Genetic And Molecular Epidemiology Of Type 2 Diabetes Mellitus

WHO reports show 30 million persons suffered from various kinds of diabetes all the world in 1985 and the number was 151 million by 2000. The patient number will reach to 300 million in 2025 and 95 percent among them is type 2 diabetes (T2DM). The diabetic of our country has already been up to 30 million people at present, accounts for the one fifth of whole world. The proportion of T2DM is probably 95%. Only strengthen the cause of disease of diabetes to study, probe into the pathogenesis and prevent method, implement primary prevention actively, could prevent of our country diabetes incidence of disease, prevalence rate and mortality rate that rise sharply in the future and reduce it to danger of the society. The type 2 diabetes is acknowledged complicated traits disease generally, the hereditary heterogeneity with height and complicated environmental risk factors. In type 2 diabetes pedigrees, the study of Genetic Epidemiology of pathogenesis would play to important theory directive significance in primary prevention and screening of high-risk population. The study of susceptible gene's single nucleotide polymorphism (SNPs) and its hereditary model is important especially.Part I Epidemiologic Study of Type 2 Diabetes PedigreesThe type 2 diabetes pedigrees were collected to study T2DM genetic and environmental risk factors during the time from 1998 to 2001. A questionnaire and laboratory tests were carried out to get the detail information of the subjects. Their characteristics and the risk factors of T2DM were analyzed based on population pedigrees. The main results are as follows:1. Collection of T2DM pedigrees140 pedigrees candidate have been collected during the collecting period. All persons were collected blood and make OGTT to confirm. Get rid of T1DM, MODY, mitochondria heredity positive pedigrees to all patients with immunology method, pedigree analysis with molecular biology method. Collect to and have building up a database that has 115 eligibility pedigrees.2. The characteristics of T2DM pedigreesThe prevalence is 38.23% in relatives and it is 8.77% to examine the appearing rate newly. It is accounting for 59.13% of all pedigrees that had patients in two or three generations. The prevalence is 48.37% in sib-ships of proband. The prevalence increases as the age (x2 trend=51.640, P = 0.000).Prevalence and appearing rate newly hasn't significant in male and female. It wasn't significant maternal effect among 115 pedigrees.3. Risk factors in T2DM pedigreesThe result of univariate analysis shows that high weight previously, family income drop, hypertension, CHD, hyperlipidemia, obesity, high WHR and waistline to be may risk factors. Multivariate Logistic regression analysis shows that age, hyperlipidemia, hypertension and WHR are the significant factors. In new cases, hypertension is only (OR=6.068, 95%CI: 1.697-21.689). Insulin resistance index (Homa IR) take place the remarkable change promptly with insulin sensitive index in diabetic early. Homa IS and Homa IR changed notably on later stage.Part II Genetic Epidemiology of Type 2 DiabetesThe type 2 diabetes is a complicated traits disease and the hereditary heterogeneity is complex. Population is need for mapping the T2DM gene that it has simple hereditary background. We studied genetic model of T2DM by genetic epidemiology method in 115 pedigrees collected. Themain results are as follows:1. Genetic model in type 2 diabetes pedigreesEstimate the heritability in 115 pedigrees with Falconer's method and the value is 83.42%+4.91%. Dominant major model might influence the gene of T2DM. Analysis of multi-factorial inheritance indicated that there are two genetic patterns. By complex segregation analysis, environment, non-transmitted and co-dominant inheritance were rejected. Autosomal dominant (AD) inheritance and autosomal recessive (AR) inheritance were accepted but AR inheritance was the best pattern. This study suggested that T2DM has significant heritability and genetic heterogeneity,2. Heterogenei...