Most of the subjects in this study were male, similar to a previous study completed by Soewondo et al.17 which identified male gender as a prediction factor for prediabetes in Indonesia (OR 0.8). This finding was due to that most of the subjects screened were taxi drivers (57.60%). Most of the prediabetes subjects was in obesity and overweight condition. The study by Sirait et al.18 found that risk of T2DM in mild obesity was two times greater, in moderate obesity was five times greater, while severe obesity was ten times greater than in non-obese individuals. Waist circumference was also showed to be greater in prediabetes subject compared to healthy subjects. From the description of the characteristics, it can be concluded that cardiovascular risk factors were more common found in the prediabetes subjects. According to the study of Michaliszyn et al.19 beta cell glucose sensitivity decreased 30% in prediabetes and 65% in T2DM. Similar condition with the incretin effect that decrease 32% in prediabetes and 38% in T2DM.
Effects of sambiloto (Andrographis paniculata) extract on GLP-1 and DPP-4 enzyme levels
This study showed that administration of sambiloto extract in healthy subjects increased GLP-1 level, but the increasing GLP-1 level also occurred in the placebo group. These findings indicate that an increased GLP-1 level is not caused by sambiloto effect, but other confounding factors such as the physiological response of postprandial glucose test with 75 gram of oral glucose solution.
The administration of sambiloto extract in the prediabetes subjects increased GLP-1 levels by 19.6% and was statistically significant when compared with placebo (p = 0.043). These results were similar to the study of Purnomo et al. in diabetic rats given Urena lobata, herbs contains flavonoids that can increase GLP-1 level.11
This study found an increasing of DPP-4 enzyme levels in both healthy and prediabetes subjects. The purpose of testing DPP-4 enzyme levels in this study was to show that the mechanism of action of sambiloto extract was through the GLP-1 pathway and not through the inhibition of DPP-4 enzyme. If the sambiloto extract worked through the DPP-4 enzyme inhibition, it was expected that there will be a decrease of the enzyme.12 In this study we found an increasing of GLP-1 and DPP-4 enzymes, therefore it could be concluded that the sambiloto extract works through the GLP-1 pathway and not through the inhibition of DPP-4 enzyme. This result was in accordance with the study conducted by Riyanti that the Andrographis paniculata extract only inhibits the DPP-4 enzyme by 37%, while other plants such as Trigonella foenum-graecum L can inhibit the DPP-4 enzyme by 71%.13
Effects of sambiloto (Andrographis paniculata) extract on fasting insulin levels and HOMA-IR
The fasting insulin levels increased after administration of sambiloto extract and placebo in the healthy subjects. This result was in line with the increasing HOMA-IR in the healthy subjects which reflects an insulin resistance status. In healthy subjects insulin resistance status can change rapidly because of many factors such as physical activity, food intake consumed, psychological condition, the presence of other metabolic stresses, and hormonal changes associated with glucose and insulin homeostasis.
In the prediabetes subjects, fasting insulin levels had no change after the administration of sambiloto extract, however there was a decrease of HOMA-IR. In contrast, the administration of placebo increased the fasting insulin level but also followed by a decrease of HOMA-IR. These findings suggesting the improvement of insulin resistance could be followed by the decreasing level of fasting insulin. This finding similar with study in diabetes rats that andrografolid can ameliorate HOMA-IR .14
Effect of sambiloto (Andrographis paniculata) extract on 2-hour postprandial insulin level
Two-hour postprandial insulin level was decreasing followed by a decrease of blood glucose level after intervention sambiloto and placebo in healthy subjects. A decrease in insulin levels in this study was not necessarily followed by an increase of blood glucose levels due to many confounding factors such as counterregulatory hormones, peripheral glucose uptake, and insulin levels in the blood.15
There was a decrease of 2-hours postprandial insulin levels followed by an increase of 2-hours postprandial blood glucose levels after intervention sambiloto and placebo in prediabetes subjects, therefore suggesting a decrease in insulin would further increase the level of blood glucose. A decrease in postprandial insulin levels was not appropriate as there was an increase of GLP-1 level in prediabetes subjects. It was difficult to answer this discrepancy due to the unavailable serial examinations of the blood glucose, GLP-1, and insulin levels. A serial examination would demonstrate the dynamics of each parameter, therefore we can observe the exact interactions between the three parameters. There were some factors that can influence the postprandial insulin level, such as a standardized daily calorie intake, physical activity before the examination, and psychological factors of the subject. Those factors were not standardized in this study.16–18
Effects of sambiloto (Andrographis paniculata) extract on glycemic control
In both groups, healthy and prediabetes, there was a decrease in the glycated albumin for 14 day of treatment. However, the changes were not statistically significant when compared to placebo. This finding suggested that during treatment the average blood glucose level was decreasing.
In healthy subjects, there was an increase in fasting blood glucose in both interventions. This finding suggested that in healthy subjects, the homeostasis of blood glucose is still adequate to compensate any changes of hormonal condition. In prediabetes subjects, the fasting blood glucose also decreased in both interventions and consistent with a decrease in glycated albumin. This finding was similar with a study in prediabetes rats which was given Psidium guajava, the herbs that contains flavonoid.19 Another study explained that andrographolide can inhibit gluconeogenesis, subsequently followed by a decreased of fasting blood glucose.20
In healthy subject found the decrement of 2-hour postprandial blood glucose after intervention either sambiloto extract or placebo. Contrary in prediabetes subject there was a decrease of 2-hour postprandial insulin followed by increasing of 2-hour postprandial blood glucose. This finding was unexpected because there was the increment of GLP-1 after receiving sambiloto intervention. The explanation of this phenomenon was possibly due to the GLP-1 resistance in prediabetes, in which GLP-1 failed to stimulate the production of insulin, therefore followed by the increased in 2-hour postprandial level of blood glucose. Many studies reported GLP-1 resistance in prediabetes and T2DM, therefore one method of diabetes treatment today is to increase incretin effect.21,22