Hindawi Publishing Corporation
Journal of Nutrition and Metabolism
Volume 2013, Article ID 765383, 7 pages
Gynostemma pentaphyllum Tea Improves Insulin Sensitivity in
Type 2 Diabetic Patients
V. T. T. Huyen,1,2,3D. V. Phan,2P. Thang,3N. K. Hoa,4and C. G. Östenson1
1Endocrine and Diabetes Unit, Department of Molecular Medicine and Surgery, Karolinska Institute, Karolinska University Hospital,
SE 17176 Stockholm, Sweden
2Hanoi Medical University, Hanoi 1000, Vietnam
3Department of Endocrinology and Diabetes, National Institute of Gerontology, Hanoi 1000, Vietnam
4Department of Internal Medicine, University of Manitoba, Winnipeg, MB, Canada R3T 2N2
Correspondence should be addressed to V. T. T. Huyen; email@example.com
Received 10 July 2012; Revised 6 December 2012; Accepted 11 December 2012
Academic Editor: Maurizio Muscaritoli
Copyright © 2013 V. T. T. Huyen et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Aims. To evaluate the effect of the traditional Vietnamese herb Gynostemma pentaphyllum tea on insulin sensitivity in drug-na¨ ıve
type 2 diabetic patients. Methods. Patients received GP or placebo tea 6g daily for four weeks and vice versa with a 2-week wash-
out period. At the end of each period, a somatostatin-insulin-glucose infusion test (SIGIT) was performed to evaluate the insulin
sensitivity. Fasting plasma glucose (FPG), HbA1C, and oral glucose tolerance tests and insulin levels were measured before, during,
and after the treatment. Results. FPG and steady-state plasma glucose (SIGIT mean) were lower after GP treatment compared to
placebo treatment (푃 < 0.001). The levels of FPG in the control group were slightly reduced to 0.2 ± 1.5 versus 1.9 ± 1.0mmol/L
pressure, and no reported hypoglycemias or acute adverse effects regarding kidney and liver parameters. Conclusion. The results of
this study suggested that the GP tea exerted antidiabetic effect by improving insulin sensitivity.
in GP group (푃 < 0.001), and the effect on FPG was reversed after exchanging treatments. The glycometabolic improvements
were achieved without any major change of circulating insulin levels. There were no changes in lipids, body measurements, blood
[1, 2]. Many currently available antidiabetic drugs improve
seen in T2D. However, they exhibit a number of limitations
such as side effects and high rates of secondary failure
and, in the case of novel drugs, rather high treatment costs
[3–5]. Thus, diabetic patients and healthcare professionals
are considering complementary and alternative approaches,
including the use of herbal medicine with antidiabetic prop-
Traditional herbal medicines have played a major role
in the management of diabetes in Vietnam and many
Asian countries for centuries . Gynostemma pentaphyllum
Makino (family Cucurbitaceae) is a perennial creeping herb
growing wild in the mountain regions of Vietnam, China,
and some other Asian countries. It has been used widely in
Southeast Asian countries as a herbal medicine and being
beneficial for the prevention and treatment of diabetes [7–9].
We have previously presented evidence that GP tea possesses
antidiabetic effect, both as a single treatment and as an add-
on therapy to sulfonylureas with good safety data in newly
diagnosed T2D patients [10, 11]. In addition, the extract
of GP has been shown to reduce both hyperglycemia and
hyperlipidemia in diabetic Zucker Fatty rats . Therefore,
this study was aimed to evaluate the effect of GP tea on
insulin sensitivity by somatostatin-insulin-glucose infusion
test (SIGIT) in drug-na¨ ıve type 2 diabetic patients.
2 Journal of Nutrition and Metabolism
2. Materials and Methods
2.1. Medication. The medication was provided in the form
of GP tea at the dose of 6g/day (3g/packet, twice a day).
The whole plants of Gynostemma pentaphyllum Makino
Cucurbitaceae were collected from the Hoa Binh Province,
in the north of Vietnam, and identified by Professor Pham
Thanh Ky, Department of Material Medica, Hanoi College
of Pharmacy. The standardized GP tea was produced by
a certified herbal manufacturing facility using the method
described in document number VN 10907/TL, including
two stages. The first stage was to confirm authenticated GP
plants which were compared with the voucher specimen
(HN-0152) deposited in the herbarium at the Department
of Material Medica, Hanoi College of Pharmacy. The second
stage was to produce the GP tea as specified. Briefly, the
by adding concentrated 70% ethanol. The 70% ethanol was
then removed by distillation at low pressure, and impurities
were removed by filtration. Thereafter, the tea was inspected
as a semifinished brown powder with typical odour of GP
tea. This powder had a humidity of approximately 6.7% and
could be dissolved in water into brown liquid with a sweet-
bitter flavour. The tea contained flavonoids, as shown by a
positive cyanidin reaction with base FeCl3(5%) [13, 14], and
foaming test [13, 14]. Thus, the standardization of the GP tea
included confirmation of its typical odour, state, and sweet-
bitter flavour, approximately 7% in humidity, and positive
reaction in the flavonoid (cyanidin reaction) and saponin
(foaming) tests. The placebo tea was green tea (Camellia
to the GP tea in shape and packaging. After grinding the
resulting GP and placebo material into a powder to form
soluble particles, the powder was packed in tin foil packets
furthermore about 18% saponins, as indicated by a positive
(6 × 5cm) by an automatic packing machine. Each packet
taken 30 minutes prior to breakfast and dinner.
contained 3g of powder, and 10 packets were packed in one
2.2. Patients. Sixteen patients with newly diagnosed T2D
were enrolled into the study from February to September
2010 from outpatients at National Institute of Gerontology
and 3 district hospitals in Hanoi. All included patients
had passed through the study by November 2010. Written
informed consent was obtained from all subjects before the
beginning of the study. The study protocol was approved
by the research ethics board at Hanoi Medical University,
Hanoi, Vietnam, and the Regional Ethics Committee at the
Karolinska Institutet, Stockholm, Sweden.
Inclusion criteria were (1) newly diagnosed T2D patients
according to WHO criteria , (2) age from 40 to 70 years
old, (3) antidiabetic drug na¨ ıve, (4) mean (of two) fasting
plasma glucose (FPG) measurements from 7 to 11mmol/L,
and (5) glycosylated hemoglobin (HbA1C) from 7 to 9%.
treatment for diabetes, (2) chronic complications related to
Exclusion criteria were (1) previously pharmacological
type 2 diabetes, (3) smoking subjects, and (4) increased titres
of GAD and IA-2 antibodies.
The evaluation at baseline included detailed medical
history and clinical examination, fasting plasma glucose
and renal function tests, fasting lipid profile, and plasma
2.3. Study Designs. The protocol of the study is presented
in Figure 1. After screening by the main investigator, the
selected patients were randomly assigned by another inde-
pendent allocator by the use of numbered containers into
two groups, matched by age, sex, fasting plasma glucose,
and HbA1C: group A and group B received GP tea and
day, 30 minutes before breakfast and dinner). After two-
week wash-out period of nontea therapy, the patients were
switched to another four weeks of 6g GP tea/day (group B)
and placebo tea (group A). At the end of both four-week
periods of treatment with GP or placebo tea (week 4 or week
10), all patients underwent a somatostatin-insulin-glucose
infusion test. All subjects received comprehensive diabetes
instructed to follow the diet as always recommended for
newly diagnosed T2D patients. Carbohydrate and monoun-
saturated fat should comprise 60–70% of total calories. They
were also instructed to walk 30 minutes a day and at least
five days a week during the study. This was reinforced at each
follow-up visit, and subjects were treated on an outpatient
placebo tea, respectively, 6g daily in divided dose (twice a
2.4. Somatostatin-Insulin-Glucose Infusion Test (SIGIT). All
subjects participated in SIGIT, performed at 8am after an 8–
10h overnight fast with only tap water allowed ad libitum.
The SIGIT, lasting 150 minutes, was conducted as described
earlier [16–18]. Briefly, an i.v. cannula (Exeflon, Exelint, Los
Angeles, CA, USA) was inserted into an antecubital vein
for the infusion of all test substances. A second cannula
was inserted into a wrist vein contralaterally to the infu-
sion site for blood sampling. Each subject was given a
150-minute intravenous infusion of somatostatin (270휇g/h;
Novo Nordisk, Denmark), and glucose (6mg/kg/min; in a
0, 30, 60, 90, 120, and 150 minutes. Somatostatin was used to
estimation of sensitivity to exogenously administered insulin
by measuring blood glucose value at 90, 120, and 150 minutes
of the test (SIGIT mean). Since similar steady-state plasma
insulin levels are achieved in all subjects, this test allows us
to compare the ability of the recruited subjects to dispose
of identical glucose loads under the same insulin stimulus.
measured during the steady-state period from 90 to 150
burg, Germany), insulin (0.4mU/kg/min; Actrapid HM,
Journal of Nutrition and Metabolism3
Group A (GP tea)
( = 8)
Group B (placebo tea)
( = 8)
Screening4 weeks2 weeks4 weeksWeeks
Group A (placebo tea)
( = 8)
Group B (GP tea)
( = 8)
Figure 1: Study protocol. Lipid, kidney, and liver function tests were performed at week 0, 4, 6, and 10. Fasting plasma glucose and insulin
were determined every second week. OGTTs (oral glucose tolerance tests) and HbA1Cwere performed at baseline. SIGIT (somatostatin-
insulin-glucose infusion test) was performed at the end of each treatment period.
utilization, that is, insulin sensitivity [17, 18].
2.5. Biochemical and Anthropometric Analyses. Blood sam-
ples of fasting subjects were taken before, during (every
second week for ten weeks), and after the treatment course
for measurement of plasma glucose, HbA1C, liver transferase
Serum samples were obtained by centrifugation and stored
at −20∘C pending for assay. Analysis of glucose concentra-
Boehringer Mannheim, Germany, wave-length Hg 546nm).
HbA1Cwas measured with BIO-RAD D-10 (Bio-Rad Stras-
measured by insulin radioimmunoassay (RIA), using our
own antibodies, human insulin as a standard, and charcoal
addition to separate antibody-bound and free insulin .
Oral glucose tolerance tests (OGTT) (75g glucose) were
performed at baseline to confirm the diabetic diagnose.
Venous blood samples were drawn before 0, 30, and 120
minutes after the glucose intake. Body weight, body mass
index (BMI), waist and hip circumference, blood pressure,
and registered adverse effects were noted in medical records
during the visits.
2.6. Statistical Analysis. Results were expressed as means ±
tion of each sample was done by enzymatic colorimetric
test, GOD-PAP in a glucose analyzer (Autolab Instrument,
bourg, Schiltigheim, France). The insulin concentration was
SD. Paired 푡-test was used to analyze data in the same group
before and after treatment as well as the steady-state of both
SIGITs. The independent sample 푡-test was used for normal
distributed variables to compare differences in mean change
between the treatment group and the control group (SPSS
version16.0).Statisticalsignificancewasdeclaredat푃 < 0.05.
3.1. Clinical Characteristics. The baseline characteristics of
the patients receiving GP treatment initially did not differ
significantly from those starting with placebo and vice versa
at week 6, after two weeks of washout (Table 1). There were
no statistically significant differences between the groups
regarding age, gender, systolic and diastolic blood pressure
(SBP and DBP), body weight, BMI, waist, hip circumference,
FPG, and HbA1C.
3.2. Effects of GP Tea on Glucose Regulation. Treatment with
decreased to 1.9 ± 1.0mmol/L, while the levels of FPG in
treatments (Figure 2), and the glycometabolic improvement
levels (Table 2, Figure 2).
The mean steady-state plasma insulin levels and plasma
glucose responses of the two groups during SIGIT study
are given in Table 2. The steady-state plasma insulin (SSPI)
response clearly indicates that similar plasma levels of exoge-
nous insulin were attained as a result of the infusion in all
plasma insulin (FPI) but resulted in lower FPG (푃 < 0.001;
Table 2). Following the treatment with GP tea, the FPG
the placebo treatment were not changed, 0.2 ± 1.5mmol/L,
<0.001. The effects were reversed after exchanging
4 Journal of Nutrition and Metabolism
Fasting plasma glucose (mmol/L)
Fasting plasma insulin (pmol/L)
Fasting plasma glucose (mmol/L)
Fasting plasma insulin (pmol/L)
GP tea Placebo tea
Figure 2: Fasting plasma glucose (mmol/L) and insulin (pmol/L) levels in Group A ((a) and (c)) and Group B ((b) and (d)). Means ± SD
(푛 = 8 in each group).
subjects. In contrast, the mean steady-state plasma glucose
(SSPG) responses were markedly decreased after the GP tea
treatment (푃 < 0.01), indicating improved insulin sensitivity.
3.3. Change in Body Weight and Other Parameters. There
were no significant differences within or between groups
regarding changes in serum triglyceride, total cholesterol,
changes in the plasma levels of AST, ALT, creatinine, and
BUN were detected during treatment (data not shown).
Neither the GP tea-treated nor placebo-treated groups expe-
rienced any acute adverse effect such as gastrointestinal,
diarrhea, and hypoglycemic symptoms during the research
period, and all patients were compliant with the treatment
protocol and completed the study.
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.
Journal of Nutrition and Metabolism5
Table 1: Clinical characteristics and laboratory findings of the patients.
Group A (GP-placebo tea)
58.6 ± 5.3
119.4 ± 10.2
8.1 ± 0.9
3.3 ± 1.2
Group B (placebo tea-GP)
56.8 ± 4.9
118.2 ± 8.3
8.1 ± 0.7
3.0 ± 0.7
58.8 ± 5.4
119.4 ± 11.5
57.1 ± 5.0
118.5 ± 7.9
Body weight (kg)
Systolic blood pressure (mmHg)
Diastolic blood pressure (mmHg)
Fasting plasma glucose (mmol/L)
Fasting plasma insulin (pmol/L)
Age (years) 58.8 ± 5.9
85.8 ± 6.2
8.3 ± 0.8
2.2 ± 1.5
58.8 ± 5.9
85.4 ± 5.8
7.4 ± 0.6
2.1 ± 0.9
58.1 ± 6.6
81.0 ± 6.1
8.4 ± 0.7
2.1 ± 1.1
58.1 ± 6.6
81.9 ± 6.0
8.0 ± 1.0
2.7 ± 1.3a
23.3 ± 1.9
74.4 ± 5.0
5.4 ± 0.8
23.4 ± 2.0
74.4 ± 4.9
5.4 ± 1.0
22.6 ± 1.8
76.3 ± 4.2
5.0 ± 0.9
22.7 ± 1.9
76.3 ± 5.1
5.4 ± 1.2a
94.4 ± 3.5
140.98 ± 38.2
1.5 ± 1.0
94.1 ± 3.3
132.0 ± 109.2
1.2 ± 0.2
91.8 ± 4.2
113.2 ± 65.3
1.1 ± 0.2
91.6 ± 4.0
122.9 ± 78.5
1.1 ± 0.2a
3.3 ± 1.03.0 ± 0.8a
Results are means ± SD of sixteen patients.a푛 = 7, after removal of one patient with an extreme triglyceride value (12mmol/L).
Table 2: Plasma glucose, insulin levels, and SIGIT mean in two kinds of treatment.
6.3 ± 0.8
130.6 ± 81.3
7.7 ± 1.9
120.1 ± 106.3
FPG before treatment (mmol/L)
FPG after treatment (mmol/L)
Change in FPG (mmol/L)
SSPG (SIGIT mean) (mmol/L)
FPI before treatment (pmol/L)
FPI after treatment (pmol/L)
Change in FPI (pmol/L)
8.2 ± 0.9
123.6 ± 59.7
7.9 ± 0.8
122.2 ± 79.9
−1.9 ± 1.0
−0.23 ± 7.8
−0.2 ± 1.5
−0.3 ± 9.8
12.5 ± 3.2
223.6 ± 91.0
16.2 ± 4.1
218.1 ± 104.9
Results are means ± SD of sixteen patients in each treatment. FPG: fasting plasma glucose, FPI: fasting plasma insulin, SSPG: steady-state plasma glucose, and
SSPI: steady-state plasma insulin.
The placebo group and the GP group did not differ in
baseline characteristics and diabetic parameters (drug-na¨ ıve
T2D, HbA1C, and FPG). The GP tea was mainly responsible
on FPG in the control group. The major antidiabetic role of
GP tea was also proven by the reduction of the FPG and the
with reversed effect after switching to placebo treatment,
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 suppres-
sion of plasma C-peptide levels during SIGIT guarantees
that glucose disappearance is governed by the infused and
not by endogenously secreted insulin. Insulin sensitivity
for the reduction of the glucose levels because all patients
measured with SIGIT is significantly correlated with 푀
[20, 21]. In a previous study, endogenous C-peptide con-
centrations, reflecting insulin secretion during SIGIT, were
almost entirely abolished by somatostatin . In addition,
in our previous study we showed that the glycometabolic
improvement was achieved without any major change of
results are in agreement with our previous findings by GP
tea [10, 11] 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 . 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
values obtained during hyperinsulinemic euglycemic clamp,
which is a “gold standard” in measuring insulin sensitivity
effect by GP tea on insulin sensitivity may be accounted for
6 Journal of Nutrition and Metabolism
in the GP tea . 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
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 .
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, 24], 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
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 0.75g/kg per day) . 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 addi-
GP extract’s antidiabetic effect, as well as effects on patient-
reported outcomes, morbidity, and mortality.
study suggested that the GP tea exerted antidiabetic effect by
improving insulin sensitivity.
Conflict of Interests
The authors have no relevant conflict of interests to disclose.
The authorsgratefullyappreciate Dr. Nguyen Trung Anh, Dr.
Nguyen Thi Tam, Dr. Nguyen Tien Truong, and Dr. Phung
hormone assays, and Ms. Kajsa Sundqvist and Kamal Yassin
for expert assistance in the preparation of SIGIT. This work
was supported by a Grant of SIDA/SAREC, Osher Centre for
Integrative Medicine, the Swedish Research Council, and the
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