Maternal Hyperglycemia and Adult Offspring Overweight and Obesity: Is Birthweight a Mediator? | Retrospective Longitudinal Cohort study | 132 patients w/insulin-dependent diabetes during pregnancy | Pregnancy cohort (PPG): 1978–1995 | Adult offspring follow-up (TEAM Study): 2017–2023 | Key Findings: | Third-trimester maternal hyperglycemia = strongest association with higher adult offspring BMI | Birthweight did NOT mediate the relationship between maternal blood sugar and adult obesity. | Higher birthweight independently increased the risk of adult overweight and obesity. | Key takeaway: Maternal glucose control during pregnancy may have lifelong effects on a child's obesity risk—and those effects aren't explained simply by how much the baby weighs at birth. | @LizzyPAC8 | @globalcastmd | @StayCurrentMD | Cincinnati Children's | https://pubmed.ncbi.nlm.nih.gov/42049055/ | McWhorter KL et. al. | Department of Epidemiology and Environmental Health, University of Kentucky, United States
Maternal Hyperglycemia and Adult Offspring Overweight and Obesity: Is Birthweight a Mediator?
Infographic · Jul 2026 · 1 min read
In brief
In brief
Longitudinal cohort study spanning 1978-2023 found that third-trimester maternal glycemic control in women with insulin-dependent diabetes independently predicts adult offspring obesity, but this relationship is not mediated by birthweight. Findings emphasize the importance of trimester-specific glucose monitoring and suggest direct metabolic programming pathways beyond fetal growth effects.
- Third-trimester maternal HbA1c shows strongest association with adult offspring BMI, independent of maternal BMI and gestational weight gain.
- Birthweight does not mediate the relationship between maternal hyperglycemia and adult offspring obesity in insulin-dependent diabetes.
- Birthweight has independent direct effect on adult BMI but does not explain the maternal glycemia-offspring obesity pathway.
- Trimester-specific glucose variability patterns matter more than birthweight alone in predicting long-term metabolic outcomes.
- Maternal glycemic control during pregnancy has transgenerational effects on obesity risk extending into adult offspring life.
Written by the GCMD Library team from the infographic.
The infographic uses a teal header, gray content blocks, and a yellow footer. A clock icon represents the longitudinal study design, while an illustration of a pregnant woman in an orange dress anchors the left side. Key findings are presented in three colored boxes (teal, purple, and orange) with white text. A glucose meter icon appears in the top right corner.
Ketrell L McWhorter, Grace Wells, Katherine Bowers, Suzanne Summer, Lawrence Dolan, Patrick Catalano, Rhonda D Szczesniak, Mekibib Altaye, Barak Rosenn, Jane C Khoury, Shelley Ehrlich
Objectives: We and others have shown that maternal hyperglycemia during pregnancy in women with insulin-dependent diabetes mellitus (IDDM) influences fetal growth. Less is understood regarding how trimester-specific glycemic patterns, particularly glucose variability, shape offspring obesity risk across the life course and whether this is mediated by birthweight. Leveraging data from the Diabetes in Pregnancy Program Grant (PPG; 1978-1995) and the Transgenerational Effects on Adult Morbidity (TEAM Study; 2017-2023) cohort, we aimed to evaluate whether the association between maternal glycemic control and adult offspring obesity status was mediated in part through infant birthweight.
Study design: Maternal glycohemoglobinA1 levels were collected monthly during pregnancy and harmonized across laboratories using standard deviation units (HbA1SD). Functional principal component analysis characterized patterns in blood glucose level and variability. TEAM Study participants, adult offspring of PPG women, completed in-person or online assessments (via Zoom) of body anthropometrics. Linear mixed-effects models and generalized estimating equations estimated associations between maternal glycemia and adult offspring outcomes. Classical mediation methods tested whether birthweight mediated observed relationships.
Results: Consistent with prior findings, third-trimester HbA1SD demonstrated the most consistent positive associations with adult offspring body mass index (BMI) outcomes, after adjustment for maternal BMI at last menstrual period, maternal education, gestational weight gain, and sex of offspring (for offspring weight only). There was no evidence that birthweight mediated the relationship between maternal glycemic patterns and adult offspring overweight and obesity; however, birthweight exhibited an independent direct effect on adult offspring BMI in fully adjusted models.
Conclusion: Infant birthweight was not shown to be a mediator in the association of maternal gestational glycemic control and overweight/obesity in adult offspring of women with IDDM. Although birthweight does not appear to mediate these long-term associations, the findings underscore the importance of trimester-specific evaluation of blood glucose level and variability, motivating further investigation into transgenerational metabolic risk pathways.
The text in the image
Educational content from recorded physician discussions — not medical advice. Talk to your (or your child's) care team about your situation.