The processes noted above do not constitute the only developmental pathway leading to intergenerational passage of risk of NCDs. It is alarming that an increasing number of women develop type 2 diabetes during their reproductive years [
21,
22]. Epidemiological studies show that children born to type 1 or 2 diabetic mothers also have a greater susceptibility to diabetes and obesity in later life [
23,
24]. That this risk is related to intra-uterine exposure to hyperglycaemia is shown by the observation that, among siblings, the risk of diabetes is higher in those born after the mother was diagnosed with diabetes [
25]. These observations have been extended recently, as offspring exposed even to mild hyperglycaemia during pregnancy have increased adiposity and are at increased risk of later diabetes and cardiometabolic disease [
26,
27]. Through perpetuation of the cycle of ‘diabetes begetting diabetes’, these factors are driving further escalation of the epidemic of NCDs [
28,
29]. Recent animal data now also raise the possibility of paternal transmission of diabetes risk between generations [
30] so the focus of potential interventions should not only be on women.
The rising prevalence of maternal obesity is of particular concern in populations undergoing rapid socio-economic transitions [
1,
2,
21]. Obesity is associated with an increased risk of many pregnancy complications such as hypertension, preeclampsia, and GDM. Evidence shows that a child of an obese mother may suffer from exposure to a suboptimal environment
in utero and is also more likely to become obese [
31,
32]. Experimentally feeding pregnant animals a high fat diet gives rise to offspring who become overweight and who demonstrate a range of metabolic and functional disorders similar to the human metabolic syndrome and which have now been shown to be associated with epigenetic changes such as DNA methylation at components of genes involved in hepatocyte production and metabolism, [
33]. Pregnancy represents a state of relative maternal insulin resistance, which helps promote the transfer of nutrients such as glucose, fatty acids and amino acids to the fetus [
34]. Placental nutrient transfer is determined by the concentration gradient, blood flow and the operation of active and facilitated transporters [
35]. However, in contrast to amino acids, there is no upper limit to placental transfer of glucose as maternal blood levels rise, suggesting that the rates of glucose exposure of the fetus that are often now experienced are novel in evolutionary terms. As a result, moderately increased fetal glucose supply will lead to fetal hyperinsulinaemia and a small increase in lean body as well as fat mass [
36‐
39]. This may be viewed as adaptive as in the neonatal period relative adiposity provides metabolic reserves for thermogenesis and critical organ function in the event of inadequate maternal care [
18]. GDM can be envisaged as the more extreme outcome of physiological processes, when maternal insulin resistance is accentuated by the woman’s own developmental, genetic and environmental circumstances: for example, women of lower birth weight have a greater risk of developing GDM [
37], whilst genetic variants associated with type 2 diabetes are also associated with increased risk of GDM [
40,
41]. In the evolutionary mismatched situation of over-nutrition and low levels of physical activity, now increasingly common for women in their reproductive years, such mechanisms contribute not only to the rise in GDM but to that in obesity and diabetes in their children, and play an important role in perpetuating a vicious cycle of disease. For example, a recent paper shows that in Canadian first nation peoples up to 30% of the incidence of type 2 diabetes has its origin in GDM in the previous generation [
42]. Conditions such as GDM carry risk of cardiovascular disease for both the mother as well as the child, a risk which increases with each pregnancy (Figure
1) [
43]. These findings have significant long-term implications for global public health. Now more than ever, effective strategies for preventing GDM are needed.