High Prevalence of Type 2 Diabetes and Pre-Diabetes in Adult Offspring of Women With Gestational Diabetes Mellitus or Type 1 Diabetes
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OBJECTIVE—The role of intrauterine hyperglycemia and future risk of type 2 diabetes in human offspring is debated. We studied glucose tolerance in adult offspring of women with either gestational diabetes mellitus (GDM) or type 1 diabetes, taking the impact of both intrauterine hyperglycemia and genetic predisposition to type 2 diabetes into account. RESEARCH DESIGN AND METHODS—The glucose tolerance status following a 2-h 75-g oral glucose tolerance test (OGTT) was evaluated in 597 subjects, primarily Caucasians, aged 18–27 years. They were subdivided into four groups according to maternal glucose metabolism during pregnancy and genetic predisposition to type 2 diabetes: 1) offspring of women with diet-treated GDM (O-GDM), 2) offspring of genetically predisposed women with a normal OGTT (O-NoGDM), 3) offspring of women with type 1 diabetes (O-type 1), and 4) offspring of women from the background population (O-BP). RESULTS—The prevalence of type 2 diabetes and pre-diabetes (impaired glucose tolerance or impaired fasting glucose) in the four groups was 21, 12, 11, and 4%, respectively. In multiple logistic regression analysis, the adjusted odds ratios (ORs) for type 2 diabetes/pre-diabetes were 7.76 (95% CI 2.58–23.39) in O-GDM and 4.02 (1.31–12.33) in O-type 1 compared with O-BP. In O-type 1, the risk of type 2 diabetes/pre-diabetes was significantly associated with elevated maternal blood glucose in late pregnancy: OR 1.41 (1.04–1.91) per mmol/l. CONCLUSIONS—A hyperglycemic intrauterine environment appears to be involved in the pathogenesis of type 2 diabetes/pre-diabetes in adult offspring of primarily Caucasian women with either diet-treated GDM or type 1 diabetes during pregnancy.
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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 [73]
The Results (p. 5) report higher type 2 diabetes/pre-diabetes prevalence and significantly higher BMI in adult offspring exposed to maternal gestational or type 1 diabetes. Higher BMI lends some support to the obesity component, but the paper does not establish obesity as an outcome or report broader cardiometabolic disease risk factors. Its conclusions (pp. 5–6) describe a possible role for intrauterine hyperglycemia rather than establishing that exposure causes these outcomes. (LLM, conf=0.88)
Experimental — accuracy not yet measuredA limited number of studies linked gestational diabetes mellitus exposure to increased cardiovascular disease risk in the offspring.
“A limited number of studies linked GDM exposure to increased CVD risk in the offspring [73,83,84,85,86].”
From Recent Experimental Studies of Maternal Obesity, Diabetes during Pregnancy and the Developmental Origins of Cardiovascular Disease (2022) · cites this paper as [73]
The Results and Conclusions (p. 5) link GDM exposure to increased type 2 diabetes/pre-diabetes risk in adult offspring, not cardiovascular disease (CVD) risk. Searches for CVD and cardiovascular risk found no passage linking GDM exposure to CVD in human offspring; a reference on p. 6 concerns cardiovascular dysfunction in rats. (LLM, conf=0.76)
Experimental — accuracy not yet measuredChildren whose mothers had diabetes in pregnancy are more likely to be obese and have features of insulin resistance than children whose mothers did not have diabetes.
“Compared with children whose mothers did not have diabetes, they were more likely to be obese and have features of insulin resistance, which is felt to be the result of both genetic and intrauterine and postnatal environmental factors.”
From Metformin in Gestational Diabetes: The Offspring Follow-Up (MiG TOFU) (2011) · cites this paper as [20]
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- Authors
- Clausen, T. D., Mathiesen, E. R., Hansen, T., Pedersen, O., Jensen, D. M., Lauenborg, J., & Damm, P.
- Affiliations
- Copenhagen University Hospital (DK)
- Steno Diabetes Center Copenhagen (DK)
- Odense University Hospital (DK)
- ORCID
- Venue
- Diabetes Care
- Publisher
- American Diabetes Association
- Published
- 2008-02-01
- Volume
- 31
- Issue
- 2
- Pages
- 340-346
- ISSN
- 0149-5992 (ISSN-L)
- 1935-5548
- OpenAlex
- W2102302842
- Cited by
- 724
- References
- 35
- Citations by year
- 2026: 25 · 2025: 30 · 2024: 49 · 2023: 46 · 2022: 62 · 2021: 56 · 2020: 41 · 2019: 46 · 2018: 63 · 2017: 38 · 2016: 45 · 2015: 34 · 2014: 31 · 2013: 33 · 2012: 28
- FWCI
- 37.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Diabetes Care (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- University of Southern Denmark Research Portal (University of Southern Denmark) (submittedVersion)
- 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 › Surgery › Pancreatic function and diabetes
- Keywords
- type 2 diabetes, prediabetes, gestational diabetes mellitus, type 1 diabetes, intrauterine hyperglycemia, adult offspring, glucose tolerance, impaired glucose tolerance, impaired fasting glucose
- MeSH terms
- Adult, Denmark, Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Female, Glucose Tolerance Test, Humans, Hyperglycemia, Prediabetic State, Pregnancy, Pregnancy Complications, Regression Analysis, Smoking, Diabetes, Gestational, Genetic Predisposition to Disease, Overweight
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