年龄、家族史对上海地区正常血糖人群胰岛β细胞功能与胰岛素敏感性的影响

发布时间：2018-06-12 09:43

本文选题：糖尿病 + 家族史　；参考：《第二军医大学》2017年硕士论文

【摘要】：研究目的:糖尿病(diabetes mellitus,DM)是一种胰岛分泌胰岛素不足或机体无法有效利用胰岛素的慢性疾病,而全球糖尿病患者数量从1980年的1亿八百万到2014的4亿2千2百万,以18岁以上人群计算,患病率从1980年的4.7%增加到了2014年的8.5%,已经成为全球性公共卫生问题。我国作为人口基数庞大的发展中国家,20岁以上人群中患病率高达15.5%。而在糖尿病中,2型糖尿病占绝大多数,以高血糖、胰岛素抵抗(insulin resistance,IR)和相对胰岛素缺乏为疾病特点。而且2型糖尿病患病率随年龄增长而增加,在60-74岁之间会达到高峰,几乎三分之一的老年人患有2型糖尿病,四分之三有糖调节受损,它的发生是遗传因素和行为、生活方式共同作用下的结果。本研究以长期在上海市居住的健康人群作为研究对象,对不同年龄状态、不同遗传背景的人群β细胞功能及胰岛素抵抗特点进行研究,对评估上海市居民的胰岛β细胞功能状态、发现2型糖尿病高危人群具有重要意义。研究方法:本研究是观察性研究,研究对象来自于上海市卫生与计划生育委员会公共卫生三年行动计划《上海市成人自身免疫性甲状腺疾病(AITD)筛查及评估系统》重点项目,自2016年11月至2017年2月以南桥镇社区、曹路镇社区、江桥镇社区、天平街道社区、南桥街道社区为调查地点,每个社区随机抽取10个居委会,居委会在管辖小区以每户一名随机抽取一定数量受试者,每户选择生日离调查日期最近的家庭成员为调查对象,共计随机抽取了344名18岁至65岁在上海居住时间大于半年的居民为研究对象,抽样方法为居委会随机抽取一定户数,以每户家庭成员中生日日期最接近流行病学调查期者为研究对象,并排除了怀孕,既往有糖耐量异常或糖尿病病史,合并多囊卵巢综合症、自身免疫性疾病等可能影响血糖水平的疾病,合并有骨折、严重精神障碍或痴呆症、卧床、肝炎、结核病、艾滋病或其他传染病以及其他严重重要脏器疾病,长期口服糖皮质激素、避孕药等影响血糖水平药物的受试者。采集受试者2型糖尿病家族史相关信息,测量身高、体重,检测血脂水平、空腹静脉血浆葡萄糖浓度、空腹静脉血浆胰岛素浓度、口服糖耐量试验(oral glucose tolerance test,OGTT)后2小时静脉血浆葡萄糖浓度、口服糖耐量试验后2小时静脉血浆胰岛素浓度,计算HOMA-β、HOMA-IS、HOMA-IR、GUTT-ISI指数评估胰岛β细胞功能与胰岛素抵抗。通过针对不同年龄段、不同遗传背景、不同遗传强度进行分组,经正态分布检验后计算均数及标准差,以Student-Newman-Keuls多重比较组间差异。结果:上海各社区344名受试者中,根据1999年WHO糖尿病专家委员会报告标准,糖尿病(DM)患者37例,空腹血糖受损(IFG)者4例,糖耐量减低(IGT)者26例,正常血糖(NGR)者277例。电话回访家族史相关信息,采集到家族史信息者共计292例,其中家族史阳性者90例,家族史阴性者202例,家族史阳性者中父系遗传者40例,母系遗传者31例,双亲遗传者11例,仅同胞有2型糖尿病者8例。校正BMI及甘油三酯水平后,针对正常血糖人群进行分析,以年龄分为8组,即18岁-24岁(YrA组)、25岁-30岁(YrB组)、31岁-36岁(YrC组)、37岁-42岁(YrD组)、43岁-48岁(YrE组)、49岁-54岁(YrF组)、55岁-60岁(YrG组)、61-65岁分组(YrH组),总体趋势上HOMA-β、HOMA-IS、GUTT-ISI在年龄较高组别偏低,SNK检验表明YrA组、YrB组、YrC组的HOMA-β分别较YrF组、YrG组、YrH组别具有明显差异,YrB组的GUTT-ISI较除YrC组外的其余组别均具有显著差异,而HOMA-IS指数组间无明显差异。根据家族史情况及遗传强度分为家族史阳性组(FH+组)、家族史阴性组(FH-组)、父系遗传(FHF组)、母系遗传(FHM组)、双系遗传(FHB组)、轻度家族史组(FH1组)、中度家族史组(FH2组)、重度家族史组(FH3组),其中轻度家族史指有1个二级亲属患有糖尿病,中度家族史指1个一级亲属+1个二级亲属/1个一级亲属/2个以上来自同一家系的二级亲属,重度家族史指至少2个一级亲属/1个一级亲属+2个以上来自同一家系的二级亲属。经Student’s t检验,FH+组HOMA-β较FH-组高。经Student’s t及SNK检验,其余指标组间无明显差异。结论:1.通过多因素组间比较,年龄为胰岛素抵抗影响因素,其中49岁以后人群胰岛素敏感性及β细胞分泌功能存在随年龄下降的表现。2.具有2型糖尿病家族史的正常血糖人群β细胞功能较无家族史者好,其余不同遗传背景、遗传家系、遗传强度之间的胰岛β功能、胰岛素敏感性无明显变化规律及相关性。不同年龄组之间各项指标无明显统计学差异,但胰岛素分泌及敏感性有随年龄下降的趋势。
[Abstract]:Research objectives: diabetes mellitus (DM) is a chronic disease of islet secreting insulin deficiency or the body's inability to use insulin effectively, and the number of diabetic patients worldwide from 1 billion to 2014 in 1980 is 422 million over 18 years of age, and the prevalence rate has increased from 4.7% in 1980 to 8.5% in 2014, As a global public health problem, as a developing country with a large population base, the prevalence rate of people over 20 years of age is up to 15.5%. while in diabetes, type 2 diabetes is the majority, with hyperglycemia, insulin resistance (insulin resistance, IR) and relative islet deficiency as the disease characteristics. And the prevalence rate of type 2 diabetes is associated with the disease. The increase of age and the peak between 60-74 years of age, almost 1/3 of the elderly people with type 2 diabetes and 3/4 impaired glucose regulation, is the result of a common effect of genetic factors and behavior and life style. This study is based on a healthy population living in Shanghai for a long time. The study of beta cell function and insulin resistance in people with different genetic backgrounds is of great significance for assessing the function status of islet beta cells in Shanghai residents and finding the high risk population of type 2 diabetes. The research method is an observational study, and the research object is from the public health of the Shanghai health and Family Planning Commission. The three year action plan, "Shanghai adult autoimmune thyroid disease (AITD) screening and evaluation system > key project, from November 2016 to February 2017, from the community in the town of Nan Qiao Town, the community in the town of Cao Lu Town, the community of Jiangqiao Town, the community of the Tian Ping Street, the community of the South Bridge, the neighborhood committee of each community, the neighborhood committee is under the jurisdiction of the neighborhood committee. Each household selected a certain number of subjects at random. Each household selected the nearest family members from the date of the date of the birthday to investigate. A total of 344 residents aged 18 to 65 and 65 years old were selected for the study. The date is most close to the epidemiological study, and excludes pregnancy, past glucose tolerance or diabetes, polycystic ovary syndrome, autoimmune diseases, and other diseases that may affect blood sugar levels, including fractures, severe mental disorders or idiosis, bed, hepatitis, tuberculosis, AIDS, or other infections. Patients with disease and other serious organ diseases, long-term oral glucocorticoids, contraceptives, and other subjects affecting blood glucose levels were collected. The family history of subjects with type 2 diabetes was collected, height, weight, blood lipid level, fasting plasma glucose concentration, fasting venous plasma insulin concentration, oral glucose tolerance test (ORA L glucose tolerance test, OGTT) venous plasma glucose concentration after 2 hours, 2 hours intravenous plasma insulin concentration after oral glucose tolerance test, and calculate HOMA- beta, HOMA-IS, HOMA-IR, GUTT-ISI index to evaluate islet beta cell function and insulin resistance. Result: among 344 Shanghai community subjects, 37 cases of diabetes (DM), 4 cases of impaired fasting blood glucose (IFG), 26 cases of impaired glucose tolerance (IGT) and 277 cases of normal blood glucose (NGR), among 344 subjects in each community of Shanghai, according to the report standard of the 1999 WHO diabetes expert committee. A total of 292 family history information were collected, including 90 family history positive, 202 family history negative, 40 paternal hereditary, 31 maternal inheritance, 11 parent hereditatrix and 8 of type 2 diabetes mellitus. After correction of BMI and triglyceride level, it was aimed at normal blood glucose. The population was divided into 8 groups, which were divided into 8 groups, namely, 18 years old (group YrA), 25 year old -30 years (group YrB), 31 year old -36 years (group YrC), 37 year old -42 (YrD group), 43 year old -48 (YrE group), 49 year old -54 years (YrF group), 55 years old (Group), 61-65 year old group (Group). Group YrC, HOMA- beta in group YrC, YrG and YrH groups were significantly different. The GUTT-ISI in group YrB had significant differences compared with the other groups except the YrC group, but there was no significant difference between the HOMA-IS index group and the family history and the genetic intensity. Heredity (group FHM), double inheritance (group FHB), mild family history group (group FH1), moderate family history group (group FH2), severe family history group (group FH3), of which 1 two degree relatives have diabetes, moderate family history refers to 1 first-degree relatives +1 two relative /1 first relatives /2 more than two degree relatives from the same family, and severe family history. Family history refers to the two degree relatives of /1 first degree relatives of at least 2 first degree relatives and more than +2 from the same family. After Student 's t test, HOMA- beta in group FH+ is higher than that of FH- group. There is no significant difference between the other index groups after Student' s t and SNK test. Conclusion: 1. through multiple factors group comparison, age is the influence factor of insulin resistance, of which 49 years after age. The expression of insulin sensitivity and beta cell secretory function in the population decreased with age..2. with the family history of type 2 diabetes, the function of beta cells in normal blood glucose population is better than those without family history. The rest of the genetic background, genetic family, the islet beta function between the genetic intensity and the islet sensitivity have no obvious change law and correlation. There was no significant difference in age between groups, but insulin secretion and sensitivity decreased with age.
【学位授予单位】：第二军医大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R587.1

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