[Socioeconomic deprivation and premature mortality in Germany, 1998-2021 : An ecological study with what-if scenarios of inequality reduction]. / Sozioökonomische Deprivation und vorzeitige Sterblichkeit in Deutschland 1998­2021 : Eine ökologische Studie mit What-if-Szenarien der Ungleichheitsreduktion.

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.

Genome-wide association study of circulating interleukin 6 levels identifies novel loci.

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.

Perceived Chronic Stress Is Associated With the German Diabetes Risk Score Among Adults Without Known Diabetes in Germany.

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.

Association of depression and obesity with C-reactive protein in Germany: A large nationally representative study.

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.

Sex-specific impact of major depressive disorder on 12-year change in glycaemic status: Results from a nationwide cohort study of adults without diabetes in Germany.

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.

Epigenetic upregulation of FKBP5 by aging and stress contributes to NF-κB-driven inflammation and cardiovascular risk.

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.

Diabetes free life expectancy and years of life lost associated with type 2 diabetes: projected trends in Germany between 2015 and 2040.

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.

[Is There an Association Between DMP Enrollment and Disability Pension in Rehabilitants With Type 2 Diabetes?] / Besteht bei Rehabilitanden mit Typ-2-Diabetes ein Zusammenhang zwischen DMP-Einschreibung und Bezug einer Erwerbsminderungsrente?

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.

[Diabetes Mellitus in the Medical Rehabilitation - Use of Rehabilitation Services During 2006-2013]. / Diabetes Mellitus in der medizinischen Rehabilitation ­ Inanspruchnahme rehabilitativer Maßnahmen im Zeitraum 2006­2013.

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.

Association between random glucose and all-cause mortality: findings from the mortality follow-up of the German National Health Interview and Examination Survey 1998.

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.