Dysregulated metabolic pathways in late pregnancy tied to higher type 2 diabetes incidence
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Key takeaways:
- Some amino and fatty acid dysregulations in late pregnancy were associated with type 2 diabetes risk.
- Dysregulated amino acids raised type 2 diabetes risk while dysregulated fatty acids and lipids lowered risk.
SAN ANTONIO — Dysregulated amino and fatty acid metabolism during late pregnancy was tied to elevated incidence of type 2 diabetes among women with a history of gestational diabetes, according to a presentation at ObesityWeek.
“Women who have gestational diabetes have over two times [the] risk for developing type 2 diabetes after their delivery compared to the normal population. In our previous research, we have conducted several cohort studies for justification for diabetes in women and looked for some common, known risk factors and how it’s forming these women’s high risk of developing type 2 diabetes,” Zhanghua Chen, PhD, assistant professor of population and public health sciences at the Keck School of Medicine at the University of Southern California, said during the presentation. “However, one interesting question to me is whether we can find some early biomarkers that could predict the gestation of diabetes in children who may have increased risk of type 2 diabetes because we know that not all women with gestational diabetes will have type 2 diabetes.”
Chen and colleagues followed 102 pregnant women with gestational diabetes from an existing cohort of women with gestational diabetes enrolled around 1992 from the third trimester to 12 years postpartum. Researchers performed oral glucose tolerance tests every 12 to 15 months until type 2 diabetes development, loss to follow-up or study end. Type 2 diabetes was defined as a fasting glucose concentration of 126 mg/dL or higher or 2-hour glucose of 200 mg/dL or higher.
Overall, researchers collected 561 samples with 9,524 features. A total of 53 women developed type 2 diabetes during the study period.
In the metabolic analysis, researchers observed arginine and proline metabolism, glycine, serine, alanine and threonine metabolism, lysine metabolism, de novo fatty acid biosynthesis and keratan sulfate degradation as the most significant dysregulated pathways among women with type 2 diabetes.
Dysregulated arginine, proline, urea cycle/amino group, alanine and aspartate were associated with higher type 2 diabetes incidence, Chen said during the presentation.
Conversely, C21-steroid hormone biosynthesis and metabolism and de novo fatty acid biosynthesis were associated with lower risk for type 2 diabetes, she said.
During late pregnancy, higher levels of some animo acids were associated with higher 2-hour glucose and lower beta-cell function at 15 to 60 postpartum months, while higher levels of fatty acids and lipids were associated with lower fasting 2-hour glucose and higher insulin sensitivity, Chen said.
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Chen Z. Oral-010. Presented at: ObesityWeek; Nov. 3-6, 2024; San Antonio.
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