The main findings of this study were that GP tea exerted a significant antidiabetic effect and that this was accounted for by enhanced insulin sensitivity.
The placebo group and the GP group did not differ in baseline characteristics and diabetic parameters (drug-naïve T2D, HbA1C, and FPG). The GP tea was mainly responsible for the reduction of the glucose levels because all patients received similar diet and exercise therapies, with minor effect on FPG in the control group. The major antidiabetic role of GP tea was also proven by the reduction of the FPG and the glucose responses to insulin during SIGIT after GP treatment with reversed effect after switching to placebo treatment, whereas the plasma insulin during SIGIT did not change after GP tea treatment in our study population.
We assessed insulin sensitivity by SIGIT, during which the endogenous production of insulin and C-peptide is inhibited by a simultaneous infusion of somatostatin and insulin. Serum glucose levels during the last part of a SIGIT are used as a measure of the sensitivity to insulin in each individual. Achievement of a continuous suppression of plasma C-peptide levels during SIGIT guarantees that glucose disappearance is governed by the infused and not by endogenously secreted insulin. Insulin sensitivity measured with SIGIT is significantly correlated with M
values obtained during hyperinsulinemic euglycemic clamp, which is a “gold standard” in measuring insulin sensitivity [20
]. In a previous study, endogenous C-peptide concentrations, reflecting insulin secretion during SIGIT, were almost entirely abolished by somatostatin [18
]. In addition, in our previous study we showed that the glycometabolic improvement was achieved without any major change of circulating insulin and C-peptide levels [11
]. Thus, our present results are in agreement with our previous findings by GP tea [10
] and indicate that the decrease in blood glucose levels is explained by the improvement in insulin sensitivity. According to our previous studies in twelve weeks, HOMA-IR decreased significantly after GP tea treatment [10
]. This observation, combined with the present results, suggests that GP tea provides improved glycemic control via a mechanism that does not involve stimulation of insulin release and thus does not place any additional burden on defective β
-cells. An effect by GP tea on insulin sensitivity may be accounted for by suppression of PTP-1B activity by dammarane compounds in the GP tea [22
]. PTP-1B is present in liver and skeletal muscle and has been shown to negatively modulate insulin's action on hepatic glucose metabolism through tyrosine dephosphorylation of the insulin receptor and/or insulin receptor substrates. Interestingly, a recent experimental study demonstrated that an ethanol extract of GP, produced in Vietnam, inhibited protein tyrosine phosphatase 1B activity, which may lead to enhanced insulin sensitivity and thereby improved glucose tolerance [22
In this study, green tea (Camellia sinensis
) was used as a placebo compound. Green tea was reported to induce antihyperglycemic effect in mice and streptozotocin-diabetic rats [23
], but there is little evidence that it improves glycemic control substantially in human type 2 diabetes [24
In the GP group, the liver and renal function tests were normal during the study period. This finding was in accordance with our previous results [10
] and was evidence for the biosecurity of using GP tea as an antihyperglycemic treatment. This notion is supported also by a study in rats where no signs of chronic toxicity were found after 6-month administration of rather high GP extract doses (up to 0.75
g/kg per day) [26
]. During the study, no patient experienced symptoms of hypoglycemia.
This trial only enrolled a modest number of patients; larger and longer trials are needed to assess, with higher accuracy, the prevalence of possible adverse effects. In addition, further research is needed to determine the durability of GP extract's antidiabetic effect, as well as effects on patient-reported outcomes, morbidity, and mortality.