Fetal overnutrition and offspring insulin resistance and β‐cell function: the Exploring Perinatal Outcomes among Children (<scp>EPOCH</scp>) study

Sauder, Katherine A.; Hockett, Christine W.; Ringham, Brandy M.; Glueck, Deborah H.; Dabelea, Dana

doi:10.1111/dme.13417

Cited by 39 publications

(41 citation statements)

References 32 publications

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“…Vohr et al reported that maternal pre-pregnancy weight status and gestational weight gain predicted offspring fat mass at birth [57] and age 1 year [58], even among women without GDM. This positive relationship between maternal weight and offspring adiposity at birth [59] and beyond [49,[60][61][62][63][64] has been confirmed in numerous settings. Moreover, the consequences of pregravid adiposity are detectable across the continuum of maternal BMI and can influence offspring metabolic risk independent of offspring adiposity [64][65][66][67].…”

Section: Maternal Obesitymentioning

confidence: 69%

“…In the Pima Indian study, acute insulin response to infused glucose was 40% lower in adults whose mothers had diabetes during pregnancy than in those whose mothers developed diabetes after delivery, despite no differences in per cent fat mass [48]. In lower-risk populations, maternal GDM has been associated with precursors of type 2 diabetes in offspring even after accounting for offspring BMI, including higher estimated insulin resistance (HOMA2-IR) among youth in EPOCH [49], and higher fasting glucose among adolescents in the Danish National Birth Cohort [50]. Similarly, in an analysis of 587 mother-offspring dyads in Denmark, Kelstrup et al found that adult offspring exposed to maternal type 1 diabetes or GDM had impaired insulin sensitivity and lower disposition index compared with adult offspring of normoglycaemic women, even after adjustment for BMI [51].…”

Section: Pathways Linking In Utero Overnutrition To Type 2 Diabetesmentioning

confidence: 95%

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Developmental overnutrition and obesity and type 2 diabetes in offspring

2019

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Childhood obesity has reached pandemic proportions, and youth-onset type 2 diabetes is following suit. This review summarises the literature on the influence of developmental overnutrition, resulting from maternal diabetes, obesity, maternal dietary intake during pregnancy, excess gestational weight gain, and infant feeding practices, on the aetiology of obesity and type 2 diabetes risk during childhood and adolescence. Key goals of this review are: (1) to summarise evidence to date on consequences of developmental overnutrition; (2) describe shared and distinct biological pathways that may link developmental overnutrition to childhood obesity and youth-onset type 2 diabetes; and (3) to translate current knowledge into clinical and public health strategies that not only target primary prevention in youth, but also encourage primordial prevention during the perinatal period, with the aim of breaking the intergenerational cycle of obesity and diabetes.

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Section: Maternal Obesitymentioning

confidence: 69%

Section: Pathways Linking In Utero Overnutrition To Type 2 Diabetesmentioning

confidence: 95%

Developmental overnutrition and obesity and type 2 diabetes in offspring

2019

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“…For the offspring, exposure to GDM in utero has been linked to an increased risk of childhood obesity and development of T2DM (Sauder et al . ).…”

Section: Introductionmentioning

confidence: 97%

“…GDM increases the risk of the mother developing subsequent type 2 diabetes mellitus (T2DM) by up to 7-fold compared to euglycaemic pregnancies (Melchior et al 2017). For the offspring, exposure to GDM in utero has been linked to an increased risk of childhood obesity and development of T2DM (Sauder et al 2017).…”

Section: Introductionmentioning

confidence: 99%

A mouse model of gestational glucose intolerance through exposure to a low protein diet during fetal and neonatal development

Szlapinski

King

Retta

et al. 2019

The Journal of Physiology

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Key points Pancreatic β‐cell dysfunction is hypothesized to be the significant determinant of gestational diabetes pathogenesis, however pancreatic samples from patients are scarce. This study reports a novel mouse model of gestational glucose intolerance in pregnancy, originating from previous nutrition restriction in utero, in which glucose intolerance was restricted to late gestation as is seen in human gestational diabetes. Glucose intolerance was attributed to reduced β‐cell proliferation, leading to impaired gestational β‐cell mass expansion in maternal endocrine pancreas, in addition to reduced glucose‐stimulated insulin secretion. This model reproduces some of the features of gestational diabetes and is suitable for testing safe therapeutic interventions that increase β‐cell mass during pregnancy and prevent or reverse gestational glucose intolerance. Abstract Gestational diabetes mellitus (GDM) is an increasingly prevalent form of diabetes that appears during pregnancy. Pathological studies link a failure to adaptively increase maternal pancreatic β‐cell mass (BCM) in pregnancy to GDM. Due to the scarcity of pancreatic samples from GDM patients, we sought to develop a novel mouse model for impaired gestational glucose tolerance. Mature female C57Bl/6 mouse offspring (F1) born to dams fed either a control (C) or low‐protein (LP) diet during gestation and lactation were randomly allocated into two subsequent study groups: pregnant (CP, LPP) or non‐pregnant (CNP, LPNP). Glucose tolerance tests were performed at gestational day (GD) 9, 12 and 18. Subsequently, pancreata were removed for fluorescence immunohistochemistry to assess α‐cell mass (ACM), BCM and β‐cell proliferation. An additional group of animals was used to measure insulin secretion from isolated islets at GD18. LPP females displayed glucose intolerance compared to CP females at GD18 (P < 0.001). BCM increased threefold at GD18 in CP females. However, LPP females had reduced BCM expansion (P < 0.01) concurrent with reduced β‐cell proliferation at GD12 (P < 0.05). LPP females also had reduced ACM expansion at GD18 (P < 0.01). LPP islets had impaired glucose‐stimulated insulin secretion in vitro compared to CP islets (P < 0.01). Therefore, impaired glucose tolerance during pregnancy is associated with a failure to adequately adapt BCM, as a result of reduced β‐cell proliferation, in addition to lower glucose‐stimulated insulin secretion. This model could be used to evaluate novel interventions during pregnancy to increase BCM or function as a strategy to prevent/reverse GDM.

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“…additionally as moderate risk in one other domain (Brandt et al, 2014;Derraik et al, 2015;Hrolfsdottir et al, 2015;Maftei et al, 2015;Sauder et al, 2017;Tam et al, 2018;Winham et al, 2006). The four studies that had the lowest risk of bias were rated in only one domain as moderate and in all other domains as low risk (Gaillard et al, 2014;Gaillard et al, 2016;Hochner et al, 2012;Oostvogels et al, 2014).…”

Section: Study Qualitymentioning

confidence: 99%

Maternal overnutrition impairs offspring's insulin sensitivity: A systematic review and meta‐analysis

Eitmann

Németh

Hegyi

et al. 2020

Maternal & Child Nutrition

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This systematic review and meta‐analysis aimed to investigate the association between maternal overnutrition and offspring's insulin sensitivity—following the Preferred Reporting Items for Systematic Reviews and Meta‐analyses statement. Studies published in English before April 22, 2019, were identified through searches of four medical databases. After selection, 15 studies aiming to explore the association between prepregnancy body mass index (ppBMI) or gestational weight gain (GWG) of non‐diabetic mothers and their offspring's insulin sensitivity (fasting insulin or glucose level and Homeostatic Measurement Assessment for Insulin Resistance [HOMA‐IR]) were included in the meta‐analysis. Associations of ppBMI and GWG with offspring's insulin sensitivity were analysed by pooling regression coefficients or standardized differences in means with 95% confidence intervals (CIs). Maternal ppBMI showed significant positive correlations with the level of both fasting insulin and HOMA‐IR in offspring (standardized regression coefficient for fasting insulin: 0.107, CI [0.053, 0.160], p < 0.001 and that for HOMA‐IR: 0.063, CI [0.006, 0.121], p = 0.031). However, the result of the analysis on coefficients adjusted for offspring's actual anthropometry (BMI and adiposity) was not significant. Independent from ppBMI, GWG tended to show a positive correlation with insulin level, but not after adjustment for offspring's anthropometry. Offspring of mothers with excessive GWG showed significantly higher HOMA‐IR than those of mothers with optimal GWG (p = 0.004). Our results demonstrate that both higher ppBMI and GWG increase the risk of offspring's insulin resistance, but the effect of ppBMI on insulin sensitivity in offspring may develop as consequence of their adiposity.

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Fetal overnutrition and offspring insulin resistance and β‐cell function: the Exploring Perinatal Outcomes among Children (EPOCH) study

Cited by 39 publications

References 32 publications

Developmental overnutrition and obesity and type 2 diabetes in offspring

Developmental overnutrition and obesity and type 2 diabetes in offspring

A mouse model of gestational glucose intolerance through exposure to a low protein diet during fetal and neonatal development

Maternal overnutrition impairs offspring's insulin sensitivity: A systematic review and meta‐analysis

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