ISSN 1662-4009 (Online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 2.10 | DOI: 10.1530/ey.16.2.10

Association of gestational diabetes with maternal disorders of glucose metabolism and childhood adiposity

Lowe WL Jr, Scholtens DM, Lowe LP, Kuang A, Nodzenski M, Talbot O, Catalano PM, Linder B, Brickman WJ, Clayton P, Deerochanawong C, Hamilton J, Josefson JL, Lashley M, Lawrence JM, Lebenthal Y, Ma R, Maresh M, McCance D, Tam WH, Sacks DA, Dyer AR, Metzger BE & HAPO Follow-up Study Cooperative Research Group



JAMA. 2018 Sep 11;320(10):1005–1016. doi: 10.1001/jama.2018.11628.

The aims of this study were to assess whether in utero exposure to untreated gestational diabetes (using the IADPSG criteria) is associated with long-term risk of a disorder of glucose metabolism among mothers and greater adiposity among their children at 10 to 14 years post-partum.

The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study was undertaken to identify risks of adverse outcomes associated with degrees of maternal glucose intolerance less severe than overt diabetes mellitus (Metzger BE et al.). It found associations between increasing levels of fasting, 1-hour, and 2-hour plasma glucose obtained on oral glucose-tolerance testing and birth weight above the 90th percentile and cord-blood serum C-peptide levels above the 90th percentile, with weaker associations between glucose levels and primary cesarean delivery and clinical neonatal hypoglycemia (Metzger BE et al.). Positive associations were also found between increasing plasma glucose levels and each of the five secondary outcomes examined: premature delivery, shoulder dystocia or birth injury, intensive neonatal care, hyperbilirubinemia, and preeclampsia. Based on the HAPO Study and other studies, new criteria for the diagnosis of gestational diabetes were proposed by the International Association of Diabetes and Pregnancy Study Groups (IADPSG) and adopted by the World Health Organization and others.

The primary aims of this current study were to assess whether in utero exposure to untreated gestational diabetes (using the IADPSG criteria) was associated with long-term risk of a disorder of glucose metabolism among mothers and greater adiposity among their children at 10 to 14 years post-partum. This study demonstrated that untreated gestational diabetes was associated with a higher risk for a maternal disorder of glucose metabolism at 10 to 14 years postpartum. The association of gestational diabetes with childhood overweight or obesity was not statistically significant. Gestational diabetes is a risk factor for type 2 diabetes and a meta-analysis of 20 studies that were performed prior to the development of the IADPSG criteria and that used varied criteria to diagnose gestational diabetes demonstrated that women with a history of gestational diabetes had a higher risk of developing type 2 diabetes compared with women with a normoglycemic pregnancy. The risk factors for progression to type 2 diabetes included maternal age, pre-partum and postpartum BMI, family history of type 2 diabetes, insulin treatment for gestational diabetes, and fasting glucose level during pregnancy. In the current study a larger population of women with lesser degrees of hyperglycemia (IADPSG-defined gestational diabetes) were at risk for progression to prediabetes and type 2 diabetes. The higher prevalence of obesity among women with gestational diabetes confounds the association of gestational diabetes with childhood obesity. Higher maternal BMI might be associated with higher childhood adiposity through shared genetics, familial lifestyle and environmental factors, and the intrauterine environment. Adjusting for maternal BMI attenuated the associations between gestational diabetes and childhood obesity in earlier studies, therefore raising the question whether the association of gestational diabetes with childhood adiposity is independent of maternal BMI. Further studies assessing the independent effects of maternal obesity/BMI and GDM on childhood obesity might help to explain these observations.

Reference: Metzger BE, Lowe LP, Dyer AR, et al; HAPO Study Cooperative Research Group. Hyperglycemia and adverse pregnancy outcomes. N Engl J Med. 2008; 358(19):1991–2002.

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