Effects Of Aggregation-dissipating On Lipids Metabolism In Metabolic Syndrome High Risk Population

Objective1. To observe clinical manifestations of central obese men at high risk of metabolic syndrome and make the features of aggregation syndrome clear so as to further the standardization of aggregation syndrome differentiation and make point of the microcosmic syndrome differentiation by basing on the laboratory examinations.2. To investigate the lipid absorption in central obese men after fat load in orde to find the metabolism features of both triglycerides and free fatty acids and evaluate the energy storage function of adipocyte.3. To measure insulin resistance and levels of some adipocytokines in central obese men so as to evaluate inflammation and fibrolysis in their bodies and discuss the roles of vital-qi deficiency (weak functional activity of qi) and pathogens excess in the generation and development of aggregation syndrome.4. To observe the effects of aggregation-dissipating on postprandial lipids metabolism, measure insulin resistance, expressions of the above adipocytokines and clinical manifestations in central obese men and discuss its mechanisms so as to verify the theory of aggregation syndrome. Methods1. Features of clinical manifestations in metabolic syndrome high risk populationForty five central obese men whose waist was or more than 90 centimeters and insulin resistance index was no less than 1 were recruited at the out-patient department. Initial screening included a medical history, physical examination, routine blood tests, and a 75-g oral glucose tolerance test. Subjects who were with abnormal fasting blood glucose or lipids or with impaired glucose tolerance were excluded. Clinical manifestations were collected and analyzed.2. Features of postprandial lipids metabolism in metabolic syndrome high risk populationSubjects The above 45 central obese men received the test. And 30 non-obese healthy male volunteers whose waist circumferences were lower than 90 centimeter with insulin resistance index lower than 1 were recruited as the normal sample.Fat load test A fat-rich meal with 1100 kcal total energy was fed to the subjects after fasting overnight. Blood was drawn at fasting state and every two hours after fat load. The 8th hour was the endpoint of the test and the samples were collected to measure the levels of serum triglyceride (TG), free fatty acid (FFA), blood glucose and insulin.Common tests Height, weight, waist and hip circumferences, systolic and diastolic blood pressure were measured. Body mass index (BMI), waist-to-hip ratio (WHR) and insulin resistance index (HOMA2-IR) were calculated and their correlations with postprandial lipids metabolism were analyzed. Other lipids indexes including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c) and lipoprotein-a were also measured.3. Levels of some related adipocytokines in metabolic syndrome high risk populationMeasurement of some related adipocytokines Blood was drawn from the above central obese men and non-obese healthy male volunteers to measure the levels of serum adiponectin, leptin, C reaction protein (CRP), interleukin-6 (IL-6), tumor necrosis factorα(TNF-α), plasma plasminogen activator inhibitor-1 (PAl-1) and tissue plasminogen activator (t-PA) with enzyme linked immunosorbent assay (ELISA) method.Correlation analysis The correlations between the above adipocytokines and obesity/insulin resistance and their correlations with postprandial lipids metabolism were analyzed with simple and multiple linear regression analysis respectively.4. Effects of aggregation-dissipating on lipids metabolism in metabolic syndrome high risk population and its mechanismEffects of aggregation-dissipating on postprandial iipids metabolism in metabolic syndrome high risk population The above 45 central obese men were separated into two groups randomly to receive 10-weeks intervention with Chinese medicine Yiqi Sanju Formula or placebo. Their former life styles were remained unchanged during the treatment. Fat load test was conducted before and after the treatment. TG. FFA, blood glucose and insulin levels was compared respectively before and after treatment.Impacts of aggregation-dissipating on general conditions in metabolic syndrome high risk population Changes of waist and hip circumference, height, blood pressure and other lipids including TC, LDL-c, HDL-c, and lipoprotein-a in the two groups were observed before and after treatment. Obesity and insulin resistance were. compared before and after treatment, too.Impacts of aggregation-dissipating on levels of some related adipocytokines in metabolic syndrome high risk population Adipocytokines including adiponectin, leptin, CRP, TNF-α,IL-6, PAI-1 and t-PA were measured and compared before and after treatment in the two groups.Impacts of aggregation-dissipating on clinical manifestations in metabolic syndrome high risk population Scores of clinical manifestations were recorded and compared before and after treatment in the two groups.Results1. Features of clinical manifestations in metabolic syndrome high risk populationIn the 45 central obese men, the most frequent clinical manifestations were obesity, heaviness in the body, shortness of breath and lassitude, spontaneous perspiration, mass and fullness in epigastrium. Other clinical manifestations were dizziness, stuffiness, numbness in the body, poor appetite, foul breath or bitter taste in the mouth, dry or loose stool, yellow or red urine, insomnia and dreaminess and so on. Tongue bodies were normal, red, or pale and enlarged with tooth dent in the margins. Tongue coatings included thin and white coating, white greasy coating, yellow greasy coating, thick greasy coating, little coating and so on. Pulses were normal, wiry, wiry and rapid, slippery, thready and rapid, full and large, soft and thready, deep and so on. The frequency of obesity was significantly higher than those of shortness of breath and lassitude, spontaneous perspiration and mass and fullness in epigastrium, while the frequency of heaviness in the body was higher than those of spontaneous perspiration and mass and fullness in epigastrium. Shortness of breath and lassitude occurred more frequently than mass and fullness in epigastrium.2. Features of postprandial lipids metabolism in metabolic syndrome high risk populationFeatures of postprandial TG and FFA metabolism in metabolic syndrome high risk population There was no difference in fating TG level between central obese and healthy men. The level of TG elevated significantly in central obese men from the 2nd hour after fat load (P＜0.01). The peak of TG in healthy men appeared at the 4th hour, earlier than that of obese men. The level of TG at 8th hour was close to its fasting TG level in healthy men, but TG level at 8th hour was still higher than its fasting TG level (P＜0.001), which indicated the slow clearance of TG in obese men. Both TG area under the curve (TGAUC) and TG peak reaction (TGPR) in obese men were significantly higher than those of healthy men.Compared with healthy men, the concentrations of FFA at fasting state and 2nd, 6th and 8th hour after fat load elevated significantly in obese men(P＜0.05). There was no statistical difference in FFA level at 4th hour between obese and healthy men. In obese men, the level of FFA at 6th elevated significantly and was higher than that of 4th hour (P＜0.05), while there was no difference in the levels at 4th and 6th hour in healthy men. FFA level from 6th to 8th hour dropped significantly in healthy men, but did not changed much in obese men.Features of postprandial glucose and insulin metabolism in metabolic syndrome high risk population There was no difference in fasting concentration of blood glucose between obese and healthy men. Compared with healthy men, levels of blood glucose at 2nd and 4th hour elevated significantly in obese men (P＜0.01 and P＜0.05 respectively). Levels of blood glucose at 6th hour were similar in the two groups. Compared with healthy men, insulin concentrations at fasting state and 2nd hour after fat load were elevated significantly in obese men (P＜0.001). Levels of insulin at 4th, 6th and 8th hour were similar in the two groups. From 4th hour after fat load, insulin levels began to drop and at 8th hour the levels were close to the fasting levels both in obese and healthy men.General conditions in metabolic syndrome high risk population: Compared with healthy men, body mass index, waist circumference and waist-to-hip ratio in obese men increased significantly (P＜0.001 for all comparisons), andf HOMA2-IR elevated significantly, too (P＜0.001). Systolic blood pressure in obese men was 7 mmHg higher than that of healthy men (P＜0.05). And the other lipids were similar in the two groups. HOMA2-IR and waist circumference were positively correlated to TGAUC and TGPR.3. Levels of some related adipocytokines in metabolic syndrome high risk populationLevels of the related adipocytokines Level of serum adiponectin in obese men was significantly lower than that of healthy men (3.15±2.18μg/ml vs 5.57±3.36μg/ml and P＜0.001 ), while leptin level was higher in obese men (P＜0.001). Compared with healthy men, levels of CRP, TNF-α, IL-6 and PAI-1 in obese men elevated significantly (P＜0.01) and t-PA decreased significantly (P＜0.001).Correlation analysis Adiponectin was negatively correlated to HOMA2-IR, waist circumference and BMI respectively. Leptin was positively correlated to HOMA2-IR, waist circumference and BMI. CRP, IL-6 and TNF-αwere positively correlated to waist circumference (P＜0.05). PAI-1 was positively correlated to HOMA2-IR and waist circumference, while t-PA was negatively correlated to waist circumference (P＜0.05). TGAUC and TGPR were closely related to adiponectin, leptin and CRP and multiple linear regression analysis showed levels of leptin and adiponectin had greatese impacts on TGAUC and TGPR.4. Effects of aggregation-dissipating on postprandial lipid metabolism in metabolic syndrome high risk populationEffects of aggregation-dissipating on postprandial lipid metabolism in metabolic syndrome high risk population There were no differences in TG concentrations at fasting state and 2nd hour before and after treatment in the two groups. TG concentration at 4th hour in Chinese medicine group was decreased by 14.1%, while TG level in placebo group increased by 15.6%. Compared with placebo, the Chinese medicine decreased TG concentrations at 2nd, 4th, 6th and 8th hour significantly (P＜0.05). After treatment, levels of TG at the five phases in Chinese medicine group were similar with those of healthy controls, and significantly lower than those of placebo group after treatment. After treatment, TG peak appeared at 4th hour and TG level at 8th hour was close to the level at fasting state in Chinese medicine group.Compared with placebo, the Chinese medicine decreased TGAUC and TGPR significantly (P＜0.05). TGAUC and TGPR in Chinese medicine group after treatment were similar with those of normal controls, but lower than those of placebo group (P＜0.01).Before treatment, levels of FFA in the two groups at the five phases were similar. After treatment, FFA levels at fasting state and 2nd and 4th hour in Chinese medicine group were decreased significantly (P＜0.01), and levels at 6th and 8th hour dropped significantly, too (P＜0.05). Compared with placebo, the Chinese medicine decreased FFA levels at all the five phases significantly (P＜0.05) and levels of FFA after treatment in Chinese medicine were close to the levels in healthy controls. After treatment, FFA level at 8th hour decreased significantly (P＜0.05 vs level at 6th hour) in Chinese medicine group and the same decrease was seen in healthy controls.Effects of aggregation-dissipating on postprandial blood glucose and insulin in metabolic syndrome high risk population: There were no significant changes in blood glucose at fasting state and 2nd, 4th and 6th hour after fat load after treatment in Chinese medicine group. The level of blood glucose at 2nd hour after treatment in Chinese medicine group was higher than that of healthy controls (P＜0.05).Compared with placebo, the Chinese medicine decreased insulin level significantly at fasting state (P＜0.01 for both comparisons). Neither the Chinese medicine nor the placebo changed insulin levels significantly at the four phases after fat load.Impacts of aggregation-dissipating on general conditions in metabolic syndrome high risk population There were significant decreases in BMI, waist circumference, waist-to-hip ratio and HOMA2-IR after treatment with the Chinese medicine (P＜0.001). Compared with placebo, the Chinese medicine decreased the four indexes significantly (P＜0.001). After treatment waist circumference and WHR in Chinese medicine group were lower than those of placebo group (P＜0.05). HOMA2-IR in Chinese medicine group was significantly lower than that of placebo group after treatment (P＜0.01) and similar with the score in healthy controls. Compared with placebo group, TC and LDL-c were decreased significantly in Chinese medicine group after treatment (P＜0.01).Impacts of aggregation-dissipating on the related adipocytokines levels in metabolic syndrome high risk population In Chinese medicine group, there was a significant increase in adiponectin level after treatment (P＜0.01) and the change was significant compared with placebo group (P＜0.01). There was a 21.6% decrease in leptin level in Chinese medicine group after treatment (P＜0.01) and the change was significant compared with placebo group (P＜0.05). Compared with placebo, the Chinese medicine decreased the levels of CRP, IL-6, TNF-αand PAI-1 by 39.7%, 25.4%, 24.4% and 18.1% respectively (P＜0.01 for CRP, IL-6, TNF-αcomparisons, and P＜0.05 for PAI-1 comparison with placebo group), and increased t-PA level by 48.5% (P＜0.001). After treatment with Chinese medicine, levels of all the above adipocytokines were similar with healthy controls.Impacts of aggregation-dissipating on clinical manifestations in metabolic syndrome high risk population The total effective rate in Chinese medicine group was 68.8%, while it was 11.9% in placebo group (P＜0.001 for the comparison of the two groups). Compared with placebo group, the symptom heaviness in the body and spontaneous perspiration were alleviated with effective rates of 78.9% and 75% respectively (P＜0.001 compared with placebo group). Symptom shortness of breath and lassitude and mass and fullness in epigastrium were also improved after treatment with the Chinese medicine with the effective rate 82.4% and 77.8% respectively (P＜0.01 and P＜0.05 for comparisons with placebo group). The other clinical manifestations including stuffiness, dizziness, numbness, dry stool were alleviated accompanied with improvement of tongue and tongue coating and pulse. The total scores of clinical manifestations in Chinese medicine group and placebo group were 5.67±2.05 and 5.82±2.16 respectively. Compared with placebo, the Chinese medicine decreased the total score of clinical manifestations significantly by 61.7% (P＜0.001 for both comparisons). Conclusions1. The energy storage function of adipocyte was impaired and postprandial lipid metabolism was abnormal in metabolic syndrome high risk population, indicated by elevation of TG concentrations, slow clearance of TG and elevation of FFA levels at postprandial state after fat load. The lipid disturbance could exit at early stage in metabolic syndrome high risk population and might be earlier than the occurrence of impaired glucose tolerance or abnormalities of fasting lipids.2. In metabolic syndrome high risk population, dysfunction of adipose tissue as an endocrine organ with chronic inflammation and impaired fribolysis was indicated by the abnormal levels of the related adipocytokines. Levels of adiponectin and t-PA were decreased while leptin, CRP, IL-6, TNF-αand PAI-1 levels increased.3. The levels of the above adipocytokines were closely related to central obesity and insulin resistance. Adiponectin, leptin and CRP was strongly correlated to TG area under curve and TG peak reaction. Abnormal levels of adiponectin and leptin might be risk factors of postprandial lipids metabolism.4. The main clinical manifestations in metabolic syndrome high risk population were obesity, heaviness in the body, shortness of breath and lassitude, spontaneous perspiration, mass and fullness in epigastrium. These manifestations were consistent with macroscopic differentiation of aggregation syndrome and microcosmic syndrome differentiation showed functional activity of qi was disordered accompanied by aggregation of pathogenic factors such as stagnated heat, turbid damp and blood stasis.5. Aggregation-dissipating reversed the abnormalities of postprandial lipids metabolism in metabolic syndrome high risk population by decreasing TG and FFA concentrations and accelerating TG clearance. Aggregation-dissipating improved central obesity and insulin resistance and regulated levels of the above adipocytokines in metabolic syndrome high risk population, which might be the mechanism of its effect on lipid metabolism.6. Aggregation-dissipating promoted functional activity of qi, dissipated aggregation of pathogenic factors, improved laboratory examinations and alleviated clinical manifestations in metabolic syndrome high risk population, which implicated efficacy of traditional Chinese medicine, verified the theory of aggregation syndrome and embodied the concept of wholism and the thought that veteran doctor took preventive measures of diseases in traditional Chinese medicine.