Archives of Medical Science (Jan 2020)

Comparison of area under the curve in various models of diabetic rats receiving chronic medication

  • Keng-Fan Liu,
  • Chiang-Shan Niu,
  • Jen-Chieh Tsai,
  • Chao-Lin Yang,
  • Wen-Huang Peng,
  • Ho-Shan Niu

DOI
https://doi.org/10.5114/aoms.2019.91471
Journal volume & issue
Vol. 18, no. 4
pp. 1078 – 1087

Abstract

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Introduction The oral glucose tolerance test (OGTT) is widely used as a diagnostic tool for impaired glucose tolerance (IGT) in clinical settings and animal experiments. The area under the curve (AUC) is then developed to quantify the total increase in blood glucose during the OGTT. Similarly, attenuation of the increased AUC indicates the improvement of IGT in animals. Variations in fasting plasma glucose between individuals stimulate the development of incremental area under the curve (iAUC). However, the iAUC determined from subtracting the baseline value of fasting plasma glucose (similar to ΔAUC) has been challenged as problematic without evidence. Material and methods We developed four different diabetic animal models. In each model, rats were treated with metformin, dapagliflozin, and insulin respectively for one week. OGTTs were performed after 7 days of the drug treatment. The acute blood glucose changes induced by one-time treatment of drugs were also compared. Results After a daily application of each drug at an effective dose for 7 days, results indicated potency in the following order: insulin > dapagliflozin > metformin. This was determined by calculation using the AUC in all diabetic models. However, the order changed when using the calculation with iAUC. Additionally, signals were changed before the OGTT in each model that received repeated treatment of each drug. Notably, drug potency was shown to be the same in OGTT calculated from iAUC and AUC in diabetic rats receiving acute treatment. Conclusions iAUC seems unsuitable for application in cases where subjects are receiving chronic medication(s).

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