Risk Factors And The Role Of Chronic Inflammation In The Pathogenesis Of NAFLD And MS

Objective To investigate the prevalence and clinical characteristics of the Nonalcoholic Fatty Liver Disease (NAFLD) and Metabolic Syndrome (MS) in the residents with high risk factors in Wuhan, China.Methods Data to be analyzed were collected from a cross sectional study carried out in a sample of 1928 aged 18-96 years in Wuhan city and persons who were enrolled in the study are or used to be engaged in a sedentary work. Questionaire about age, sex, diet, sport, medical record (such as diabetes, hypertension and hyperlipidemia), and family history was conducted. Body mass index (BMI), waist circumference (WC), blood pressure plasma sugar and lipid profiles were measured. Diagnosis of NAFLD was based on the criteria suggested by Chinese Society of Hepatology (CMA), and the diagnosis of MS and its components followed the 2005 International Diabetes Federation (IDF) and 2004 Chinese Medical Association Diabetes Society (CDS) criteria.Results The prevalences of MS and NAFLD were 18.2%(IDF criteria),16.9%(CDS criteria) and 26.5% respectively, and the hypertension, diabetes, hypertriglyceridemia, hypercholesteremia, low plasma high-density lipoprotein cholesterol, and high plasma low-density lipoprotein cholesterol were 49.9%,9.8%,21.8%,7.8%,47.1%, and 2.8%, respectively. The prevalences of high blood pressure and hyperglycemia were increasing with aging. The peak prevalence of hypertriglyceridemia, overall obesity and NAFLD was between 40 and 70 years old while the peak prevalence of abdominal obesity and MS was between 50 and 70 years old. The prevalences of hypertriglyceridemia and overweight/obesity in young people were as high as 27%-30%, and the prevalences of MS (IDF 2005) and NAFLD were also nearly 10%. The prevalence of NAFLD was higher in patients with hypertension, hypertriglyceridemia, hypercholesteremia, and low plasma high-density lipoprotein cholesterol than that of MS (P<0.01) in those patients. The prevalence of NAFLD was higher than MS in patients of hypertension with hyperglycemia or hiperlipidemia, and in patients of NAFLD or MS, the most common disorders were hypertension, hypertriglyceridemia, and diabetes. The prevalence of NAFLD in our people was nearly 2 times than that was reported in 2005 in Shanghai city and the peak onset of age was 10 years earlier than that in Shanghai city. The prevalence of MS was lower than that was reported in Beijing in 2009, and higher than that was reported in Wuhan city in 2006.Conclusions There was a higher prevalence of the NAFLD and MS in the residents of Wuhan city who are or used to be engaged in a sedentary work than it was reported in national census, and the prevlances of NAFLD and MS were even higher in those with metabolic related diseases. And the younger onset age of the two diseases were in accordance with-the high incidence of diabetes and pre-diabetes in national census, which implied that great attention should be paid to the young. Objective To investigate the clinical feature and risk factors of Nonalcoholic Fatty Liver Disease (NAFLD) and Metabolic Syndrome (MS)Methods Persons were selected from the part one and grouped to four groups:those only with MS (MS); those only with NAFLD (NAFLD); those with both of the two diseases (MN); those with neither of the two diseases (control). Questionaire about medical record, diet, sport and family history was conducted, and fast plasma sugar, lipid profile, body mass index (BMI), waist circumference (WC) as well as blood pressure were measured. Use the recalibration of the Framingham functions to develop coronary heart disease risk and use another original Framingham model to assess the risk of atherosclerotic cardiovascular disease events (coronary, cerebrovascular, and peripheral arterial disease and heart failure).Diagnosis of NAFLD was based on the criteria suggested by Chinese Society of Hepatology (CMA), and the diagnosis of metabolic syndrome its components followed the 2005 International Diabetes Federation (IDF) criteria.Results The prevalences of hypertension, diabetes and hyperlipemia were higher in MS, NAFLD and MN than that in control group (P<0.05 or P<0.01). The diastolic blood pressure, BMI, waist circumference, waist-to-hip ratio, WBC, fasting blood glucose, glycosylated hemoglobin, TC, TG, LDL-C, ALT and GGT were significantly higher in MS, NAFLD and MN than that in control group (P<0.05 or P<0.01). The blood pressure, waist circumference, waist-to-hip ratio and TG were significantly higher in MS than that in NAFLD (P<0.05 or P<0.01). The BMI, WBC, TC and TG were significantly higher in MN than that in MS (P<0.05 or P<0.01); and the blood pressure, BMI, waist circumference, waist-to-hip ratio, WBC, fasting blood sugar, glycosylated hemoglobin and TG were significantly higher in MN than that in NAFLD (P<0.05 or P<0.01). The ten years'coronary heart disease and atherosclerotic cardiovascular disease events risk was higher in MS and MN groups than that in control group (P<0.01), and ten years'coronary heart disease risk of MN group was higher than that of MS and NAFLD (P<0.01), and ten years'coronary heart disease risk of MS group was higher than that of NAFLD (P<0.01), All of the three groups of NAFLD, MS and MN shared the common independent risk factors which were waist circumference and ALT (OR=1.03～1.81, P<0.01). BMI was the common independent risk factor of NAFLD and MN (OR=1.25, OR=1.34 respectively, P <0.01). Systolic pressure, fasting blood sugar and LDL-C were the common independent risk factors of NAFLD and MN (OR=1.02-1.74, P<0.01). TG was the strongest risk factor of MN, following by LDL-C, FBG, BMI, WC, ALT and systolic blood pressure.Conclusions The components and extent of metabolic abnormal were similar between NAFLD and MS, and the metabolic disorders was even worse and the risks of years' coronary heart disease and atherosclerotic cardiovascular disease events were higher when the two diseases co-existance. The hypertriglyceridemia was the strongest predictor of NAFLD with MS. Objective:To explore the mechanisms of obesity related inflammation in patients with MS and NAFLD by comparing the balance status of Interleukin-18 (IL-18) and Interleukin-18 binding protein (IL-18BP) between patients of MS with NAFLD and control ones, as well as the differences of mRNA expressing of proinflammatory and anti-inflammatory factors in the obese adipose tissue.Methods:This was a case-control study. Objects include two parts. One part was from our people of health examination and the other was from persons undertaken gallstone surgery. The first part includes 140 (male,100 and female,40) persons with MS and NAFLD, and 160 (male,114 and female,46) control ones. The second part includes 9 (male,5 and female,4) persons with MS and NAFLD, and 7 (male,3 and female,4) control ones. Body mass index (BMI), waist circumference (WC) and blood pressure were measured. Diagnosis of NAFLD was based on the criteria suggested by Chinese Society of Hepatology (CMA), and the diagnosis of metabolic syndrome its components followed the 2005 International Diabetes Federation (IDF). Fast plasma sugar, lipid profile, liver function and renal function were detected by the automatic biochemistry analyzer. Insulin was measured by radioimmunoassay. Plasma IL-18. TNF-α, adiponectin and plasma IL-18BP concentration were measured with the enzyme-linked immunosorbent assay (ELISA) kit. Visceral and subcutaneous adipose tissue were obtained by abdominoscope and mRNA expression of adiponectin, IL-18, IL-18 receptor and TNF-αwere detected by RT-PCR.Results:The WC, WBC, GC, UA, BMI, TC, LDL, SBP, DBP, ALT, GGT, IL-18, IL-18/IL-18BP ratio, TNF-α, TG, fast insulin and HOMA-IR were significantly higher while HDL and adiponectin were significantly lower in case group than that in control group (all P<0.01 or P<0.05). IL-18/IL-18BP ratio was significantly and positively related with WC, blood pressure, UA, ALT, GGT, BMI, FBG, TC, TG, LDL-C, TNF-α, fast insulin as well as HOMA-IR (rs=0.183～0.585, P<0.01 or P<0.05), and negatively related with adiponectin and HDL-C (rs=-0.312, and-0.369, respectively, all P<0.01); Coefficient of partial correlation of IL-18/IL-18BP ratio with WC, insulin and HOMA-IR were among 0.266 and 0.341 after controlling for age, WBC, ALT, GGT, UA, blood pressure, blood sugar, lipids and BMI (P<0.01). IL-18/IL-18BP ratio was still positively correlated with WC (rs=0.229, P<0.01) after futher controlling for insulin and HOMA-IR. The cases of MS and NAFLD were increased with the increasing quartiles of the IL-18 (x2=32.17, P=0.000) and IL-18/IL-18BP ratio (%2=77.65, P=0.000). ALT (OR=1.036, CI: 1.001～1.072; P=0.042),IL-18/IL-18BP ratio (OR=18.043, CI:2.852～114.139; P=0.002),TNF-α(OR=1.364, CI:1.062～1.752; P=0.015) and TG (OR=2.864, CI:1.269～6.462; P=0.011) were independent risk predictors for MS and NAFLD. The mRNA expression of IL-18, IL-18 receptor and TNF-a were significantly higher in visceral and subcutaneous adipose tissue while adiponectin mRNA expression was lower in MS and NAFLD group than that in control group. The adipotissue mRNA expression of IL-18 was correlated with the elevation of plasma IL-18 (rs=0.668～0.692, P<0.01). Conclusion:Our findings support that obesity related inflammation played an important role in pathogenesis of MS and NAFLD and it was reasonable to consider the IL-18BP when evaluating the function of IL-18 in these diseases.