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The Correlation Study Of Bone Metabolism Indexes In Middle-aged Men With Non-alcoholic Fatty Liver Disease And Carotid Atherosclerosis

Posted on:2019-12-05Degree:DoctorType:Dissertation
Country:ChinaCandidate:H DengFull Text:PDF
GTID:1364330572954176Subject:Internal Medicine Endocrinology and Metabolism
Abstract/Summary:PDF Full Text Request
Background:Non-alcoholic fatty liver disease(NAFLD)is characterized by intrahepatic triglyceride deposition,which can develop from simple steatosis to steatohepatitis and even to cirrhosis.In the epidemiological studies,the prevalence of NAFLD has become the leading cause of chronic liver disease.In addition to lipid metabolic disorders,patients with NAFLD are accompanied by obesity,hyperglycemia,hypertension,high uric acid,high microalbuminuria and so on.It is considered that the insulin resistance is the common pathogenesis of these diseases presented as the liver metabolic syndrome.Recently,the relationship between bone metabolism and insulin resistance becomes a hot topic in research.Exceptional to be a conventional calcium and phosphorus storage organ,more and more studies have proven bone involved in the glucose and energy metabolism to be an endocrine organ.One of the important evidences of this argument is that the osteoblast-specific secreted non-collagenous osteocalcin(OCN)has been shown to be involved in the regulation of insulin secretion,improvement of insulin sensitivity,decrement of blood glucose and triglyceride,weight loss,increment of energy consuming and so on.OCN is closely related to glucose and lipid metabolism as well as the body fat distribution,and is recognized to be an important predictor of insulin resistance and abdominal obesity.In addition to OCN,the bone metabolic indicators such as the bone formation factor procollagen type I N-terminal propeptide(PINP)and bone turnover indicator Beta-C-terminal telopeptide of type I collagen(β-CTX)were also detected.It was believed that the OCN was not the only key molecule involved in the signaling pathway of glycolipid and bone metabolism.However,there is no study on P1 NP andβ-CTX involved in the energy metabolism and body fat distribution.Therefore,the correlation between various bone metabolic indicators and the occurrence of NAFLD was investigated in this study via studying the NAFLD in middle-aged men,by which the association between bone metabolism and the development of NAFLD could be further explored.Objective:To investigate the relationship between bone metabolic indicators and NAFLD in middle-aged men.Methods:The bone metabolic indicators of 232 healthy middle-age men with NAFLD(NAFLD group)and 308 healthy controls without fatty liver(Control group)were measured,including non-collagenous osteocalcin,the procollagen type I N-terminal propeptide(PINP),beta-C-terminal telopeptide of type I collagen(β-CTX).The Student’s t-test was used to analyze the differences in the bone metabolic indicators,age,clinical data,biochemical indicators,and the indicators of glucose and lipid metabolism between the two groups.The correlation of fatty liver related indicators were detected using the logistic regression analysis.Result:The body mass index(BMI)(P< 0.01)and diastolic blood pressure(P < 0.05)in NAFLD group were significantly higher than those in Control group.Among the indicators of glucose and lipid metabolism in NAFLD group,the levels of blood glucose [fasting plasma glucose,postprandial blood glucose and hemoglobin A1c(Hb A1c)] were significantly higher than those in Control group(P < 0.01).In addition,the insulin resistance were also significantly higher than those in Control group(P < 0.01).The levels of lipid metabolic indicators such as triglyceride were higher,but high-density lipoprotein cholesterol was lower than that in Control group(P < 0.01).In addition,there were significant differences in alanine aminotransferase,glutamyl transpeptidase,uric acid and urinary microalbumin between the two groups(P < 0.01).From logistic regression analysis,Low PINP,high BMI,hyperglycemia(FPG and Hb A1c),high UA and low HDL-C were associated with NAFLD.Conclusion:The bone metabolic indicator PINP might be a potential predicator for the diagnosis of NAFLD.Background:Atherosclerosis-induced cardiovascular events and cerebrovascular events,cause death in almost 50% of cases in developed countries.Of these fatal cases,20% are related with carotid artery.Patients with concomitant carotid atherosclerotic disease and coronary artery disease are more likely to have widespread atherosclerosis,and are related with higher risk of recurrent symptoms and complications.Several risk factors of carotid atherosclerotic disease,including smoking,age,hypertension,abnormal levels of triglyceride and lipoprotein cholesterol,have been identified.Notably,aggregating evidence demonstrated that the diabetes mellitus is an predicator of atherosclerosis.Recently an increasing number of investigations found that bone metabolism could be related with carotid atherosclerosis.Carotid intima-media thickness(CIMT),known as a significant factor to increase the risk of myocardial infarction and ischemic stroke,was also reported to be closely related with lumbar spine BMD in postmenopausal women.Atherogenic stimuli not only induces the transformation of smooth cells into osteoblast-like cells and acceleration of vascular calcification,but also prompt the release of bone formation markers and osteoclast differentiation and activation.Osteocalcin(OCN),for example,a bone formation marker which is produced by osteoblastic cells and derived from procollagen metabolism,is a specific and sensitive parameter of bone remodeling involved in bone mineralization and calcium homeostasis.OCN is reported to participate in the regulation of the adipose-related gene expression,and influence the glucose tolerance,fat consumption,insulin resistance.Previous studies also found that bone remodeling could be regulated by adipose tissues through the effects of leptin on osteoblasts,therefore a feedback loop with bone-regulated energy metabolism,and that bone is skeleton is indicated to be an endocrine organ.Previously,the level of serum OCN was found to be closely related with the participants who had self-reported cardiovascular disease in middle and elderly aged Chinese.Similarly,OCN is also found to be a critical determinant of coronary atherosclerotic severity in Chinese male participants.On this basis,it is reasonable to deduce that serum OCN is a potential candidate for detecting the risk of carotid atherosclerosis and the abnormal glucose metabolism.In our study,to address this issue,we collected anthropometric parameters,serum OCN level,blood glucose and lipoid profile in a total of 355 middle age(40-60 years old)man who were divided into AS group and control group according to the measurement of carotid intima–media thicknesses(CIMTs),and their association with carotid atherosclerosis was analyzed.Objective:To investigate the the role of osteocalcin in carotid atherosclerosis in human.Methods:A total of 335 male middle-aged participants(40-60,52.4 ± 3.87 years old averagely)were enrolled from the institute.The carotid intima–media thicknesses(CIMT)of each subject were measured.All subjects were included either in the carotid atherosclerosis(AS)group or the control group according to the CAS diagnosis criteria.Serum osteocalcin and other markers of each patient were assessed following standard laboratory tests protocol.Result:135 subjects were included in AS group,and 199 subjects were included in control group.The average osteocalcin level in AS group was 18.71 ± 6.20 ng/ml,and was significantly different from that in control group,which was 20.38 ± 7.19 ng/ml(P = 0.039).Logistic regression analysis revealed that OCN(standardized β=-0.024,P = 0.013)and FINS(standardized β=-0.065,P = 0.010)were independently and inversely associated with the carotid atherosclerosis,while FPG(standardizedβ=0.538,P = 0.006)was independently and positively associated with the carotid atherosclerosis.Conclusion:Our study suggests that OCN is independently related with carotid atherosclerosis in middle-aged male individuals.
Keywords/Search Tags:non-alcoholic fatty liver, osteocalcin, TypeⅠcollagen Amino-extended peptide, β-collagen special sequence, carotid atherosclerosis, atherosclerosis
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