Association of Gestational Diabetes and Type 2 Diabetes Exposure In Utero With the Development of Type 2 Diabetes in First Nations and Non–First Nations Offspring
Open accessAbstract
Importance: Type 2 diabetes is increasing worldwide, disproportionately affecting First Nations (FN) people. Identifying early-life determinants of type 2 diabetes is important to address the intergenerational burden of illness. Objective: To investigate the association of in utero exposure to gestational diabetes and type 2 diabetes, stratified by FN status, with the development of type 2 diabetes in offspring. Design, Setting, and Participants: This cohort study was derived from the linkage of a pediatric diabetes clinical database and a population-based research data repository in Manitoba, Canada. Mother-infant dyads with a hospital birth or midwifery report in the data repository between April 1, 1984, and April 1, 2008, were identified. The dates of analysis were August through December 2017. Children identified with type 1 diabetes, monogenic diabetes, or secondary diabetes were excluded. Exposures: Primary exposures included maternal gestational diabetes or type 2 diabetes and FN status. Main Outcomes and Measures: The primary outcome was incident type 2 diabetes in offspring by age 30 years. Results: In this cohort study of 467 850 offspring (mean follow-up, 17.7 years; 51.2% male), FN status and diabetes exposure were associated with incident type 2 diabetes in offspring after adjustment for sex, maternal age, socioeconomic status, birth size, and gestational age. Type 2 diabetes exposure conferred a greater risk to offspring compared with gestational diabetes exposure (3.19 vs 0.80 cases per 1000 person-years, P < .001). Compared with no diabetes exposure, any diabetes exposure accelerated the time to the development of type 2 diabetes in offspring by a factor of 0.74 (95% CI, 0.62-0.90) for gestational diabetes and a factor of 0.50 (95% CI, 0.45-0.57) for type 2 diabetes. First Nations offspring had a higher risk compared with non-FN offspring (0.96 vs 0.14 cases per 1000 person-years, P < .001). First Nations offspring had accelerated type 2 diabetes onset by a factor of 0.52 (95% CI, 0.49-0.55) compared with non-FN offspring. Neither interaction between FN and type 2 diabetes (0.92; 95% CI, 0.80-1.05) nor interaction between FN and gestational diabetes (0.97; 95% CI, 0.77-1.20) was significant (P = .21 and P = .75, respectively). Conclusions and Relevance: Important differences exist in offspring risk based on type of diabetes exposure in utero. These findings have implications for future research and clinical practice guidelines, including early pregnancy screening and follow-up of the offspring.
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Diabetes during pregnancy predisposes offspring for the development of obesity, type 2 diabetes and cardiometabolic disease risk factors.
“Diabetes during pregnancy also predisposes offspring for the development of obesity, T2D and cardiometabolic disease risk factors [33,70,71,72,73,74,75,76,77] (Figure 1).”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [71]
The Discussion reports that diabetes during pregnancy is associated with offspring type 2 diabetes, and the introductory passage labelled Abstract describes childhood obesity as a risk associated with maternal diabetes. The paper does not report offspring cardiometabolic disease risk factors as an outcome, and its observational findings do not establish causation. Page numbers are unavailable in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredIn utero exposure to hyperglycaemia is associated with long term cardiometabolic risks in the baby, including diabetes and obesity.
“In utero exposure to hyperglycaemia is also associated with long term cardiometabolic risks in the baby, including diabetes and obesity. 8 , 9 , 10”
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Identifying Type 2 Diabetes Risk at Birth: A New Frontier for Early Prevention
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Prevalence of youth type 2 diabetes in global Indigenous populations: a systematic review
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Diagnosis of Gestational Diabetes: More Questions Than Answers
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Vitamin D Prevents Gestational Diabetes Mellitus via Modulating Glucose Metabolism in a Mouse Model
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Vitamin D prevents gestational diabetes mellitus via modulating glycometabolismPreprint
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Self-citation
- Authors
- Wicklow, B. A., Sellers, E. A. C., Sharma, A. K., Kroeker, K., Nickel, N. C., Philips-Beck, W., & Shen, G. X.
- Affiliations
- Children's Hospital Research Institute of Manitoba (CA)
- University of Manitoba (CA)
- George & Fay Yee Centre for Healthcare Innovation (CA)
- Nanaandawewigamig, First Nations Health and Social Secretariat of Manitoba, Winnipeg, Manitoba, Canada
- Corresponding author
- Wicklow, Brandy A.
- ORCID
- Venue
- JAMA Pediatrics
- Publisher
- American Medical Association (AMA)
- Published
- 2018-08-01
- Volume
- 172
- Issue
- 8
- Pages
- 724
- ISSN
- 1072-4710 (ISSN-L)
- 2168-6203
- PMC
- PMC6142931
- OpenAlex
- W2808406323
- Cited by
- 88
- References
- 30
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 15 · 2023: 10 · 2022: 14 · 2021: 5 · 2020: 9 · 2019: 8 · 2018: 2
- FWCI
- 6.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Archives of Pediatrics and Adolescent Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Keywords
- gestational diabetes mellitus, maternal type 2 diabetes, prenatal exposure, First Nations, offspring diabetes risk, socioeconomic status, birth size, gestational age, sex differences in diabetes risk, health equity
- MeSH terms
- Adolescent, Adult, Canada, Child, Child, Preschool, Diabetes Mellitus, Type 2, Female, Humans, Indians, North American, Infant, Infant, Newborn, Male, Pregnancy, Prenatal Exposure Delayed Effects, Cohort Studies, Diabetes, Gestational, Risk Assessment
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