DNA甲基化调控在慢性病发生、发展过程中的作用

DNA甲基化是重要的表观遗传学修饰,与基因表达异常、 DNA损伤修复、基因组不稳定性,遗传性状的改变密切相关。以往的研究已经证实许多肿瘤的发生与DNA甲基化调控相关,最近有不少报道表明在慢性病[如肥胖,糖尿病,心脑血管疾病,哮喘,慢性阻塞性肺疾病（ COPD）等]发生发展过程中,一些特异性基因启动子区域CpG岛甲基化发生了改变,可能是导致慢性病发病的主要因素。文章阐述了DNA甲基化水平在一些慢性病发生、发展过程中的变化及其影响,为相关疾病的预防、诊断以及治疗提供新的思路。     

The association of psychiatric diagnoses, health service use, and expenditures in children with obesity-related health conditions

Objective To examine the association of psychiatric diagnosesand use of health care services in children with obesity-relatedhealth conditions. Method A retrospective, longitudinal designwas used to examine Medicaid claims data. The data set consistedof 13,688 youth diagnosed with type 2 diabetes, metabolic syndrome,dyslipidemia, or obesity. Results The presence of any type ofpsychiatric diagnosis was associated with higher health serviceuse. In particular, the presence of an internalizing diagnosiswas more consistently associated with higher service use thanthe presence of an externalizing diagnosis. Children with bothan externalizing and internalizing disorder diagnosis had greaterservice use than children with a diagnosis in only one of thesecategories. Conclusions These data highlight a subgroup of childrenwith obesity-related health conditions who are at greater riskfor higher health service use, and the need for further researchon the association between psychiatric diagnosis and healthservice use.     

Short-term results of community-based interventions for improving physical activity: Isfahan Healthy Heart Programme

Introduction

To assess the effect of a comprehensive community-based programme for increasing physical activity (PA) after 2 years of interventions.

Material and methods

A 6-year, action-oriented, comprehensive, and integrated community-based study, entitled the Isfahan Healthy Heart Programme, was conducted in Iran from the year 2000. The interventions targeted the whole population of nearly 2,180,000 living in two cities, and were compared with another city considered as a reference. Educational, environmental and legislative interventions were conducted at the community level. Annual evaluations were performed among 6,000 representative individuals. This paper presents the changes in PA habits after 2 years of interventions for increasing PA. The PA habits were assessed by using the Baecke questionnaire, and an energy expenditure of 150 kcal for daily leisure time physical activity was adopted as a cut-off for defining active and inactive lifestyle.

Results

In the intervention and reference areas, respectively 85 and 83% of the population were physically inactive. From 2000 to 2002, the daily PA among both genders decreased in both intervention and reference communities. Meanwhile, the leisure-time PA increased significantly in the intervention area, but decreased in the reference area. The transportation PA did not significantly change in the intervention area, but showed a remarkable decline in the reference area.

Conclusions

We suggest that the synergism resulting from community collaborations has been effective in improving some aspects of PA in our community. The ongoing changes in environmental factors and policies can help in increasing the worksite and transportation PA in later stages of this community-based programme.     

99th Dahlem Conference on Infection,Inflammation and Chronic Inflammatory Disorders: The normal gut microbiota in health and disease

Mammals are metagenomic, in that they are composed not only of their own genome but also those of all of their associated microbes (microbiome). Individual variations in the microbiome influence host health and may be implicated in disease aetiology. Therefore, it is not surprising that decreased microbial diversity is associated with both obesity and inflammatory bowel disease. Studies in germ‐free mice have demonstrated that the gut microbiota is required for development of diet‐induced obesity as well as inflammatory diseases. However, the underlying molecular mechanism(s) for how the gut microbiota causes metabolic diseases is only beginning to be clarified. Furthermore, emerging data suggest that the gut microbiota may predispose or protect against other important diseases such as cardiovascular disease and diabetes.     

不同糖代谢状态人群的肥胖指标与动脉硬化的相关性

目的研究北京市社区不同糖代谢状态人群的肥胖指标与动脉硬化的相关性。方法用臂-踝脉搏波传导速度(baPWV)反映动脉硬化程度。对北京市石景山区两个社区大于或等于40岁居民进行体格检查,测量体重(weight)、腰围(WC)、体重指数(BMI)、腰臀比(WHR)、腰围升高比(WHtR)及标准化问卷调查、生化和糖化血红蛋白检测、75 g葡萄糖耐量实验及baPWV测量。对数据资料完整及BMI大于或等于18.5 kg/m2的9 080名人员根据75OGTT试验及糖尿病史分为NGT、IGR和DM组,分析BMI、WC、WHR、WHtR与baPWV之间的关系。结果在NGT、IGR、DM组,根据WC、WHR、WHtR分成亚组,中心型肥胖组的baPWV明显高于正常组(P0.01),在DM组内,以BMI作为肥胖标准,baPWV仅在NGT和IGR组内有统计学意义,在DM组无显著差异(P0.05)。在NGT、IGR和DM组内,中心型肥胖指标(WC、WHR、WHtR)与baPWV呈显著正相关(P0.05),BMI仅在NGT组内与baPWV呈正相关,在IGR和DM组内无明显相关(P0.05)。校正年龄、性别、心血管危险因素,通过多元回归分析发现,WHR和WHtR每增加0.1,baPWV则随之升高40.6 cm/s和55.3 cm/s。结论在糖代谢异常人群中,中心性肥胖指标(WC、WHR、WHtR)与动脉硬化呈正相关,较BMI更能反映动脉硬化程度。     

Avoiding the under-diagnosis of low bone mineral density in Egyptian children with chronic medical conditions affecting bone health

Introduction

The International Society for Clinical Densitometry recommended that the lumbar spine and total body less head (TBLH) are the most accurate and reproducible skeletal sites for performing areal bone mineral density (BMD) measurements. Our objective is to evaluate the role of measurement of femoral neck BMD in avoiding the under-diagnosis of low BMD being a risk for fractures in subjects with chronic medical conditions that might affect bone health.

Material and methods

Subjects with chronic medical conditions that might affect bone health were studied (n = 468) and 36 healthy children were recruited as control subjects. Physical examinations, height, weight measurements and BMI were calculated. Dual-energy radiographic absorptiometry of the lumbar spine and femoral neck were measured.

Results

Bone mineral density z scores in both sites were significantly reduced in chronic patients, compared with control subjects. Prevalence of very low BMD z scores (–2 or more) using lumbar DXA, femoral DXA, and either of the sites were 1.38%, 3.37%, and 3.96%, respectively, while low BMD Z scores (–1 to less than –2) were 9.52%, 18.05% and 21.14% respectively.

Conclusions

We identified a significant decrease in both lumbar and femoral BMDs in studied children. Sometimes femoral BMD is decreased while lumbar BMD is still within the normal range. For this reason we recommend that, when technically feasible and there is no facility to measure TBLH, all those patients should have lumbar spine and femoral neck bone mineral density measurements to avoid under-diagnosis of low BMD being a risk for fractures.     

The relative efficacy of two exercise methods for older adults with chronic low back pain: A preliminary randomized control study

The objective of the current study was to examine the relative efficacy of two exercise techniques—a multidimensional treatment (MDT) and a traditional senior exercise therapy treatment (TET)—in older adults diagnosed with chronic low back pain (CLBP). Participants (N = 16) were randomly assigned to either the MDT (n = 8) or TET (n = 8) groups after meeting the requirements for the presence of CLBP. Participants in the MDT group received an individualized exercise program, while participants in the TET participated in a group exercise program. A Mann–Whitney test was conducted to determine differences between psychosocial and physical variables pre- and post-intervention. Statistical analyses indicated no significant differences in physical or psychosocial variables at pre-intervention assessment. However, participants in the MDT group reported a decrease in fatigue and pain interference, with an increase in physical functioning, when compared to the TET group. Additionally, the MDT group displayed a significant decrease pain interference, while the TET group had an increase grip strength. Patients who received the MDT reported less fatigue and pain interference, and an increase in their overall physical functioning. Overall, the MDT was a more efficacious method to manage CLBP.     

Analysis of three glucose transporter genes in a Caucasian population: no associations with non-insulin-dependent diabetes and obesity

The significance of variation within the genes coding for three glucose transporter proteins in the aetiology of non-insulin dependent diabetes mellitus was assessed by analysing restriction fragment length polymorphisms in an English Caucasian population. Two polymorphisms at the HepG2/erythrocyte glucose transporter (GLUT1) locus, four at the liver/pancreatic glucose transporter (GLUT2) locus and one at the muscle/adipocyte glucose transporter (GLUT4) were analysed in a sample of diabetic and non-diabetic subjects. No significant differences in the allelic, genotypic or haplotypic frequencies of the polymorphisms at these three loci were observed between the diabetic or non-diabetic populations. No significant linkage disequilibrium was observed between the two GLUT1 polymorphic sites, whereas the four polymorphic sites at the GLUT2 locus, one of which appears to be due to a 100-200 base pair DNA insertion/deletion, were found to be in significant linkage disequilibrium. In order to study the possible role of glucose transporter gene variants contributing to the development of obesity, the body mass indexes were compared in the different genotypic groups of diabetic and non-diabetic subjects. No differences in body mass index between genotype groups were found at the p < 0.005 level of significance.     

The use of carcinogen-DNA adduct antisera for quantitation and localization of genomic damage in animal models and the human population

The use of antibodies to detect chemical carcinogen-induced DNA damage involves quantitative determination and morphological localization utilizing antisera specific for carcinogen-DNA adducts. In recent years a large number of polyclonal and monoclonal antisera have been produced against individual adducts and modified DNAs with addition products varying in structure from ethyl and methyl groups to aromatic amines, polycyclic aromatic hydrocarbons, aflatoxins, and platinum-ammine complexes. The quantitative assays developed through the use of these antisera are able to detect attomole (10(-18) M) adduct concentrations, corresponding to one adduct in 10(8) nucleotides or a few hundreds of modifications per mammalian cell genome. This review focuses on data generated during the past 3 yr utilizing this immunotechnology as a tool to probe mechanisms of carcinogen-DNA interactions in various model systems and in the human population. Areas discussed in depth include quantitative and morphological studies involving detection of 2-acetylaminofluorene-DNA adducts in rat liver, O6-ethyl and O6-methyl deoxyguanosine adducts in rat brain, benzo[a]pyrene-DNA adducts in mouse skin and cis-diamminedichloroplatinum (II)-DNA adducts in peripheral nucleated blood cells of cancer patients.     

Effectiveness of an education intervention associated with an exercise program in improving disease-related knowledge and health behaviours among diabetes patients

Objectiveto assess the effectiveness of an education intervention associated with an exercise program in improving knowledge and health behaviours among diabetes patients.MethodsDiabetes and prediabetes patients were exposed to an evidence- and theoretically-based comprehensive education intervention over 24 weeks. Patients completed surveys assessing knowledge, physical activity, food intake, self-efficacy, and health literacy. Functional capacity was measured by oxygen uptake. All outcomes were assessed pre- and post-CR. Satisfaction about the education provided was assessed at post-CR. Paired t-tests, Pearson correlation coefficients, and linear regression models were computed to investigate the effectiveness of this intervention.Results84 patients consented to participate, of which 47(56.0%) completed post-CR assessments. There was a significant improvement in patients’ overall knowledge pre- to post-CR, as well as in physical activity, food intake, self-efficacy, and health literacy (p < 0.05). Peak VO₂ has clinically significant improved. Results showed a low significant positive correlation was between post-CR knowledge and food intake(r = 0.297;p = 0.04). Linear regression analysis revealed that age(B=-0.051; p = 0.01) was influential in changing post-CR knowledge.ConclusionThe benefits of an education intervention designed for diabetes and prediabetes patients associated with an exercise program have been supported.Practice ImplicationsThis work shows one effective education strategy taken in place that can be replicated in different settings.     

The usefulness of circulating adipokine levels for the assessment of obesity-related health problems

Because the prevalence of obesity has increased dramatically in recent years, one of the key targets of public health is obesity and its associated pathological conditions. Obesity occurs as a result of white adipose tissue enlargement, caused by adipocyte hyperplasia and/or hypertrophy. Recently, endocrine aspects of adipose tissue have become an active research area and these adipose tissue-derived factors are referred to as adipokines. These adipokines interact with a range of processes in many different organ systems and influence a various systemic phenomena. Therefore, dysregulated production of adipokines has been found to participate in the development of metabolic and vascular diseases related to obesity. The obese state is also known to be associated with increased local and systemic inflammation. Adipokines influence not only systemic insulin resistance and have pathophysiological roles in the metabolic syndrome and cardiovascular disease, but also contribute toward an increase in local and systemic inflammation. Thus, circulating levels of adipokines can be used as high-throughput biomarkers to assess the obesity-related health problems, including low grade inflammation. This review focuses on the usefulness of measuring circulating adipokine levels for the assessment of obesity-related health problems.     

The success of sleeve gastrectomy in the management of metabolic syndrome and obesity

The rapid reversal of diabetes,hypertension,hyperlipidaemia and obesity by surgical means has challenged accepted doctrines regarding the management of metabolic syndrome.Sleeve gastrectomy,which developed initially as a preparatory procedure for biliopancreatic diversion with duodenal switch,has seen an exponential rise in popularity as an effective lone laparoscopic bariatric procedure.Superior excess weight loss,a low complication rate,and excellent food tolerance,combined with a short hospital stay,have made this the procedure of choice for patients and surgeons across the globe.High volume centres nurture the ongoing development of experienced and specialized teams,pathways and regimens.Optimum surgical outcomes allow minimization of metabolic syndrome,reducing cardiovascular and cerebrovascular risk.     

不同阶段的运动疗法对妊娠期糖尿病患者的长期预后作用

目的:探讨不同阶段的运动疗法对妊娠期糖尿病(gestational diabetes mellitus,GDM)患者预后的作用.方法:选取2010年7月~2014年7月我们妇产科接诊的560例妊娠期糖尿病患者作为研究对象,根据运动疗法的不同阶段将患者分成三组:单纯的妊娠期运动疗法组200例(A组)、单纯的产后运动疗法组180例(B组)以及妊娠期和产后均运动的联合运动组180例(C组),进行队列研究,分析三组患者进展为2型糖尿病的风险差异.结果:三组患者的随访时间分别为2.7±1.1、2.9±0.8及2.8±1.7年,三组患者在平均随访时间上无显著差异(P>0.05).在随访期间,共发现2型糖尿病病例68例,其中A组38例,B组20例,C组10例.C组进展为2型糖尿病的风险明显低于A组和B组(P<0.05), B组疗法发展成2型糖尿病的风险低于A组疗法,但通过调整协变量体重指数后,这种差异仍显著(P<0.05).结论:强化运动治疗,特别是强化产后运动,能明显降低妊娠期糖尿病患者发展为2型糖尿病的风险,值得临床推广应用.     

Associations of sleep duration and quality with serum and hepatic lipids: The Netherlands Epidemiology of Obesity Study

Short and long sleep duration and poor sleep quality may affect serum and hepatic lipid content, but available evidence is inconsistent. Therefore, we aimed to investigate the associations of sleep duration and quality with serum and hepatic lipid content in a large population‐based cohort of middle‐aged individuals. The present cross‐sectional study was embedded in the Netherlands Epidemiology of Obesity (NEO) study and consisted of 4260 participants (mean age, 55 years; proportion men, 46%) not using lipid‐lowering agents. Self‐reported sleep duration and quality were assessed using the Pittsburgh Sleep Quality Index questionnaire (PSQI). Outcomes of this study were fasting lipid profile (total cholesterol, low‐density lipoprotein [LDL]‐cholesterol, high‐density lipoprotein [HDL]‐cholesterol and triglycerides), postprandial triglyceride (response) levels, and hepatic triglyceride content (HTGC) as measured with magnetic resonance spectroscopy. We performed multivariable linear regression analyses, adjusted for confounders and additionally for measures that link to adiposity (e.g. body mass index [BMI] and sleep apnea). We observed that relative to the group with median sleep duration (≈7.0 hr of sleep), the group with shortest sleep (≈5.0 hr of sleep) had 1.5‐fold higher HTGC (95% confidence interval [CI]: 1.0‐2.2). The group with PSQI score ≥ 10 had a 1.1‐fold (95% CI: 1.0‐1.2) higher serum triglyceride level compared with the group with PSQI ≤ 5. However, these associations disappeared after adjustment for BMI and sleep apnea. Therefore, we concluded that previously observed associations of shorter sleep duration and poorer sleep quality with an adverse lipid profile, may be explained by BMI and sleep apnea, rather than by a direct effect of sleep on the lipid profile.     

Cross-validation of pedometer-determined cut-points for healthy weight in British children from White and South Asian backgrounds

Background: Evidence-based pedometer cut-points for health have not been sufficiently examined in the context of ethnicity.

Objective: To (1) evaluate previously described steps/day cut-points in a sample of White and South Asian British primary school children and (2) use ROC analysis to generate alternative, ethnic specific, steps/day cut-offs for children.

Methods and procedures: Height, body mass and pedometer determined physical activity were assessed in 763 British children (357 boys and 406 girls) from White (n?=?593) and South Asian (n?=?170) ethnic groups, aged 8–11 years.

Results: The Vincent and Pangrazi cut-points significantly predicted BMI in white (p?=?0.006, Adjusted R^2?=?0.08) and South Asian children (p?=?0.039, Adjusted R^2?=?0.078). The Tudor-Locke et al. cut-points significantly predicted BMI in White children (p?=?0.0001, Adjusted R^2?=?0.079) but not South Asian children (p?p?=?0.04 or better, Adjusted R^2?=?0.091 for White and 0.09 for South Asian children). Subsequent cut-points associated with healthy weight, when translated to steps/day were 13?625 for White boys, 13?135 for White girls, 10?897 for South Asian boys and 10 161 for South Asian girls.

Conclusions: Previously published steps/day cut-points for healthy weight may not account for known ethnic variation in physical activity between White and South Asian children in the UK. Alternative, ethnic-specific, cut-points may be better placed to distinguish British children based on pedometer-determined physical activity.     

The Stress of Being Chronically Ill: From Disease-Specific to Task-Specific Aspects

The assumption that disease-related stressors are exclusive for particular diagnoses characterizes many studies of chronically ill patients. In this study the perceptions of 1305 patients from 10 different chronic disease categories were compared with respect to a number of important stressors. Differences were found in the amount and type of stressors experienced, but these differences could not solely be explained by type of disease. Personal characteristics such as age, sex, education level, living situation, and illness duration were also important in determining the degree and type of stress experienced. The implications of these findings for stress/coping research as well as the clinical implications are discussed.     

Replication of genetic variants from genome-wide association studies with metabolic traits in an island population of the Adriatic coast of Croatia

Twenty-two single-nucleotide polymorphisms (SNPs) in 10 gene regions previously identified in obesity and type 2 diabetes (T2D) genome-wide association studies (GWAS) were evaluated for association with metabolic traits in a sample from an island population of European descent. We performed a population-based study using 18 anthropometric and biochemical traits considered as continuous variables in a sample of 843 unrelated subjects (360 men and 483 women) aged 18-80 years old from the island of Hvar on the eastern Adriatic coast of Croatia. All eight GWAS SNPs in FTO were significantly associated with weight, body mass index, waist circumference and hip circumference; 20 of the 32 nominal P-values remained significant after permutation testing for multiple corrections. The strongest associations were found between the two TCF7L2 GWAS SNPs with fasting plasma glucose and HbA1c levels, all four P-values remained significant after permutation tests. Nominally significant associations were found between several SNPs and other metabolic traits; however, the significance did not hold after permutation tests. Although the sample size was modest, our study strongly replicated the association of FTO variants with obesity-related measures and TCF7L2 variants with T2D-related traits. The estimated effect sizes of these variants were larger or comparable to published studies. This is likely attributable to the homogenous genetic background of the relatively isolated study population.     

Assessing chronic illness representations: The implicit models of illness questionnaire

Data were collected from three samples using the Implicit Models of Illness Questionnaire (IMIQ) to assess illness representations as described in the self-regulation model of common sense illness representations. A factor structure was identified which displayed some similarities to the common sense model. This structure was used to examine illness representations of students and patients concerning three illnesses—rheumatoid arthritis (RA), multiple sclerosis (MS), and human immunodeficiency virus (HIV). Representations differed across illnesses and respondent status (patient vs. student). Students rate individuals as having more personal responsibility for RA or MS than did patients; moreover, the difference between patient/student ratings was greater with respect to MS than it was for RA. Patients were more aware of the variable nature of RA and MS symptoms than were students. This study demonstrates the value of the IMIQ as a tool for assessing illness cognitions and suggests that illness representations differ as a function of personal experience and personal relevance.The study presented here was supported by an Arthritis Foundation Traineeship Grant to the first author and grants from the National Institute of Health (AM36679) and the Professional Staff Congress—CUNY to Tracey A. Revenson and by a grant to the first author from Fordham University.