 05/01/2023] [Indexed: 06/27/2023]
Abstract
Type 2 diabetes disparities in the USA persist in both the prevalence of disease and diabetes-related complications. We conducted a literature review related to diabetes prevention, management, and complications across racial and ethnic groups in the USA. The objective of this review is to summarise the current understanding of diabetes disparities by examining differences between and within racial and ethnic groups and among young people (aged <18 years). We also examine the pathophysiology of diabetes as it relates to race and ethnic differences. We use a conceptual framework built on the socioecological model to categorise the causes of diabetes disparities across the lifespan looking at factors in five domains of health behaviours and social norms, public awareness, structural racism, economic development, and access to high-quality care. The range of disparities in diabetes prevalence and management in the USA calls for a community-engaged and multidisciplinary approach that must involve community partners, researchers, practitioners, health system administrators, and policy makers. We offer recommendations for each of these groups to help to promote equity in diabetes prevention and care in the USA.
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Affiliation(s)
- Saria Hassan
- Department of Medicine, Emory University, Atlanta, GA, USA; Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA; Hubert Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA.
| | - Unjali P Gujral
- Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA; Hubert Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA
| | - Rakale C Quarells
- Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA; Department of Community Health and Preventive Medicine, Morehouse School of Medicine, Atlanta, GA, USA
| | - Elizabeth C Rhodes
- Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA; Hubert Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA
| | - Megha K Shah
- Department of Family and Preventive Medicine, Emory University, Atlanta, GA, USA; Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA
| | - Jane Obi
- Emory School of Medicine, and the Nutrition and Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA, USA; Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA
| | - Wei-Hsuan Lee
- Department of Medicine, Emory University, Atlanta, GA, USA
| | - Luwi Shamambo
- Department of Medicine, Emory University, Atlanta, GA, USA
| | - Mary Beth Weber
- Emory School of Medicine, and the Nutrition and Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA, USA; Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA; Hubert Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA
| | - K M Venkat Narayan
- Department of Medicine, Emory University, Atlanta, GA, USA; Emory School of Medicine, and the Nutrition and Health Sciences Doctoral Program, Laney Graduate School, Emory University, Atlanta, GA, USA; Emory Global Diabetes Research Center, Emory University, Atlanta, GA, USA; Hubert Department of Global Health, Rollins School of Public Health, Atlanta, GA, USA
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13
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Newman C, Rabbitt L, Ero A, Dunne FP. Focus on Metformin: Its Role and Safety in Pregnancy and Beyond. Drugs 2023:10.1007/s40265-023-01899-0. [PMID: 37354354 PMCID: PMC10322786 DOI: 10.1007/s40265-023-01899-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/23/2023] [Indexed: 06/26/2023]
Abstract
Metformin is used worldwide in the treatment of type 2 diabetes and has been used in the treatment of diabetes in pregnancy since the 1970s. It is highly acceptable to patients due to its ease of administration, cost and adverse effect profile. It is effective in reducing macrosomia, large-for-gestational-age infants and reduces maternal weight gain. Despite its many advantages, metformin has been associated with reductions in foetal size and has been associated with an increase in infants born small-for-gestational-age in certain cohorts. In this article, we review its efficacy, adverse effects and long-term follow-up before, during and after pregnancy for both mother and infant. We also evaluate the other forms of treatment for gestational diabetes, including oral therapies, insulin therapy and emerging treatments.
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Affiliation(s)
- Christine Newman
- Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospital, Galway, Ireland.
- Diabetes Collaborative Clinical Trial Network, Clinical Research Facility, University of Galway, Galway, Ireland.
| | - Louise Rabbitt
- Department of Clinical Pharmacology and Therapeutics, Galway University Hospital, Galway, Ireland
- Discipline of Pharmacology and Therapeutics, School of Medicine, University of Galway, Galway, Ireland
| | - Adesuwa Ero
- Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospital, Galway, Ireland
| | - Fidelma P Dunne
- Centre for Diabetes, Endocrinology and Metabolism, Galway University Hospital, Galway, Ireland
- Diabetes Collaborative Clinical Trial Network, Clinical Research Facility, University of Galway, Galway, Ireland
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14
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Aldahmash W, Harrath AH, Aljerian K, Sabr Y, Alwasel S. Expression of Glucose Transporters 1 and 3 in the Placenta of Pregnant Women with Gestational Diabetes Mellitus. Life (Basel) 2023; 13:life13040993. [PMID: 37109521 PMCID: PMC10143906 DOI: 10.3390/life13040993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 03/29/2023] [Accepted: 04/06/2023] [Indexed: 04/29/2023] Open
Abstract
BACKGROUND The annual prevalence of gestational diabetes mellitus-characterized by an increase in blood glucose in pregnant women-has been increasing worldwide. The goal of this study was to evaluate the expression of glucose transporter 1 (GLUT1) and glucose transporter 3 (GLUT3) in the placenta of women with gestational diabetes mellitus. METHODS Sixty-five placentas from women admitted to the King Saud University Medical City, Riyadh, Saudi Arabia, were analyzed; 34 and 31 placentas were from healthy pregnant women and women with gestational diabetes, respectively. The expressions of GLUT1 and GLUT3 were assessed using RT-PCR, Western blotting, and immunohistochemical methods. The degree of apoptosis in the placental villi was estimated via a TUNEL assay. RESULTS The results of the protein expression assays and immunohistochemical staining showed that the levels of GLUT1 and GLUT3 were significantly higher in the placentas of pregnant women with gestational diabetes than those in the placentas of healthy pregnant women. In addition, the findings showed an increase in apoptosis in the placenta of pregnant women with gestational diabetes compared to that in the placenta of healthy pregnant women. However, the results of gene expression assays showed no significant difference between the two groups. CONCLUSIONS Based on these results, we conclude that gestational diabetes mellitus leads to an increased incidence of apoptosis in the placental villi and alters the level of GLUT1 and GLUT3 protein expressions in the placenta of women with gestational diabetes. Understanding the conditions in which the fetus develops in the womb of a pregnant woman with gestational diabetes may help researchers understand the underlying causes of the development of chronic diseases later in life.
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Affiliation(s)
- Waleed Aldahmash
- Zoology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Abdel Halim Harrath
- Zoology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
| | - Khaldoon Aljerian
- Pathology Department, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
| | - Yasser Sabr
- Obstetrics and Gynaecology Department, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia
| | - Saleh Alwasel
- Zoology Department, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia
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15
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Karavanaki K, Paschou SA, Tentolouris N, Karachaliou F, Soldatou A. Type 2 diabetes in children and adolescents: distinct characteristics and evidence-based management. Endocrine 2022; 78:280-295. [PMID: 36029440 DOI: 10.1007/s12020-022-03172-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 08/08/2022] [Indexed: 11/03/2022]
Abstract
PURPOSE Since the dramatic rise of obesity prevalence in childhood and adolescence has contributed to increased rates of type 2 diabetes (T2D) in youth, we sought to explore current evidence-based management options for pediatric T2D patients. METHODS A comprehensive literature search was performed for studies of T2D in childhood and adolescence until September 2021. RESULTS Special pathophysiological and diagnostic characteristics of T2D in this age are presented, while the main focus of the article is on management. Lifestyle interventions with healthy diet and exercise are of great importance for the treatment of T2D in children and adolescents. Metformin and insulin remain the traditional therapeutical means, while liraglutide recently gained indication for children older than 10 years both in USA and Europe. Data on the use, efficacy, safety and therapeutic considerations of other pharmacological treatments in children and adolescents with T2D are critically discussed. CONCLUSION Although many new and promising therapeutic strategies have been introduced during recent years for the management of T2D in adults, available therapeutic options for the management of pediatric T2D remain limited.
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Affiliation(s)
- Kyriaki Karavanaki
- Diabetes and Obesity Unit, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, "P&A Kyriakou" Children's Hospital, Athens, Greece
| | - Stavroula A Paschou
- Endocrine Unit and Diabetes Centre, Department of Clinical Therapeutics, Alexandra Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Nicholas Tentolouris
- Diabetes Centre, First Department of Internal Medicine, Medical School, National and Kapodistrian University of Athens, "Laikon" General Hospital, Athens, Greece
| | - Foteini Karachaliou
- Diabetes and Endocrine Clinic, 3rd Department of Pediatrics, National and Kapodistrian University of Athens, Attikon General Hospital, Athens, Greece
| | - Alexandra Soldatou
- Diabetes and Obesity Unit, 2nd Department of Pediatrics, National and Kapodistrian University of Athens, "P&A Kyriakou" Children's Hospital, Athens, Greece.
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16
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Ormazabal V, Nair S, Carrión F, Mcintyre HD, Salomon C. The link between gestational diabetes and cardiovascular diseases: potential role of extracellular vesicles. Cardiovasc Diabetol 2022; 21:174. [PMID: 36057662 PMCID: PMC9441052 DOI: 10.1186/s12933-022-01597-3] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 08/05/2022] [Indexed: 11/25/2022] Open
Abstract
Extracellular vesicles are critical mediators of cell communication. They encapsulate a variety of molecular cargo such as proteins, lipids, and nucleic acids including miRNAs, lncRNAs, circular RNAs, and mRNAs, and through transfer of these molecular signals can alter the metabolic phenotype in recipient cells. Emerging studies show the important role of extracellular vesicle signaling in the development and progression of cardiovascular diseases and associated risk factors such as type 2 diabetes and obesity. Gestational diabetes mellitus (GDM) is hyperglycemia that develops during pregnancy and increases the future risk of developing obesity, impaired glucose metabolism, and cardiovascular disease in both the mother and infant. Available evidence shows that changes in maternal metabolism and exposure to the hyperglycemic intrauterine environment can reprogram the fetal genome, leaving metabolic imprints that define life-long health and disease susceptibility. Understanding the factors that contribute to the increased susceptibility to metabolic disorders of children born to GDM mothers is critical for implementation of preventive strategies in GDM. In this review, we discuss the current literature on the fetal programming of cardiovascular diseases in GDM and the impact of extracellular vesicle (EV) signaling in epigenetic programming in cardiovascular disease, to determine the potential link between EV signaling in GDM and the development of cardiovascular disease in infants.
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Affiliation(s)
- Valeska Ormazabal
- Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine + Biomedical Sciences, The University of Queensland, Building 71/918, Herston, QLD, 4029, Australia.,Faculty of Biological Sciences, Pharmacology Department, University of Concepcion, Concepción, Chile
| | - Soumyalekshmi Nair
- Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine + Biomedical Sciences, The University of Queensland, Building 71/918, Herston, QLD, 4029, Australia
| | - Flavio Carrión
- Departamento de Investigación, Postgrado y Educación Continua (DIPEC), Facultad de Ciencias de la Salud, Universidad del Alba, Santiago, Chile
| | - H David Mcintyre
- Mater Research, Faculty of Medicine, University of Queensland, Mater Health, South Brisbane, Australia
| | - Carlos Salomon
- Exosome Biology Laboratory, Centre for Clinical Diagnostics, UQ Centre for Clinical Research, Royal Brisbane and Women's Hospital, Faculty of Medicine + Biomedical Sciences, The University of Queensland, Building 71/918, Herston, QLD, 4029, Australia. .,Departamento de Investigación, Postgrado y Educación Continua (DIPEC), Facultad de Ciencias de la Salud, Universidad del Alba, Santiago, Chile.
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17
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Al-Beltagi M, Bediwy AS, Saeed NK. Insulin-resistance in paediatric age: Its magnitude and implications. World J Diabetes 2022; 13:282-307. [PMID: 35582667 PMCID: PMC9052009 DOI: 10.4239/wjd.v13.i4.282] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Revised: 03/12/2022] [Accepted: 03/27/2022] [Indexed: 02/06/2023] Open
Abstract
Insulin resistance (IR) is insulin failure in normal plasma levels to adequately stimulate glucose uptake by the peripheral tissues. IR is becoming more common in children and adolescents than before. There is a strong association between obesity in children and adolescents, IR, and the metabolic syndrome components. IR shows marked variation among different races, crucial to understanding the possible cardiovascular risk, specifically in high-risk races or ethnic groups. Genetic causes of IR include insulin receptor mutations, mutations that stimulate autoantibody production against insulin receptors, or mutations that induce the formation of abnormal glucose transporter 4 molecules or plasma cell membrane glycoprotein-1 molecules; all induce abnormal energy pathways and end with the development of IR. The parallel increase of IR syndrome with the dramatic increase in the rate of obesity among children in the last few decades indicates the importance of environmental factors in increasing the rate of IR. Most patients with IR do not develop diabetes mellitus (DM) type-II. However, IR is a crucial risk factor to develop DM type-II in children. Diagnostic standards for IR in children are not yet established due to various causes. Direct measures of insulin sensitivity include the hyperinsulinemia euglycemic glucose clamp and the insulin-suppression test. Minimal model analysis of frequently sampled intravenous glucose tolerance test and oral glucose tolerance test provide an indirect estimate of metabolic insulin sensitivity/resistance. The main aim of the treatment of IR in children is to prevent the progression of compensated IR to decompensated IR, enhance insulin sensitivity, and treat possible complications. There are three main lines for treatment: Lifestyle and behavior modification, pharmacotherapy, and surgery. This review will discuss the magnitude, implications, diagnosis, and treatment of IR in children.
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Affiliation(s)
- Mohammed Al-Beltagi
- Department of Pediatrics, Faculty of Medicine, Tanta University, Tanta 31511, Egypt
- Department of Pediatrics, University Medical Center, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
| | - Adel Salah Bediwy
- Department of Chest Disease, Faculty of Medicine, Tanta University, Tanta 31527, Egypt
- Department of Pulmonology, University Medical Center, Arabian Gulf University, Dr. Sulaiman Al Habib Medical Group, Manama 26671, Bahrain
| | - Nermin Kamal Saeed
- Medical Microbiology Section, Department of Pathology, Salmaniya Medical Complex, Ministry of Health, Manama 12, Bahrain
- Microbiology Section, Department of Pathology, Irish Royal College of Surgeon, Busaiteen 15503, Bahrain
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18
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Dessì A, Tognazzi C, Bosco A, Pintus R, Fanos V. Metabolomic profiles and microbiota of GDM offspring: The key for future perspective? Front Pediatr 2022; 10:941800. [PMID: 36275053 PMCID: PMC9579340 DOI: 10.3389/fped.2022.941800] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2022] [Accepted: 08/15/2022] [Indexed: 11/13/2022] Open
Abstract
Gestational diabetes mellitus (GDM), or any degree of glucose intolerance recognized for the first time during pregnancy, is one of the diseases that most frequently aggravates the course of gestation. Missed or late diagnosis and inadequate treatment are associated with high maternal and fetal morbidity, with possible short- and long-term repercussions. Estimates on the prevalence of GDM are alarming and increasing by about 30% in the last 10-20 years. In addition, there is the negative influence of the SARS-CoV-2 emergency on the glycemic control of pregnant women, making the matter increasingly topical. To date, knowledge on the metabolic maturation of newborns is still incomplete. However, in light of the considerable progress of the theory of "developmental origins of health and disease," the relevant role of the intrauterine environment cannot be overlooked. In fact, due to the high plasticity of the early stages of development, some detrimental metabolic alterations during fetal growth, including maternal hyperglycemia, are associated with a higher incidence of chronic diseases in adult life. In this context, metabolomic analysis which allows to obtain a detailed phenotypic portrait through the dynamic detection of all metabolites in cells, tissues and different biological fluids could be very useful for the early diagnosis and prevention of complications. Indeed, if the diagnostic timing is optimized through the identification of specific metabolites, the detailed understanding of the altered metabolic pathway could also allow better management and more careful monitoring, also from a nutritional profile, of the more fragile children. In this context, a further contribution derives from the analysis of the intestinal microbiota, the main responsible for the fecal metabolome, given its alteration in pregnancies complicated by GDM and the possibility of transmission to offspring. The purpose of this review is to analyze the available data regarding the alterations in the metabolomic profile and microbiota of the offspring of mothers with GDM in order to highlight future prospects for reducing GDM-related complications in children of mothers affected by this disorder.
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Affiliation(s)
- Angelica Dessì
- Neonatal Intensive Care Unit, Department of Surgical Sciences, Azienda Ospedaliera Universitaria (AOU) Cagliari, University of Cagliari, Cagliari, Italy
| | - Chiara Tognazzi
- Neonatal Intensive Care Unit, Department of Surgical Sciences, Azienda Ospedaliera Universitaria (AOU) Cagliari, University of Cagliari, Cagliari, Italy
| | - Alice Bosco
- Neonatal Intensive Care Unit, Department of Surgical Sciences, Azienda Ospedaliera Universitaria (AOU) Cagliari, University of Cagliari, Cagliari, Italy
| | - Roberta Pintus
- Neonatal Intensive Care Unit, Department of Surgical Sciences, Azienda Ospedaliera Universitaria (AOU) Cagliari, University of Cagliari, Cagliari, Italy
| | - Vassilios Fanos
- Neonatal Intensive Care Unit, Department of Surgical Sciences, Azienda Ospedaliera Universitaria (AOU) Cagliari, University of Cagliari, Cagliari, Italy
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19
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Zengul AG, Hoover SET, Chandler-Laney PC. Secondary analysis of gut hormone data from children with and without in utero exposure to gestational diabetes: Differences in the associations among ghrelin, GLP-1, and insulin secretion. Pediatr Obes 2021; 16:e12757. [PMID: 33236516 PMCID: PMC8105267 DOI: 10.1111/ijpo.12757] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 10/05/2020] [Accepted: 11/09/2020] [Indexed: 12/01/2022]
Abstract
BACKGROUND Intrauterine exposure to gestational diabetes mellitus (GDM) increases risk for type 2 diabetes (T2D). Ghrelin and GLP-1 have opposite functions in nutritional homeostasis and are associated with insulin secretion, but it is not known if individuals exposed to GDM exhibit dysregulation in these associations. OBJECTIVE Test the hypothesis that children exposed to GDM in utero will exhibit dysregulation among ghrelin, GLP-1, and C-peptide (reflecting insulin secretion). METHODS Data from N = 43 children aged 5 to 10 years were included in this secondary analysis of ghrelin, GLP-1, and C-peptide response to a liquid meal test. Repeated measures mixed model analyses were used to measure associations among hormones. RESULTS The association of ghrelin and GLP-1 was moderated by GDM group (P < .01), such that ghrelin was inversely associated with GLP-1 in children without GDM exposure, but not for those exposed to GDM. GLP-1 was positively associated with C-peptide in both groups, but the association was stronger in those exposed to GDM (estimate = 1.06 vs 1.01). CONCLUSIONS Differences in the associations among ghrelin, GLP-1, and C-peptide displayed here suggest novel lines of research about whether the regulation of gut hormones and insulin secretion contribute to obesity and risk for T2D in children exposed to GDM.
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Affiliation(s)
- Ayse G. Zengul
- Department of Nutrition Sciences, the University of Alabama at Birmingham (UAB), 1720 2nd Avenue South, Birmingham, AL 35294, USA
| | - Sarah ET Hoover
- Department of Nutrition Sciences, the University of Alabama at Birmingham (UAB), 1720 2nd Avenue South, Birmingham, AL 35294, USA
| | - Paula C. Chandler-Laney
- Department of Nutrition Sciences, the University of Alabama at Birmingham (UAB), 1720 2nd Avenue South, Birmingham, AL 35294, USA
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Parveen N, Dhawan S. DNA Methylation Patterning and the Regulation of Beta Cell Homeostasis. Front Endocrinol (Lausanne) 2021; 12:651258. [PMID: 34025578 PMCID: PMC8137853 DOI: 10.3389/fendo.2021.651258] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2021] [Accepted: 04/21/2021] [Indexed: 12/14/2022] Open
Abstract
Pancreatic beta cells play a central role in regulating glucose homeostasis by secreting the hormone insulin. Failure of beta cells due to reduced function and mass and the resulting insulin insufficiency can drive the dysregulation of glycemic control, causing diabetes. Epigenetic regulation by DNA methylation is central to shaping the gene expression patterns that define the fully functional beta cell phenotype and regulate beta cell growth. Establishment of stage-specific DNA methylation guides beta cell differentiation during fetal development, while faithful restoration of these signatures during DNA replication ensures the maintenance of beta cell identity and function in postnatal life. Lineage-specific transcription factor networks interact with methylated DNA at specific genomic regions to enhance the regulatory specificity and ensure the stability of gene expression patterns. Recent genome-wide DNA methylation profiling studies comparing islets from diabetic and non-diabetic human subjects demonstrate the perturbation of beta cell DNA methylation patterns, corresponding to the dysregulation of gene expression associated with mature beta cell state in diabetes. This article will discuss the molecular underpinnings of shaping the islet DNA methylation landscape, its mechanistic role in the specification and maintenance of the functional beta cell phenotype, and its dysregulation in diabetes. We will also review recent advances in utilizing beta cell specific DNA methylation patterns for the development of biomarkers for diabetes, and targeting DNA methylation to develop translational approaches for supplementing the functional beta cell mass deficit in diabetes.
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Affiliation(s)
| | - Sangeeta Dhawan
- Department of Translational Research and Cellular Therapeutics, Arthur Riggs Diabetes and Metabolism Research Institute, City of Hope, Duarte, CA, United States
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21
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Han JC, Weiss R. Obesity, Metabolic Syndrome and Disorders of Energy Balance. SPERLING PEDIATRIC ENDOCRINOLOGY 2021:939-1003. [DOI: 10.1016/b978-0-323-62520-3.00024-5] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Sheiner E. Gestational Diabetes Mellitus: Long-Term Consequences for the Mother and Child Grand Challenge: How to Move on Towards Secondary Prevention? FRONTIERS IN CLINICAL DIABETES AND HEALTHCARE 2020; 1:546256. [PMID: 36993989 PMCID: PMC10041873 DOI: 10.3389/fcdhc.2020.546256] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/27/2020] [Accepted: 10/12/2020] [Indexed: 03/28/2023]
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Antoun E, Kitaba NT, Titcombe P, Dalrymple KV, Garratt ES, Barton SJ, Murray R, Seed PT, Holbrook JD, Kobor MS, Lin DTS, MacIsaac JL, Burdge GC, White SL, Poston L, Godfrey KM, Lillycrop KA. Maternal dysglycaemia, changes in the infant's epigenome modified with a diet and physical activity intervention in pregnancy: Secondary analysis of a randomised control trial. PLoS Med 2020; 17:e1003229. [PMID: 33151971 PMCID: PMC7643947 DOI: 10.1371/journal.pmed.1003229] [Citation(s) in RCA: 58] [Impact Index Per Article: 11.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2020] [Accepted: 10/06/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Higher maternal plasma glucose (PG) concentrations, even below gestational diabetes mellitus (GDM) thresholds, are associated with adverse offspring outcomes, with DNA methylation proposed as a mediating mechanism. Here, we examined the relationships between maternal dysglycaemia at 24 to 28 weeks' gestation and DNA methylation in neonates and whether a dietary and physical activity intervention in pregnant women with obesity modified the methylation signatures associated with maternal dysglycaemia. METHODS AND FINDINGS We investigated 557 women, recruited between 2009 and 2014 from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), a randomised controlled trial (RCT), of a lifestyle intervention (low glycaemic index (GI) diet plus physical activity) in pregnant women with obesity (294 contol, 263 intervention). Between 27 and 28 weeks of pregnancy, participants had an oral glucose (75 g) tolerance test (OGTT), and GDM diagnosis was based on diagnostic criteria recommended by the International Association of Diabetes and Pregnancy Study Groups (IADPSG), with 159 women having a diagnosis of GDM. Cord blood DNA samples from the infants were interrogated for genome-wide DNA methylation levels using the Infinium Human MethylationEPIC BeadChip array. Robust regression was carried out, adjusting for maternal age, smoking, parity, ethnicity, neonate sex, and predicted cell-type composition. Maternal GDM, fasting glucose, 1-h, and 2-h glucose concentrations following an OGTT were associated with 242, 1, 592, and 17 differentially methylated cytosine-phosphate-guanine (dmCpG) sites (false discovery rate (FDR) ≤ 0.05), respectively, in the infant's cord blood DNA. The most significantly GDM-associated CpG was cg03566881 located within the leucine-rich repeat-containing G-protein coupled receptor 6 (LGR6) (FDR = 0.0002). Moreover, we show that the GDM and 1-h glucose-associated methylation signatures in the cord blood of the infant appeared to be attenuated by the dietary and physical activity intervention during pregnancy; in the intervention arm, there were no GDM and two 1-h glucose-associated dmCpGs, whereas in the standard care arm, there were 41 GDM and 160 1-h glucose-associated dmCpGs. A total of 87% of the GDM and 77% of the 1-h glucose-associated dmCpGs had smaller effect sizes in the intervention compared to the standard care arm; the adjusted r2 for the association of LGR6 cg03566881 with GDM was 0.317 (95% confidence interval (CI) 0.012, 0.022) in the standard care and 0.240 (95% CI 0.001, 0.015) in the intervention arm. Limitations included measurement of DNA methylation in cord blood, where the functional significance of such changes are unclear, and because of the strong collinearity between treatment modality and severity of hyperglycaemia, we cannot exclude that treatment-related differences are potential confounders. CONCLUSIONS Maternal dysglycaemia was associated with significant changes in the epigenome of the infants. Moreover, we found that the epigenetic impact of a dysglycaemic prenatal maternal environment appeared to be modified by a lifestyle intervention in pregnancy. Further research will be needed to investigate possible medical implications of the findings. TRIAL REGISTRATION ISRCTN89971375.
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Affiliation(s)
- Elie Antoun
- Biological Sciences, Institute of Developmental Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, United Kingdom
| | - Negusse T. Kitaba
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Philip Titcombe
- MRC Lifecourse Epidemiology Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Kathryn V. Dalrymple
- Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, United Kingdom
| | - Emma S. Garratt
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
- NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Trust, Southampton, United Kingdom
| | - Sheila J. Barton
- MRC Lifecourse Epidemiology Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Robert Murray
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Paul T. Seed
- Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, United Kingdom
| | - Joanna D. Holbrook
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Michael S. Kobor
- BC Childrens Hospital Research Institute, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
| | - David TS Lin
- BC Childrens Hospital Research Institute, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
| | - Julia L. MacIsaac
- BC Childrens Hospital Research Institute, Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada
| | - Graham C. Burdge
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
| | - Sara L. White
- Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, United Kingdom
| | - Lucilla Poston
- Department of Women and Children’s Health, School of Life Course Sciences, King’s College London, London, United Kingdom
| | - Keith M. Godfrey
- Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom
- NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Trust, Southampton, United Kingdom
| | - Karen A. Lillycrop
- Biological Sciences, Institute of Developmental Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, United Kingdom
- NIHR Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton NHS Trust, Southampton, United Kingdom
- * E-mail:
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Abstract
PURPOSE OF REVIEW This review examines the impact of early life exposures on glucose metabolism in the offspring and explores potential metabolic mechanisms leading to type 2 diabetes in childhood. RECENT FINDINGS One in five adolescents is diagnosed with prediabetes. Recent studies have elucidated the impact of early exposures such as maternal diabetes, but also hyperglycemia below the threshold of gestational diabetes, obesity, hyperlipidemia, and paternal obesity on the future metabolic health of the offspring. Mechanisms affecting the developmental programing of offspring toward type 2 diabetes include epigenetic modifications, alterations in stem cell differentiation, metabolome and microbiome variation, immune dysregulation, and neonatal nutrition. The risk of type 2 diabetes in offspring is increased not only by diabetes exposure in utero but also by exposure to a heterogeneous milieu of factors that accompany maternal obesity that provoke a vicious cycle of metabolic disease. The key period for intervention to prevent type 2 diabetes is within the first 1000 days of life.
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Affiliation(s)
- Ankur Rughani
- Division of Pediatric Diabetes/Endocrinology, Harold Hamm Diabetes Center, Children's Hospital, The University of Oklahoma Health Sciences Center, 1200 Children's Ave Suite 4D, Oklahoma City, OK, 73104, USA
| | - Jacob E Friedman
- Division of Pediatric Diabetes/Endocrinology, Harold Hamm Diabetes Center, Children's Hospital, The University of Oklahoma Health Sciences Center, 1200 Children's Ave Suite 4D, Oklahoma City, OK, 73104, USA
| | - Jeanie B Tryggestad
- Division of Pediatric Diabetes/Endocrinology, Harold Hamm Diabetes Center, Children's Hospital, The University of Oklahoma Health Sciences Center, 1200 Children's Ave Suite 4D, Oklahoma City, OK, 73104, USA.
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25
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Zhang Q, Li X, Liu X, Dong M, Xiao J, Wang J, Zhou M, Wang Y, Ning D, Ma W, Zhu W, Liu T, Zhang B. Association between maternal antimony exposure and risk of gestational diabetes mellitus: A birth cohort study. CHEMOSPHERE 2020; 246:125732. [PMID: 31927364 DOI: 10.1016/j.chemosphere.2019.125732] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2019] [Revised: 12/05/2019] [Accepted: 12/22/2019] [Indexed: 06/10/2023]
Abstract
BACKGROUND A small number of epidemiological studies have suggested the association of antimony (Sb) exposure with type 2 diabetes risk. However, little is known about the relationship between Sb exposure during pregnancy and risk of gestational diabetes mellitus (GDM). OBJECTIVES To investigate the associations of urinary Sb concentrations with GDM risk and blood glucose levels in pregnant women. METHODS We analyzed the baseline data of 1789 pregnant women enrolled in the Birth Cohort Study on Prenatal Environments and Offspring Health (PEOH) in Guangzhou, China. Sb concentrations in urine were measured by inductively coupled plasma mass spectrometry (ICP-MS). Logistic regression and analysis of covariance were used to evaluate associations of Sb exposure with GDM risk and blood glucose levels. RESULTS A total of 437 (24.4%) women were diagnosed with GDM. The relative risk of GDM for women in the highest quartile of creatinine-corrected Sb (CC-Sb) concentrations was 1.55 [RR (95% CI) = 1.55 (1.12, 2.15), p-trend = 0.005], compared with women in the lowest quartile. Moreover, the women in the top quartile of CC-Sb levels had a 5.2% higher 1 h blood glucose and a 4.2% higher 2 h blood glucose than those in the bottom quartile. We also found an interactive effect between maternal age and CC-Sb on the risk of GDM (p-interaction < 0.001). CONCLUSION This study suggested significant positive associations of Sb exposure with increased GDM risk and impaired blood glucose homeostasis in pregnant women, and the Sb-GDM association might be modified by maternal age.
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Affiliation(s)
- Qianqian Zhang
- Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China
| | - Xiaona Li
- Department of Occupational and Environmental Health, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, China
| | - Xin Liu
- Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 511430, Guangdong, China
| | - Moran Dong
- Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 511430, Guangdong, China
| | - Jianpeng Xiao
- Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 511430, Guangdong, China
| | - Jing Wang
- Institute of Public Health Service Testing, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 511430, Guangdong, China
| | - Mengya Zhou
- Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Yiding Wang
- Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, 510515, Guangdong, China
| | - Dan Ning
- Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 511430, Guangdong, China
| | - Wenjun Ma
- Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 511430, Guangdong, China
| | - Wei Zhu
- Department of Toxicology, Guangzhou Center for Disease Control and Prevention, Guangzhou, 510440, Guangdong, China
| | - Tao Liu
- Guangdong Provincial Institute of Public Health, Guangdong Provincial Center for Disease Control and Prevention, Guangzhou, 511430, Guangdong, China.
| | - Bo Zhang
- Food Safety and Health Research Center, School of Public Health, Southern Medical University, Guangzhou, 510515, Guangdong, China.
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Cardiovascular risk factors in offspring exposed to gestational diabetes mellitus in utero: systematic review and meta-analysis. J Dev Orig Health Dis 2020; 11:599-616. [PMID: 31902382 DOI: 10.1017/s2040174419000850] [Citation(s) in RCA: 48] [Impact Index Per Article: 9.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Gestational diabetes mellitus (GDM) is a pregnancy complication that affects one in seven pregnancies. Emerging evidence demonstrates that children born of pregnancies complicated by GDM may be at increased risk of cardiovascular disease (CVD) in adulthood. Therefore, the aim of this study was to determine cardiovascular risk factors in offspring exposed to GDM in utero. PubMed, CINAHL, SCOPUS, and EMBASE databases were searched. Information was extracted on established CVD risk factors including blood pressure, lipids, blood glucose, fasting insulin, body mass index (BMI), and endothelial/microvascular function. The review protocol is registered in PROSPERO (CRD42018094983). Prospective and retrospective studies comparing offspring exposed to GDM compared to controls (non-GDM pregnancies) were considered. We included studies that defined GDM based on the International Association of Diabetes and Pregnancy Study Groups (IADPSG) definition, or prior definitions. The PRISMA guidelines were followed in conducting this systematic review. Methodological quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Study selection, data extraction, and quality assessment were done by two independent reviewers. The data were pooled using a random-effects model. Of 59 eligible studies, 24 were included in the meta-analysis. Offspring exposed to GDM had higher systolic blood pressure (mean difference (MD): 1.75 mmHg, 95% CI 0.57-2.94; eight studies, 7264 participants), BMI z-score (MD 0.11, 95% CI 0.02-0.20; nine studies, 8759 participants), and glucose (standard MD 0.43, 95% CI 0.08-0.77; 11 studies, 6423 participants) than control participants. In conclusion, offspring exposed to GDM have elevated systolic blood pressure, BMI, and glucose. Those exposed to GDM in utero may benefit from early childhood blood pressure measurements.
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Bergman RN. Origins and History of the Minimal Model of Glucose Regulation. Front Endocrinol (Lausanne) 2020; 11:583016. [PMID: 33658981 PMCID: PMC7917251 DOI: 10.3389/fendo.2020.583016] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2020] [Accepted: 12/22/2020] [Indexed: 01/17/2023] Open
Abstract
It has long been hoped that our understanding of the pathogenesis of diabetes would be helped by the use of mathematical modeling. In 1979 Richard Bergman and Claudio Cobelli worked together to find a "minimal model" based upon experimental data from Bergman's laboratory. Model was chosen as the simplest representation based upon physiology known at the time. The model itself is two quasi-linear differential equations; one representing insulin kinetics in plasma, and a second representing the effects of insulin and glucose itself on restoration of the glucose after perturbation by intravenous injection. Model would only be sufficient if it included a delay in insulin action; that is, insulin had to enter a remote compartment, which was interstitial fluid (ISF). Insulin suppressed endogenous glucose output (by liver) slowly. Delay proved to be due to initial suppression of lipolysis; resultant lowering of free fatty acids reduced liver glucose output. Modeling also demanded that normalization of glucose after injection included an effect of glucose itself on glucose disposal and endogenous glucose production - these effects were termed "glucose effectiveness." Insulin sensitivity was calculated from fitting the model to intravenous glucose tolerance test data; the resulting insulin sensitivity index, SI, was validated with the glucose clamp method in human subjects. Model allowed us to examine the relationship between insulin sensitivity and insulin secretion. Relationship was described by a rectangular hyperbola, such that Insulin Secretion x Insulin Sensitivity = Disposition Index (DI). Latter term represents ability of the pancreatic beta-cells to compensate for insulin resistance due to factors such as obesity, pregnancy, or puberty. DI has a genetic basis, and predicts the onset of Type 2 diabetes. An additional factor was clearance of insulin by the liver. Clearance varies significantly among animal or human populations; using the model, clearance was shown to be lower in African Americans than Whites (adults and children), and may be a factor accounting for greater diabetes prevalence in African Americans. The research outlined in the manuscript emphasizes the powerful approach by which hypothesis testing, experimental studies, and mathematical modeling can work together to explain the pathogenesis of metabolic disease.
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28
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Abstract
PURPOSE OF REVIEW This review will focus on the long-term outcomes in offspring exposed to in utero hyperglycemia and gestational diabetes (GDM), including obesity, adiposity, glucose metabolism, hypertension, hyperlipidemia, nonalcoholic fatty liver disease, and puberty. RECENT FINDINGS There is evidence, mostly from observational studies, that offspring of GDM mothers have increased risk of obesity, increased adiposity, disorders of glucose metabolism (insulin resistance and type 2 diabetes), and hypertension. In contrast, evidence from the two intervention studies of treatment of mild GDM and childhood measures of BMI, adiposity, and glucose tolerance do not demonstrate that GDM treatment significantly reduces adverse childhood metabolic outcomes. Thus, more evidence is needed to understand the impact of maternal GDM on offspring's adiposity, glucose metabolism, lipid metabolism, risk of fatty liver disease, and pubertal onset. Offspring of GDM mothers may have increased risk for metabolic and cardiovascular complications. Targeting this group for intervention studies to prevent obesity and disorders of glucose metabolism is one potential strategy to prevent adverse metabolic health outcomes.
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Affiliation(s)
- Monica E Bianco
- Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
- Division of Endocrinology, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago Avenue, Box 54, Chicago, IL, 60611, USA
| | - Jami L Josefson
- Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
- Division of Endocrinology, Ann & Robert H. Lurie Children's Hospital of Chicago, 225 E. Chicago Avenue, Box 54, Chicago, IL, 60611, USA.
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Systemic endocrinopathies (thyroid conditions and diabetes): impact on postnatal life of the offspring. Fertil Steril 2019; 111:1076-1091. [PMID: 31155115 DOI: 10.1016/j.fertnstert.2019.04.039] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2019] [Revised: 04/25/2019] [Accepted: 04/26/2019] [Indexed: 12/22/2022]
Abstract
Fetal programming may influence childhood and adult life, determining the risk of specific diseases. During earlier stages of pregnancy, the transfer of maternal thyroid hormones to the fetus is vital for adequate neurologic development. The presence of severe maternal thyroid dysfunction, particularly severe iodine deficiency, is devastating, leading to irreversible neurologic sequelae. Moreover, mild maternal thyroid conditions, such as a mild-to-moderate iodine deficiency, may also lead to milder neurologic and behavioral conditions later during the life of the offspring. Maternal dysglycemia due to pregestational or gestational diabetes mellitus is another common situation in which fetal development encounters a hostile environment. Hyperglycemia in utero may trigger metabolic conditions in the offspring, including abnormalities of glucose tolerance and weight excess. Physicians assisting pregnant women have to be aware about these conditions, because they may go unnoticed if not properly screened. Because an early diagnosis and appropriate management may prevent most of the possible negative consequences for the progeny, the prevention, early diagnosis, and proper management of these endocrine conditions should be offered to all women undergoing pregnancy. Here, we comprehensively review the current evidence about the effects of maternal thyroid dysfunction and maternal dysglycemia on the cognitive function and carbohydrate metabolism in the offspring, two prevalent conditions of utmost importance for the child's health and development.
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Abstract
Although it has been accepted for decades that women with gestational diabetes mellitus (GDM) are at high risk for future development of type 2 diabetes, vigorous debate regarding the value of detecting and treating GDM has persisted into the twenty-first century. Although results from 2 randomized trials provide strong evidence that treating GDM reduces adverse perinatal outcomes, it remains to be determined whether treatment impacts long-term offspring outcomes. Insulin is the first-line pharmacologic treatment and is added when glycemic goals are not met with nutritional modifications. Oral agent use is controversial, as data on long-term offspring outcomes are lacking.
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Affiliation(s)
- Emily D Szmuilowicz
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, 645 North Michigan Avenue, 530-24, Chicago, IL 60611, USA
| | - Jami L Josefson
- Division of Endocrinology, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, 225 East Chicago Avenue, Box 54, Chicago, IL 60611, USA
| | - Boyd E Metzger
- Division of Endocrinology, Metabolism and Molecular Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Tarry Building, Room 12-703, 300 East Superior, Chicago, IL 60611, USA.
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Obesity and abnormal glucose tolerance in the offspring of mothers with diabetes. Curr Opin Obstet Gynecol 2019; 30:361-368. [PMID: 30102607 DOI: 10.1097/gco.0000000000000479] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
PURPOSE OF REVIEW Type 2 diabetes and obesity during childhood, puberty, and adulthood have become more common. This trend presents a global problem in terms of public health and health economics. Associations between intrauterine exposure to hyperglycemia, obesity, and abnormal glucose tolerance (AGT) in offspring have been reported in populations at high risk of diabetes such as Pima Indians, but these associations have not been established in other groups. In this review, we summarize the evidence on obesity and AGT in the offspring of mothers with diabetes. RECENT FINDINGS Although there are many reports indicating that the incidence of obesity or overweight is higher in the offspring of mothers with gestational diabetes, there is no consensus on whether maternal prepregnancy obesity has a larger impact than intrauterine exposure to hyperglycemia. While the risk of AGT or type 2 diabetes in the offspring of mothers with gestational diabetes is thought to increase after puberty, the incidence of AGT is elevated by the age of 7 years in the offspring of mothers with untreated gestational diabetes. Maternal gestational diabetes is a risk factor for AGT or type 2 diabetes independent of maternal prepregnancy BMI. When the offspring of women who had gestational diabetes and received therapeutic intervention in two randomized controlled studies were followed, the prevalence of obesity and impaired fasting glucose was lower in some 7-year-old girls, but the effect of maternal intervention was limited. The risk of obesity or overweight is higher in the offspring of mothers with type 1 diabetes, even after adjustment for maternal prepregnancy BMI. The risk of type 2 diabetes in such offspring is also higher. Although the offspring of mothers with type 2 diabetes are likely to be at high risk for type 2 diabetes, there are only limited reports supporting this hypothesis. SUMMARY Intrauterine exposure to hyperglycemia is associated with obesity and AGT among offspring. The present review suggests that these associations might depend on the type of maternal diabetes, that is, the timing and degree of exposure to hyperglycemia. There are only a small number of studies on the effect of therapeutic interventions for maternal diabetes on metabolism in the offspring.
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Li Y, Xu S, Li Y, Zhang B, Huo W, Zhu Y, Wan Y, Zheng T, Zhou A, Chen Z, Huang Z, Hu J, Zhang W, Wang X, Ye D, Xia W. Association between urinary parabens and gestational diabetes mellitus across prepregnancy body mass index categories. ENVIRONMENTAL RESEARCH 2019; 170:151-159. [PMID: 30579989 DOI: 10.1016/j.envres.2018.12.028] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/03/2018] [Revised: 12/12/2018] [Accepted: 12/13/2018] [Indexed: 06/09/2023]
Abstract
Increasing evidence suggests a potential role of endocrine disrupting chemicals (EDCs) in inducing gestational diabetes mellitus (GDM). However, as far as we know, no study has examined the associations between GDM and exposure to parabens, a kind of EDCs. In this study, we explored the association between urinary parabens of pregnant women and GDM and studied the modification effect of prepregnancy body mass index (BMI). Urine samples were collected from 696 pregnant women and parabens were measured, including four alkyl side chain substituted para-hydroxybenzoic acid ester, substituents varying from methyl to butyl (abbreviates as MeP, EtP, PrP and BuP), and benzyl substituted para-hydroxybenzoic acid ester (BzP). Logistic regression models adjusting for potential confounders were used to study the association of parabens and GDM in the overall population, and further stratified analysis by prepregnancy BMI categories was also performed. The detection rates for the five parabens in the urine samples were 97.70% (MeP), 71.26% (EtP), 96.55% (PrP), 15.80% (BuP) and 2.73% (BzP). No significant association was found between parabens and GDM among the overall population. However, significant non-linear associations of PrP and the summed estrogenic activity of parabens with GDM were found in the stratified analysis by prepregnancy BMI in the overweight/obese population, with adjusted odds ratios (aORs) of 3.47 (95% CI: 1.28, 9.42) and 2.87 (95% CI: 1.07, 7.73) for GDM in the second tertile of urinary PrP and the summed estrogen activity, respectively, when compared to the first tertile. Although no statistically significant association between parabens and GDM was found in the overall population, we found that among the overweight/obese pregnant women, who represent a subgroup more prone to GDM, moderately higher levels of PrP and summed estrogenic activity of parabens were significantly associated with an increasing GDM prevalence.
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Affiliation(s)
- Ying Li
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Shunqing Xu
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Yuanyuan Li
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Bin Zhang
- Women and Children Medical and Healthcare Center of Wuhan, Wuhan, Hubei, People's Republic of China
| | - Wenqian Huo
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Yingshuang Zhu
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Yanjian Wan
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Tongzhang Zheng
- Department of Epidemiology, Brown University, Providence, RI, USA
| | - Aifen Zhou
- Women and Children Medical and Healthcare Center of Wuhan, Wuhan, Hubei, People's Republic of China
| | - Zhong Chen
- Women and Children Medical and Healthcare Center of Wuhan, Wuhan, Hubei, People's Republic of China
| | - Zheng Huang
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Jie Hu
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Wenxin Zhang
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China
| | - Xianliang Wang
- National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100021, People's Republic of China
| | - Dan Ye
- National Institute of Environmental Health, Chinese Center for Disease Control and Prevention, Beijing 100021, People's Republic of China
| | - Wei Xia
- Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, and State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
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Scholtens DM, Kuang A, Lowe LP, Hamilton J, Lawrence JM, Lebenthal Y, Brickman WJ, Clayton P, Ma RC, McCance D, Tam WH, Catalano PM, Linder B, Dyer AR, Lowe WL, Metzger BE. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Glycemia and Childhood Glucose Metabolism. Diabetes Care 2019; 42:381-392. [PMID: 30617141 PMCID: PMC6385697 DOI: 10.2337/dc18-2021] [Citation(s) in RCA: 183] [Impact Index Per Article: 30.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/24/2018] [Accepted: 11/29/2018] [Indexed: 02/03/2023]
Abstract
OBJECTIVE This study examined associations of maternal glycemia during pregnancy with childhood glucose outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. RESEARCH DESIGN AND METHODS HAPO was an observational international investigation that established associations of maternal glucose with adverse perinatal outcomes. The HAPO Follow-up Study included 4,832 children ages 10-14 years whose mothers had a 75-g oral glucose tolerance test (OGTT) at ∼28 weeks of gestation. Of these, 4,160 children were evaluated for glucose outcomes. Primary outcomes were child impaired glucose tolerance (IGT) and impaired fasting glucose (IFG). Additional outcomes were glucose-related measures using plasma glucose (PG), A1C, and C-peptide from the child OGTT. RESULTS Maternal fasting plasma glucose (FPG) was positively associated with child FPG and A1C; maternal 1-h and 2-h PG were positively associated with child fasting, 30 min, 1-h, and 2-h PG, and A1C. Maternal FPG, 1-h, and 2-h PG were inversely associated with insulin sensitivity, whereas 1-h and 2-h PG were inversely associated with disposition index. Maternal FPG, but not 1-h or 2-h PG, was associated with child IFG, and maternal 1-h and 2-h PG, but not FPG, were associated with child IGT. All associations were independent of maternal and child BMI. Across increasing categories of maternal glucose, frequencies of child IFG and IGT, and timed PG measures and A1C were higher, whereas insulin sensitivity and disposition index decreased. CONCLUSIONS Across the maternal glucose spectrum, exposure to higher levels in utero is significantly associated with childhood glucose and insulin resistance independent of maternal and childhood BMI and family history of diabetes.
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Lowe WL, Scholtens DM, Kuang A, Linder B, Lawrence JM, Lebenthal Y, McCance D, Hamilton J, Nodzenski M, Talbot O, Brickman WJ, Clayton P, Ma RC, Tam WH, Dyer AR, Catalano PM, Lowe LP, Metzger BE. Hyperglycemia and Adverse Pregnancy Outcome Follow-up Study (HAPO FUS): Maternal Gestational Diabetes Mellitus and Childhood Glucose Metabolism. Diabetes Care 2019; 42:372-380. [PMID: 30655380 PMCID: PMC6385693 DOI: 10.2337/dc18-1646] [Citation(s) in RCA: 350] [Impact Index Per Article: 58.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2018] [Accepted: 10/15/2018] [Indexed: 02/03/2023]
Abstract
OBJECTIVE Whether hyperglycemia in utero less than overt diabetes is associated with altered childhood glucose metabolism is unknown. We examined associations of gestational diabetes mellitus (GDM) not confounded by treatment with childhood glycemia in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) cohort. RESEARCH DESIGN AND METHODS HAPO Follow-up Study (FUS) included 4,160 children ages 10-14 years who completed all or part of an oral glucose tolerance test (OGTT) and whose mothers had a 75-g OGTT at ∼28 weeks of gestation with blinded glucose values. The primary predictor was GDM by World Health Organization criteria. Child outcomes were impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes. Additional measures included insulin sensitivity and secretion and oral disposition index. RESULTS For mothers with GDM, 10.6% of children had IGT compared with 5.0% of children of mothers without GDM; IFG frequencies were 9.2% and 7.4%, respectively. Type 2 diabetes cases were too few for analysis. Odds ratios (95% CI) adjusted for family history of diabetes, maternal BMI, and child BMI z score were 1.09 (0.78-1.52) for IFG and 1.96 (1.41-2.73) for IGT. GDM was positively associated with child's 30-min, 1-h, and 2-h but not fasting glucose and inversely associated with insulin sensitivity and oral disposition index (adjusted mean difference -76.3 [95% CI -130.3 to -22.4] and -0.12 [-0.17 to -0.064]), respectively, but not insulinogenic index. CONCLUSIONS Offspring exposed to untreated GDM in utero are insulin resistant with limited β-cell compensation compared with offspring of mothers without GDM. GDM is significantly and independently associated with childhood IGT.
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Farahvar S, Walfisch A, Sheiner E. Gestational diabetes risk factors and long-term consequences for both mother and offspring: a literature review. Expert Rev Endocrinol Metab 2019; 14:63-74. [PMID: 30063409 DOI: 10.1080/17446651.2018.1476135] [Citation(s) in RCA: 138] [Impact Index Per Article: 23.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Accepted: 05/09/2018] [Indexed: 12/16/2022]
Abstract
INTRODUCTION Established risk factors for gestational diabetes mellitus (GDM) include ethnicity, obesity, and family history of diabetes. Untreated GDM patients have higher rates of maternal and perinatal morbidity. GDM is an independent risk factor for future longer-term risk of type 2 diabetes mellitus (T2DM), metabolic syndrome, cardiovascular morbidity, malignancies, ophthalmic, psychiatric, and renal disease in the mother. Offspring risk long-term adverse health outcomes, including T2DM, subsequent obesity, impacted neurodevelopmental outcome, increased neuropsychiatric morbidity, and ophthalmic disease. AREAS COVERED We critically review data from retrospective, prospective, and meta-analysis studies pertaining to established GDM risk factors, complications during pregnancy and birth (both mother and offspring), and long-term consequences (both mother and offspring). EXPERT COMMENTARY Many of the adverse consequences of GDM might be avoided with proper management and treatment. Patients belonging to high-risk ethnic groups, and/or with body mass index ≥ 25 kg/m2, and/or known history of diabetes in first-degree relatives may benefit from universal screening and diagnostic criteria proposed by the International Association of Diabetes and Pregnancy Study Group (IADPSG). The IADPSG one-step method has several advantages, including simplicity of execution, greater patient-friendliness, and higher diagnostic accuracy. Additionally, evidence suggests that the recent increased popularity of bariatric surgery will help to decrease GDM rates over next 5 years. Similarly, metformin may be useful for treating and preventing obstetrical complications in confirmed GDM patients.
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Affiliation(s)
- Salar Farahvar
- a Department of Obstetrics and Gynecology, Faculty of Health, Sciences, Soroka University Medical Center, Ben-Gurion , University of the Negev , Beer Sheva , Israel
| | - Asnat Walfisch
- a Department of Obstetrics and Gynecology, Faculty of Health, Sciences, Soroka University Medical Center, Ben-Gurion , University of the Negev , Beer Sheva , Israel
| | - Eyal Sheiner
- a Department of Obstetrics and Gynecology, Faculty of Health, Sciences, Soroka University Medical Center, Ben-Gurion , University of the Negev , Beer Sheva , Israel
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Garcia-Martin I, Penketh RJA, Janssen AB, Jones RE, Grimstead J, Baird DM, John RM. Metformin and insulin treatment prevent placental telomere attrition in boys exposed to maternal diabetes. PLoS One 2018; 13:e0208533. [PMID: 30533028 PMCID: PMC6289439 DOI: 10.1371/journal.pone.0208533] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2018] [Accepted: 11/18/2018] [Indexed: 12/30/2022] Open
Abstract
Shortened leukocyte and placental telomeres associated with gestational diabetes mellitus (GDM) suggest this exposure triggers telomere attrition contributing to adverse outcomes. We applied high resolution Single Telomere Length Analysis (STELA) to placenta from GDM pregnancies with different treatment pathways to determine their effectiveness at preventing telomere attrition. Differences in telomere length between control (N = 69), GDM lifestyle intervention (n = 14) and GDM treated with metformin and/or insulin (n = 17) was tested by Analysis of Covariance (ANCOVA) followed by group comparisons using Fisher's least significant difference. For male placenta only, there were differences in mean telomere length (F(2,54) = 4.98, P = 0.01) and percentage of telomeres under 5 kb (F(2,54) = 4.65, P = 0.01). Telomeres were shorter in the GDM lifestyle intervention group compared to both controls (P = 0.02) and medically treated pregnancies (P = 0.003). There were more telomeres under 5 kb in the GDM lifestyle intervention group compared to the other two groups (P = 0.03 and P = 0.004). Although further work is necessary, we suggest that early adoption of targeted medical treatment of GDM pregnancies where the fetus is known to be male may be an effective strategy for ameliorating adverse outcomes for children.
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Affiliation(s)
- Isabel Garcia-Martin
- Division of Biomedicine, Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, United Kingdom
| | - Richard J. A. Penketh
- Department of Obstetrics and Gynaecology, University Hospital Wales, Cardiff, Wales, United Kingdom
| | - Anna B. Janssen
- Division of Biomedicine, Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, United Kingdom
| | - Rhiannon E. Jones
- Division of Cancer and Genetics, Cardiff School of Medicine, Cardiff University, Cardiff, Wales, United Kingdom
| | - Julia Grimstead
- Division of Cancer and Genetics, Cardiff School of Medicine, Cardiff University, Cardiff, Wales, United Kingdom
| | - Duncan M. Baird
- Division of Cancer and Genetics, Cardiff School of Medicine, Cardiff University, Cardiff, Wales, United Kingdom
| | - Rosalind M. John
- Division of Biomedicine, Cardiff School of Biosciences, Cardiff University, Cardiff, Wales, United Kingdom
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Antvorskov JC, Halldorsson TI, Josefsen K, Svensson J, Granström C, Roep BO, Olesen TH, Hrolfsdottir L, Buschard K, Olsen SF. Association between maternal gluten intake and type 1 diabetes in offspring: national prospective cohort study in Denmark. BMJ 2018; 362:k3547. [PMID: 30232082 PMCID: PMC6283375 DOI: 10.1136/bmj.k3547] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
OBJECTIVE To examine the association between prenatal gluten exposure and offspring risk of type 1 diabetes in humans. DESIGN National prospective cohort study. SETTING National health information registries in Denmark. PARTICIPANTS Pregnant Danish women enrolled into the Danish National Birth Cohort, between January 1996 and October 2002, MAIN OUTCOME MEASURES: Maternal gluten intake, based on maternal consumption of gluten containing foods, was reported in a 360 item food frequency questionnaire at week 25 of pregnancy. Information on type 1 diabetes occurrence in the participants' children, from 1 January 1996 to 31 May 2016, were obtained through registry linkage to the Danish Registry of Childhood and Adolescent Diabetes. RESULTS The study comprised 101 042 pregnancies in 91 745 women, of whom 70 188 filled out the food frequency questionnaire. After correcting for multiple pregnancies, pregnancies ending in abortions, stillbirths, lack of information regarding the pregnancy, and pregnancies with implausibly high or low energy intake, 67 565 pregnancies (63 529 women) were included. The average gluten intake was 13.0 g/day, ranging from less than 7 g/day to more than 20 g/day. The incidence of type 1 diabetes among children in the cohort was 0.37% (n=247) with a mean follow-up period of 15.6 years (standard deviation 1.4). Risk of type 1 diabetes in offspring increased proportionally with maternal gluten intake during pregnancy (adjusted hazard ratio 1.31 (95% confidence interval 1.001 to 1.72) per 10 g/day increase of gluten). Women with the highest gluten intake versus those with the lowest gluten intake (≥20 v <7 g/day) had double the risk of type 1 diabetes development in their offspring (adjusted hazard ratio 2.00 (95% confidence interval 1.02 to 4.00)). CONCLUSIONS High gluten intake by mothers during pregnancy could increase the risk of their children developing type 1 diabetes. However, confirmation of these findings are warranted, preferably in an intervention setting.
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Affiliation(s)
- Julie C Antvorskov
- Bartholin Institute, Rigshospitalet, Ole Måløes Vej 5, 2200 Copenhagen K, Denmark
| | - Thorhallur I Halldorsson
- Centre for Foetal Programming, Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark
- Unit for Nutrition Research, Landspitali University Hospital, Reykjavik, Iceland
- Faculty of Food Science and Nutrition, University of Iceland, Reykjavik, Iceland
| | - Knud Josefsen
- Bartholin Institute, Rigshospitalet, Ole Måløes Vej 5, 2200 Copenhagen K, Denmark
| | - Jannet Svensson
- Copenhagen Diabetes Research Center (CPH-DIRECT), Department of Children and Adolescents, Copenhagen University Hospital Herlev, Herlev, Denmark
| | - Charlotta Granström
- Centre for Foetal Programming, Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark
| | - Bart O Roep
- Department of Diabetes Immunology, Diabetes and Metabolism Research Institute at the Beckman Diabetes Research Institute, City of Hope, Duarte, CA, USA
- Departments of Immunohematology and Blood Transfusion, Leiden University Medical Centre, Leiden, Netherlands
| | - Trine H Olesen
- Centre for Foetal Programming, Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark
| | - Laufey Hrolfsdottir
- Department of Education, Science, and Quality, Akureyri Hospital, Akureyri, Iceland
| | - Karsten Buschard
- Bartholin Institute, Rigshospitalet, Ole Måløes Vej 5, 2200 Copenhagen K, Denmark
| | - Sjudur F Olsen
- Centre for Foetal Programming, Department of Epidemiology Research, Statens Serum Institute, Copenhagen, Denmark
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
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Camilo DF, Vasques ACJ, Hayashi K, Tura A, da Silva CDC, Zambon MP, Antônio MÂRDGM, Geloneze B. Adiposity and family history of type 2 diabetes in an admixed population of adolescents: Associations with insulin sensitivity, beta-cell function, and hepatic insulin extraction in BRAMS study. Diabetes Res Clin Pract 2018; 137:72-82. [PMID: 29320718 DOI: 10.1016/j.diabres.2017.12.013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2017] [Revised: 11/15/2017] [Accepted: 12/18/2017] [Indexed: 12/21/2022]
Abstract
AIMS Insulin resistance and beta-cell dysfunction manifest differently across racial/ethnic groups, and there is a lack of knowledge regarding the pathophysiology of type 2 diabetes mellitus (T2DM) for ethnically admixed adolescents. This study aimed to investigate the influence of adiposity and family history (FH) of T2DM on aspects of insulin sensitivity, beta-cell function, and hepatic insulin extraction in Brazilian adolescents. METHODS A total of 82 normoglycemic adolescents were assessed. The positive FH of T2DM was defined as the presence of at least one known family member with T2DM. The hyperglycemic clamp test consisted of a 120-min protocol. Insulin secretion and beta-cell function were obtained from C-peptide deconvolution. Analysis of covariance considered pubertal stage as a covariate. RESULTS Both lean and overweight/obese adolescents had similar glycemic profiles and disposition indexes. Overweight/obese adolescents had about 1/3 the insulin sensitivity of lean adolescents (1.1 ± 0.2 vs. 3.4 ± 0.3 mg·kg·min·pmol ∗ 1000), which was compensated by an increase around 2.5 times in basal (130 ± 7 vs. 52 ± 10 pmol·l·min) and total insulin secretion (130,091 ± 12,230 vs. 59,010 ± 17,522 pmol·l·min), and in the first and second phases of insulin secretion; respectively (p < 0.001). This increase was accompanied by a mean reduction in hepatic insulin extraction of 35%, and a 2.7-time increase in beta-cell glucose sensitivity (p < 0.05). The positive FH of T2DM was not associated with derangements in insulin sensitivity, beta-cell function, and hepatic insulin extraction. CONCLUSIONS In an admixed sample of adolescents, the hyperglycemic clamp test demonstrated that adiposity had a strong influence, and FH of T2DM had no direct influence, in different aspects of glucose metabolism.
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Affiliation(s)
- Daniella F Camilo
- Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas (Unicamp), Campinas, São Paulo, Brazil; Postgraduate Program in Child and Adolescent Health, Faculty of Medical Science, University of Campinas, (Unicamp), Campinas, São Paulo, Brazil
| | - Ana Carolina J Vasques
- Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas (Unicamp), Campinas, São Paulo, Brazil; Postgraduate Program in Child and Adolescent Health, Faculty of Medical Science, University of Campinas, (Unicamp), Campinas, São Paulo, Brazil; School of Applied Sciences, University of Campinas, Limeira, São Paulo, Brazil
| | - Keila Hayashi
- Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas (Unicamp), Campinas, São Paulo, Brazil; Postgraduate Program in Child and Adolescent Health, Faculty of Medical Science, University of Campinas, (Unicamp), Campinas, São Paulo, Brazil
| | - Andrea Tura
- Metabolic Unit, CNR Institute of Neuroscience, Padova, Italy
| | - Cleliani de Cassia da Silva
- Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas (Unicamp), Campinas, São Paulo, Brazil; Postgraduate Program in Child and Adolescent Health, Faculty of Medical Science, University of Campinas, (Unicamp), Campinas, São Paulo, Brazil
| | - Mariana P Zambon
- Postgraduate Program in Child and Adolescent Health, Faculty of Medical Science, University of Campinas, (Unicamp), Campinas, São Paulo, Brazil; Department of Pediatrics, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
| | - Maria Ângela R de G Monteiro Antônio
- Postgraduate Program in Child and Adolescent Health, Faculty of Medical Science, University of Campinas, (Unicamp), Campinas, São Paulo, Brazil; Department of Pediatrics, University of Campinas (Unicamp), Campinas, São Paulo, Brazil
| | - Bruno Geloneze
- Laboratory of Investigation on Metabolism and Diabetes (Limed), Gastroenterological Diagnosis and Research Center (Gastrocentro), University of Campinas (Unicamp), Campinas, São Paulo, Brazil; Postgraduate Program in Child and Adolescent Health, Faculty of Medical Science, University of Campinas, (Unicamp), Campinas, São Paulo, Brazil; National Institute of Science and Technology of Obesity and Diabetes, Brazil.
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Meregaglia M, Dainelli L, Banks H, Benedetto C, Detzel P, Fattore G. The short-term economic burden of gestational diabetes mellitus in Italy. BMC Pregnancy Childbirth 2018; 18:58. [PMID: 29471802 PMCID: PMC5824573 DOI: 10.1186/s12884-018-1689-1] [Citation(s) in RCA: 26] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2017] [Accepted: 02/15/2018] [Indexed: 02/07/2023] Open
Abstract
Background The incidence of Gestational Diabetes Mellitus (GDM) is rising in all developed countries. This study aimed at assessing the short-term economic burden of GDM from the Italian healthcare system perspective. Methods A model was built over the last pregnancy trimester (i.e., from the 28th gestational week until childbirth included). The National Hospital Discharge Database (2014) was accessed to estimate delivery outcome probabilities and inpatient costs in GDM and normal pregnancies (i.e., euglycemia). International Classification of Disease-9th Revision-Clinical Modification (ICD9-CM) diagnostic codes and Diagnosis-Related Group (DRG) codes were used to identify GDM cases and different types of delivery (i.e., vaginal or cesarean) within the database. Neonatal outcomes probabilities were estimated from the literature and included macrosomia, hypoglycemia, hyperbilirubinemia, shoulder dystocia, respiratory distress, and brachial plexus injury. Additional data sources such as regional documents, official price and tariff lists, national statistics and expert opinion were used to populate the model. The average cost per case was calculated at national level to estimate the annual economic burden of GDM. One-way sensitivity analyses and Monte Carlo simulations were performed to quantify the uncertainty around base case results. Results The amount of pregnancies complicated by GDM in Italy was assessed at 54,783 in 2014 using a prevalence rate of 10.9%. The antenatal outpatient cost per case was estimated at €43.7 in normal pregnancies compared to €370.6 in GDM patients, which is equivalent to a weighted sum of insulin- (14%; €1034.6) and diet- (86%; €262.5) treated women’s costs. Inpatient delivery costs were assessed at €1601.6 and €1150.3 for euglycemic women and their infants, and at €1835.0 and €1407.7 for GDM women and their infants, respectively. Thus, the overall cost per case difference between GDM and normal pregnancies was equal to €817.8 (+ 29.2%), resulting in an economic burden of about €44.8 million in 2014 at national level. Probabilistic sensitivity analysis yielded a cost per case difference ranging between €464.9 and €1164.8 in 80% of simulations. Conclusions The economic burden of GDM in Italy is substantial even accounting for short-term medical costs only. Future research also addressing long-term consequences from a broader societal perspective is recommended.
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Affiliation(s)
- Michela Meregaglia
- CERGAS (Centre for Research on Health and Social Care Management), Bocconi University, Via Roentgen 1, 20136, Milan, Italy.
| | - Livia Dainelli
- Nestlé Research Center, Nestec SA, Route du Jorat 57, 1000, Lausanne, Switzerland
| | - Helen Banks
- CERGAS (Centre for Research on Health and Social Care Management), Bocconi University, Via Roentgen 1, 20136, Milan, Italy
| | - Chiara Benedetto
- Department of Gynecology & Obstetrics, S. Anna Hospital, University of Turin, Via Ventimiglia 3, 10126, Turin, Italy
| | - Patrick Detzel
- Nestlé Research Center, Nestec SA, Route du Jorat 57, 1000, Lausanne, Switzerland
| | - Giovanni Fattore
- CERGAS (Centre for Research on Health and Social Care Management), Bocconi University, Via Roentgen 1, 20136, Milan, Italy.,Department of Policy Analysis and Public Management, Bocconi University, Via Roentgen 1, 20136, Milan, Italy
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Kawasaki M, Arata N, Miyazaki C, Mori R, Kikuchi T, Ogawa Y, Ota E. Obesity and abnormal glucose tolerance in offspring of diabetic mothers: A systematic review and meta-analysis. PLoS One 2018; 13:e0190676. [PMID: 29329330 PMCID: PMC5766126 DOI: 10.1371/journal.pone.0190676] [Citation(s) in RCA: 105] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/01/2017] [Accepted: 12/19/2017] [Indexed: 12/21/2022] Open
Abstract
Background Rising prevalence of childhood obesity and type 2 diabetes mellitus (T2DM) is an emerging public health issue. Objectives To investigate the association of maternal hyperglycemia exposure during pregnancy with obesity and abnormal glucose tolerance in offspring, and the age at occurrence. Methods We searched MEDLINE and EMBASE for observational studies on obesity and diabetes in offspring of diabetic mothers (gestational diabetes mellitus (GDM), type 1 diabetes mellitus (T1DM) and T2DM), and those on non-diabetic mothers. We performed fixed effect meta-analysis for all studies except when heterogeneity was detected. The quality of studies was evaluated using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS) Results Twenty observational studies were included involving a total of 26,509 children. Offspring of GDM mother had higher BMI z-score in childhood (pooled MD: 0.14, 95%CI: 0.04–0.24, seven studies, 21,691children, low quality of evidence). Offspring of T1DM mothers had higher BMI z-score from prepubertal to adolescent (pooled MD: 0.35, 95% CI: 0.13–0.58, three studies, 844 children, low quality of evidence) compared with control. After adjustment for maternal pre-pregnancy BMI, this association remained in offspring of T1DM, but disappeared in those of GDM mothers. Offspring of GDM mother had higher 2-hour plasma glucose from prepubertal to early adulthood (pooled MD: 0.43 mmol/L, 95% CI: 0.18–0.69, five studies, 890 children), while those of T1DM mothers had higher rate of T2DM in 2–5 years old to early adulthood (pooled odds ratio [OR], 6.10: 95% CI: 1.23–30.37, two studies, 448 children, very low quality of evidence) compared with control. As there was only one study with offspring of T2DM mothers, evidence is sparse. Limitations Only observational studies were included, with a few adequately adjusted for covariables. Conclusions Exposure to maternal hyperglycemia was associated with offspring obesity and abnormal glucose tolerance especially in offspring of T1DM mothers, but the evidence relies on observational studies with low quality of evidence only.
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Affiliation(s)
- Maki Kawasaki
- Department of Health Policy, National Center for Child Health and Development, Tokyo, Japan
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Naoko Arata
- Division of Maternal Medicine, Center for Maternal-Fetal, Neonatal and Reproductive Medicine, National Center for Child Health and Development, Tokyo, Japan
- * E-mail:
| | - Celine Miyazaki
- Department of Health Policy, National Center for Child Health and Development, Tokyo, Japan
| | - Rintaro Mori
- Department of Health Policy, National Center for Child Health and Development, Tokyo, Japan
| | - Toru Kikuchi
- Department of Pediatrics, Saitama Medical University Hospital, Saitama, Japan
| | - Yoshihiro Ogawa
- Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
- Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Erika Ota
- Department of Health Policy, National Center for Child Health and Development, Tokyo, Japan
- St. Luke’s International University, Graduate School of Nursing, Global Health Nursing, Tokyo, Japan
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Dabelea D, Sauder KA. Intrauterine Exposure to Maternal Diabetes and Childhood Obesity. CONTEMPORARY ENDOCRINOLOGY 2018. [DOI: 10.1007/978-3-319-68192-4_13] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
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Pathogenesis of Insulin Resistance and Glucose Intolerance in Childhood Obesity. CONTEMPORARY ENDOCRINOLOGY 2018. [DOI: 10.1007/978-3-319-68192-4_23] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
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Ighbariya A, Weiss R. Insulin Resistance, Prediabetes, Metabolic Syndrome: What Should Every Pediatrician Know? J Clin Res Pediatr Endocrinol 2017; 9:49-57. [PMID: 29280741 PMCID: PMC5790325 DOI: 10.4274/jcrpe.2017.s005] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The Metabolic syndrome describes a clustering of typical cardiovascular risk factors. The syndrome is also known as "Insulin Resistance syndrome" as a substantial part of the pathophysiology is driven by resistance to the metabolic effects of insulin. The major cause of insulin resistance in childhood is a typical lipid partitioning pattern characterized by increased deposition of lipids within insulin responsive tissues, such as the liver and skeletal muscle and within the viscera. This lipid deposition pattern is also associated with infiltration of intra-abdominal tissues with cells of the immune system, inducing systemic, low-grade inflammation typically observed in insulin resistant obese children and adolescents. Several clues derived from a careful history and physical examination, along with a basic laboratory workup, provide clues in regards to risk stratification in obese children.
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Affiliation(s)
- Ahmad Ighbariya
- Ruth Rappaport Children’s Hospital, Clinic of Pediatrics, Haifa, Israel
,* Address for Correspondence: Ruth Rappaport Children’s Hospital, Clinic of Pediatrics, Haifa, Israel E-mail:
| | - Ram Weiss
- Ruth Rappaport Children’s Hospital, Clinic of Pediatrics, Haifa, Israel
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Grunnet LG, Hansen S, Hjort L, Madsen CM, Kampmann FB, Thuesen ACB, Granstrømi C, Strøm M, Maslova E, Frikke-Schmidt R, Damm P, Chavarro JE, Hu FB, Olsen SF, Vaag A. Adiposity, Dysmetabolic Traits, and Earlier Onset of Female Puberty in Adolescent Offspring of Women With Gestational Diabetes Mellitus: A Clinical Study Within the Danish National Birth Cohort. Diabetes Care 2017; 40:1746-1755. [PMID: 29038315 PMCID: PMC5711331 DOI: 10.2337/dc17-0514] [Citation(s) in RCA: 90] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2017] [Accepted: 09/06/2017] [Indexed: 02/03/2023]
Abstract
OBJECTIVE 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. RESEARCH DESIGN AND METHODS 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. RESULTS 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. CONCLUSIONS 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.
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Affiliation(s)
- Louise G Grunnet
- Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen, Denmark .,The Danish Diabetes Academy, Odense, Denmark
| | - Susanne Hansen
- Centre for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut
| | - Line Hjort
- Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen, Denmark.,The Danish Diabetes Academy, Odense, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Camilla M Madsen
- Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen, Denmark
| | - Freja B Kampmann
- Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen, Denmark.,Centre for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut.,Division for Diet, Disease Prevention and Toxicology, National Food Institute, Technical University of Denmark, Søborg, Denmark
| | | | - Charlotta Granstrømi
- Centre for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut
| | - Marin Strøm
- Centre for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut.,Faculty of Natural and Health Sciences, University of the Faroe Islands, Tórshavn, Faroe Islands
| | - Ekaterina Maslova
- The Danish Diabetes Academy, Odense, Denmark.,Centre for Fetal Programming, Department of Epidemiology Research, Statens Serum Institut.,Department of Primary Care and Public Health, Imperial College, London, U.K
| | | | - Peter Damm
- Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
| | - Jorge E Chavarro
- Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA.,Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA
| | - Frank B Hu
- Departments of Nutrition and Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
| | | | - Allan Vaag
- Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, Copenhagen, Denmark.,AstraZeneca, Early Clinical Development, Göteborg, Sweden
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45
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Ali A, Shastry S, Nithiyananthan R, Ali A, Ganapathy R. Gestational diabetes-Predictors of response to treatment and obstetric outcome. Eur J Obstet Gynecol Reprod Biol 2017; 220:57-60. [PMID: 29172068 DOI: 10.1016/j.ejogrb.2017.11.014] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2017] [Revised: 11/18/2017] [Accepted: 11/19/2017] [Indexed: 11/26/2022]
Abstract
OBJECTIVE Evaluate patient characteristics that are predictors of treatment response and outcomes in gestational diabetes STUDY DESIGN: Retrospective cohort of 265 women with gestational diabetes treated with diet/metformin and/or insulin in a single centre over 2 years. RESULTS Multinomial logistic regression showed that (after adjusting for age and ethnicity) women who were of normal weight were more likely to be on diet and women who were obese were more likely to be on metformin or metformin and insulin(p=0.014). Women who were obese were twice more likely to have labour induced than those with normal weight. Onset of labour was the only parameter significantly associated with a treatment modality among the three groups (p<0.001). There was no difference in the incidence of large for gestational age, neonatal admission, shoulder dystocia or still birth between the three groups. CONCLUSIONS Maternal BMI appears to be the only parameter that is predictive of need for treatment with metformin/insulin and the modality of treatment does not have an effect on maternal and neonatal outcomes.
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Affiliation(s)
- Amanda Ali
- Epsom and St. Helier University Hospitals NHS Trust, UK
| | | | | | - Amira Ali
- Senior Epidemiologist, Ottawa Public Health, Canada
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Sauder KA, Hockett CW, Ringham BM, Glueck DH, Dabelea D. Fetal overnutrition and offspring insulin resistance and β-cell function: the Exploring Perinatal Outcomes among Children (EPOCH) study. Diabet Med 2017; 34. [PMID: 28636758 PMCID: PMC5603388 DOI: 10.1111/dme.13417] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
AIMS To examine the associations of intrauterine exposure to maternal diabetes and obesity with offspring insulin resistance, β-cell function and oral disposition index in a longitudinal observational study of ethnically diverse offspring. METHODS A total of 445 offspring who were exposed (n=81) or not exposed (n=364) to maternal diabetes in utero completed two fasting blood measurements at mean (sd) ages of 10.5 (1.5) and 16.5 (1.2) years, respectively, and an oral glucose tolerance test at the second visit. We used linear mixed models and general linear univariate models to evaluate the associations of maternal diabetes and pre-pregnancy BMI with offspring outcomes. RESULTS Maternal diabetes in utero predicted increased insulin resistance [18% higher updated homeostatic model assessment of insulin resistance (HOMA2-IR), P=0.01; 19% lower Matsuda index, P=0.01 and 9% greater updated homeostatic model assessment of β-cell function (HOMA2-β), P=0.04]. Each 5-kg/m2 increase in pre-pregnancy BMI predicted increased insulin resistance (11% greater HOMA2-IR, P<0.001; 10% lower Matsuda index, P<0.001; 6% greater HOMA2-β, P<0.001). Similar results were obtained in a combined model with both exposures. After adjustment for offspring BMI, only maternal diabetes was associated with higher HOMA2-IR (β=1.12, P=0.03) and lower Matsuda index (β=0.83, P=0.01). Neither exposure was associated with early insulin response or oral disposition index. CONCLUSIONS Intrauterine exposure to diabetes or obesity is associated with greater offspring insulin resistance than non-exposure, supporting the hypothesis that fetal overnutrition results in metabolic abnormalities during childhood and adolescence.
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Affiliation(s)
- K A Sauder
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
| | - C W Hockett
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA
| | - B M Ringham
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, USA
| | - D H Glueck
- Department of Biostatistics and Informatics, Colorado School of Public Health, Aurora, CO, USA
| | - D Dabelea
- Department of Pediatrics, University of Colorado School of Medicine, Aurora, CO, USA
- Department of Epidemiology, Colorado School of Public Health, Aurora, CO, USA
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Abstract
Obesity has been estimated to decrease life expectancy by as little as 0.8 to as much as 7 years being the second leading cause of preventable death in the United States after smoking. Along with the increase in the prevalence of obesity, there has been a dramatic rise of the prevalence of prediabetes and type 2 diabetes among adolescents. Despite that, very little is known about the pathogenesis of these conditions in pediatrics and about how we could detect prediabetes in an early stage in order to prevent full blown diabetes. In this review we summarize the current knowledge on the pathophysiology of prediabetes and type 2 diabetes in adolescents and describe how biomarkers of beta-cell function might help identifying those individuals who are prone to progress from normal glucose tolerance towards prediabetes and overt type 2 diabetes. To better understand and fight this disease, we will need to explore and develop novel therapeutic strategies and individuate more sensitive and specific biomarkers that can allow an earlier detection of the disease.
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Gagné-Ouellet V, Houde AA, Guay SP, Perron P, Gaudet D, Guérin R, Jean-Patrice B, Hivert MF, Brisson D, Bouchard L. Placental lipoprotein lipase DNA methylation alterations are associated with gestational diabetes and body composition at 5 years of age. Epigenetics 2017; 12:616-625. [PMID: 28486003 DOI: 10.1080/15592294.2017.1322254] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/07/2023] Open
Abstract
Gestational diabetes mellitus (GDM) is associated with obesity in childhood. This suggests that consequences of in utero exposure to maternal hyperglycemia extend beyond the fetal development, possibly through epigenetic programming. The aims of this study were to assess whether placental DNA methylation (DNAm) marks were associated with maternal GDM status and to offspring body composition at 5 years old in a prospective birth cohort. DNAm levels were measured in the fetal side of the placenta in 66 samples (24 from GDM mothers) using bisDNA-pyrosequencing. Anthropometric and body composition (bioimpedance) were measured in children at 5 years of age. Mann-Whitney and Spearman tests were used to assess associations between GDM, placental DNAm levels at the lipoprotein lipase (LPL) locus and children's weight, height, body mass index (BMI), body fat, and lean masses at 5 years of age. Weight, height, and BMI z-scores were computed according to the World Health Organization growth chart. Analyses were adjusted for gestational age at birth, child sex, maternal age, and pre-pregnancy BMI. LPL DNAm levels were positively correlated with birth weight z-scores (r = 0.252, P = 0.04), and with mid-childhood weight z-scores (r = 0.314, P = 0.01) and fat mass (r = 0.275, P = 0.04), and negatively correlated with lean mass (r = -0.306, P = 0.02). We found a negative correlation between LPL DNAm and mRNA levels in placenta (r = -0.459; P < 0.001), which highlights the regulation of transcriptional activity by these epivariations. We demonstrated that alterations in fetal placental DNAm levels at the LPL gene locus are associated with the anthropometric profile in children at 5 years of age. These findings support the concept of fetal metabolic programming through epigenetic changes.
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Affiliation(s)
- Valérie Gagné-Ouellet
- a Department of Biochemistry , Université de Sherbrooke , Sherbrooke , QC , Canada.,b ECOGENE-21 Biocluster , Chicoutimi , Quebec , Canada , QC , Canada
| | - Andrée-Anne Houde
- c Department of Medicine , Université de Montréal , Montréal , QC , Canada
| | - Simon-Pierre Guay
- a Department of Biochemistry , Université de Sherbrooke , Sherbrooke , QC , Canada.,b ECOGENE-21 Biocluster , Chicoutimi , Quebec , Canada , QC , Canada.,e Department of Medicine , Université de Sherbrooke , Sherbrooke , QC , Canada
| | - Patrice Perron
- b ECOGENE-21 Biocluster , Chicoutimi , Quebec , Canada , QC , Canada.,e Department of Medicine , Université de Sherbrooke , Sherbrooke , QC , Canada
| | - Daniel Gaudet
- b ECOGENE-21 Biocluster , Chicoutimi , Quebec , Canada , QC , Canada.,f Clinical Lipidology and Rare Lipid Disorders Unit, Department of Medicine , Université de Montréal Community Gene Medicine Center, Chicoutimi Department of Medicine, Université de Montréal , Montréal , QC , Canada
| | - Renée Guérin
- d Department of Medical Biology , CIUSSS Saguenay-Lac-Saint-Jean - Chicoutimi Hospital , Saguenay , QC , Canada
| | | | - Marie-France Hivert
- e Department of Medicine , Université de Sherbrooke , Sherbrooke , QC , Canada.,g Department of Population Medicine , Harvard Pilgrim Health Care Institute, Harvard Medical School , Boston , MA , USA
| | - Diane Brisson
- b ECOGENE-21 Biocluster , Chicoutimi , Quebec , Canada , QC , Canada.,f Clinical Lipidology and Rare Lipid Disorders Unit, Department of Medicine , Université de Montréal Community Gene Medicine Center, Chicoutimi Department of Medicine, Université de Montréal , Montréal , QC , Canada
| | - Luigi Bouchard
- a Department of Biochemistry , Université de Sherbrooke , Sherbrooke , QC , Canada.,b ECOGENE-21 Biocluster , Chicoutimi , Quebec , Canada , QC , Canada.,d Department of Medical Biology , CIUSSS Saguenay-Lac-Saint-Jean - Chicoutimi Hospital , Saguenay , QC , Canada
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Kim SH, Silvers A, Viren J, Reaven GM. Relationship between insulin sensitivity and insulin secretion rate: not necessarily hyperbolic. Diabet Med 2016; 33:961-7. [PMID: 26670479 PMCID: PMC4911331 DOI: 10.1111/dme.13055] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 12/07/2015] [Indexed: 12/28/2022]
Abstract
AIMS There is general acceptance that the physiological relationship between insulin sensitivity and insulin secretion is hyperbolic. This conclusion has evolved from studies in which one test assessed both variables, and changes in plasma insulin concentration were used as a surrogate measure for insulin secretion rate. The aim of this study was to see if a hyperbolic relationship would also emerge when separate and direct measures were used to quantify both insulin sensitivity and insulin secretion rate. METHODS Steady-state plasma glucose (SSPG) was determined in 146 individuals without diabetes using the insulin suppression test, with 1/SSPG used to quantify insulin sensitivity. The graded-glucose infusion test was used to quantify insulin secretion rate. Plasma glucose and insulin concentrations obtained during an oral glucose tolerance test (OGTT) were used to calculate surrogate estimates of insulin action and insulin secretion rate. A hyperbolic relationship was assumed if the β coefficient was near -1 using the following model: log (insulin secretion measure) = constant + β × log (insulin sensitivity measure). RESULTS OGTT calculations of insulin sensitivity (Matsuda) and plasma insulin response [ratio of insulin/glucose area-under-the-curve (AUC) or insulin total AUC] provided the expected hyperbolic relationship [β = -0.95, 95% CI (-1.09, -0.82); -1.06 (-1.14, -0.98)]. Direct measurements of insulin sensitivity and insulin secretion rate did not yield the same curvilinear relationship [β = -1.97 (-3.19, -1.36)]. CONCLUSIONS These findings demonstrate that the physiological relationship between insulin sensitivity and insulin secretion rate is not necessarily hyperbolic, but will vary with the method(s) by which it is determined.
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Affiliation(s)
- S H Kim
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
| | | | | | - G M Reaven
- Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA
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50
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Sun M, Song MM, Wei B, Gao Q, Li L, Yao B, Chen L, Lin L, Dai Q, Zhou X, Tao J, Chen J, He C, Jin P, Xu Z. 5-Hydroxymethylcytosine-mediated alteration of transposon activity associated with the exposure to adverse in utero environments in human. Hum Mol Genet 2016; 25:2208-2219. [PMID: 27005421 DOI: 10.1093/hmg/ddw089] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2015] [Accepted: 03/11/2016] [Indexed: 12/18/2022] Open
Abstract
Preeclampsia and gestational diabetes mellitus (GDM) are the most common clinical conditions in pregnancy that could result in adverse in utero environments. Fetal exposure to poor environments may raise the long-term risk of postnatal disorders, while epigenetic modifications could be involved. Recent research has implicated involvement of 5-hydroxymethylcytosine (5hmC), a DNA base derived from 5-methylcytosine, via oxidation by ten-eleven translocation (TET) enzymes, in DNA methylation-related plasticity. Here, we show that the TET2 expression and 5hmC abundance are significantly altered in the umbilical veins of GDM and preeclampsia. Genome-wide profiling of 5hmC revealed its specific reduction on intragenic regions from both GDM and preeclampsia compared to healthy controls. Gene Ontology analysis using loci bearing unique GDM- and preeclampsia-specific loss-of-5hmC indicated its impact on several critical biological pathways. Interestingly, the substantial alteration of 5hmC on several transposons and repetitive elements led to their differential expression. The alteration of TET expression, 5hmC levels and 5hmC-mediated transposon activity was further confirmed using established hypoxia cell culture model, which could be rescued by vitamin C, a known activator of TET proteins. Together, these results suggest that adverse pregnancy environments could influence 5hmC-mediated epigenetic profile and contribute to abnormal development of fetal vascular systems that may lead to postnatal diseases.
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Affiliation(s)
- Miao Sun
- Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu 215006, China
| | - Mingxi M Song
- Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Bin Wei
- Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu 215006, China
| | - Qinqin Gao
- Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu 215006, China
| | - Lingjun Li
- Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu 215006, China
| | - Bing Yao
- Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Li Chen
- Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Li Lin
- Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Qing Dai
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, USA
| | - Xiuwen Zhou
- Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu 215006, China
| | - Jianying Tao
- Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu 215006, China
| | - Jie Chen
- Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu 215006, China
| | - Chuan He
- Department of Chemistry, Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, Howard Hughes Medical Institute, The University of Chicago, Chicago, IL, USA
| | - Peng Jin
- Department of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA
| | - Zhice Xu
- Institute for Fetology, The First Affiliated Hospital of Soochow University, Suzhou City, Jiangsu 215006, China
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