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Infants of mothers with diabetes have altered urinary metabolic profile at birth

Presented at the Neonatal Society 2012 Summer Meeting (programme).

Logan KM, Wijeyesekera AD, Perez IG, Hyde MJ, Romero MG, Jeffries S, Andreas N, Gale C, Holmes E, Modi N

Imperial College London, UK

Background: In addition to their genetic risk, babies exposed to diabetes in the womb have greater risks of childhood obesity (1) and a fourfold increased risk of T2D (2). Identification of pathways and markers of T2D risk in infants of mothers with diabetes (IDM) could bring targeted surveillance and early detection nearer. Using metabolomics, large numbers of metabolites may be analysed in small volumes of urine. Metabolic profile has not been studied in newborn IDM and we hypothesised that this differs between IDM and control infants in the newborn period. The study was conducted with Research Ethics Committee approval (08/H07/11/43).

Methods: Infants were recruited from the postnatal wards at Chelsea and Westminster Hospital between July 2010 and Jan 2012. A urine sample was collected within 72 hours using cotton wool and stored at -80șC until analysis. Samples were analysed using one-dimensional 1H NMR spectroscopy at 300K on a Bruker Avance 600 MHz spectrometer, using standard parameters and pre-processing algorithms, as previously described (3). The spectra were automatically phased; baseline corrected, referenced using an in-house MATLAB routine, normalised using probabilistic quotient normalisation to the median profile and aligned; continuous spectral data was used for statistical analysis. Spectra were analysed on the basis of experimental group using principal component analysis (PCA) and partial least square-discriminant analysis (PLS-DA).

Results: We analysed urine samples from 18 IDM and 12 healthy term control infants. The urinary metabolome of IDM and term neonates appears to differ (Fig 1). Differences appear to be seen in the following metabolites; glucose and formate, fumarate, succinate and citrate, which are involved in the TCA cycle.

Figure 1: Partial least squares discriminant analysis (PLS-DA) scores plot of UV scaled, continuous data
from 1H NMR spectra of urine collected within 72 hours of birth from infants of diabetic mothers(; 37+3 - 39+5 weeks GA; n=18) compared with healthy term infants (▲; born 39+2 - 42 weeks GA; n=12). R2=0.79, Q2=0.09.

Conclusion: These preliminary data indicate differences in the metabolism of IDM and control infants in the newborn period. These findings require confirmation and reassessment in later infancy. The next step will be to study infant metabolite alterations in relation to the continuum of maternal glycaemia in pregnancy.

Corresponding author:

1. Phillips L et al (2011) Diabetologia 54:1957-1966
2. Dabelea D, et al. (2000) Diabetes 49:2208-2211
3. Beckonert O et al (2007) Nature Protocols 2: 2692-703

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