Danish Diabetes Birth Registry 2

During pregnancy in women with type 1 and type 2 (pre-existing) diabetes development of complications is 2-4 times higher than in the background population, as among women with pre-existing diabetes up to 50% of the offspring becomes large for gestational age (LGA), and one out of five are delivered preterm. Strict glycemic control and appropriate gestational weight gain are important for a healthy pregnancy outcome. However, a large proportion of pregnant women with diabetes do not reach the goals for glycemic control or weight gain during pregnancy.

From 1992-2000, all pregnancies in women with type 1 diabetes were reported to the Danish Diabetes Birth Registry (DDBR), which gave rise to several important international publications on perinatal outcomes and long-term follow-up studies in mother and child. During the last 20 years type 2 diabetes has become increasingly common in young women. Today up to 60% of pregnant women with pre-existing diabetes have type 2 diabetes. In Denmark we have no national surveillance of pregnancies in women with pre-existing diabetes. It is also relevant to obtain information in a national setting on partner, socioeconomic factors as well as collecting biological samples to get the information needed for a more personalized treatment of pregnant women with pre-existing diabetes.

Offspring born to women with type 1 diabetes have a higher risk of type 1 diabetes per se (5.3%) compared to the background population, but a lower risk compared to offspring of fathers with type 1 diabetes (7.8%). This fact suggests that either differences in inheritability of maternal vs. paternal susceptibility genes or maternal imprinting or maternal diabetes (i.e., the intrauterine environment) modify a child's inherited risk of developing type 1 diabetes.

For type 2 diabetes, genome-wide association studies have described approximately 250 loci being associated with type 2 diabetes. However, the genetic composition of type 2 diabetes is dominated by common alleles with small impact on the risk of disease. As opposed to type 1 diabetes, the risk of type 2 diabetes is higher in the offspring if the mother has type 2 diabetes rather than if the father has type 2 diabetes. Genetically, this can be associated with a unique parent-of-origin transmission of the risk alleles, and it relates to genetic programming during the intrauterine period.

However, the DNA sequence alone cannot explain the phenotypical variation seen in offspring born to women with diabetes. Let alone, describe how the intrauterine environment can influence the long term health of the offspring. Later in life offspring of women with diabetes faces an increased risk of obesity, pre-diabetes and type 2 diabetes, beyond what can be explained by the DNA sequence. This increase in risk of disease is for now unexplained. However, the suboptimal intrauterine environment associated with diabetes in pregnancy, may lead to epigenetic changes of the fetal DNA. Such "fetal programming of adult disease" could provide a pathogenic explanation.