Hypoglycaemia on an oral glucose tolerance test in pregnancy - Is it clinically significant?

AIM: During pregnancy, some women have a low glucose level on the 75 g oral glucose tolerance test (OGTT). The implications of this are unclear and there is no guideline on how to manage these women. METHOD: We recruited pregnant women with a glucose level <3.5 mmol/L at 1- or 2-h during a screening antenatal OGTT. These women (Group 1) underwent self-monitoring of blood glucose (SMBG) over a two-week period. We also compared Group 1's demographic and pregnancy outcomes data with women who had normal OGTT results (Group 2) and women diagnosed with gestational diabetes mellitus (GDM) (Group 3). RESULTS: 52 women were recruited. Post-hoc analysis of the SMBG results revealed 50% of women experienced 2 or more elevated fasting BGLs (>5.1 mmol/L) in a week when using the Australian Diabetes in Pregnancy Society (ADIPS) criteria. A further 8% women had elevated 2-h glucose levels (above 6.7 mmol/L). Group 1 women tended to have higher booking weight. They were less likely to have a history of macrosomia or be of East or South-East Asian ethnicity. There were no differences in pregnancy outcomes between Groups 1 and 2, but Group 1 had a higher rate of congenital abnormality (6%) than Group 3 (2%). CONCLUSION: A large proportion of pregnant women who had a low glucose level on OGTT had elevated glucose levels on SMBG, however their pregnancy outcomes were not significantly different to women who had a normal OGTT. Currently there is not enough evidence to advocate routine SMBG and treatment for this group of women.

Negative autoregulation of GTF2IRD1 in Williams-Beuren syndrome via a novel DNA binding mechanism.

The GTF2IRD1 gene is of principal interest to the study of Williams-Beuren syndrome (WBS). This neurodevelopmental disorder results from the hemizygous deletion of a region of chromosome 7q11.23 containing 28 genes including GTF2IRD1. WBS is thought to be caused by haploinsufficiency of certain dosage-sensitive genes within the deleted region, and the feature of supravalvular aortic stenosis (SVAS) has been attributed to reduced elastin caused by deletion of ELN. Human genetic mapping data have implicated two related genes GTF2IRD1 and GTF2I in the cause of some the key features of WBS, including craniofacial dysmorphology, hypersociability, and visuospatial deficits. Mice with mutations of the Gtf2ird1 allele show evidence of craniofacial abnormalities and behavioral changes. Here we show the existence of a negative autoregulatory mechanism that controls the level of GTF2IRD1 transcription via direct binding of the GTF2IRD1 protein to a highly conserved region of the GTF2IRD1 promoter containing an array of three binding sites. The affinity for this protein-DNA interaction is critically dependent upon multiple interactions between separate domains of the protein and at least two of the DNA binding sites. This autoregulatory mechanism leads to dosage compensation of GTF2IRD1 transcription in WBS patients. The GTF2IRD1 promoter represents the first established in vivo gene target of the GTF2IRD1 protein, and we use it to model its DNA interaction capabilities.