Gene variants which influence insulin metabolism can also affect birth weight

Nov 12 2009

Low birth weight increases the risk of developing type 2 diabetes later in life. Until recently scientists had attributed this to maternal malnutrition during pregnancy. However, now it seems that genetic background may also play a major role. A research team of Technische Universität München and Helmholtz Zentrum München has now demonstrated, that gene variants which influence insulin metabolism can also affect birth weight.

In the BABYDIAB study led by Professor Anette-Gabriele Ziegler, director of the Institut für Diabetesforschung der Forschergruppe Diabetes e.V. at Helmholtz Zentrum München and Forschergruppe Diabetes at the Technische Universität München analyzed the data of 729 children whose mothers had type 1 diabetes and who thus had a higher diabetes risk.

The scientists investigated the genetic background of fetuses for alterations in individual DNA bases, termed single nucleotide polymorphisms (SNPs). Here they focused on three gene regions which are known to be risk alleles for diabetes caused by reduced insulin secretion. They looked at these in relation to birth weight.

It turned out that there was a significant association between the two SNPs of the HHEX-IDE gene region and low birth weight. This was independent of HbA1c levels (long-term blood glucose levels) of the expectant mother, indicating a lesser correlation between maternal nutrition and blood glucose regulation. "Interestingly, we found this effect in children whose mothers had type 1 diabetes. This could mean that an a priori reduced insulin secretion also plays a role in the development of autoimmune type 1 diabetes," explained Dr. Christiane Winkler of the Forschergruppe Diabetes at Helmholtz Zentrum München and first author of the publication.

In contrast, the researchers found no correlation between the two SNPs of the other gene regions that were studied (CDKAL1 and SLC30A8) and birth weight. However, this does not entirely exclude an association - such an effect could become apparent with higher numbers of participants. "Indications of genetic associations are usually only found in very large populations. As we see here, it is important to substantiate these in smaller, but very well-phenotyped study populations. We can thus gain information about the possible mechanism of the original results", emphasized PD Dr. Thomas Illig, head of the Epidemiology - Biological Samples - Genomics research unit at Helmholtz Zentrum München.

With their findings, the Munich researchers have come a step closer to understanding the underlying genetic mechanisms of diabetes diseases. "Next, we want to investigate whether the genetic associations observed in this study could also have an effect on body weight later in life. Due to the long-term BABYDIAB study, which has run continuously since 1989, this data already exists," Christiane Winkler explained.