1.       Introduction

Oral Glucose Tolerance Test (OGTT) is widely used in clinics to diagnose for the Impaired Glucose Tolerance (IGT) and/or type-2 DM (T2DM) [1]. Recently, the risk of transient postprandial hypoglycemia in patients with Non-Alcoholic Fatty Liver Disease (NAFLD) has also been identified using OGTT [2]. Moreover, non-alcoholic steatohepatitis (NASH) linked with T2DM has been focused, because a high prevalence of NASH (56.49%) observed in patients with T2DM with duration of more than 5 years [3]. Therefore, application of OGTT for diagnosis of NAFLD or NASH without overt T2DM is also performed in clinical practice.

In basic research, OGTT is also used in animal studies focusing on glucose homeostasis in main. Insulin Resistance (IR) or insulin sensitivity has ever been characterized in animals using the data named glucose-insulin index obtaining from OGTT [4]. Additionally, OGTT has also been used as a model to mimic the postprandial state of hyperglycemia, which may provide information on the glucose-lowering effect as a consequence of changes in glucose utilization [5]. Generally, OGTT or meal tolerance test mimics the glucose and insulin dynamics under physiological conditions more closely than glucose clamp or insulin sensitivity test in animal studies. The postprandial rise in plasma insulin enables appropriate disposal of blood glucose in the absorptive state, while the fall in plasma insulin contributes to keeping the glucose homeostasis in the post-absorptive state and during the starvation. Therefore, it is not suitable to ignore the blood insulin level, which indicated the ability of pancreatic β-cells in response to plasma glucose. Moreover, some limitations for application of OGTT in animal studies shall be concerned.

First, results are easily affected by many physiological and environmental factors in addition to the pathological conditions. Therefore, an adequate experience of the test is important to avoid the bias in animal studies of OGTT. Next, anesthesia is another factor that may influence the data of OGTT, such as isoflurane has been documented to inhibit OGTT [6].

In addition to the dynamic response of β cells, many factors are known to involve in the response of OGTT including the total Glucagon-Like Peptide 1 (GLP-1), Glucose-Dependent Insulinotropic Polypeptide (GIP), and pancreatic polypeptide. Thus, application of OGTT in the understanding of impaired glucose tolerance in animals is useful, but it seems still limited in the study of glucose utilization in T2DM without another indicator(s).

The 4th limitation is that diabetic disorders are known to be progressive [7] in addition to the variations between rodents and human subjects [8]. Impaired glucose tolerance is mostly reflected in a larger incremental Area Under the Curve (AUC) of the plasma glucose disappearance curve during OGTT. Results in OGTT showed a marked increase in AUC0-120 min from the diabetic group indicating the success of the diabetic model. Then, diabetic animals were used to treat with the test substance, either herbal extract or nutrient. Once the slope of the glucose disposal phase is markedly increased and AUC is more decreased than the vehicle-treated control, it means that the test substance has an ability to alleviate the impaired glucose tolerance. However, researcher(s) did not concern the differences between patients and diabetic animals. Then, the obtained results are not easy to link with clinical applications.

Interestingly, a test substance usually induced the attenuation of AUC from OGTT in animal studies when it has the ability to enhance glucose utilization [9]. However, results from a marked reduction in AUC only using OGTT are not enough to support the conclusion indicating increased glucose utilization as the action mechanism for test substance because the a-glucosidase inhibitor-like action may result in the same changes [10]. Therefore, more studies are basically required, such as insulin-tolerance test, glucose uptake, glycolysis and others [11].

Finally, the basal glucose level in each group that received treatment with test substance was not the same during OGTT. Similarly, the basal glucose level is also significantly varied in mutant mice from the wild-type littermates [12]. It can be criticized that glucose tolerance is changed due to the difference in basal glucose level. Correction of the data in basal glucose level has been suggested [12]. But no paper ignored the values of basal glucose level in OGTT during the calculation of AUC. Therefore, scientific evidence for the important role of basal glucose level showing at the 0 min during OGTT is required.

2.       Conclusion

Taken together, OGTT applied in the clinic is also useful in animal studies while the diagnosis of diseases is not included in the basic research. The impaired glucose tolerance in animals is the main target used in basic studies. However, many limitations observed in the application of OGTT in animal studies. We indicate six factors as potential limitations as a reference in the current report.

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