Abstract
Diabetes in pregnancy is a major burden with acute and long-term consequences. Its treatment requires adequate diagnosis and monitoring of therapy. Many experimental research on diabetes during pregnancy has been performed in rats. Recently, continuous blood glucose monitoring of non-pregnant diabetic rats revealed an increased circadian variability of blood glucose that made a single blood glucose measurement per day inappropriate to reflect glycemic status. Continuous blood glucose measurement has never been performed in pregnant rats. We wanted to perform continuous blood glucose monitoring in pregnant rats to decipher the influence of pregnancy on blood glucose in diabetic and normoglycemic status. We used the transgenic Tet29 diabetes rat model with an inducible knock down of the insulin receptor via RNA interference upon application of doxycycline (DOX) leading to insulin resistant type II diabetes. All Tet29 rats received a HD-XG telemetry implant (Data Sciences International, USA) that measured blood glucose and activity continuously. Rats were divided into four groups and blood glucose was monitored until end of pregnancy or the corresponding period: Tet29 + DOX (diabetic) non-pregnant, Tet29 + DOX (diabetic) pregnant, Tet29 (normoglycemic) non-pregnant, Tet29 (normoglycemic) pregnant. All analyzed rats displayed a circadian variation in blood glucose concentration. Circadian variability was much more pronounced in pregnant diabetic rats than in normoglycemic pregnant rats. Pregnancy ameliorated variation in blood glucose in diabetic situation. Pregnancy continuously decreased blood glucose during normoglycemic pregnancy. Diabetic rats were less active than normoglycemic rats. We performed a calculation showing that application of continuous blood glucose measurement reduces animal numbers needed to detect a given effect in experimental setting by decreasing variability and SD. Continuous blood glucose monitoring via a telemetry device in pregnant rats provides a more informative picture of the glycemic situation in comparison to single measurements. This could improve diagnosis and therapy of diabetes, decrease animal numbers within experimental settings, and add another physiological parameter (activity) to the analysis that could be helpful in testing therapeutic concepts targeting blood glucose levels and peripheral muscle function. We propose continuous glucose monitoring as a new tool for the evaluation of pregnant diabetic rats.
Highlights
Preexisting diabetes during pregnancy and gestational diabetes are a major burden in modern western countries with increasing incidence
The blood glucose values initially increased in most Tet29 + DOX rats, followed by DOX = Doxycyclin; There is a circadian variation of blood glucose in all four groups with higher values at night. (B) Shown is the mean difference ± SD between mean night and mean day blood glucose during pregnancy or the corresponding period per group
Pregnant Tet29 + DOX rats had a higher difference in night and day blood glucose values than pregnant Tet29 rats, and non-pregnant Tet29 + DOX rats had a higher difference in night and day blood glucose values than non-pregnant Tet29 rats. (C) Shown is the mean difference ± SD between mean night and mean day blood glucose during the different periods of pregnancy or the corresponding periods in non-pregnant rats within the Tet29 + DOX rats
Summary
Preexisting diabetes during pregnancy and gestational diabetes are a major burden in modern western countries with increasing incidence. It causes acute obstetric and neonatal problems [1, 2] and influences offspring health in later life [3, 4]. Human pregnancy is unique and no animal model provides completely comparable features to human reproduction, the rat offers important similarities to human pregnancy such as hemochorial placentation with deeply into the uterus invading trophoblast cells that mediate uterine spiral artery remodeling [7]. This makes the rat an appropriate model to study human pregnancy
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