Improved glycemic control protects the oocytes, but not uterine environment in diabetes, according to researchers from Karolinska Institutet. Their findings based on studies of Swedish registry data, animal models and human samples, are now published in EMBO Reports as the cover story.
Diabetes is a condition in which the blood glucose levels are high. Type 1 diabetes is a type of diabetes where an autoimmune reaction destroys the insulin producing cells in the pancreas, leading to higher levels of blood glucose. Type 1 diabetes normally has its onset in childhood and adolescence, and patients therefore are affected during their reproductive age.
Previous studies have identified that when blood glucose levels are very high, the oocytes are affected which causes metabolic dysfunction in their offspring. However, treatment options have steadily improved over time, and it is now less common for patients to have bad control over their blood glucose levels. Hence, there is a need to investigate the effects of appropriately managed blood glucose levels on mothers with diabetes.
Used registry data
In this study, the researchers first used Swedish registry data to confirm that the proportion of patients with appropriate blood glucose levels is steadily increasing. Therefore, the authors optimized a well-used mouse model for the study of diabetes reflecting appropriately managed blood glucose levels. Thereafter, the oocytes from female mice were analyzed to identify potential alterations under a long period of maternal diabetes. Oocytes from human donors were also collected for culture to mimic maternal diabetes with different glucose levels. Moreover, the mouse model was used to mate with healthy male mice, and the embryo development and placenta function were analyzed.
“By optimizing the mouse model, we can now investigate the long-term effects of the appropriately managed state of diabetes, which is understudied to this date. As this patient group continues to grow due to improvement in treatment options, these are highly relevant medical questions”, says , MD, Ph.D. student and the first author of this study.
The results show that appropriate management of blood glucose could protect the oocytes, as no alterations were found in these experiments. However, the fetal development was still compromised, which was associated with hypoxia and placental dysfunction.
“Our findings highlight the need for appropriate disease management before pregnancy, in order to protect the germline from blood glucose-induced alterations. This could serve as an important motivating factor for young female patients with T1D to strive for good disease management. However, we also highlight the need for further additional interventions during pregnancy to prevent the placental dysfunction that is still seen in appropriately managed T1D.”, says , Associate Professor and the corresponding author of this paper.
Following these findings, the authors are now collecting the offspring from these female mice. They will continue to study metabolic function in male and female offspring along the longitudinal development to understand if there is sex dimorphic effects.
Qiaolin Deng is Wallenberg Academy Fellow and this study was financed by the Swedish Research Council, Diabetesfonden, Barndiabetesfonden, and Karolinska Institutet. The authors have reported no potential conflicts of interest.
Publication
“Appropriate glycemic management protects the germline but not the uterine environment in hyperglycemia”, Allan Zhao, Hong Jiang, Arturo Reyes Palomares, Alice Larsson, Wenteng He, Jacob Grünler, Xiaowei Zheng, Kenny A. Rodriguez Wallberg, Sergiu-Bogdan Catrina, Qiaolin Deng, EMBO Reports, online March 15, 2024.
