INTRODUCTION

Xuezhikang, a newly developed lipid-regulating medicine in China, has been used in clinical observations after more than two years fundamental studies. This paper studied 45 cases of type II diabetic patients associated with hyperlipoidemia in terms of changes of serum lipid, blood sugar and insulin levels and further explored the influence of Xuezhikang on lipid metabolism and islet b cell functions.


PATIENTS AND METHODS

Selection of Patients
Patients were selected from diabetes department according to Recommended Clinical Standard of Diabetes Patients stipulated by WHO in 1985. They should have a minimum stable symptom period of 2 months after proper diet, physical exercise and/or blood sugar regulating medicine treatment. Two or more consecutive tests with 1 ~ 2 weeks intermittence showed their FBG ³ 7.8 mmol/L, 2h-PG ³ 11.1 mmol/L. These above patients were chosen as clinical targets. And those patients with serum TC ³ 5.72 mmol/L(220 mg/dl), TG > 1.7 mmol/L (150 mg/dl) tested at least one month after low cholesterol diet were regarded as type II diabetes patients coupled with hyperlipoidemia. Meanwhile, those with HDL-C < 0.91 mmol/L were classified as low lipid patients.

Patients with syndromes, within 6 months, such as acute myocardial infarction, cerebrovascular accidents, renal disease resulting from diabetes, protein urea quality analysis higher than (++), IV type or higher retinosis caused by diabetes and/or large scale fundus oculi bleeding, diabetes hyperosmolar coma, ketoacidosis, or serious injury caused by major surgery had been excluded. In addition, hyperlipoidemia resulting from family genes, or diseases of liver, gallbladder, kidney and thyroid or from drug were also excluded. Those patients satisfying the above standards and not taking lipid regulating agents in the past two months were finally selected totaling 45 cases with 20 males and 25 females, age from 35.1 to 71.5 years old, the average 57.78 ± 8.22. These patients had a medical history of 1 week to 11.5 years averaging 3.51 years. There were 7 male patients with body weight measuring index [BMI(kg/m2)] > 25 and 15 female patients with BMI > 24. And 23 cases had lower BMI index. At the same time, 30 type II diabetic patients without hyperlipoidemia, 12 male, 20 female, age from 34.2 ~ 72.5, the average of 58.12 ± 3.42 were chosen as control group. They had 1 week to 10 years medical history averaging 3.11 years. Among them, there were 5 male with BMI> 25 and 10 female BMI > 24.

Methods
Direct observation was employed in the study. Every one in the treatment group took two capsules of Xuezhikang (manufactured by WBL Peking University Biotech Limited Company) twice a day, one after breakfast and one after dinner for 8 weeks. During treatment, the lifestyle and diet habit as well as other pharmaceutical treatment kept the same.

Observation Indexes
Before and after the treatment, patients were tested on their height and body weight (after relieving bowels and urine) to calculate their BMI. They were also required to test blood pressure, heart rate, blood sugar, serum lipid, serum insulin, glutamic-pyruvic transaminase, BUN and blood creatinine. High cholesterol diet and alcohol were prohibited one day before blood sampling and venous blood samples were taken from 12h-fasting patients to identify the concentrations of blood sugar, lipid and insulin. Two hours after a standard meal, venous blood samples were taken again to determine the levels of blood sugar and insulin. Blood sugar and lipid were determined by oxidase method and insulin by radioimmunoassay method.

Criteria for Effects
Effects of Xuezhikang refers to Guiding Standards on Clinical Study of Medicines (Draft) stipulated by Ministry of Public Health P. R. China in July 1993:

• Highly effective
  TC reduction ³ 20%, or TG decrease ³ 40%, or HDL-C increase ³ 0.26 mmol/L, FBG < 7.2 mmol/L then 2h-PG < 8.3 mmol/L.
• Effective
  TC reduction 10% ~ 20%, or TG decrease 20% ~ 40%, or HDL-C increase by 0.1 ~ 0.25 mmol/L(4 - 10 mg/dl), FBG < 8.3 mmol/L and then 2h-PG < 10 mmol/L.
• Ineffective
  not reaching any one of the above criteria.
• Deterioration
  TC increase ³ 10%, or TG elevation ³ 10%, or HDL-C decrease ³ 0.1mmol/L (4mg/dl).

Statistical Methods
Serum lipid, blood sugar, insulin and Sensitivity analysis of insulin employed t-test with all parameters expressed in the form of average value ± standard deviation (X ± S).

RESULTS

Effects on Type II Diabetic Patients Associated with Hyperlipoidemia
Study results showed that at 4 and 8 weeks after treatment, TC decreased by 20.8% and 27.06% respectively; TG decreased by 19.27% and 42.3% respectively; HDL-C elevated by 24.32% and 54.95% and AS index decreased by 32.35% and 49.13% respectively.

Effects on Islet b Cell Functions of Type II Diabetic Patients with Hyperlipoidemia
The findings illustrated that levels of FBG, FBI, 2h-PG and 2h-PI decreased significantly at the end of both 4 weeks and 8 weeks treatment with P < 0.05 ~ 0.001.

Effects Comparison on Blood Sugar and Serum Lipid Reduction of Type II Diabetic Patients with Hyperlipoidemia
The study showed that after the treatment, serum TC and TG of diabetes II patients with hyperlipoidemia reduced dramatically with total efficacy of 88.9% and 90.3% respectively. HDL-C level elevates with total efficacy of 97.8%. Whereas reduction occurred for both FBG and PBG with total efficacy rate of 100% and 95.9% respectively.

Effects of Xuezhikang on Islet b Cell Functions of Type II Diabetic Patients without Hyperlipoidemia
Both blood sugar and insulin levels of type II diabetic patients without hyperlipoidemia dropped obviously after 8 weeks treatment with P < 0.05 ~ 0.001 compared with that of post treatment.

Side-effects
None of the 45 cases had reported any discomfort or malaise after Xuezhikang treatment, and liver and renal functions lay in normal range.


DISCUSSION
It is reported that about 50% diabetic patients accompanying with hyperlipoidemia. [1] And high concentrations of blood sugar, serum lipid, insulinemia or high insulin sensitive index are pathological causes of diabetes syndrome and usually lead to cardiocerebrovascular disease. Xuezhikang contains HMG-CoA reductase inhibitor Lovastatin and various kinds of unsaturated fatty acids and many effective ingredients like essential amino acids. HMG-GoA reductase inhibitor is the speed limited enzyme of cholesterol synthesis. The product of HMG-CoA reductase catalysis reaction ¾mevalonic acid is the necessity of DNA synthesis and cell proliferation. Xuezhikang competes to suppress the activity of this enzyme, reduce the synthesis of cholesterol in liver. Meanwhile, HMG-CoA reductase inhibitor stimulates the activity of LDL-C receptor on liver cell surface and facilitates the elimination of serum LDL-C, affects metabolism of cholesterol and TG in human body therefore reduces the concentration of serum TC, TG and LDL-C. In this study, 45 diabetes patients with hyperlipoidemia had been treated with Xuezhikang. Total efficacy rate of TC reduction reached 88.1% 4 weeks after and 88.9% 8 weeks after the treatment. Total efficacy rate of TG reduction went to 77.4% 4 weeks after treatment and 90.3% 8 weeks after. Whereas total efficacy rate of HDL-C reached 84.2% 4 weeks after and 94.7% 8 weeks after the treatment. Compared with the level before treatment, TC decreased by 27.06%, TG by 42.3% and HDL-C increased by 54.94%..

TC - HDL-C/HDL-C ratio is one of the most sensitive variables which is called as arteriosclerosis index (AS index). This study showed a remarkable decrease of AS index after Xuezhikang treatment, P < 0.001 or 0.01. It has been illustrated by some study that Xuezhikang can protect the functions of neointimal cells of high diet fed rabbit. [2] It can also inhibit the proliferation and migration of vessel SMC of rabbit.[3] This is essential to prevent the formation of atherosclerosis. The research findings showed that, keeping the same lifestyle and blood sugar regulating agents, type II diabetic patients associated with hyperlipoidemia could lower their concentrations of blood sugar and lipid and elevate insulin sensitive index by way of lipid regulation. It is also true for type II diabetic patients without hyperlipoidemia in the control group. It is assumed that diabetes and hyperlipoidemia may possess the same pathological causes¾ insulin resistance. Because Xuezhikang contains various unsaturated fatty acids, it inhibits the synthesis of TG and fatty acids, and accelerates their metabolism, thus enhancing the secretion of insulin from islet b cells and improving the sensitivity of surrounding tissues. The observations in this study showed a slight reduction of blood sugar and insulin after 4 weeks treatment, but a distinct decrease 8 weeks after. This may have something to do with the above mechanism. As for the effects of Xuezhikang on improving vascular complications of diabetes, it is still open to further study.


REFERENCES