Clinical Observation of Xiaokeping Mixture in Improving the Function of
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Clinical Observation of Xiaokeping Mixture in Improving the Function of Islet β Cells in Newly-onset Type 2 Diabetes XIN Chuanweia, HUANG Pinga, CHEN Xiongweib, WANG Jieshengb, LI Weijiab, TIAN Yunlongb (Tong De Hospital of Zhejiang Province, a. Department of Pharmacy, b. Department of Endocrinology, Hangzhou 310012, China) ABSTRACT: OBJECTIVE To observe the curative effect of Xiaokeping mixture in improving the islet β-cell function in patients with newly diagnosed Type 2 diabetes. METHODS 90 patients with newly diagnosed Type 2 diabetes were randomly divided into 3 Group s (Group s A, B & C) and they were given oral hypoglycemic drugs. Group A was given glipizide or gliclazide sustained-release tablets (30 patients, 1 patient dropped out), Group B was given insulin (30 patients, 2 patients dropped out), and Group C was given insulin combined with Xiaokeping mixture (30 patients, 2 patients dropped out). All these 3 Group s were treated for 12 weeks. The changes in clinical syndromes, FBG, P2hPG, HbA1c, fasting and postprandial 0.5, 1, 2, 3 h C peptide, Insulin Resistance Index and Islet βCell Function Index. were observed before and after treatment. RESULTS After treatment, the clinical symptoms, FBG, P2hPG, HbA1c, fasting C peptide and HOMA-IS of the 3 Group s of patients were statistically different from those before treatment (P
Kuijun of our hospital according to the medical practice experience for many years, and has effects of tonifying qi and yin and promoting blood circulation to remove blood stasis. Several literatures[1-2] reported the clinical studies on the hypoglycemic effect of Xiaokeping Preparation, but the study on the improvement effect of Xiaokeping Preparation on islet β-cell function was not seen in the existing literatures. In order to further investigate the mechanism of Xiaokeping Preparation in the treatment of DM, this study investigated the improvement of the islet β-cell function before and after treatment with Xiaokeping Mixture among subjects, i.e.,newly-onsetType 2 DM patients, who were treated with oral hypoglycemic drugs, insulin, or a combination of insulin and Xiaokeping Mixture. 1 Materials and Methods 1.1 Research Subjects Diagnosis and typing were in accordance with WHO standard 1999, and the subjects shall meet the following criteria: Age < 65 years; medical history less than 3 months, absence of medication, and increase in fasting blood-glucose (FGB), 2hour postprandial blood glucose (P2hPG) and glycosylated hemoglobin (HbA1c) (FBG ≤ 7.0 mmol•L-1, PG2h ≤ 11.0 mmol•L-1, and HbA1c ≤ 6.2%); The pregnant women, and the patients with ketoacidosis, serious heart, liver and kidney diseases and diseases influencing the glycometabolism were excluded. 1.2 General Information 90 newly-onsetType 2 DM patients admitted to Department of Endocrinology of our hospital from May 2009 to May 2010 were selected, and randomly divided into Group s A, B and C in an order of visit time. Group A was treated with the oral hypoglycemic drugs (30 patients in total, 1 patient dropped out), Group B was treated with insulin (30 patients, 2 patients dropped out), and Group C was treated with a combination of insulin and Xiaokeping Mixture (30 patients, 2 patients dropped out). Group A included 16 males and 14 females, mean age: 47.61±5.52 years, BMI: 19.21 ±4.42kg• m-2, and HbA1c: 7.9±2.13%. Group B included 17 males and 13 females, mean age: 45.92±5.73 years, BMI: 20.13±4.72kg•m-2, and HbA1c: 8.22±1.91%. Group C included 15 males and 15 females, mean age: 46.52±5.62 years, BMI: 19.82±4.24kg•m-2, and HbA1c: 8.43±2.05%. The dropout patients were out of touch, and the data of three Group s were not statistically different (P > 0.05), and were comparable. 1.3 Therapy The three Group s underwent diet control and appropriate kinesitherapy during observation. Group A was treated with the oral hypoglycemic drug (glipizide or gliclazide sustained-release tablets), whose dose was adjusted according to the blood glucose level. Group B and Group C received intensive insulin treatment from week 1 to week 2, i.e., Novolin R (short-acting human insulin) for subcutaneous injection 20-30min before breakfast, lunch and dinner, and Novolin N (intermediate-acting human insulin) for subcutaneous injection before sleeping, starting from 0.4-0.5U per day, with dose gradually increased, and the dose was adjusted every 3d according to the blood glucose level. One to two weeks later, Novolin 30R (premixed human insulin) was administrated by subcutaneous injection 20-30min before breakfast and dinner. Group C was administrated with Xiaokeping Mixture (prepared by the Drug Manufacturing Room of our hospital, Approval No.: Zhe Yao Zhi Z20050035, Batch No.: 100130, 500mL•vial-1), 50mL, bid, before the meal in addition to insulin. The observation time of the 3 Group s was 12 weeks. 1.4 Observation Items •82• Chin JMAP, 2011 January, Vol.28 No.1 (C) 1994-2020 China Academic Journal Electronic Publishing House. All rights reserved, http://www.cnki.net
Morning FPG, P2hPG and HbA1c of the patients before treatment and after 12 weeks were
observed, and were determined by the full-automatic biochemical tester. During the treatment
course, the peripheral blood glucose was determined by Germany ROCHE Advantage
glucometer, and for the islet β cell function, glucose tolerance test was used to determine fasting
C peptide and C peptide 0.5, 1, 5 and 3h after a meal. The insulin resistance index (HOMA-IR)
and islet β cell function index (HOMA-IS) were calculated by homeostasis model assessment
(HOMA)[3]; HOMA-IR = FPG × fasting insulin (FINS)/22.5; HOMA-IS = FINS×20/(FPG-3.5).
1.5 Evaluation criteria of TCM curative effect
Refer to Guideline for Clinical Study on Treatment of Diabetes Mellitus with New Traditional
Chinese Medicine developed by National Medical Products Administration (NMPA) in 2002.
Significantly effective: Obvious improvement of TCM clinical symptoms and signs, and
percentage reduction of symptom score ≤ 70%. Effective: percentage reduction of score: 30-70%.
Ineffective: percent reduction of score: < 30%. Percent reduction of score = (score before
treatment - score after treatment)/score before treatment * 100%.
1.6 Statistical Method
SPSS13.0 statistical software was used for statistical processing, t test for intragroup comparison,
variance test for intergroup comparison, and χ2 test for enumeration data.
2 Results
2.1 Influence on Chinese symptoms total score
Before treatment, there was no obvious difference in the Chinese symptoms total score among 3
groups (P > 0.05). In Group A, the numbers of significantly effective, effective and ineffective
patients were 1, 23 and 5 respectively, and the total effective rate was 82.75%. In Group B, the
numbers of significantly effective, effective and ineffective patients were 2, 22 and 4 respectively,
and the total effective rate was 85.71%. In Group C, the numbers of significantly effective,
effective and ineffective patients were 5, 22 and 1 respectively, and the total effective rate was
96.42%. The Chinese symptoms total score of Group C was reduced significantly as compared to
Groups A and B (P < 0.05). See Table 1 for the results.
Tab 1 Changes of Chinese symptoms total score before and after treatment in three Group
s ( x ± s)
Group Time n Chinese symptoms total score
Before Treatment 30 27.93±5.25
Group A
AfterTreatment 29 15.73±5.181)
Before Treatment 30 28.22±5.02
Group B
AfterTreatment 28 13.92±4.751)
Before Treatment 30 28.43±5.90
Group C
AfterTreatment 28 10.73 ±4.221)2)3)
Note: Compared with the same group before treatment, 1)P < 0.01; after treatment, compared to Group A, 2)P <
0.05, compared to Group B, 3)P < 0.05
2.2 Influence on blood glucose and HbA1c
FPG, P2hPG and HbA1c of 3 groups were reduced obviously after treatment (P < 0.01).
Relatively significant reduction was seen in Groups B and C. FBG and HbA1c of Group C was
reduced most obviously. The reduction of FBG and HbA1c had significant difference between
Group C and Group B (P < 0.05). See Table 2 for the results.
Chin JMAP, 2011 January, Vol.28 No.1 •83•
(C) 1994-2020 China Academic Journal Electronic Publishing House. All rights reserved, http://www.cnki.netTab 2 Changes of FPG, P2hPG, HbA1c before and after treatment in three Groups ( x ± s)
Group Time n FPG/mmol•L-1 P2hPG/mmol•L-1 HbA1c/%
Before Treatment 30 10.21±2.11 16.32±2.56 7.91±2.13
Group A
AfterTreatment 29 7.37±1.051) 9.56±1.68 7.13±0.851)
Before Treatment 30 9.68±2.07 15.98±2.33 8.22±1.91
Group B
AfterTreatment 28 7.09± 0.951) 9.15±1.72 6.75±0.821)
Before Treatment 30 9.94±2.14 16.24±2.1 8.43±2.05
Group C
AfterTreatment 28 6.32± 0.722)3) 8.92±1.66 6.12±0.681)2)3)
Note: Compared with the same group before treatment, 1)P < 0.01; after treatment, compared to Group B, 2)P <
0.05; compared to Group A, 3)P < 0.01
2.3 Influence on C Peptide
The secretion peaks of C peptide of the 3 Groups were delayed before treatment, indicating β cell
function impairment. The secretion peak of C peptide of Group A was still delayed after
treatment with oral hypoglycemic drugs, and was decreased slightly, indicating further β cell
function impairment. The secretion of C peptide 1h after treatment was improved obviously in
Group s B and C (P < 0.01), indicating recovery of β cell function. The fasting C peptide and 1h
postprandial C peptide were improved more obviously in Group C than in Group B (P < 0.05),
indicating the therapeutic effect of a combination of Xiaokeping Mixture and insulin was better
than insulin alone, as shown in Table 3.
Tab 3 Changes of C-peptide before and after treatment in three Group s ( x ± s)
C peptide/nmol·L-1
Group Time n
Fasting 0.5h 1h 2h 3h
Before Treatment 30 0.86±0.43 1.02±0.51 1.35±0.66 2.36±0.84 2.15±0.72
Group A
AfterTreatment 29 0.96±0.471) 1.06±0.52 1.32±0.65 2.27±0.81 1.84±0.92
Before Treatment 30 0.87±0.45 1.04±0.52 1.32±0.65 2.44±0.85 2.18±0.64
Group B
AfterTreatment 28 1.05±0.511) 1.22±0.74 1.65±0.722) 2.46±0.86 2.13±0.68
Before Treatment 30 0.85±0.42 1.03±0.52 1.38±0.67 2.50±0.88 2.11±0.65
Group C
AfterTreatment 28 1.18±0.581)3)4) 1.28±0.78 1.86±0.783)4) 2.52±0.89 2.09±0.63
Note: Compared with the same group before treatment, 1)P < 0.05, 2)PGroup Time n HOMA-IR HOMA-IS
AfterTreatment 29 6.52±1.82 55.43±32.02
Before Treatment 30 6.95±2.02 16.47±4.25
Group B
AfterTreatment 28 4.13±1.611) 70.68± 46.382)
Before Treatment 30 7.13±2.05 15.98±3.91
Group C
AfterTreatment 28 3.36±1.321)3)4) 81.92±60.252)3)4)
Note: Compared with the same Group before treatment, 1)P < 0.05, 2)P < 0.01; after treatment, compared to
Group B, 3)P < 0.05, compared to Group A, 4)P < 0.01
2.5 Evaluation of adverse reactions before and after treatment
During treatment, 2 patients had hypoglycemia in Group A, 3 patients in Group B, and 3 patients
in Group C, which was alleviated after eating. There was no statistical difference among 3
groups (P > 0.05). Other adverse drug reactions were not observed in 3 groups.
3 Discussion
Type 2 DM was a slowly progressive disease. Islet β cell dysfunction and insulin resistance were
the two major factors. The studies such as UKPDS proposed that about 50% of the average β cell
function was lost for newly diagnosed T2DM patients without treatment, which provides the
basis for blood glucose control with exogenous insulin. The studies demonstrate that[4-5] the β
cells are in “glucose sensitivity loss” stage at the early stage of T2DM, the β cell function
impairment is reversible, and the early insulin treatment enables metabolism control, to reduce
the high and lipotoxicity obviously, improve insulin resistance, and protect and recover β cell
function.
The study found the average secretion peaks of postprandial C peptide of 3 groups appeared 2h
post meal, instead of 1h post meal after treatment for 12 weeks, which showed that the secretion
of islet β cells of the 3 groups delayed, and the islet cells had dysfunction already. The secretion
peak of C peptide of DM patients in Group A still delayed, and decreased to some extent,
indicating that the sulfonylurea hypoglycemic drugs cannot prevent further impairment of islet β
cell in newly-onsetType 2 DM patients. After treatment, the 1h postprandial C peptide was
recovered obviously in Groups B and C, and more significant improvement of HbA1c, FBG and
insulin secretion index were also seen in Group B and C as compared to Group A, showing that
the islet β cell function of Groups B and C were recovered to some extent, the early insulin
treatment is very important for the newly-onsetType 2 DM patients, and the treatment effect of a
combination of Xiaokeping Mixture and insulin was more obvious in Group C.
A study demonstrates that[6] the abnormal islet β cell function is due to a multilayer, multilink
and multiattribute complex mechanism, and the treatment with the traditional Chinese medicine
alone or western medicine alone have respective limitations. Therefore, the combined treatment
of traditional Chinese medicine and western medicine has become the hotspot of clinical studies
in recent years. DM belongs to the category of the dispersion-thirst disease in TCM, and is
mainly caused by yin deficiency and dryness-heat arising from depletion and injuries of yin of
lung, stomach and kidney due to constitutional insufficiency, improper diet, uneven allocation of
work, attack of six climate pathogenic factors and internal injury due to emotional disorder.
Xiaokeping Mixture used in this study was prepared from astragalus roots, Chinese yams, dried
rehamnnia roots, lilyturf roots, trichosanthes roots, salvia miltiorrhiza, chrysanthemum flowers
and barbary wolfberry fruits. The astragalus roots and Chinese yams have effects of benefiting qi
Chin JMAP, 2011 January, Vol.28 No.1 •85•
(C) 1994-2020 China Academic Journal Electronic Publishing House. All rights reserved, http://www.cnki.netfor activating blood circulationand invigorating the spleen and kidney. An experiment[7] shows
the astragalus roots and Chinese yams have a certain effect of reducing the blood glucose and
improving the insulin sensitivity, and can also reduce platelet aggregation, and improve
hemorheology and microcirculation. The dried rehamnnia roots, lilyturf roots and trichosanthes
roots nourish the stomach yin, purge fire stasis. The salvia miltiorrhiza and chrysanthemum
flowers promote blood circulation to remove blood stasis. The barbary wolfberry fruits nourish
the liver and kidney and replenish vital essence to improve eyesight. A combination of the above
herbal medicines has the effects of tonifying qi and yin and promoting blood circulation to
remove blood stasis, can reduce the blood glucose and improve insulin sensitivity, and therefore
improves the islet β cell function. The obvious adverse drug reaction is not seen during the
clinical application of Xiaokeping Mixture, and the combined therapy of traditional Chinese
medicine and western medicine may be taken as an effective and safe therapy for
clinicalnewly-onsetType 2 DM.
The study had the limitations of small sample size, limitation in a department of endocrinology
of a single hospital, and short observation time. In future, these patients will be further followed
up, and the sample size will be increased to make a more comprehensive evaluation on the
improvement of islet β cell function.
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Received: July 5, 2010
•86• Chin JMAP, 2011 January, Vol.28 No.1
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