Associations of maternal type 1 diabetes with childhood adiposity and metabolic health in the offspring: a prospective cohort study
Exposure to an intrauterine hyperglycaemic environment has been suggested to increase the offspring’s later risk for being overweight or having metabolic abnormalities, but conclusive evidence for pregnancies affected by maternal type 1 diabetes is still lacking. This study aims to analyse the relationship between maternal type 1 diabetes and the offspring’s metabolic health and investigate whether birthweight and/or changes in the offspring’s metabolome are in the potential pathway.
We analysed data from 610 and 2169 offspring having a first-degree relative with type 1 diabetes from the TEENDIAB and BABYDIAB/BABYDIET cohorts, respectively. Anthropometric and metabolic outcomes, assessed longitudinally at 0.3–18 years of age, were compared between offspring of mothers with type 1 diabetes and offspring of non-diabetic mothers but with fathers or siblings with type 1 diabetes using mixed regression models. Non-targeted metabolomic measurements were carried out in 500 individuals from TEENDIAB and analysed with maternal type 1 diabetes and offspring overweight status.
The offspring of mothers with type 1 diabetes had a higher BMI SD score (SDS) and an increased risk for being overweight than the offspring of non-diabetic mothers (e.g. OR for overweight status in TEENDIAB 2.40 [95% CI 1.41, 4.06]). Further, waist circumference SDS, fasting levels of glucose, insulin and C-peptide, and insulin resistance and abdominal obesity were significantly increased in the offspring of mothers with type 1 diabetes, even when adjusted for potential confounders and birthweight. Metabolite patterns related to androgenic steroids and branched-chain amino acids were found to be associated with offspring’s overweight status, but no significant associations were observed between maternal type 1 diabetes and metabolite concentrations in the offspring.
Maternal type 1 diabetes is associated with offspring’s overweight status and metabolic health in later life, but this is unlikely to be caused by alterations in the offspring’s metabolome.
KeywordsBirthweight Maternal type 1 diabetes Offspring metabolic health Offspring metabolome Offspring overweight
Branched-chain amino acid
Dietary inflammatory index
Standard deviation score
We thank L. Lachmann, C. Matzke, J. Stock, S. Krause, A. Knopff, F. Haupt, M. Pflüger, M. Scholz, A. Gavrisan, S. Schneider, K. Remus, S. Biester (Bläsig), E. Sadeghian and A. Bokelmann for data collection and expert technical assistance. We also thank all families participating in the BABYDIAB/BABYDIET and TEENDIAB studies and also all paediatricians, diabetologists and family doctors in Germany for recruitment and continuous support.
AP reviewed data, undertook statistical analysis, interpreted results and wrote the first and final draft of the manuscript together with AB. MJ contributed to data management and statistical analysis and reviewed the manuscript. CW, SH, NH, JR and OK acquired data and reviewed the manuscript. JK and GK interpreted results and reviewed the manuscript. A-GZ is the principal investigator of the BABYDIAB/BABYDIET and TEENDIAB studies, designed the studies and concept, interpreted the results and critically reviewed the manuscript for intellectual content. All authors approved the final version of the manuscript. A-GZ is the guarantor of this work.
The work was supported by grants from the Competence Network for Diabetes Mellitus (Kompetenznetz Diabetes Mellitus) funded by the Federal Ministry of Education and Research (FKZ 01GI0805-07), JDRF (JDRF-No 17-2012-16, JDRF-No 2-SRA-2015-13-Q-R) and the European Union’s HORIZON 2020 research and innovation programme (grant agreement number 633595 DynaHEALTH). This work was supported by iMed, the Helmholtz Initiative on Personalized Medicine.
Duality of interest
The authors declare that there is no duality of interest associated with this manuscript.
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