Continuous Blood Glucose Monitoring Reveals Enormous Circadian Variations in Pregnant Diabetic Rats
Continuous Blood Glucose Monitoring Reveals Enormous Circadian Variations in Pregnant Diabetic Rats
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DOI：
10.3389/fendo.2018.00271
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发表时间：
2018-05-29
影响因子：
5.2
通讯作者：
Dechend, Ralf
中科院分区：
文献类型：
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作者：
Golic, Michaels;Kraker, Kristin;Dechend, Ralf
目的：妊娠期糖尿病是一种具有急性和长期后果的主要负担。其治疗需要充分的诊断和治疗监测。许多关于妊娠期糖尿病的实验研究已经在大鼠身上进行了。最近，对未怀孕的糖尿病大鼠的连续血糖监测显示，血糖的昼夜变异性增加，使得每天一次血糖测量不适合反映血糖状态。在怀孕大鼠中从未进行过连续血糖测量。我们想对妊娠大鼠进行持续的血糖监测，以破译妊娠对糖尿病和正常血糖状态的血糖的影响。方法：采用转基因Tet29糖尿病大鼠模型，应用多西环素（DOX）诱导胰岛素受体通过RNA干扰下调，导致胰岛素抵抗型II型糖尿病。所有Tet29大鼠均接受HD-XG遥测植入物（Data Sciences International， USA），连续测量血糖和活动。将大鼠分为Tet29 + DOX（糖尿病）未妊娠、Tet29 + DOX（糖尿病）妊娠、Tet29（正常血糖）未妊娠、Tet29（正常血糖）妊娠四组，监测血糖至妊娠结束或相应时期。结果：所有分析的大鼠血糖浓度均呈现昼夜变化。与血糖正常的妊娠大鼠相比，妊娠糖尿病大鼠的昼夜节律变异性更为明显。妊娠可改善糖尿病患者的血糖变化。正常妊娠期间持续降低血糖。糖尿病大鼠比血糖正常的大鼠活动少。我们进行了一项计算，显示连续血糖测量的应用减少了解释：与单次测量相比，通过遥测设备对怀孕大鼠进行连续血糖监测提供了更有信息的血糖状况。这可以改善糖尿病的诊断和治疗，减少实验环境中的动物数量，并在分析中增加另一个生理参数（活动），这可能有助于测试针对血糖水平和外周肌肉功能的治疗概念。我们建议将连续血糖监测作为评估妊娠糖尿病大鼠的新工具。
Aim: 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.Methods: 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.Results: Allanalyzed 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 reducesInterpretation: 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.