For more than 20 years epidemiologists have warned of a looming public health disaster caused by the increasing prevalence of childhood obesity. One of the consequences of this epidemic is expected to be a massive surge in Type 2 diabetes mellitus (T2D) in youth and young adults. This surge may already be upon us, with T2D accounting for increasing proportions of newly diagnosed cases of diabetes among children and adolescents in the USA, with particularly high prevalence among some ethnic minority groups Citation[1,2]. What was once believed to be the consequence of a lifetime of unhealthy eating and sedentary behavior among an aging population, is now recognized to have more complex underpinnings.
Lifestyle, and environmental, genetic and epigenetic factors are all likely to contribute to the development of obesity and T2D. The fact that children of obese and diabetic women have an increased risk of obesity, impaired glucose tolerance and T2D compared with children of healthy women Citation[3–7], argues that shared genetic or environmental factors may be important. However, evidence from dicordant sibling studies argue against a significant role of shared genotype in this risk Citation[8,9] and evidence from adoption stuidies marginalize the role of the postnatal environment Citation[10,11]. Conversely, the importance of the prenatal environment has been highlighted by studies in which treatment for maternal diabetes during pregnancy attenuates the risk of obesity among offspring Citation[5]. Therefore, the prevention of obesity and T2D might best begin in utero.
Although the mechanism linking the prenatal environment to Children’s outcomes has not been elucidated, increasing evidence suggests that maternal glucose contributes to the intergenerational transmission of obesity, at least in part. The multisite, multinational observational Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study revealed a robust continuous association between maternal glucose concentrations among nondiabetic pregnant women, and neonatal body fat and umbilical cord blood C-peptide concentrations Citation[12]. Increased neonatal body fat is associated with a greater risk for childhood obesity, while increased C-peptide concentrations in cord blood suggest that the fetal pancreas may have been programmed in utero to secrete relatively high levels of insulin. Furthermore, higher insulin concentrations in the amniotic fluid of pregnant diabetic women suggest that fetal insulin sensitivity may also have been compromised by prenatal exposure to high maternal glucose Citation[13]. These data portray an individual who begins life with excess adiposity, reduced insulin sensitivity and increased insulin secretion – a phenotype that, if permanent, threatens to sabotage health at an early age.
In a pilot study conducted by our research group and presented recently at the Endocrine Society Meeting, we report evidence suggesting that associations between maternal glucose and a child‘s body composition, insulin sensitivity and secretion persist into the middle of childhood Citation[14]. Importantly, reduced insulin sensitivity among children exposed to relatively high glucose in utero was not a consequence of their greater adiposity. Similarly, their greater insulin secretion did not appear to be caused by compensation for reduced insulin sensitivity. These data support the hypothesis that the prenatal environment impacts fetal metabolic programming in a manner that potentially contributes to the development of T2D. The idea that the prenatal environment plays a critical role in predisposing or, potentially, protecting children from obesity and the development of related metabolic health problems is not new. For more than 50 years, investigators have been hypothesizing about the importance of the prenatal environment after observing associations between maternal health during gestation and the presentation of chronic disease among offspring in later life Citation[15–18]. Despite increasing support for these hypotheses in the published literature, to date, there is a dearth of longitudinal studies investigating whether prenatal interventions can improve offspring outcomes. There is good reason to be optimistic about the effectiveness of prenatal interventions. Treatment of even mild gestational diabetes has been demonstrated to improve several neonatal outcomes that are associated with subsequent obesity among offspring Citation[19]. In addition, as mentioned previously, the risk of obesity among children is attenuated if their mothers received treatment for gestational diabetes Citation[5]. To date, no research has examined whether treatment of maternal hyperglycemia attenuates the risk of T2D among offspring. However, while the prospect that maternal glucose programs the offspring‘s risk of obesity and T2D is alarming, there is also hope that adequate control of maternal glucose during pregnancy may, ultimately, impede the epidemic of obesity and T2D.
Some may criticize this opinion as being overly simplistic, and I concede the point. Adequete control of maternal glucose during pregnancy is impossible to assure and even if it were not, it alone is unlikely to abolish childhood obesity and T2D. Other factors are almost certainly at play. However, I would argue that management of the glycemic profile in high-risk women is the best option we have at present to lower Children’s predisposition for obesity and T2D. We cannot change a child‘s family history or genetic background, and we cannot feasibly change a woman‘s external environment during pregnancy and, even if we could, we have little evidence that it would help her offspring. Furthermore, with 50% of pregnancies in the USA being unplanned Citation[20], we cannot expect that a large proportion of women will make significant changes themselves prior to pregnancy in order to reduce the risks to their offspring. Since the relative safety and efficacy of treatment for mild gestational diabetes has been demonstrated Citation[19], perhaps it is now time to increase surveillance of gestational glycemia, and to further manage pregnancies as appropriate. While thoughts of such a large-scale effort are often met with trepidation, we must also weigh the consequences of waiting 10–20 years before we have ‘proof of concept’ from longitudinal studies. It should be obvious to all that if we do not act soon, the burden on future generations will be even more physically and economically crippling than it is at present.
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The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
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