Gestational Diabetes Mellitus Is Associated with Altered Abundance of Exosomal MicroRNAs in Human Milk

Kruti B. Shah, David A. Fields, Nathan P. Pezant, Harmeet K Kharoud, Shelly Gulati, Katherine M Jacobs, Cheryl A Gale, Elyse O. Kharbanda, Emily M Nagel, Ellen W. Demerath, Jeanie B. Tryggestad

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Purpose: Human milk (HM) is a unique biological fluid that is enriched with a variety of factors, including microRNAs (miRNAs) that potentially provide both short- and long-term benefits to the infants. miRNAs are packaged within exosomes, making them bioavailable to infants. Gestational diabetes mellitus (GDM) may affect the abundance of exosomal miRNAs in HM, providing a mechanism for growth and adiposity variation in infants of mothers with GDM in early life. Therefore, the purposes of this study were to examine the impact of GDM on select miRNAs (miRNA-148a, miRNA-30b, miRNA-let-7a, and miRNA-let-7d) involved in metabolism and to examine the association of these miRNAs with measures of infant body composition in the first 6 months of life. Methods: Milk samples were collected from a cohort of 94 mothers (62 mothers without GDM and 32 mothers with GDM) matched on body mass index strata at 1 month post partum. miRNA abundance was measured by real-time polymerase chain reaction. Linear regression models were used to examine potential differences in miRNA abundance in women with and without GDM, testing associations between miRNA abundance and infant growth and body composition measures from 1 to 6 months. Findings: The abundances of miRNA-148a, miRNA-30b, miRNA-let-7a, and miRNA-let-7d were reduced in milk from mothers with GDM. Independent of GDM status, higher maternal diet quality was associated with increased abundance of each of the measured miRNAs. miRNA-148a was negatively associated with infant weight, percentage of body fat, and fat mass, whereas miRNA-30b was positively associated with infant weight and fat mass at 1 month of age. There was no association of milk miRNA-148a and miRNA-30b with infant weight at 1 month of age or with body composition measures at 3 months of age; however, miRNA-148a was negatively associated with infant weight at 6 months of age. Implications: If supported by randomized dietary supplementation or other intervention trials, HM miRNAs may be a therapeutic target to mitigate risk of metabolic outcomes in offspring of women with GDM.

Original languageEnglish (US)
Pages (from-to)172-185.e1
JournalClinical Therapeutics
Volume44
Issue number2
DOIs
StatePublished - Feb 2022

Bibliographical note

Funding Information:
We acknowledge and thank all the women and infants and health care practitioners who contributed to the Mothers and Infants Linked for Healthy Growth (MILk) study (NCT03301753), the Maternal Metabolism, Milk, and the Microbiome (4M) Study, and the study teams. We also thank Neely Miller and Kristin Sandness from the Center for Neurodevelopmental Behavior and Rebecca Hollister from the Center for Pediatric Obesity at the University of Minnesota for expert technical assistance and data collection support. The study could not be completed without the work of Lauren Asfaw from the University of Minnesota Department of Obstetrics and Gynecology and the Maternal-Fetal Medicine Clinic. Many thanks go to staff at the University of Oklahoma Health Sciences Center, especially Katy Duncan for her work in all aspects of the study, and to Elisabeth Seburg, Elanadora Sour, Abhilash Muthineni, and Prasanthi Kodhala at the HealthPartners Institute. A special thank you to Laurie Foster for her innovation and dedication to the MILk Study and 4M Study from the start. We also thank Lauren Asfaw at the Department of Obstetrics, Gynecology, and Women's Health, University of Minnesota. We also greatly acknowledge Kathy Kyler for assistance with technical and language editing and proofreading of the manuscript. We also acknowledge the Oklahoma Medical Research Foundation Quantitative Analysis Core for providing statistical analysis that was supported in part by Oklahoma Center of Biomedical Research Excellence (COBRE) grant 1 P30 GM110766-01. Author contributions are as follows: conceptualization: K.B. Shah, D.A. Fields, E.W. Demerath, and J.B. Tryggestad; methodology: K.B. Shah, D.A. Fields, S. Gulati, E.W. Demerath, and J.B. Tryggestad; formal analysis: K.B. Shah and N.P. Pezant; data curation: K.B. Shah, N.P. Pezant, H.K. Kharoud; writing-original draft preparation: K.B. Shah; writing, review and editing: K.B. Shah, D.A. Fields, N.P. Pezant, K. Jacobs, C.A. Gale, E.O. Kharbanda, E.M. Nagel, E.W. Demerath, and J.B. Tryggestad; supervision: D.A. Fields, E.W. Demerath, and J.B. Tryggestad; funding acquisition: K.B. Shah, D.A. Fields, K. Jacobs, and E.W. Demerath. All authors have read and agreed to the published version of the manuscript.

Funding Information:
We acknowledge and thank all the women and infants and health care practitioners who contributed to the Mothers and Infants Linked for Healthy Growth (MILk) study (NCT03301753), the Maternal Metabolism, Milk, and the Microbiome (4M) Study, and the study teams. We also thank Neely Miller and Kristin Sandness from the Center for Neurodevelopmental Behavior and Rebecca Hollister from the Center for Pediatric Obesity at the University of Minnesota for expert technical assistance and data collection support. The study could not be completed without the work of Lauren Asfaw from the University of Minnesota Department of Obstetrics and Gynecology and the Maternal-Fetal Medicine Clinic. Many thanks go to staff at the University of Oklahoma Health Sciences Center, especially Katy Duncan for her work in all aspects of the study, and to Elisabeth Seburg, Elanadora Sour, Abhilash Muthineni, and Prasanthi Kodhala at the HealthPartners Institute. A special thank you to Laurie Foster for her innovation and dedication to the MILk Study and 4M Study from the start. We also thank Lauren Asfaw at the Department of Obstetrics, Gynecology, and Women's Health, University of Minnesota. We also greatly acknowledge Kathy Kyler for assistance with technical and language editing and proofreading of the manuscript. We also acknowledge the Oklahoma Medical Research Foundation Quantitative Analysis Core for providing statistical analysis that was supported in part by Oklahoma Center of Biomedical Research Excellence (COBRE) grant 1 P30 GM110766-01. Author contributions are as follows: conceptualization: K.B. Shah, D.A. Fields, E.W. Demerath, and J.B. Tryggestad; methodology: K.B. Shah, D.A. Fields, S. Gulati, E.W. Demerath, and J.B. Tryggestad; formal analysis: K.B. Shah and N.P. Pezant; data curation: K.B. Shah, N.P. Pezant, H.K. Kharoud; writing-original draft preparation: K.B. Shah; writing, review and editing: K.B. Shah, D.A. Fields, N.P. Pezant, K. Jacobs, C.A. Gale, E.O. Kharbanda, E.M. Nagel, E.W. Demerath, and J.B. Tryggestad; supervision: D.A. Fields, E.W. Demerath, and J.B. Tryggestad; funding acquisition: K.B. Shah, D.A. Fields, K. Jacobs, and E.W. Demerath. All authors have read and agreed to the published version of the manuscript. This work was supported by Clinician Scientist Development Grant C5121701 from the Presbyterian Health Foundation (K.B. Shah), National Institutes of Health grant 2R01HD080444 (E.W. Demerath and D.A. Fields), and a Faculty Research Development grant from the University of Minnesota Office of Academic Clinical Affairs (K. Jacobs, C.A. Gale, and E.W. Demerath,). Emily Nagel is supported by National Institutes of Health grant T32DK083250.

Funding Information:
This work was supported by Clinician Scientist Development Grant C5121701 from the Presbyterian Health Foundation (K.B. Shah), National Institutes of Health grant 2R01HD080444 (E.W. Demerath and D.A. Fields), and a Faculty Research Development grant from the University of Minnesota Office of Academic Clinical Affairs (K. Jacobs, C.A. Gale, and E.W. Demerath,). Emily Nagel is supported by National Institutes of Health grant T32DK083250.

Publisher Copyright:
© 2022

Keywords

  • breast milk microRNA
  • exosomes
  • infant body composition
  • infant growth
  • maternal gestational diabetes mellitus

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

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