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The Effect Of The Nesfatin-1Level On Type2Diabetes Mellitus And Its Mechanism

Posted on:2015-12-27Degree:DoctorType:Dissertation
Country:ChinaCandidate:N XuFull Text:PDF
GTID:1224330431975135Subject:Epidemiology and Health Statistics
Abstract/Summary:PDF Full Text Request
Objective:(1) To compare the levels of fast blood nesfatin-1between type2diabetes mellitus patients and non-type2DM patients in old people aged equal and over60years and to analyze the correlated factors to different levels of nesfatin-1. To explore nesfatin-1and other risk factors for type2diabetes mellitus.(2) To investigate whether human recombinant nesfatin-1has the effect on the secretion of insulin and glucagon of isolated mice islets.(3) A meta-analysis To evaluate the diagnostic value of glycosylated hemoglobin Alc (HbAlc)≥6.5%for diabetes in Chinese adults by a Meta-analysis.Methods:(1) A community-based case-control study was conducted. The case group with type2diabetes millituw and the control group without it are from the same community. The study subjects are generated based on a cross-sectional study. They are elders equal and over60year old. All the information was collected by questionnaire in face-to-face interview, including demographic data, lifestyle and behaviors, knowledge on diabetes, state of illness, diabetes family history, clinical data and laboratory data. Independent sample t-test method was used to compare the difference of nesfatin-1between case group and control group. Linear correlation and regression analysis were used to analyze the related factors of nesfatin-1. Unconditional Logistic regression model by was used to analyze the risk factors of diabetes.(2) Mice pancreas were digested by collagenase V through common bile-duct injection and islets were isolated manually. The islets were incubated with different concentrations of human recombinant nesfatin-1. The glucose-stimulated secretion test was used to investigate whether the amount of insulin and glucagon secreted by the islet were changed after incubation. Using the enzyme linked immunosorbent assay (ELISA) to measure the levels of insulin and glucagon.(3) Oral glucose tolerance test (OGTT) was selected as the reference standard. PubMed, EMBASE, CNKI, Wanfang Data, and VIP were searched to obtain all diagnostic tests with HbAlc≥6.5%for diabetes in Chinese adults published between January2003and October2013. Meta-DiSc software was used to conduct a comprehensive quantitative assessment, and summary receiver operating characteristic (sROC) curves were obtained.Results:(1)224subjects including122cases and112controls were investigated and analysed. The constitute of age and gender are comparable between case group and control group. In comparison with control group, case group has lower level of nesfatin-1. The Logistic regression analysis shows that the risk factors for type2diabetes are:higher BMI (OR=1.682,95%CI:1.162-2.436), drinking (OR=0.522,95%CI:0.290-0.943), eating more fruits (OR=0.215,95%CI:0.106-0.436)、eating more eggs(OR=1.853,95%CI:1.051-3.268), eating more meat(OR=2.100,95%CI:1.097-4.021) number of having chronic diseases (OR=1.933,95%CI:1.239-3.017), having coronary heart disease(OR=1.679,95%CI:1.001-2.817), having hypertension (OR=2.280,95%CI:1.334-3.866), having high blood lipids (OR=2.049,95%CI:1.093-3.841), having cerebrovascular diseases (OR=2.528,95%CI:1.329-4.808), family history of diabetes (OR=2.940,95%C:1.658-5.213), higher urea (OR=1.273,95%CI:1.008-1.607), higher creatinine (OR=1.466,95%CI:1.151-1.866), higher level of glucagon (OR=1.521,95%CI:1.197-1.931), insulin resistance (OR=1.396,95%CI:1.103-1.768).And the protective factors are lower level of nesfatin-1(OR=0.738,95%CI:0.583-0.935), p cell function (OR=0.272,95%CI:0.195-0.379), insulin sensitivity (OR=0.708,95%CI:0.559-0.898). The results of multivariate Logistic regression analysis shows that the following factors are risk factors for type2diabetes:higher BMI (OR=1.599,95%CI:1.052-2.429)、 family history of diabetes (OR=2.622,95%CI:1.411-4.875), number of having chronic diseases (OR=1.831,95%CI:1.109-3.022), higher level of creatinine (OR=1.429,95%CI:1.093-1.868), higher level of glucagon (OR=1.549,95%CI:1.185-2.025); while the protective factor is higher level of nesfatin-1(OR=0.755,95%CI:0.576-0.988).(2) The pancreatic islets were successfully isolated. Islets were incubated with different concentrations of human recombinant nesfatin-1for60minutes. At2.8mM glucose, none of the tested concentrations of nesfatin-1caused any statistically significant change in insulin secretion during the1h incubation. At2.8mM glucose, the amount of glucagon secretion after1h incubation is statistically higher than baseline (F=5.869, P=0.026); however, there is no statistically difference between the different concentrations (F=2.283, P=0.131).At16.7mM glucose, nesfatin-1induced dose-dependent increase in insulin secretion in isolated mouse islets (F=53.760, P<0.001). At16.7mM glucose, none of the tested concentrations of nesfatin-1caused any statistically significant change in glucagon secretion during the1h incubation.(3) A total of nine studies with25932subjects were included. Pooled sensitivity was0.518. Pooled specificity was0.956. Pooled positive likelihood ratio was19.007. Pooled negative likelihood ratio was0.477. Pooled diagnostic odds ratio was40.631. AUCsROC was0.9294.Conclusion:(1) In comparison to non type2diabetes patients aged equal and over60years, type2diabetes mellitus patients aged equal and over60years have lower lever of nesfatin-1. This study suggests that higher BMI, family history of diabetes, number of chronic diseases, higher level of creatinine, higher level of glucagon may increase the risk for type2diabetes, while higher level of nesfatin-1may decrease the risk.(2) nesfatin-1stimulates glucose-induced insulin secretion of islets.(3) Compared with OGTT, employing HbAlc≥6.5%(48mmol/mol) to diagnose diabetes in Chinese adults exhibited high specificity and low sensitivity, which would have failed to diagnose48.7%of newly diagnosed diabetes. The diagnostic value could be reduced to improve sensitivity. Long-term prospective studies are required to establish an appropriate HbAlc value as a diagnostic criterion for diabetes in China.
Keywords/Search Tags:diabetes mellitus, nesfatin-1, case-control study, Logisticregression, insulin, glucagon, meta-analysis
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