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

• Published in: Clinical therapeutics Vol. 44; no. 2; pp. 172 - 185.e1
• Main Authors: Shah, Kruti B., Fields, David A., Pezant, Nathan P., Kharoud, Harmeet K., Gulati, Shelly, Jacobs, Katherine, Gale, Cheryl A., Kharbanda, Elyse O., Nagel, Emily M., Demerath, Ellen W., Tryggestad, Jeanie B.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.02.2022; Elsevier Limited
• Subjects: Abundance; Adipose tissue; Age; Babies; Body composition; Body fat; Body Mass Index; Breast milk; breast milk microRNA; Breastfeeding & lactation; Child; Diabetes mellitus; Diabetes, Gestational - genetics; Dietary supplements; Exosomes; Exosomes - genetics; Exosomes - metabolism; Female; Gestational diabetes; Glucose; Humans; Infant; infant body composition; infant growth; Infants; Insulin; Internal Medicine; maternal gestational diabetes mellitus; Medical records; Metabolism; MicroRNAs; MicroRNAs - genetics; MicroRNAs - metabolism; Milk, Human - metabolism; miRNA; Mothers; Nutrition research; Obesity; Overweight; Polymerase chain reaction; Pregnancy; Questionnaires; Regression analysis; Software; Statistical analysis; Therapeutic targets; Womens health; United States > US; California; maternal gestational diabetes mellitus; GDM; HM; breast milk microRNA; exosomes; miRNA; NW; infant body composition; infant growth; OW/OB; Normal weight; Gestational Diabetes Mellitus; Human milk; microRNA; Overweight/Obese
• ISSN: 0149-2918; 1879-114X; 1879-114X
• DOI: 10.1016/j.clinthera.2022.01.005

•Gestational Diabetes Mellitus is associated with reduced abundance of human milk exosomal microRNAs involved in important metabolic processes.•Highly abundant microRNAs in breast milk (miR-148a and miR-30b) are associated with infant growth and adiposity early in infancy.•Higher maternal diet quality is associated with increased abundance of each of measured miRNAs (miR-148a, miR-30n, miR-let-7a and miR-let-7d).•Human Milk miRNAs may be a therapeutic target to mitigate risk of metabolic outcomes in offspring of women with gestational diabetes mellitus. 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. 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. 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. 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.