Dissertation
Dissertation > Medicine, health > Internal Medicine > Digestive and abdominal diseases > Liver and gall bladder disease > Liver metabolic disorders

Circulating Angiotensin Ⅱ Concentration in Men with Nonalcoholic Fatty Liver Disease

Author XuYiZhi
Tutor WuXiaoZuo
School Chongqing Medical University
Course Internal Medicine
Keywords metabolic syndrome nonalcoholic fatty liver disease coronary heart disease hepatic fibrosis angiotensin II
CLC R575.5
Type PhD thesis
Year 2013
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Part1: Relationship between circulating angiotensin IIconcentration with metabolic characteristics in men withnonalcoholic fatty liver diseasePart1.1: Relationship between circulating angiotensin Ⅱconcentrationwith metabolic components in men with nonalcoholic fatty liver diseaseObjective:(1) To analyze the clinical characteristics, circulating angiotensinogen(AGT) and angiotensin Ⅱ(Ang II) concentrations in male nonalcoholicfatty liver disease (NAFLD) patients plus different metabolic components.(2) To investigate the relationship between metabolic components withcirculating Ang Ⅱconcentration in male NAFLD patients.Methods:Thirty-five normal controls and85ultrasonography-proven NAFLDpatients were enrolled. All participants were non-smoking males and hadan alcohol intake less than140g per week, without additional acute orchronic diseases and medication. Insulin resistance was estimated byhomeostasis model assessment of insulin resistance (HOMA-IR).According to the International Diabetes Federation (IDF)(2005) criteria formetabolic syndrome (MS), NAFLD patients were divided into with MS (MS (+)) and without MS (MS (-)) groups; NAFLD patients were dividedinto with metabolic components (component (+)) and without metaboliccomponents (component (-)) groups. The comparisons among groupscomplicated with different numbers of the components of MS wereperformed. All participants performed a75-g oral glucose tolerance test(OGTT) to assay for fasting plasma glucose and2-hour postprandialglucose. Fasting insulin, AGT and Ang Ⅱconcentrations were measured.Results:(1) Among85NAFLD patients,47(55%) were complicated with MS,and83(55%) were complicated with more than1component of MS. Theincidence of visceral obesity, dyslipidemia, hypertension andhyperglycemia in NAFLD patients was86%,75%,41%and33%,respectively. Among all NAFLD patients,33%had an increase FPG and14%had an abnormal glucose tolerance with normal FPG.(2) Serum AGT and Ang Ⅱconcentrations in MS (-) group weresignificantly higher compared to the controls (P <0.001). MS (+) grouponly exhibited a trend towards high AGT and Ang Ⅱconcentrations ratherthan significant difference.(3) Serum Ang Ⅱconcentration was significantly higher in NAFLDpatients with5metabolic components than those with less metaboliccomponents. Serum AGT concentration was significantly higher in NAFLDpatients with5metabolic components than those with5metaboliccomponent (P <0.05).(4) Serum AGT concentration was significantly higher in visceralobesity component (+) group compared to component (-) group (P <0.001).Serum Ang Ⅱconcentration was significantly higher in hypertensioncomponent (+) group compared to component (-) group (P <0.05). SerumAng Ⅱconcentration in hyperglycemia component (+) group only showed an increasing trend compared to component (-) group (P>0.05).(5) Serum Ang Ⅱconcentration was significantly associated withHOMA-IR,2-hour postprandial glucose, fasting insulin and AGTconcentrations in NAFLD patients (r’=0.263,0.238,0.336,0.667; P’<0.01,0.05,0.001,0.001).Conclusions:(1) Metabolic components such as visceral obesity, dyslipidemia,hypertension and hyperglycemia are general in male NAFLD patients.Male NAFLD patients are always complicated with MS.(2) Increased circulating Ang Ⅱconcentration in all male NAFLDpatients was associated with HOMA-IR.(3) Circulating Ang Ⅱconcentration is negatively associated withpostprandial glucose, and has an increasing trend in male NAFLD patientsplus hyperglycemia component. It is presumed that abnormalglycometabolism in male NAFLD patients may result from increased AngII. Male NAFLD patients should be divided into different gourps accordingto different fasting and postprandial blucose. Changes in circulating Ang IIconcentration of different groups will be analysed in our next study.Part1.2: Relationship between circulating angiotensin Ⅱconcentrationwith blood glucose in men with nonalcoholic fatty liver diseaseObjective:(1) To analyze the clinical characteristics, circulating AGT and Ang IIconcentrations in male NAFLD patients with different blood glucose.(2) To investigate the relationship of circulating Ang Ⅱand adiponectinconcentrations with hyperglycemia in male NAFLD patients. Methods:Thirty-five normal controls and85ultrasonography-proven NAFLDpatients without prior known T2DM were enrolled. All participants werenon-smoking males and had an alcohol intake less than140g per week,without additional acute or chronic diseases and medication. Insulinresistance was estimated by HOMA-IR. According to American DiabetesAssociation (ADA)(2006) criteria, NAFLD patients were divided into theeuglycemia and hyperglycemia groups. NAFLD patients withhyperglycemia were subdivided into the isolated impaired fasting glucose(I-IFG) and postprandial hyperglycemia subgroups. All participantsperformed a75-g OGTT to assay for fasting plasma glucose and2-hourpostprandial glucose. Fasting serum AGT, Ang Ⅱand adiponectinconcentrations were measured.Results:(1) Among85NAFLD patients,40(47%) had hyperglycemia, including25(18%) with I-IFG and25(29%) with postprandial hyperglycemia.Among25NAFLD patients with postprandial hyperglycemia,12(14%)had isolated impaired glucose tolerance.(2) Serum Ang Ⅱconcentration in the euglycemia and hyperglycemiagroups was significantly higher compared to the control and euglycemiagroups, respectively (P <0.001, P <0.01); whereas serum adiponectinconcentration was significantly lower (P <0.05). Serum Ang IIconcentration was significantly higher in the postprandial hyperglycemiasubgroup compared to the I-IFG subgroup (P <0.01).(3) Serum Ang Ⅱand adiponectin concentrations were independentpredictors for hyperglycemia in NAFLD patients (OR=1.405,0.654; P <0.01,0.05). Serum Ang Ⅱconcentration was significantly associated withserum adiponectin and2-hour postprandial glucose concentrations inNAFLD patients (r’=-0.337,0.238; P’<0.001,0.05). Conclusions:(1) Hyperglycemia was general in male NAFLD patients. If onlyfasting blood glucose was measured,15%of isolated abnormal glucosetolerance in male NAFLD patients could be missed. It is necessary for allNAFLD patients to perform75-g OGTT.(2) Increased circulating Ang Ⅱconcentration was an independentpredictor for hyperglycemia in male NAFLD patients and associated withpostprandial hyperglycemia and hypoadiponectinemia. It is presumed thatincreased Ang Ⅱmay be involved in the pathogenesis of type2diabetesmellitus in NAFLD patients by promoting insulin resistance, reducing thesecretion of insulin and adiponectin.Part2: Relationship between circulating angiotensin IIconcentration with coronary heart disease risk in men withnonalcoholic fatty liver diseaseObjective:(1) To evaluate the effects of MS on coronary heart disease (CHD) riskin male NAFLD patients.(2) To investigate the relationship between CHD risk with serum Ang IIconcentration in male NAFLD patients.Methods:Thirty-five normal controls and85ultrasonography-proven NAFLDpatients were enrolled. All participants were non-smoking males and hadan alcohol intake less than140g per week, without additional acute orchronic diseases and medication. Insulin resistance was estimated byHOMA-IR and10-year CHD risk was assessed by Framingham risk score(FRS). According to the International Diabetes Federation (IDF)(2005) criteria for MS, NAFLD patients were divided into with MS (MS (+)) andwithout MS (MS (-)) groups. According to FRS, NAFLD patients weredivided into FRS <0and FRS≥0groups. All participants performed a75-g OGTT to assay for fasting plasma glucose and2-hour postprandialglucose. Fasting serum Ang Ⅱconcentration was measured.Results:(1) Serum Ang Ⅱconcentration was significantly higher in MS(-) and FRS≥0groups than in control group and FRS <0group,respectively (P <0.001, P <0.05). There was no significant difference inAng Ⅱconcentration between MS (+) and MS (-) groups. FRS wassignificantly higher in the MS (-) and MS (+) groups than in the control andMS (-) group, respectively (P <0.05, P <0.05).(2) Ten-year CHD risk ratio was positively associated with HOMA-IR,fasting plasma insulin and serum Ang Ⅱconcentrations (r’=0.334,0.245,0.235; P’<0.001,0.05,0.01).Conclusions:(1) Ten-year CHD risk is elevated in male NAFLD patients plus MS orhyperglycemia.(2) Increased10-year CHD risk in male NAFLD patients is positivelyassociated with insulin resistance and serum Ang Ⅱconcentration. It ispresumed that increased Ang Ⅱmay be involved in the pathogenesis ofCHD in NAFLD patients.Part3: Relationship between circulating angiotensin IIconcentration with the degree of hepatic fibrosis in men withnonalcoholic fatty liver diseaseObjective:(1) To evaluate the effects of MS and hyperglycemia on the degree hepatic fibrosis in male NAFLD patients.(2) To investigate the relationship between the degree of hepatic fibrosiswith serum Ang Ⅱconcentration in male NAFLD patients.Methods:Eighty-five ultrasonography-proven NAFLD patients were enrolled. AllNAFLD patients were non-smoking males and had an alcohol intake lessthan140g per week, without additional acute or chronic diseases andmedication. Insulin resistance was estimated by HOMA-IR and the degreeof hepatic fibrosis was assessed by NAFLD fibrosis score (NFS).According to the international diabetes federation criteria for metabolicsyndrome (MS), NAFLD patients were subdivided into MS (MS (+)) andMS (MS (-)) groups. According to American Diabetes Association (ADA)(2006) criteria, NAFLD patients were divided into the euglycemia andhyperglycemia groups. All NAFLD patients performed a75-g OGTT toassay for fasting plasma glucose and2-hour postprandial glucose. Fastingserum Ang Ⅱconcentration was measured.Results:(1) Among85NAFLD patients,25were indeterminate,2had advancedfibrosis and58did not.(2) NFS was significantly higher in the MS (+) and hyperglycemiagroups than in the MS (-) and euglycemia groups, respectively (P <0.05);whereas the ratio of absence of advanced fibrosis was significiantly lower(P <0.05).(3) The degree of hepatic fibrosis was positively associated with serumAng Ⅱconcentration (r’=0.260, P’<0.05).Conclusions:(1) The ratio of absence of advanced fibrosis is elevated in male NAFLDpatients plus MS or hyperglycemia. (2) The degree of hepatic fibrosis is positively associated with serumAng Ⅱconcentration.

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