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Transgenerational cycle of obesity and diabetes: investigating possible metabolic precursors in cord blood from the PREOBE study

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Abstract

Aims

Offspring of mothers suffering from obesity and/or gestational diabetes mellitus (GDM) were reported to be at risk of higher birth weight (BW), later obesity and diabetes. We hypothesize that infant anthropometry changes related to maternal pathological status are due to dysregulated infant metabolism.

Methods

First, we inspected differences in BMI z-scores (z-BMI) between three infant groups: born to normal weight (NW; n = 49), overweight/obese (OV/OB; n = 40) and GDM mothers (n = 27) at birth and 1 year. Then, we inspected associations between cord blood metabolites and 1-year Δ z-BMI in the three infant groups at birth and 1 year.

Results

No statistically significant difference was detected in z-BMI between the study groups at birth; however, GDM was associated with heavier infants at 1 year. Regarding the associations between the metabolites and z-BMI, phospholipids, especially those containing polyunsaturated fatty acids, were the species most impacted by the maternal metabolic status, since numerous phosphatidylcholines–PUFA were positively associated with z-BMI in NW but negatively in OV/OB and GDM groups at birth. Conversely, the sum of lysophosphatidylcholines was only positively associated with z-BMI in NW at birth but of no relation in the other two groups. At 1 year, most of the associations seen at birth were reversed in NW and lost in OV/OB and GDM groups. In the NW group, PC-PUFA were found to be negatively associated with Δ z-BMI at 1 year in addition to some medium-chain acylcarnitines, tricarboxylic acid metabolites, Asp and Asn-to-Asp ratio. In OV/OB and GDM groups, the non-esterified fatty acid (NEFA26:0) and His correlated with Δ z-BMI at 1 year in negative and positive directions, respectively.

Conclusions

GDM was associated with overweight in offspring at 1 year, independent of the BW with lack of evidence on existing correlation of this finding with metabolic alterations detected in cord blood metabolome. Associations were found between cord blood metabolites and infant anthropometry at birth and were influenced by maternal OB and GDM. However, an extension of the findings monitored at birth among the three groups was not detected longitudinally showing a lack of predictive power of cord blood metabolome for later development at least 1 year.

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Acknowledgements

The authors thank the study participants, the obstetricians, paediatricians and technicians of the EURISTIKOS team and the PREOBE team at the University of Granada. We are grateful to Stephanie Winterstetter, Alexander Haag and Tina Honsowitz for their support in the analysis.

Funding

This work was supported by Andalusian Ministry of Economy, Science and Innovation, PREOBE Excellence Project (Ref. P06-CTS-02341), Spanish Ministry of Economy and Competitiveness (Ref. BFU2012-40254-C03-01 and Ref. SAF2015-69265-C2-2-R), the European Research Council Advanced Grant META-GROWTH (ERC-2012-AdG 322605), European Commission research projects EarlyNutrition, FP7–FP7 KBBE-2011-1 (289346 y) and Horizon2020 DynaHEALTH (633595).

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Authors and Affiliations

  1. Division of Metabolic and Nutritional Medicine, Dr. von Hauner Children’s Hospital, LMU-Ludwig-Maximilians-Universität München, University of Munich Medical Centre, Campus Innenstadt, Lindwurmstr. 4, 80337, Munich, Germany

    Engy Shokry, Linda Marchioro, Olaf Uhl & Berthold Koletzko

  2. Department of Paediatrics, School of Medicine, EURISTIKOS Excellence Centre for Paediatric Research, University of Granada, Avenida de la Investigación 11, 18016, Granada, Spain

    Mercedes G. Bermúdez, Jose Antonio García-Santos, Mª Teresa Segura & Cristina Campoy

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  1. Engy Shokry
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Correspondence to Berthold Koletzko.

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The study was approved by the Bioethical Committees for Clinical Research of the Clinical University Hospital San Cecilio, the Mother-Infant University Hospital of Granada, Spain.

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Participation was voluntary, and written informed consent was obtained from participants at study entry.

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Shokry, E., Marchioro, L., Uhl, O. et al. Transgenerational cycle of obesity and diabetes: investigating possible metabolic precursors in cord blood from the PREOBE study. Acta Diabetol 56, 1073–1082 (2019). https://doi.org/10.1007/s00592-019-01349-y

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