Frontiers in Endocrinology (May 2018)

Continuous Blood Glucose Monitoring Reveals Enormous Circadian Variations in Pregnant Diabetic Rats

  • Michaela Golic,
  • Michaela Golic,
  • Michaela Golic,
  • Michaela Golic,
  • Michaela Golic,
  • Kristin Kräker,
  • Kristin Kräker,
  • Kristin Kräker,
  • Kristin Kräker,
  • Kristin Kräker,
  • Caroline Fischer,
  • Caroline Fischer,
  • Caroline Fischer,
  • Caroline Fischer,
  • Natalia Alenina,
  • Natalia Alenina,
  • Natalia Alenina,
  • Nadine Haase,
  • Nadine Haase,
  • Nadine Haase,
  • Nadine Haase,
  • Nadine Haase,
  • Florian Herse,
  • Florian Herse,
  • Florian Herse,
  • Florian Herse,
  • Till Schütte,
  • Till Schütte,
  • Wolfgang Henrich,
  • Dominik N. Müller,
  • Dominik N. Müller,
  • Dominik N. Müller,
  • Dominik N. Müller,
  • Dominik N. Müller,
  • Andreas Busjahn,
  • Michael Bader,
  • Michael Bader,
  • Michael Bader,
  • Michael Bader,
  • Ralf Dechend,
  • Ralf Dechend,
  • Ralf Dechend,
  • Ralf Dechend

DOI
https://doi.org/10.3389/fendo.2018.00271
Journal volume & issue
Vol. 9

Abstract

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AimDiabetes 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.MethodsWe 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.ResultsAll 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.InterpretationContinuous 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.

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