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BACKGROUND: Earlier mortality in socioeconomically disadvantaged population groups represents an extreme manifestation of health inequity. This study examines the extent, time trends, and mitigation potentials of area-level socioeconomic inequalities in premature mortality in Germany. METHODS: Nationwide data from official cause-of-death statistics were linked at the district level with official population data and the German Index of Socioeconomic Deprivation (GISD). Age-standardized mortality rates before the age of 75 were calculated stratified by sex and deprivation quintile. A what-if analysis with counterfactual scenarios was applied to calculate how much lower premature mortality would be overall if socioeconomic mortality inequalities were reduced. RESULTS: Men and women in the highest deprivation quintile had a 43% and 33% higher risk of premature death, respectively, than those in the lowest deprivation quintile of the same age. Higher mortality rates with increasing deprivation were found for cardiovascular and cancer mortality, but also for other causes of death. Socioeconomic mortality inequalities had started to increase before the COVID-19 pandemic and further exacerbated in the first years of the pandemic. If all regions had the same mortality rate as those in the lowest deprivation quintile, premature mortality would be 13% lower overall. DISCUSSION: The widening gap in premature mortality between deprived and affluent regions emphasizes that creating equivalent living conditions across Germany is also an important field of action for reducing health inequity.
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Causas de Muerte , Mortalidad Prematura , Humanos , Mortalidad Prematura/tendencias , Alemania/epidemiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Anciano , Disparidades en el Estado de Salud , COVID-19/mortalidad , Preescolar , Adulto Joven , Factores Socioeconómicos , Adolescente , Niño , Lactante , Recién Nacido , SARS-CoV-2RESUMEN
Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10-11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10-10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10-122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
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Estudio de Asociación del Genoma Completo , Cadenas HLA-DRB1/genética , Proteína Antagonista del Receptor de Interleucina 1/genética , Interleucina-1/genética , Interleucina-6/genética , Receptores de Interleucina-6/genética , Estudios de Cohortes , Regulación de la Expresión Génica , Sitios Genéticos , Predisposición Genética a la Enfermedad , Humanos , Interleucina-6/sangre , Polimorfismo de Nucleótido Simple , Población Blanca/genéticaRESUMEN
OBJECTIVE: There is evidence that psychological distress increases the risk of type 2 diabetes (T2D), but implications for prevention remain elusive. We examined the association between chronic stress and the German Diabetes Risk Score (GDRS) among adults without diabetes in Germany. METHODS: The study population consisted of 4654 persons aged 18 to 64 years without known diabetes drawn from the German Health Interview and Examination Survey for Adults (2008-2011). The predicted 5-year T2D risk (in percent) was estimated using the GDRS. Perceived chronic stress was assessed by the Screening Scale of the Trier Inventory for the Assessment of Chronic Stress and categorized into "up to average," "above average," and "high." The cross-sectional association of chronic stress with log-transformed GDRS (expressed as geometric mean ratio [GMR]) was analyzed in multivariable linear regression models. Covariables included age, sex, community size, region, educational level, living alone, social support, depression, and alcohol use. RESULTS: The mean predicted 5-year T2D risk rates were 2.7%, 2.9%, and 3.0% for chronic stress up to average, above average, and high chronic stress, respectively. Adjusted mean predicted 5-year risk was significantly higher among persons with chronic stress above average (GMR = 1.10, 95% confidence interval = 1.02-1.19) and high stress (GMR = 1.21, 95% CI = 1.06-1.39) compared with persons with chronic stress up to average. No interactions with sex or other covariables were found. CONCLUSIONS: Perceived chronic stress is independently associated with an increased predicted T2D risk in cross-sectional analysis and should be considered as T2D risk factor in longitudinal studies.
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Diabetes Mellitus Tipo 2 , Adulto , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/complicaciones , Estudios Transversales , Factores de Riesgo , Estudios Longitudinales , Encuestas y Cuestionarios , Alemania/epidemiologíaRESUMEN
INTRODUCTION: Depression and obesity often occur comorbidly, and once both are present, they further increase the risk of developing other medical comorbidities, likely due to the underlying chronic low-grade inflammation. We investigated to what extent depression and obesity are associated with levels of high-sensitivity C-reactive protein (hsCRP) in a nationally representative sample of the German adult population. METHODS: We analyzed data from the German Health Interview and Examination Survey for Adults (DEGS1, N = 7115), and its mental health module (DEGS1-MH; N = 4483). Two different depression measures were used: current depressive symptoms assessed by the self-administered German version of the Patient Health Questionnaire-9 and major depressive disorder (MDD) in the last 12 months assessed by a modified German version of the Composite International Diagnostic Interview. Obesity was defined by body mass index calculated from measured data. Associations with log(x + 1)-transformed hsCRP levels were analyzed using multivariable linear regression models. RESULTS: Obese participants with depressive symptoms had significantly higher hsCRP compared to non-obese participants with depressive symptoms adjusted for sociodemographic and behavioral variables and medication use. In non-obese individuals, depressive symptoms were inversely associated with hsCRP, whereas MDD was not associated with hsCRP after adjustment for covariates. Additional analyses suggested symptom-specific associations of hsCRP as higher levels were linked to fatigue (ß = 0.10, p <.001) while lower levels were linked to cognitive problems (ß = -0.09, p <.001). Low SES, current smoking, lower levels of physical exercise, and the use of anti-inflammatory/anti-rheumatic medication and antidepressants were additional determinants of hsCRP in the fully adjusted models. CONCLUSIONS: Our data suggest that obesity status is more strongly associated with increased inflammation than depressive symptoms or MDD. The relationship between depression and hsCRP in our population-based sample is substantially influenced by obesity status as well as other medical factors, lifestyle, and socioeconomic status. Furthermore, our findings suggest that the association between hsCRP and depression is symptom-specific rather than generalized.
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Proteína C-Reactiva , Trastorno Depresivo Mayor , Adulto , Antiinflamatorios , Proteína C-Reactiva/metabolismo , Estudios Transversales , Depresión/diagnóstico , Depresión/epidemiología , Trastorno Depresivo Mayor/diagnóstico , Trastorno Depresivo Mayor/epidemiología , Alemania/epidemiología , Humanos , Inflamación/epidemiología , Inflamación/psicología , Obesidad/epidemiologíaRESUMEN
AIMS: There is evidence for an increased type 2 diabetes (T2D) risk associated with depression, but its role for diabetes prevention remains unclear. This study aimed to add insight by investigating the impact of major depressive disorder (MDD) on prospective glycaemic changes. METHODS: The study was based on a cohort of n = 1,766 adults without diabetes (776 men, 990 women; 18-65 years of age) who participated in the mental health supplement of the German National Health Interview and Examination Survey (GNHIES98-MHS, 1997-1999) and in a follow-up survey (DEGS1, 2008-2011). Glycaemic status was defined as normoglycaemia [HbA1c < 39 mmol/mol (<5.7%)], prediabetes [39 ≤ HbA1c < 48 mmol/mol (5.7-6.4%)] and diabetes [HbA1c ≥ 48 mmol/mol (≥ 6.5%), diagnosed diabetes, or antidiabetic medication], and glycaemic changes categorized as 'remission', 'stability' and 'progression'. Baseline MDD was assessed via a modified German version of the WHO Composite International Diagnostic Interview. Multivariable logistic regressions were applied to analyse the association of MDD with glycaemic changes and incident T2D, adjusting for socio-demographics, lifestyle conditions, chronic diseases, antidepressant use and mental health care. RESULTS: MDD prevalence was 21.4% for women and 8.9% for men. Among women, MDD was associated with a lower chance for remission (RRR 0.43; 95% CI 0.23, 0.82). Among men, MDD was not significantly related to glycaemic changes. MDD had no significant effect on incident T2D (men: OR 1.58; 0.55, 4.52; women: OR 0.76; 0.37, 1.58). CONCLUSIONS: Findings of the current study highlight the role of depression in T2D prevention, particularly among women.
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Glucemia/metabolismo , Trastorno Depresivo Mayor/sangre , Diabetes Mellitus Tipo 2/sangre , Hemoglobina Glucada/metabolismo , Estado Prediabético/sangre , Adolescente , Adulto , Anciano , Estudios de Cohortes , Trastorno Depresivo Mayor/epidemiología , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/psicología , Femenino , Alemania/epidemiología , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estado Prediabético/epidemiología , Estado Prediabético/psicología , Prevalencia , Distribución por Sexo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Aging and psychosocial stress are associated with increased inflammation and disease risk, but the underlying molecular mechanisms are unclear. Because both aging and stress are also associated with lasting epigenetic changes, a plausible hypothesis is that stress along the lifespan could confer disease risk through epigenetic effects on molecules involved in inflammatory processes. Here, by combining large-scale analyses in human cohorts with experiments in cells, we report that FKBP5, a protein implicated in stress physiology, contributes to these relations. Across independent human cohorts (total n > 3,000), aging synergized with stress-related phenotypes, measured with childhood trauma and major depression questionnaires, to epigenetically up-regulate FKBP5 expression. These age/stress-related epigenetic effects were recapitulated in a cellular model of replicative senescence, whereby we exposed replicating human fibroblasts to stress (glucocorticoid) hormones. Unbiased genome-wide analyses in human blood linked higher FKBP5 mRNA with a proinflammatory profile and altered NF-κB-related gene networks. Accordingly, experiments in immune cells showed that higher FKBP5 promotes inflammation by strengthening the interactions of NF-κB regulatory kinases, whereas opposing FKBP5 either by genetic deletion (CRISPR/Cas9-mediated) or selective pharmacological inhibition prevented the effects on NF-κB. Further, the age/stress-related epigenetic signature enhanced FKBP5 response to NF-κB through a positive feedback loop and was present in individuals with a history of acute myocardial infarction, a disease state linked to peripheral inflammation. These findings suggest that aging/stress-driven FKBP5-NF-κB signaling mediates inflammation, potentially contributing to cardiovascular risk, and may thus point to novel biomarker and treatment possibilities.
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Envejecimiento/genética , Enfermedades Cardiovasculares/genética , Epigénesis Genética/genética , Inflamación/genética , FN-kappa B/genética , Estrés Psicológico/genética , Proteínas de Unión a Tacrolimus/genética , Regulación hacia Arriba/genética , Senescencia Celular/genética , Preescolar , Trastorno Depresivo Mayor/genética , Femenino , Estudio de Asociación del Genoma Completo/métodos , Humanos , Masculino , Factores de Riesgo , Transducción de Señal/genéticaRESUMEN
BACKGROUND: Type 2 diabetes (T2D) causes substantial disease burden and is projected to affect an increasing number of people in coming decades. This study provides projected estimates of life years free of type 2 diabetes (T2D) and years of life lost ([Formula: see text]) associated with T2D for Germany in the years 2015 and 2040. METHODS: Based on an illness-death model and the associated mathematical relation between prevalence, incidence and mortality, we projected the prevalence of diagnosed T2D using currently available data on the incidence rate of diagnosed T2D and mortality rates of people with and without diagnosed T2D. Projection of prevalence was achieved by integration of a partial differential equation, which governs the illness-death model. These projected parameters were used as input values to calculate life years free of T2D and [Formula: see text] associated with T2D for the German population aged 40 to 100 years in the years 2015 and 2040, while accounting for different assumptions on future trends in T2D incidence and mortality. RESULTS: Assuming a constant incidence rate, women and men at age 40 years in 2015 will live approximately 38 years and 33 years free of T2D, respectively. Up to the year 2040, these numbers are projected to increase by 1.0 years and 1.3 years. Assuming a decrease in T2D-associated excess mortality of 2% per year, women and men aged 40 years with T2D in 2015 will be expected to lose 1.6 and 2.7 years of life, respectively, compared to a same aged person without T2D. In 2040, these numbers would reduce by approximately 0.9 years and 1.6 years. This translates to 10.8 million and 6.4 million [Formula: see text] in the German population aged 40-100 years with prevalent T2D in 2015 and 2040, respectively. CONCLUSIONS: Given expected trends in mortality and no increase in T2D incidence, the burden due to premature mortality associated with T2D will decrease on the individual as well as on the population level. In addition, the expected lifetime without T2D is likely to increase. However, these trends strongly depend on future improvements of excess mortality associated with T2D and future incidence of T2D, which should motivate increased efforts of primary and tertiary prevention.
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Diabetes Mellitus Tipo 2 , Adulto , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Predicción , Humanos , Incidencia , Esperanza de Vida , Masculino , Mortalidad PrematuraRESUMEN
Efficacy of treatment of working-age patients with diabetes mellitus can be increased by rehabilitative measures. This treatment option is explicitly mentioned in the guidelines of the disease management program (DMP) for type 2 diabetes (T2D). With research data from the pension insurance fund, it is shown that for rehabilitation patients with T2D and DMP enrolment, the chance of disability pension is 23% lower than without DMP enrolment, irrespective of relevant covariates.
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Diabetes Mellitus Tipo 2 , Personas con Discapacidad , Manejo de la Enfermedad , Diabetes Mellitus Tipo 2/terapia , Alemania , Humanos , Pensiones/estadística & datos numéricosRESUMEN
BACKGROUND AND AIMS: Over the last years the prevalence of diabetes mellitus (DM) has risen. Due to the disease pattern an increasing importance of rehabilitation services is assumed as well. This article contributs to the debate by analyising the use of medical rehabilitations from 2006 to 2013. METHODS: The secondary data analysis is based on a scientific use file. DM is defined according to ICD-10 (E10-E14). The trends stratified by age and gender are displayed crude and standardized per 100.000. The use will be correlated with the population-based prevalence on the level of federal states. RESULTS: The standardized use rose from 2006 to 2013 in men from 170 to 204.4 and woman from 99 to 123.6 per 100.000. While it declined for people under 60 years old, it rose by about 80% in the age group of the 60-64 year-olds. The use correlated positively (r=0.64) with the population-based prevalence. CONCLUSION: As a result of increasingly late retierment, the importance of rehabilitation services in people with DM incesases.
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Diabetes Mellitus/rehabilitación , Aceptación de la Atención de Salud/estadística & datos numéricos , Centros de Rehabilitación/estadística & datos numéricos , Adulto , Anciano , Femenino , Alemania , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Random glucose is widely measured in epidemiological studies and in the clinical setting when standardized fasting protocols and oral glucose tolerance testing or HbA1c measuring are not feasible. The relationship between random glucose and all-cause mortality has hardly been studied so far and was examined in the present study. METHODS: We ascertained mortality status among 5955 persons aged 18-79 years and free of known diabetes when participating in the German National Health Interview and Examination Survey 1998 (mean observation time 11.7 years, 458 deaths). Cox regression was applied to analyze the association of random serum glucose with all-cause mortality taken potential confounders into account. Relative mortality risks were estimated as hazard ratios (HRs) with 95% confidence intervals (CIs) modeling random glucose as categorical or continuous variable. RESULTS: Compared to random glucose levels of 4.3 - < 5.3 mmol/L, HRs (95% CIs) were 1.94 (0.85-4.45) for levels < 4.3 mmol/L and 1.16 (0.89-1.50), 1.20 (0.91-1.58), 1.42 (0.88-2.29), 2.02 (1.26-3.25) and 4.71 (2.20-10.10) for levels 5.3 - < 5.8, 5.8 - < 6.8, 6.8 - < 7.8, 7.8 - < 11.1 and ≥ 11.1 mmol/L, adjusted for age, sex, lifestyle, anthropometry and chronic diseases. An additional adjustment for fasting time or HbA1c yielded similar estimates. Modeling continuous random glucose by restricted cubic spline functions revealed comparable findings. CONCLUSIONS: In the present epidemiological study drawn from the general population, random glucose showed a significant association with all-cause mortality, independent of main potential confounders. Thus, random glucose measures are highly relevant to health risk assessment among people without known diabetes when fasting glucose or HbA1c are difficult to obtain.
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Glucemia/metabolismo , Encuestas Epidemiológicas/tendencias , Adolescente , Adulto , Anciano , Femenino , Estudios de Seguimiento , Alemania/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Adulto JovenRESUMEN
BACKGROUND: Job insecurity has been associated with impaired self-rated health (SRH) in cross-sectional studies, but prospective findings with short, medium and long-term follow-up yielded mixed findings. Therefore, the aim of the present study was to assess the long-term association between perceived job insecurity and SRH, after controlling for baseline levels of health status and life-style choices. Furthermore, three different follow-up periods (14, 19 and 24 years) were considered. METHODS: Data were derived from the prospective population-based MONICA/KORA cohort study (southern Germany). N = 4356 participants (2622 men and 1734 women), aged between 25 and 64 years at baseline, were included in the sample, mean follow-up was after 19.1 years. Job insecurity, SRH and risk factors were assessed at baseline during three independent surveys (1984-1995). SRH was additionally assessed in 2009. The association of job insecurity and impaired SRH at follow-up was estimated using logistic regression analyses. RESULTS: Overall, perceiving job insecurity at baseline was significantly associated with a 20% higher risk of developing impaired SRH at follow-up in the pooled analysis (OR = 1.20, 95% CI = 1.01-1.43, p = .034), even after controlling for baseline SRH, socio-demographic characteristics, lifestyle, clinical and work-related factors. The association was strongest and significant after 14 years (OR = 1.58, 95% CI 1.17-2.13, p = .003) and weaker and not significant to 19 (OR = 1.20, 95% CI 0.89-1.62, p = .24) and 24 years (OR = 0.98, 95% CI 0.73-1.32, p = .89) of follow-up in the fully adjusted models. CONCLUSIONS: We found that perceived job insecurity during working life was independently and significantly associated with impaired SRH both cross-sectionally as well as after 14 years, but not after 19 and 24 years.
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Autoevaluación Diagnóstica , Empleo/psicología , Adulto , Femenino , Estudios de Seguimiento , Alemania , Humanos , Masculino , Persona de Mediana Edad , Percepción , Estudios Prospectivos , Factores de Riesgo , Encuestas y CuestionariosRESUMEN
OBJECTIVES: Emerging cross-sectional research has identified lack of supportive leadership behavior (SLB) as a risk factor for workforce health. However, prospective evidence is hitherto lacking. SLB denotes support in difficult situations, recognition and feedback on work tasks. This study aims to determine the effect of SLB on suboptimal self-rated health (SRH) after 10 years considering potential moderators such as ages, sex, occupation and job strain. METHODS: The sample included 884 employed participants drawn from the population-based prospective MONICA/KORA Study. SLB, SRH, as well as job strain were assessed by questionnaire. Logistic regressions estimated odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the effect of SLB at baseline on suboptimal SRH at follow-up. Analyses were adjusted for age, gender, lifestyle (alcohol, smoking, physical activity), socioeconomic status as well as for SRH and job strain at baseline. RESULTS: Lack of SLB was associated with suboptimal SRH at baseline [OR 2.00, (95% CI 1.19-3.46)] and at follow-up [OR 2.33, (95% CI 1.40-3.89)]. Additional adjustment for job strain did not substantially alter this association [OR 2.06, (95% CI 1.20-3.52)]. However, interactions between SLB and job strain as well as gender became evident, indicating moderating influences on the association between SLB and SRH. CONCLUSION: Lack of supportive leadership was associated with suboptimal SRH at 10 years' follow-up in men, even if SRH at baseline and other risk factors were taken into account. This effect is likely to be moderated by job strain.
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Estado de Salud , Liderazgo , Estrés Laboral/psicología , Lugar de Trabajo/psicología , Adulto , Femenino , Humanos , Relaciones Interprofesionales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Distribución por Sexo , Apoyo Social , Encuestas y CuestionariosRESUMEN
Erratum to:Bundesgesundheitsbl (2018) https://doi.org/10.1007/s00103-018-2793-0 The original publication of this article contained an error in the list of the authors, in which the contributing author Christian Schmidt was missing. The full list of authors has now been updated. The original article .
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BACKGROUND: Evidence-based policy measures need non-interest-guided information about the health status of a population and the diseases that affect the population the most. In such cases, a national burden of disease study can provide reliable insights at the regional level. AIM: This article presents the potential of the BURDEN 2020 project and its expected outcome for Germany at the national and regional level. METHODS: The BURDEN 2020 project uses several indicators including years of life lost (YLL) to cover the impact of mortality and years lived with disability (YLD) to cover morbidity. The sum of both is the measure of population health called disability adjusted life years (DALY). RESULTS: The study ranks individual diseases and risk factors based on their impact on population health. The burden of disease approach is assumed to be sensitive to subnational differences and may generate immediate benefits for regional planning. The BURDEN 2020 study will pilot a national burden of disease study for Germany that will later be transformed into a continuous data processing and visualization tool. This is done by using, modifying and supplementing the methodology employed by the Global Burden of Disease (GBD) study to better fit the needs of health policy in Germany. This study is aimed at calculating the disease burden for up to 17 preselected diseases. Furthermore, the estimates of burden of disease are attributed to a selected set of risk factors. CONCLUSION: The Burden 2020 study will provide the results of a new, health-related data processing system to the public. This includes a noninterest-guided presentation of the burden of disease (DALY) in Germany at the national and regional level.
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Personas con Discapacidad , Carga Global de Enfermedades , Años de Vida Ajustados por Calidad de Vida , Alemania , Humanos , Factores de RiesgoRESUMEN
Diabetes mellitus and other noncommunicable diseases (NCDs) represent an emerging global public health challenge. In Germany, about 6.7â¯million adults are affected by diabetes according to national health surveys, including 1.3â¯million with undiagnosed diabetes. Complications of diabetes result in an increasing burden for individuals and society as well as enormous costs for the health care system. In response, the Federal Ministry of Health commissioned the Robert Koch Institute (RKI) to implement a diabetes surveillance system and the Federal Center for Health Education (BZgA) to develop a diabetes prevention strategy. In a two-day workshop jointly organized by the RKI and the BZgA, representatives from public health institutes in seven countries shared their expertise and knowledge on diabetes prevention and surveillance. Day one focused on NCD surveillance systems and emphasized both the strengthening of sustainable data sources and the timely and targeted dissemination of results using innovative formats. The second day focused on diabetes prevention strategies and highlighted the importance of involving all relevant stakeholders in the development process to facilitate its acceptance and implementation. Furthermore, the effective translation of prevention measures into real-world settings requires data from surveillance systems to identify high-risk groups and evaluate the effect of measures at the population level based on analyses of time trends in risk factors and disease outcomes. Overall, the workshop highlighted the close link between diabetes prevention strategies and surveillance systems. It was generally stated that only robust data enables effective prevention measures to encounter the increasing burden from diabetes and other NCDs.
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Diabetes Mellitus , Enfermedades no Transmisibles , Salud Pública , Adulto , Diabetes Mellitus/prevención & control , Alemania , Objetivos , Humanos , Enfermedades no Transmisibles/prevención & controlRESUMEN
Blood pressure (BP) is a heritable risk factor for cardiovascular disease. To investigate genetic associations with systolic BP (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and pulse pressure (PP), we genotyped ~50,000 SNPs in up to 87,736 individuals of European ancestry and combined these in a meta-analysis. We replicated findings in an independent set of 68,368 individuals of European ancestry. Our analyses identified 11 previously undescribed associations in independent loci containing 31 genes including PDE1A, HLA-DQB1, CDK6, PRKAG2, VCL, H19, NUCB2, RELA, HOXC@ complex, FBN1, and NFAT5 at the Bonferroni-corrected array-wide significance threshold (p < 6 × 10(-7)) and confirmed 27 previously reported associations. Bioinformatic analysis of the 11 loci provided support for a putative role in hypertension of several genes, such as CDK6 and NUCB2. Analysis of potential pharmacological targets in databases of small molecules showed that ten of the genes are predicted to be a target for small molecules. In summary, we identified previously unknown loci associated with BP. Our findings extend our understanding of genes involved in BP regulation, which may provide new targets for therapeutic intervention or drug response stratification.
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Presión Sanguínea , Diástole , Genética de Población , Sístole , Población Blanca/genética , Presión Arterial , Biología Computacional/métodos , Europa (Continente) , Sitios Genéticos , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , Fenotipo , Polimorfismo de Nucleótido Simple , Control de Calidad , Sitios de Carácter Cuantitativo , Factores de RiesgoRESUMEN
OBJECTIVE: To examine the interaction between waist circumference (WC) and serum 25-hydroxyvitamin D (25(OH)D) level in their associations with serum lipids. DESIGN: Cross-sectional study. The associations of serum 25(OH)D with total cholesterol, HDL cholesterol (HDL-C), LDL cholesterol (LDL-C), LDL-C:HDL-C and TAG were examined using multiple linear regression. Effect modification by WC was assessed through cross-product interaction terms between 25(OH)D and WC categories (abdominal overweight, 80-<88 cm in females/94-<102 cm in males; abdominal obesity, ≥88 cm in females/≥102 cm in males). SETTING: The US National Health and Nutrition Examination Survey waves 2001-2006. SUBJECTS: Non-pregnant fasting participants (n 4342) aged ≥20 years. RESULTS: Lower 25(OH)D levels were significantly associated with lower HDL-C levels as well as with higher LDL-C:HDL-C and TAG levels in abdominally obese participants, but not in abdominally overweight or normal-waist participants. In contrast, lower 25(OH)D levels were associated with lower levels of total cholesterol and LDL-C in abdominally overweight and normal-waist participants only, but this association was only partly significant. However, a significant difference in the association between 25(OH)D and the lipids according to WC category was found only for LDL-C:HDL-C (P for interaction=0·02). CONCLUSIONS: Our results from this large, cross-sectional sample suggest that the association between lower 25(OH)D levels and an unfavourable lipid profile is stronger in individuals with abdominal obesity than in those with abdominal overweight or a normal WC.
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Lípidos/sangre , Encuestas Nutricionales/estadística & datos numéricos , Vitamina D/análogos & derivados , Circunferencia de la Cintura , Adulto , Anciano , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estados Unidos , Vitamina D/sangre , Adulto JovenRESUMEN
Epidemiological data provide evidence that diabetes mellitus is a highly relevant public health issue in Germany as in many other countries. The Robert Koch Institute (RKI) is in the process of building a national diabetes surveillance system that is aimed at establishing indicator-based public health monitoring of diabetes population dynamics using primary and secondary data. The purpose of the workshop was to conduct an inventory of available secondary data sources and to discuss data contents, data access, data analysis examples in addition to the options for ongoing data use for diabetes surveillance.
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Minería de Datos/métodos , Bases de Datos Factuales/estadística & datos numéricos , Diabetes Mellitus/epidemiología , Registro Médico Coordinado/métodos , Metadatos/estadística & datos numéricos , Vigilancia de la Población/métodos , Sistema de Registros/estadística & datos numéricos , Registros Electrónicos de Salud/estadística & datos numéricos , Alemania/epidemiología , Humanos , PrevalenciaRESUMEN
Insufficiently treated diabetes mellitus can lead to severe comorbidities. National and international analyses show a continuous increase in diabetes prevalence over the last decades. Currently, an indicator-based national diabetes surveillance system is implemented at the Robert Koch Institute (RKI) to monitor and report on diabetes development on the basis of available primary and secondary data. The aim of the meeting was to go into deeper discussions and to integrate expectations and expertise of the federal states into the design of the national surveillance system. A close collaboration between the RKI and the federal states is intended.
Asunto(s)
Complicaciones de la Diabetes/epidemiología , Diabetes Mellitus/epidemiología , Vigilancia de la Población , Programas Médicos Regionales/estadística & datos numéricos , Proyectos de Investigación/estadística & datos numéricos , Adolescente , Adulto , Anciano , Niño , Estudios Transversales , Complicaciones de la Diabetes/prevención & control , Diabetes Mellitus/prevención & control , Diabetes Mellitus/terapia , Diabetes Mellitus Tipo 1/epidemiología , Diabetes Mellitus Tipo 1/prevención & control , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/prevención & control , Diabetes Mellitus Tipo 2/terapia , Diabetes Gestacional/epidemiología , Diabetes Gestacional/prevención & control , Diabetes Gestacional/terapia , Conducta Alimentaria , Femenino , Alemania , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Embarazo , RiesgoRESUMEN
Waist circumference (WC) and waist-to-hip ratio (WHR) are surrogate measures of central adiposity that are associated with adverse cardiovascular events, type 2 diabetes and cancer independent of body mass index (BMI). WC and WHR are highly heritable with multiple susceptibility loci identified to date. We assessed the association between SNPs and BMI-adjusted WC and WHR and unadjusted WC in up to 57 412 individuals of European descent from 22 cohorts collaborating with the NHLBI's Candidate Gene Association Resource (CARe) project. The study population consisted of women and men aged 20-80 years. Study participants were genotyped using the ITMAT/Broad/CARE array, which includes â¼50 000 cosmopolitan tagged SNPs across â¼2100 cardiovascular-related genes. Each trait was modeled as a function of age, study site and principal components to control for population stratification, and we conducted a fixed-effects meta-analysis. No new loci for WC were observed. For WHR analyses, three novel loci were significantly associated (P < 2.4 × 10(-6)). Previously unreported rs2811337-G near TMCC1 was associated with increased WHR (ß ± SE, 0.048 ± 0.008, P = 7.7 × 10(-9)) as was rs7302703-G in HOXC10 (ß = 0.044 ± 0.008, P = 2.9 × 10(-7)) and rs936108-C in PEMT (ß = 0.035 ± 0.007, P = 1.9 × 10(-6)). Sex-stratified analyses revealed two additional novel signals among females only, rs12076073-A in SHC1 (ß = 0.10 ± 0.02, P = 1.9 × 10(-6)) and rs1037575-A in ATBDB4 (ß = 0.046 ± 0.01, P = 2.2 × 10(-6)), supporting an already established sexual dimorphism of central adiposity-related genetic variants. Functional analysis using ENCODE and eQTL databases revealed that several of these loci are in regulatory regions or regions with differential expression in adipose tissue.