Developmental overnutrition and obesity and type 2 diabetes in offspring

Diabetologia October 2019, Volume 62, Issue 10, pp 1779–1788 | Cite as Developmental overnutrition and obesity and type 2 diabetes in offspring AuthorsAuthors and affiliations Wei PerngEmily OkenDana Dabelea Review First Online: 27 August 2019 10 Shares 999 Downloads 1 Citations Abstract 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. KeywordsDevelopmental programming Lifecourse development Obesity Overnutrition Review Type 1 diabetes Type 2 diabetes  Abbreviations EPOCH Exploring Perinatal Outcomes in Children GDM Gestational diabetes mellitus GUTS Growing Up Today Study GWG Gestational weight gain HAPO Hyperglycemia and Adverse Pregnancy Outcomes HEI Healthy Eating Index Electronic supplementary material The online version of this article ( https://doi.org/10.1007/s00125-019-4914-1) contains a slide of the figure for download, which is available to authorised users. Introduction The obesity pandemic has spared no age group, including young children [1]. Following in its footsteps is youth-onset type 2 diabetes, a novel paediatric condition on the rise in the USA [2] and worldwide [3]. The existence and rise in prevalence of paediatric type 2 diabetes is undoubtedly related to trends in childhood obesity given that excess adiposity is the leading risk factor for type 2 diabetes [4, 5] and emerging evidence suggest that both conditions have origins in utero [6, 7, 8, 9]. Little remains known of specific pathways and mechanisms underlying development of youth-onset type 2 diabetes, an important first step to stemming the tide of type 2 diabetes among children and adolescents. As depicted in Fig. 1, this review expands upon the literature surrounding developmental overnutrition, resulting from maternal diabetes, obesity, diet during pregnancy, and excess gestational weight gain, and infant feeding practices, in relation to childhood obesity and youth-onset type 2 diabetes. We start by summarising and appraising the evidence on consequences of developmental overnutrition and discussing shared and distinct biological pathways that may link developmental overnutrition to obesity and type 2 diabetes in youth. We then translate current knowledge into clinical and public health strategies that not only target primary prevention in youth, but also encourage primordial preventions during the perinatal period, with the aim of breaking the intergenerational cycle of obesity and diabetes [8, 10]. Open image in new window Fig. 1 Pathways through which exposure to developmental overnutrition during pregnancy (obesity, maternal diabetes, gestational weight gain, diet during pregnancy, and infant feeding) may influence the development of obesity and type 2 diabetes across the life course. Topics in boxes with a solid border are discussed in depth in this review. This figure is available as a downloadable slide Developmental overnutrition In utero overnutritionMaternal diabetes Longstanding evidence links maternal diabetes to larger offspring birth size and adiposity across life, and these associations are thought to be driven by maternal fuels: hyperglycaemia and altered lipid and/or amino acid metabolism. While earlier studies evaluated maternal diabetes as a combination of type 1, type 2 and/or gestational diabetes mellitus (GDM), more recent investigations consider diabetes subtypes and degree of hyperglycaemia, which may be more appropriate. Maternal diabetes, fetal growth and neonatal adiposity In the 1950s, Pedersen proposed the fuel-mediated teratogenesis hypothesis, which postulated that intrauterine exposure to hyperglycaemia leads to higher birthweight and future obesity and type 2 diabetes risk [6]. This hypothesis is supported by studies showing that women with pre-existing diabetes and those who develop GDM deliver infants with higher birthweight [11, 12, 13] and fat mass [14, 15]. In a study of 195 women with GDM and 220 control individuals [15], mid-pregnancy fasting glucose was the strongest correlate of newborn fat mass, in comparison with demographic characteristics, family history and maternal anthropometry [15]. Several other studies have since identified associations of maternal hyperglycaemia with offspring adiposity at birth and beyond: (1) maternal glucose levels across all of pregnancy and in the absence of diagnosed diabetes were associated with directly measured neonatal fat mass in the Colorado-based Healthy Start Study (n = 804) [16]; (2) mid-pregnancy oral glucose challenge test glucose levels correlated with higher birthweight among 6854 non-diabetic pregnancies in a study conducted in Texas [17]; (3) higher mid-pregnancy oral glucose tolerance test glucose levels were associated with higher birthweight among >25,000 mother–infant pairs in the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study [18]; and (4) late pregnancy dysglycaemia among non-GDM pregnancies (HbA1c ≥39 mmol/mol at delivery) predicted greater offspring weight gain during early childhood and higher BMI at age 4 years among 898 mother–child pairs in Germany [19]. Together, these findings emphasise the relevance of both degree and timing of maternal hyperglycaemia—even in the absence of frank diabetes—as determinants of offspring adiposity. Type 1 diabetes, type 2 diabetes and GDM are each associated with altered lipid metabolism [20, 21, 22], another fuel-mediated pathway through which maternal diabetes may influence newborn adiposity [23]. In the context of GDM, maternal serum NEFA and/or triacylglycerols are associated with higher birthweight [24, 25, 26]. Findings in the general population have been mixed, with some studies suggesting that the relationship between maternal lipids and neonatal outcomes differs by pre-pregnancy weight status [27, 28, 29, 30]. In the Healthy Heart Study [16] there was a positive association of NEFA during the second half of pregnancy with birthweight independent of pre-pregnancy BMI, but not with newborn fat mass, among 804 mother–infant pairs. There was also a positive relationship between late pr (...truncated)