A new study on gestational diabetes conducted by researchers at the University of Helsinki, together with colleagues at Massachusetts General Hospital and the Broad Institute of Harvard and MIT, provides significant advances in our understanding of the genetics underlying the condition.
The results of research were published in Nature.
Gestational diabetes: improved genetic understanding
Gestational diabetes is a common pregnancy disorder affecting more than 16 million pregnancies worldwide each year, with substantial implications for the health of both mothers and their children. It is characterized by high blood sugar levels in pregnant women who did not have diabetes before pregnancy.
Despite the fact that gestational diabetes constitutes a major global health problem, there is very little research on its molecular causes.
The now published study is the largest genome-wide association study of gestational diabetes conducted to date, including more than 12,000 patients and 131,000 female controls from the Finnish genomics initiative FinnGen.
This groundbreaking research has nearly tripled the number of known genetic areas associated with gestational diabetes, identifying a total of 13 distinct chromosomal regions linked to the condition.
Using recently developed analysis methods, researchers were able to demonstrate that there are two distinct classes of genetic variants linked to gestational diabetes: those shared with type 2 diabetes and those predominantly associated only with the gestational form of diabetes.
“Our findings suggest that gestational diabetes has a unique genetic basis that is partially separate from type 2 diabetes, challenging previous hypotheses about the shared genetic basis of the two conditions,” says Dr. Elisabeth Widén of the Institute for Molecular Medicine Finnish (FIMM), University of Helsinki, who conducted the study.
The study results also provide important information on potential physiological mechanisms linked to the development of diabetes during pregnancy. These mechanisms involve adaptive changes in the brain, as well as altered insulin sensitivity in the mother.
The hypothalamus has emerged as a key target, with some of the identified risk genes active in brain cell types known to be important for adaptive responses to maintain blood sugar regulation during pregnancy.
“Biobank-based studies like FinnGen, with in-depth and ongoing clinical data, facilitate large-scale studies of many reproductive and female health phenotypes where research funding has been sorely lacking,” said Dr. Mark Daly, former director from FIMM and a genetic researcher from Massachusetts General Hospital and the Broad Institute who jointly supervised the study. “It is exciting to see this work bear fruit in important and understudied diseases.”
Although the study focused primarily on the Finnish population, the findings have broader implications. Most risk variants are common, highlighting the potential relevance of these findings to diverse populations at risk for gestational diabetes.
By putting the spotlight on a very common pregnancy disorder that has remained understudied for years, the work is of great relevance to women's health in general. Furthermore, the findings improve the overall understanding of dysregulation of glucose metabolism in a broader context.
“By providing new data on critical genetic factors and pathways, our study has the potential to transform attitudes and approaches not only toward gestational diabetes research, but also toward research targeting pregnancy-related health outcomes in general, ultimately benefiting of the health of mothers and their newborns”, concludes Dr. Widén.
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