| Objective:Metabolic syndrome (MS) is a cluster of metabolic disorders at high risk of cardiovascular disease and type 2 diabetes, including abdominal fat accumulation, atherogenic vascular abnormalities, hypertension, hyperglycaemia, insulin resistance, pro-inflammatory state and pro-thrombotic state. Dietary factors are closely related with metabolic syndrome. It has been shown that the more diverse the food, the less risk of hypertension, hypertriglyceridemia and impaired glucose tolerance. Gene is also a factor that can not be ignored in developing metabolic syndrome. Lipoprotein lipase (LPL) is one of key enzymes in lipoprotein metabolism, and plays a major role in triglyceride-rich lipoprotein metabolism, closely related with many cardiovascular diseases such as atherosclerosis, diabetes and obesity.Lifestyle interventions such as diet and exercise are now the widely used control measures. However,there are less studies considering the genetic background of MS patients in evaluating the effect of intervention. This thesis would explore the gene-diet interaction in controlling MS, including its effect on adipokines (adiponectin, leptin), inflammatory factors (C reactive protein, tumor necrosis factor a) and serum LPL levels. The concerned gene polymorphism would be LPL Pvu II, Hind III and s447x polymorphism.Subject and Method:A multistage cluster random sampling method was used to select MS subjects in two urban districts in Shanghai. In those who participated in physical examination,272 subjects were diagnosed as MS according to the definition of MS by International Diabetes Federation. One district was chosen as intervention group, and the other as control group. One year health education was performed in intervention group and the health education included:reducing salt, simple sugar and fat consumption especially pork lard and cooking oil while taking appropriate energy; taking in various types of food for their energy level according to Dietary Guidelines for Chinese Residents, increasing the proportion of coarse grains, and also half of vegetables and fruit should be of the dark color. At the end of the study,235 MS subjects complete the entire year of study,including 41 male and 79 female in control group,34 male and 81 female in intervention group.Results:At baseline, the average dietary fiber intake of MS subjects was lower than 25g/d (t=-29.80, P<0.001)。The average protein intake in male was lower than 75g/d(t=-3.64,P<0.001), the average protein intake in female was lower than 65g/d(t=-9.61,P<0.001)。Carbohydrate for energy ratio was lower than the lower limit of AI (Adequate Intake) limit 55%(t=-10.69, P<0.001), fat for energy ratio was higher than the upper limit of AI 30%(t=12.21,P<0.001)。Average K intake was lower than AI 2000mg/d (t=-18.80, P<0.001)。There was nutrients for energy imbalance, inadequate vegetable and dietary fiber intake in MS subjects.At baseline, adiponectin, leptin, lipoprotein lipase levels was lower in male subjects than in female subjects. After adjusting for gender, those correlated with adiponectin at P<0.05 level were waist hip ratio (rs=-0.139, P=0.035), fasting glucose (rs=-0.134, P=0.042), insulin resistance index (rs=-0.162, P=0.015), triglycerides (rs=-0.186, P=0.005), lipoprotein lipase (rs=0.239, P<0.001). After adjusting for gender, leptin was correlated with BMI (rs=0.416, P<0.001), waist circumference (rs=0.259, P<0.001), fasting insulin (rs=0.357, P<0.001), insulin resistance index (rs=0.305, P<0.001), total cholesterol (rs=0.133, P=0.042), high density lipoprotein cholesterol (rs=0.190, P=0.004) and C-reactive protein (rs=0.181, P=0.006). C-reactive protein was associated with BMI (rs=0.243, P<0.001), waist circumference (rs=0.197, P=0.003), fasting insulin (rs=0.350, P<0.001), insulin resistance index (rs=0.279, P<0.001), leptin (rs=0.181, P=0.006) and lipoprotein lipase (rs=-0.182, P=0.005). After adjustment for gender, lipoprotein lipase was associated with fasting plasma glucose (rs=-0.129, P=0.050), fasting insulin (rs=-0.202, P=0.002), insulin resistance index (rs=-0.237, P<0.001), triglycerides (rs=-0.227, P<0.001) and C-reactive protein (rs=-0.182, P=0.005).PvuII (x2=1.97, P=0.373), HindⅢ(x2=0.67, P=0.716) and S447x (x2=0.03, P=0.984) polymorphisms in MS subjects meet Hardy-Weinberg equilibrium law. There was no difference in physiological and biochemical measures between three PvuII genotype(p-p,p-p+,p+p+) in MS subjects. Male lipoprotein lipase was higher in HindⅢh-h+ genotype than it was in h+h+(t=2.21, P=0.031). In h+h+, total cholesterol of women was higher in the p-allele than it was in p+p+ genotype (t=4.12, P<0.001), the differences was still significant after adjusting for age and BMI (t=-4.25, P<0.001). LPL was higher in xx and sx genotype than it was in ss genotype (z=2.93, P=0.003).Robust regression analysis was applied with dietary factors, genotype and genotypexdietary factors as predictor variables, physiological and biochemical measures as dependent variable. After adjusting for sex, age and BMI, a PvuII site-ω-6 polyunsaturated fatty acids (ω-6PUFA) interaction on insulin resistance was found. MS p+p+ subjects were resistant to the risk of insulin resistance that may be caused byω-6PUFA high intake. In addition, s447x site and saturated fat (carbohydrate, energy) interaction on insulin levels, s447x site and carbohydrate interaction on insulin resistance were also found. MS ss genotype subjects were resistant to the risk of higher insulin levels that may be caused by saturated fatty acids, carbohydrates and high energy intake. MS ss genotype subjects were resistant to the risk of insulin resistance that may be caused by high carbohydrate intake.After one year intervention in intervention group, the nutrition-related knowledge, attitudes, behavior were all improved in intervention group. After the intervention, counted in food for energy ratio, carbohydrate (χ2=26.82, P<0.001), cereal (χ2=5.50, P=0.019), vegetable (χ2=9.26, P=0.002), fruit (χ2=34.08, P<0.001) intake increased,and K (χ2=19.39, P<0.001) also increased; fat (χ2=32.42, P<0.001), other food (χ2=24.79, P<0.001) intake decreased, and sodium (χ2=4.33, P=0.037) also decreased. Also after the intervention, counted in food for energy ratio, carbohydrate (χ2=5.91, P=0.015), vegetable (χ2=4.20, P=0.040), fruit (χ2=5.92, P=0.015) intake were higher, fat intake (χ2=4.55, P=0.033) was lower in intervention group compared with they were in the control group. All the above change reflected higher intake of vegetable and fruit in intervention group and dietary pattern was closer to the recommended diet in intervention group.After intervention, waist circumference (χ2=7.99, P=0.005) was lower and the magnitude of the decrease was more significant (z=-2.91, P=0.004) in intervention group than it was in control group. Waist to hip ratio (χ2=20.54, P<0.001) decreased only in intervention group, and the level after intervention was lower (χ2= 15.46, P<0.001) in intervention group than it of the control group, the magnitude of the decrease was more significant (z=-4.19, P<0.001) in intervention group than it was in control group.After the intervention, triglyceride decreased both in intervention group and control group, but triglyceride in control group was higher than 1.7mmol/L (t=1.78, P=0.039), while triglyceride in intervention group was equal to 1.7mmol/L (t=0.46, P=0.324). High-density lipoprotein cholesterol (χ2=8.47, P=0.004) increased in intervention group and it was higher (χ2=10.59, P=0.001), also the magnitude of the increase was more significant (z=2.02, P=0.044) in intervention group compared with they are in control group. Total cholesterol in control group decreased (z=-7.39, P<0.001) while it in intervention group increased (χ2=2.17, P<0.001), but there was no statistic difference between two groups, the overall total cholesterol level were less than 5.2mmol/L(t=-6.61, P<0.001). LPL in intervention group decreased (χ2=4.16, P=0.041), but there was no significant difference between groups.After the intervention, leptin (χ2=10.34, P=0.001), tumor necrosis factor a (χ2=25.13, P<0.001) was lower in intervention group than that of the control group, the decrease of tumor necrosis factor a (z=-5.11, P<0.001) was more significant compared with it was in control group. Adiponectin increased (χ2=9.37, P=0.002) in intervention group, the increase was more significant (z=2.05, P=0.040) compared with it was in control group.After stratification of LPL gene PvuII (HindⅢ, s447x) polymorphism, the LPL gene-diet interaction was analyzed. After the intervention, physiological measures, serum lipids, glucose, adiponectin, leptin, tumor necrosis factor a in intervention group were improved in p+p+, h+h+, ss genotype, or the magnitude of improvement were greater. The stratification analysis implied that p+p+, h+h+ and ss genotype were more susceptible to intervention, which may be beneficial for MS subjects.
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