Association of the habitual dietary intake with the fatty liver index and effect modification by metabotypes in the population-based KORA-Fit study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is an emerging threat for public health with diet being a major risk factor in disease development and progression. However, the effects of habitual food consumption on fatty liver are still inconclusive as well as the proposed role of the individuals' metabolic profiles. Therefore, the aim of our study is to examine the associations between diet and NAFLD with an emphasis on the influence of specific metabotypes in the general population. METHODS: A total of 689 participants (304 men and 385 women) of the KORA-Fit (S4) survey, a follow-up study of the population-based KORA cohort study running in the Region of Augsburg, Germany, were included in this analysis. Dietary information was derived from repeated 24-h food lists and a food frequency questionnaire. The intake of energy and energy-providing nutrients were calculated using the national food composition database. The presence of fatty liver was quantified by the fatty liver index (FLI), and metabotypes were calculated using K-means clustering. Multivariable linear regression models were used for the analysis of habitual food groups and FLI; for the evaluation of macronutrients, energy substitution models were applied. RESULTS: A higher consumption of nuts and whole grains, and a better diet quality (according to Alternate Healthy Eating Index and Mediterranean Diet Score) were associated with lower FLI values, while the intake of soft drinks, meat, fish and eggs were associated with a higher FLI. The isocaloric substitution of carbohydrates with polyunsaturated fatty acids was associated with a decreased FLI, while substitution with monounsaturated fatty acids and protein showed increased FLI. Statistically significant interactions with the metabotype were observed for most food groups. CONCLUSION: The consumption of plant-based food groups, including nuts and whole grains, and diet quality, were associated with lower FLI values, whereas the intake of soft drinks and products of animal origin (meat, fish, eggs) were associated with a higher FLI. The observed statistically significant interactions with the metabotype for most food groups could help to develop targeted prevention strategies on a population-based level if confirmed in independent prospective studies.

Associations between anthropometric parameters and immune-phenotypical characteristics of circulating Tregs and serum cytokines.

OBJECTIVE: To investigate the associations between several anthropometric parameters and regulatory T cells (Tregs) and circulating cytokines in a population-based cohort. METHODS: Between 2018 and 2021, a total of 238 participants were examined up to three times within the scope of the MEGA study in Augsburg, Germany. Tregs were analyzed using flow cytometry and the serum concentrations of 52 cytokines were determined. Anthropometric parameters were measured, using also bioelectrical impedance analysis: body mass index (BMI), relative total body fat, relative visceral adipose tissue (rVAT), waist circumference (WC), waist-to-hip ratio (WHR) and body fat distribution. Associations were analyzed using linear mixed models with random intercept (Tregs) and conventional linear regression models (cytokines). RESULTS: WC and WHR were inversely associated with the general Treg subset. Four parameters (BMI, rVAT, WC, and WHR) were inversely associated with the conventional Treg population. Three cytokines showed a particularly strong association with several anthropometric parameters: the cutaneous T-cell attracting chemokine was inversely associated with anthropometric parameters, while hepatocyte growth factor and interleukine-18 showed positive associations. CONCLUSIONS: Anthropometric measures are associated with Tregs and serum cytokine concentrations revealing new important interconnections between obesity and the adaptive immune system.

Sex-specific associations between systolic, diastolic and pulse pressure and hemostatic parameters in the population-based KORA-Fit study: a cross-sectional study.

BACKGROUND: Several prior studies postulated an effect of hypertension on coagulation factors. However, population-based studies investigating the sex-specific associations between hypertension and hemostatic parameters are scarce. Therefore, we investigated the relationship between blood pressure and parameters of coagulation, namely activated partial thromboplastin time (aPTT), international normalized ratio (INR), fibrinogen, factor VIII, antithrombin III, protein C, protein S, and D-dimer in men and women from the general population. METHODS: Based on 803 participants (376 men, 427 women) from the KORA-Fit Study the sex-specific relationship between systolic, diastolic, and pulse pressure and commonly measured coagulation factors were investigated using multivariable-adjusted linear regression models. RESULTS: Hypertensive males had significantly higher median fibrinogen levels and factor VIII activity in comparison to normotensive males. There was a statistically significant difference between females with and without hypertension regarding the parameter fibrinogen, D-dimers, Protein S activity, and factor VIII activity. In multivariable linear regression analyses no significant association between systolic blood pressure, diastolic blood pressure, as well as pulse pressure and the investigated hemostatic parameters was found in men. In women, a significant positive association could be observed between systolic blood pressure and D-dimer level [ß-estimate per mmHg increase 3.37 (95% CI 0.935-5.804; p = 0.007)] and between pulse pressure and D-dimer level [ß-estimate per mmHg increase 5.351 (95% CI 1.772-8.930; p = 0.003)]. CONCLUSIONS: It appears that sex differences exist in the association between blood pressure parameters and commonly measured coagulation markers in the general population. Further studies are needed to identify the underlying causes.

COVID-19 risk perceptions, worries and preventive behaviors in patients with previous myocardial infarction: results from the myocardial infarction registry Augsburg.

Despite the known association of chronic cardiovascular diseases and more severe courses of COVID-19, little is known about individual risk perception of patients with a history of acute myocardial infarction (AMI) and resulting preventive behaviours. In May 2020, a postal survey was conducted, including 150 patients with previous AMI from the myocardial infarction registry Augsburg. The study objective was to assess COVID-19 knowledge, individual risk perception, worries, infection likelihood and preventive behaviours in this patient cohort. From the 100 respondents, 69.7% perceived themselves to be at high risk of developing a severe course of COVID-19. There was a significant positive correlation between dangerousness assessment and knowledge on COVID-19. Despite a majority (70%) of patients rating their susceptibility for an infection as moderate to very high, the individual likelihood of being infected was rated at only 3%. Almost 70% of patients with previous MI classified themselves at high risk for a severe course of COVID-19 infection. As seen in other risk groups as well, the availability of valuable information sources as well as the support in individual risk reduction strategies and psychological coping mechanisms are mandatory, especially since higher knowledge correlates with dangerousness assessment and might lead to better compliance with preventive behaviours.

Inflammatory plasma proteins predict short-term mortality in patients with an acute myocardial infarction.

BACKGROUND: The aim of this study was to investigate the association between inflammatory markers and 28-day mortality in patients with ST-elevation myocardial infarction (STEMI). METHODS: In 398 STEMI patients recorded between 2009 and 2013 by the population-based Myocardial Infarction Registry Augsburg, 92 protein biomarkers were measured in admission arterial blood samples using the OLINK inflammatory panel. In multivariable-adjusted logistic regression models, the association between each marker and 28-day mortality was investigated. The values of the biomarkers most significantly associated with mortality were standardized and summarized to obtain a prediction score for 28-day mortality. The predictive ability of this biomarker score was compared to the established GRACE score using ROC analysis. Finally, a combined total score was generated by adding the standardized biomarker score to the standardized GRACE score. RESULTS: The markers IL-6, IL-8, IL-10, FGF-21, FGF-23, ST1A1, MCP-1, 4E-BP1, and CST5 were most significantly associated with 28-day mortality, each with FDR-adjusted (false discovery rate adjusted) p-values of < 0.01 in the multivariable logistic regression model. In a ROC analysis, the biomarker score and the GRACE score showed comparable predictive ability for 28-day mortality (biomarker score AUC: 0.7859 [CI: 0.6735-0.89], GRACE score AUC: 0.7961 [CI: 0.6965-0.8802]). By combining the biomarker score and the Grace score, the predictive ability improved with an AUC of 0.8305 [CI: 0.7269-0.9187]. A continuous Net Reclassification Improvement (cNRI) of 0.566 (CI: 0.192-0.94, p-value: 0.003) and an Integrated Discrimination Improvement (IDI) of 0.083 ((CI: 0.016-0.149, p-value: 0.015) confirmed the superiority of the combined score over the GARCE score. CONCLUSIONS: Inflammatory biomarkers may play a significant role in the pathophysiology of acute myocardial infarction (AMI) and AMI-related mortality and might be a promising starting point for personalized medicine, which aims to provide each patient with tailored therapy.

Relationship between atopic dermatitis, depression and anxiety: a two-sample Mendelian randomization study.

BACKGROUND: Growing evidence suggests that atopic dermatitis (AD) is associated with an increased risk of depressive disorders and anxiety. However, existing studies were observational and may have uncovered correlations but could not easily disentangle noncausal or reverse-causal associations because these associations could be confounded and may not reflect true causal relationships. OBJECTIVES: To examine, in a two-sample Mendelian randomization study, the potential effect of AD on the risk of depressive disorders and anxiety. METHODS: Genetic instruments from the largest available genome-wide association study (GWAS) for AD (10 788 cases and 30 047 controls) were used to investigate the relationship to broad depression (170 756 cases and 329 443 controls), major depressive disorder (MDD; 30 603 cases and 143 916 controls) and anxiety (5580 cases and 11 730 controls). A set of complementary approaches were carried out to assess horizontal pleiotropy and related potential caveats occurring in MR studies. RESULTS: We observed no causal impact of AD on the risk of depressive disorders and anxiety, with close-to-zero effect estimates. The inverse weighted method revealed no associations of AD on broad depression [odds ratio (OR) 1·014; P = 0·431], probable MDD (OR 1·002; P = 0·568), International Classification of Diseases, Ninth/Tenth Revision-based MDD (OR 1·001; P = 0·466) or anxiety (OR 1·097; P = 0·180). CONCLUSIONS: This MR study does not support a causal effect of AD on depression and anxiety.

Burden of cardiovascular risk factors and cardiovascular disease in childhood cancer survivors: data from the German CVSS-study.

Aims: The cardiac and vascular late sequelae in long-term survivors of childhood cancer (CVSS)-study aimed to quantify the prevalence of cardiovascular risk factors (CVRF) and cardiovascular disease (CVD) in German childhood cancer survivors (CCS). Methods and results: In the CVSS-study (NCT02181049), 1002 CCS (age range 23-48 years) diagnosed with neoplasia prior to 15 years of age between 1980 and 1990 prospectively underwent a systematic, standardized clinical and laboratory cardiovascular screening, identical to the population-based Gutenberg Health Study (GHS) cohort. For 951 individuals, prevalences of CVRF and CVD were primarily compared to the GHS sample and to two further German population-based cohorts. Using log-binomial regression models, an increased risk for occurrence of arterial hypertension [relative risk (RR) 1.38, 95% confidence interval (95% CI 1.21-1.57)] and dyslipidaemia [RR 1.26 (95% CI 1.12-1.42)] was found. This indicates a premature occurrence compared to the general population of approximately 6 and 8 years, respectively [rate advancement period estimator, RAPhypertension 5.75 (95% CI 3.5-8.0) and RAPdyslipidaemia 8.16 (95% CI 4.4-11.9)]. Overall, no differences were observed for obesity and diabetes. Overt CVD was present in 4.5% (95% CI 3.0-6.6%) of CCS [RR 1.89 (95% CI 1.34-2.66), RAPCVD 7.9 (95% CI 4.1-11.7)], of which the most frequent entities were congestive heart failure and venous thromboembolism. Prevalences of CVRF and CVD increased with age without reaching a plateau over time. Conclusion: This large CCS screening examination revealed consistently in comparison to three population samples a considerably increased risk for premature CVD. The findings in these young adult CCS indicate a high burden of cardiovascular morbidity and mortality in the long term. Clinicaltrials. gov-Nr: NCT02181049.

Prediabetes is associated with microalbuminuria, reduced kidney function and chronic kidney disease in the general population: The KORA (Cooperative Health Research in the Augsburg Region) F4-Study.

BACKGROUND AND AIMS: We investigated the associations of serum fasting (FG) and 2-h postload (2HG) glucose from an oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), fasting insulin and the homeostasis model assessment-insulin resistance index (HOMA-IR) with urinary albumin-to-creatinine ratio (ACR) and estimated glomerular filtration rate (eGFR). METHODS AND RESULTS: We performed cross-sectional analyses of 2713 subjects (1429 women; 52.7%) without known type 2 diabetes, aged 31-82 years, from the KORA (Cooperative Health Research in the Augsburg Region) F4-Study. FG, 2HG, HbA1c, fasting insulin, HOMA-IR and glucose tolerance categories were analyzed for association with ACR and eGFR in multivariable adjusted linear and median regression models, and with isolated microalbuminuria (i-MA), isolated reduced kidney function (i-RKF) and chronic kidney disease (CKD, defined as MA and/or RKF) in multivariable adjusted logistic regression models. Among the 2713 study participants, 28% revealed prediabetes (isolated impaired fasting glucose [i-IFG], isolated glucose tolerance [i-IGT] or both by American Diabetes Association definition), 4.2% had unknown type 2 diabetes, 6.5% had i-MA, 3.1% i-RKF and 10.9% CKD. In multivariable adjusted analysis, all continuous variables (FG, 2HG, HbA1c, fasting insulin and HOMA-IR) were associated with i-MA, i-RKF and CKD. The odds ratios (ORs) for i-MA and CKD were 1.54 (95% confidence interval: 1.02-2.33) and 1.58 (1.10-2.25) for individuals with i-IFG. Moreover, the OR for i-RKF was 2.57 (1.31-5.06) for individuals with IFG + IGT. CONCLUSION: Our findings suggest that prediabetes might have harmful effects on the kidney.

Physical activity, muscular strength, and polypharmacy among older multimorbid persons: Results from the KORA-Age study.

The purpose of this study was to examine whether physical activity (PA) and muscular strength (MS) are related to polypharmacy. Our cross-sectional analysis was based on 711 patients with multimorbidity (MMB), aged 65-94 years, who participated in the KORA-Age study. Participants underwent a face-to-face interview and extensive physical examinations including anthropometric measurements, registration of chronic diseases, determination of health-related behaviors (smoking, alcohol intake, physical activity, etc.), collection of blood samples and measurement of hand-grip strength. PPha was defined as the use of >4 drugs and MMB as having ≥2 of 13 chronic diseases. Prevalence of PPha was 44.6% (n=317), and a significant difference was found in the number of drugs used between participants with and without PPha (7.2±2.1 vs 2.5±1.2, P<.001). Patients in the lower compared to the upper tertile of physical activity had a significantly increased odds to be on PPha (OR: 1.64, 95% CI: 1.05-2.56, P=.031) after controlling for age, gender, BMI, family status, education, alcohol intake, smoking habits, number of diseases, hs-CRP, and telomere length. On the contrary, no significant association between muscular strength and PPha was found (OR: 1.04, 95% CI: 0.66-1.63, P=.873) after multivariable adjustment. Among older persons with MMB, lower levels of physical activity, but not low muscular strength, are associated with higher odds of PPha. Increasing the levels of physical activity appears to be highly recommended in order to potentially reduce the risk of PPha among multimorbid persons aged 65 and older.

Sex differences in the association of social network satisfaction and the risk for type 2 diabetes.

BACKGROUND: The role of an individual's social network satisfaction (SNS) in the association of social isolation or living alone and incident type 2 diabetes (T2D) is unclear. We assessed the association of SNS with incident T2D and analysed potential modifications of the SNS-T2D association by social isolation or living alone. METHODS: The study population (N = 6839 aged 25-74 years without diabetes at baseline) derived from the prospective population-based MONICA/KORA study (1989-2009). Social network satisfaction was assessed by a single item. Cox regression was used to estimate hazard ratios (HR) for SNS separately in men and women. RESULTS: In men with low SNS, risk for incident T2D increased significantly (HR: 2.15, 95% CI: 1.33-3.48, p value 0.002). After additional adjustments for social isolation or living alone, the risk for incident T2D was still significant, albeit less pronounced (HRs 1.85 or 2.05, p values 0.001 or 0.004). The interaction analysis showed an increased T2D risk effect for low SNS compared to high SNS in women living in a partnership (HR: 2.11, 95% CI: 1.00-4.44, p value for interaction: 0.047) and for moderate SNS compared to high SNS in socially connected women (1.56, 1.01-2.39, 0.010). CONCLUSIONS: Further research is needed to address the complexities of the perception of social relationships and social interactions, or interdependence, especially when another major public health issue such as T2D is concerned.

Poor structural social support is associated with an increased risk of Type 2 diabetes mellitus: findings from the MONICA/KORA Augsburg cohort study.

AIMS: Several psychosocial factors have been shown to increase the risk of Type 2 diabetes mellitus. This study investigated the association between structural social support and incidence of Type 2 diabetes mellitus in men and women. METHODS: Data were derived from three population-based MONICA/KORA surveys conducted in 1984-1995 in the Augsburg region (southern Germany) and followed up by 2009. The study population comprised 8952 participants (4669 men/4283 women) aged 30-74 years without diabetes at baseline. Structural social support was assessed using the Social Network Index. Sex-specific hazard ratios were estimated from Cox proportional hazard models. RESULTS: Within follow-up, 904 incident Type 2 diabetes mellitus cases (558 men, 346 women) were observed. Crude incidence rates for Type 2 diabetes mellitus per 10 000 person-years were substantially higher in poor compared with good structural social support (men: 94 vs. 69, women: 58 vs. 43). After adjustment for age, survey, parental history of diabetes, smoking status, alcohol intake, physical activity, hypertension, dyslipidaemia, BMI, education, sleep complaints and depressed mood, risk of Type 2 diabetes mellitus for participants with poor compared with good structural social support was 1.31 [95% confidence interval (CI) = 1.11-1.55] in men and 1.10 (95% CI = 0.88-1.37) in women. Stratified analyses revealed a hazard ratio of 1.50 (95% CI = 1.23-1.83) in men with a low level of education and 0.87 (95% CI = 0.62-1.22) in men with a high level of education (P for interaction: 0.0082). CONCLUSIONS: Poor structural social support is associated with Type 2 diabetes mellitus in men. This association is independent of risk factors at baseline and is particularly pronounced in men with a low level of education.

[From the MONICA-project via KORA to the NAKO-study: Practical Utility of Epidemiological Studies in Augsburg Region]. / Vom MONICA-Projekt über KORA zur NAKO-Studie: Vom praktischen Nutzen von Bevölkerungsstudien in der Region Augsburg.

The objective of the WHO-MONICA study was to determine the influence of changing risk factors and treatment options on myocardial infarction rates in populations in a 10-year time period. For this purpose, a population-based myocardial infarction registry was established in 1984 in Augsburg (covering the city of Augsburg and 2 adjacent counties) in order to continuously register all inhabitants of the region who had a myocardial infarction during the study period. In addition, three cross-sectional studies based on random population samples (1984/85, 1989/90 and 1994/95) were carried out. Our data revealed a continuous decrease of myocardial infarction incidence and demonstrated that the decrease of coronary mortality can be ascribed to decreasing myocardial infarction incidence and longer survival after myocardial infarction. Until today the myocardial infarction registry continues to be a permanent part of the Cooperative Health Research in the Region of Augsburg (KORA). Moreover, within the framework of KORA, a fourth population-based cross-sectional study was carried out in 1999/2001. Meanwhile, more than 18 000 study participants have been followed-up for specific endpoints for up to 30 years. A large number of publications, which address cardiovascular diseases, type 2 diabetes mellitus, lung diseases, environmental and genetic questions, health services research and numerous other topics, are based on the KORA study. Today we know that the development of chronic diseases can be ascribed to a complex interaction of social factors, health policy conditions, health behavior, risk factors and molecular mechanisms. To tackle the challenges posed by these multiple factors in Germany, NAKO (Nationale Kohorte), the largest nation-wide long-term study so far, was initiated. Within the framework of the NAKO study, 200 000 persons aged between 20 and 69 years in Germany - thereof 20 000 persons in the region of Augsburg - will be examined and interviewed in the next 10 years, and widespread diseases will be investigated with modern epidemiological methods. The results of these epidemiological long-term studies will contribute to the prevention, early diagnosis and best possible treatment of widespread diseases.

Association between apolipoprotein A-IV concentrations and chronic kidney disease in two large population-based cohorts: results from the KORA studies.

BACKGROUND: Apolipoprotein A-IV (apoA-IV) is an anti-atherogenic and antioxidative glycoprotein. Plasma apoA-IV levels are elevated in patients with primary chronic kidney disease (CKD) or renal failure. The association between apoA-IV and kidney function has not been investigated in the general population; therefore, we analysed this relationship in two large population-based cohorts. METHODS: Plasma apoA-IV concentrations were measured in the Cooperative Health Research in the Region of Augsburg (KORA) F3 (n = 3159) and KORA F4 (n = 3061) studies. CKD was defined by the serum creatinine-estimated glomerular filtration rate (eGFR) and/or urine albumin-to-creatinine ratio. RESULTS: Mean (±SD) apoA-IV concentration was 17.3 ± 4.7 mg dL(-1) in KORA F3 and 15.3 ± 4.3 mg dL(-1) in KORA F4. Fully adjusted linear mixed models revealed a significant association between apoA-IV concentration and lower eGFR in the third and fourth versus the first quartile of apoA-IV (ß = -1.78 mL min(-1) /1.73 m², P = 0.0003 and ß = -5.09 mL min(-1) /1.73 m², P = 2.83 × 10(-23) , respectively). ApoA-IV was significantly associated with an eGFR of <60 mL min(-1) /1.73 m², which was observed in 601 of the 6220 study participants [odds ratio (OR) 1.46, P = 0.03 and OR 3.47, P = 6.84 × 10(-15) for the third and fourth vs. the first quartile of apoA-IV, respectively]. Adding apoA-IV (fourth vs. first quartile) to the fully adjusted model significantly improved discrimination of eGFR <60 mL min(-1) /1.73 m² in KORA F3 [integrated discrimination improvement (IDI) 0.03, P = 1.30 × 10(-7) ] and KORA F4 (IDI 0.04, P = 1.32 × 10(-9) ) beyond classical risk factors for CKD. CONCLUSION: The present analysis in two population-based cohorts revealed that high plasma apoA-IV concentrations are strongly associated with low kidney function defined by eGFR independent of major CKD risk factors. ApoA-IV appears to be an early marker of impaired kidney function.

Low serum omentin levels in the elderly population with Type 2 diabetes and polyneuropathy.

AIMS: To investigate the hypothesis that high serum levels of omentin, an adipokine with anti-inflammatory, insulin-sensitizing and cardioprotective properties, may be related to a lower risk of diabetic sensorimotor polyneuropathy. METHODS: The association between serum omentin level and polyneuropathy was estimated in people aged 61-82 years with Type 2 diabetes (47 with and 168 without polyneuropathy) from the population-based KORA F4 study. The presence of clinical diabetic sensorimotor polyneuropathy was defined as bilateral impairment of foot vibration perception and/or foot pressure sensation. Omentin levels were determined by enzyme-linked immunosorbent assay. RESULTS: Serum omentin level was inversely associated with polyneuropathy after adjustment for age, sex, height, waist circumference, hypertension, total cholesterol, smoking, alcohol intake and physical activity [odds ratio 0.45 (95% CI 0.21-0.98); P = 0.043]. Although omentin was positively correlated with adiponectin (r = 0.55, P < 0.0001) and inversely with tumour necrosis factor-α (r = -0.30, P = 0.019), additional adjustment for adiponectin and tumour necrosis factor-α had little impact on the association. CONCLUSIONS: Serum levels of omentin are reduced in people with Type 2 diabetes and diabetic sensorimotor polyneuropathy, independently of established risk factors of polyneuropathy. This association is only partially explained by biomarkers of subclinical inflammation.

Association of neighbourhood unemployment rate with incident Type 2 diabetes mellitus in five German regions.

AIM: To analyse the association of neighbourhood unemployment with incident self-reported physician-diagnosed Type 2 diabetes in a population aged 45-74 years from five German regions. METHODS: Study participants were linked via their addresses at baseline to particular neighbourhoods. Individual-level data from five population-based studies were pooled and combined with contextual data on neighbourhood unemployment. Type 2 diabetes was assessed according to a self-reported physician diagnosis of diabetes. We estimated proportional hazard models (Weibull distribution) in order to obtain hazard ratios and 95% CIs of Type 2 diabetes mellitus, taking into account interval-censoring and clustering. RESULTS: We included 7250 participants residing in 228 inner city neighbourhoods in five German regions in our analysis. The incidence rate was 12.6 per 1000 person-years (95% CI 11.4-13.8). The risk of Type 2 diabetes mellitus was higher in men [hazard ratio 1.79 (95% CI 1.47-2.18)] than in women and higher in people with a low education level [hazard ratio 1.55 (95% CI 1.18-2.02)] than in those with a high education level. Independently of individual-level characteristics, we found a higher risk of Type 2 diabetes mellitus in neighbourhoods with high levels of unemployment [quintile 5; hazard ratio 1.72 (95% CI 1.23-2.42)] than in neighbourhoods with low unemployment (quintile 1). CONCLUSIONS: Low education level and high neighbourhood unemployment were independently associated with an elevated risk of Type 2 diabetes mellitus. Studies examining the impact of the residential environment on Type 2 diabetes mellitus will provide knowledge that is essential for the identification of high-risk populations.

Increased amino acids levels and the risk of developing of hypertriglyceridemia in a 7-year follow-up.

BACKGROUND: Recently, five branched-chain and aromatic amino acids were shown to be associated with the risk of developing type 2 diabetes (T2D). AIM: We set out to examine whether amino acids are also associated with the development of hypertriglyceridemia. MATERIALS AND METHODS: We determined the serum amino acids concentrations of 1,125 individuals of the KORA S4 baseline study, for which follow-up data were available also at the KORA F4 7 years later. After exclusion for hypertriglyceridemia (defined as having a fasting triglyceride level above 1.70 mmol/L) and diabetes at baseline, 755 subjects remained for analyses. RESULTS: Increased levels of leucine, arginine, valine, proline, phenylalanine, isoleucine and lysine were significantly associated with an increased risk of hypertriglyceridemia. These associations remained significant when restricting to those individuals who did not develop T2D in the 7-year follow-up. The increase per standard deviation of amino acid level was between 26 and 40 %. CONCLUSIONS: Seven amino acids were associated with an increased risk of developing hypertriglyceridemia after 7 years. Further studies are necessary to elucidate the complex role of these amino acids in the pathogenesis of metabolic disorders.

Feasibility and quality development of biomaterials in the pretest studies of the German National Cohort.

BACKGROUND: The German National Cohort (GNC) is designed to address research questions concerning a wide range of possible causes of major chronic diseases (e.g. cancer, diabetes, infectious, allergic, neurologic and cardiovascular diseases) as well as to identify risk factors and prognostic biomarkers for early diagnosis and prevention of these diseases. The collection of biomaterials in combination with extensive information from questionnaires and medical examinations represents one of the central study components. OBJECTIVES: In two pretest studies of the German National Cohort conducted between 2011 and 2013, a range of biomaterials from a defined number of participants was collected. Ten study centres were involved in pretest 1 and 18 study centres were involved in pretest 2. Standard operation procedures (SOP) were developed and evaluated to minimize pre-analytical artefacts during biosample collection. Within the pretest studies different aspects concerning feasibility of sample collection/preparation [pretest 1 (a)] and quality control of biomarkers and proteome analyses were investigated [pretest 1 (b), (c)]. Additionally, recruitment of study participants for specific projects and examination procedures of all study centres in a defined time period according to common standards as well as transportation and decentralized storage of biological samples were tested (pretest 2). These analyses will serve as the basis for the biomaterial collection in the main study of the GNC starting in 2014. MATERIALS AND METHODS: Participants, randomly chosen from the population (n = 1000 subjects recruited at ten study sites in pretest 1) were asked to donate blood, urine, saliva and stool samples. Additionally, nasal and oropharyngeal swabs were collected at the study sites and nasal swabs were collected by the participants at home. SOPs for sample collection, preparation, storage and transportation were developed and adopted for pretest 2. In pretest 2, 18 study sites (n = 599 subjects) collected biomaterials mostly identical to pretest 1. Biomarker analyses to test the quality of the biomaterials were performed. RESULTS: In pretest 1 and 2, it was feasible to collect all biomaterials from nearly all invited participants without major problems. The mean response rate of the subjects was 95 %. As one important result we found for example that after blood draw the cellular fraction should be separated from the plasma and serum fractions during the first hour with no significant variation for up to 6 h at 4 ℃ for all analysed biomarkers. Moreover, quality control of samples using a proteomics approach showed no significant clustering of proteins according to different storage conditions. All developed SOPs were validated for use in the main study after some adaptation and modification. Additionally, electronic and paper documentation sheets were developed and tested to record time stamps, volumes, freezing times, and aliquot numbers of the collected biomaterials. DISCUSSION: The collection of the biomaterials was feasible without major problems at all participating study sites. However, the processing times were in some cases too long. To avoid pre-analytical artefacts in sample collection, appropriate standardisation among the study sites is necessary. To achieve this, blood and urine collection will have to be adapted to specific conditions of usage of liquid handling robots, which will be available at all participating study centres in the main study of the GNC. Strict compliance with the SOPs, thorough training of the staff and accurate documentation are mandatory to obtain high sample quality for later analyses. The so obtained biomaterials represent a valuable resource for research on infectious and other common complex diseases in the GNC.

Associations between longevity of parents and glucose regulation in their offspring: the KORA S4/F4 Study.

AIMS: Type 2 diabetes was less prevalent in studies of the offspring of centenarians and a separate study of nonagenarian siblings. We examined whether this reduction would also be found when less extreme criteria of parental longevity (a lifespan of at least 80 years) were applied. Moreover, we looked for an association between parental longevity and incidence of dysglycaemia, which has not yet been reported for a population-based study group. METHODS: Baseline and 7-year follow-up data on 55-74-year-old participants in the population-based German Cooperative Health Research in the Region of Augsburg (KORA) S4/F4 cohort study were used for the analyses. Participants whose parents had died from traumatic causes were excluded. Diabetes was assessed by validated physician diagnosis or OGTTs. Using logistic regression models, adjusted OR and 95% CIs were calculated for the associations between parental longevity and the prevalence or incidence of dysglycaemia, which was defined as including either type 2 diabetes or prediabetes (defined in this study as comprising impaired glucose tolerance [IGT] and impaired fasting glucose [IFG]). RESULTS: In age- and sex-adjusted models, the prevalence of type 2 diabetes was lower in individuals with one (OR 0.63, 95% CI 0.43, 0.93) or two (OR 0.46, 95% CI 0.25, 0.85) long-lived parents. Among participants with normal glucose tolerance at baseline, the odds of incident dysglycaemia were lower in those with one (OR 0.65, 95% CI 0.40, 1.03) or two long-lived parents (OR 0.46, 95% CI 0.22, 0.96) after adjustment for age and sex. CONCLUSIONS/INTERPRETATION: This study showed that longevity of the parents, defined by a lifespan of at least 80 years, was associated with a lower prevalence and incidence of dysglycaemia in their offspring in an older German population.

Serum potassium is associated with prediabetes and newly diagnosed diabetes in hypertensive adults from the general population: the KORA F4-study.

AIMS/HYPOTHESIS: Evidence suggests that low serum potassium concentrations or hypokalaemia induced by the intake of diuretics are associated with incident diabetes and increased risk for diabetes in persons with hypertension. We examined a possible association between serum potassium and prediabetes (defined as isolated impaired fasting glucose [i-IFG], isolated impaired glucose tolerance [i-IGT] or combined IFG/IGT), as well as known and newly diagnosed diabetes (NDD), in 32- to 81-year-old men and women with and without hypertension. METHODS: This cross-sectional analysis was based on 2,948 participants in the Cooperative Health Research in the Region of Augsburg (KORA) F4 study conducted in 2006-2008 in southern Germany. Serum concentrations of potassium were measured by indirect potentiometry. RESULTS: In the total sample there was no association between serum potassium concentrations and prediabetes. In hypertensive persons however serum potassium levels in the first and second quartile compared with the highest quartile were independently significantly associated with prediabetes after multivariable adjustment (OR for prediabetes, 2.02 [95% CI 1.27, 3.21] for quartile 2 and 2.00 [95% CI 1.27, 3.15] for quartile 1), while in persons without hypertension no association was found. In multinomial logistic regression analysis these findings could be confirmed. In hypertensive participants after multivariable adjustment the associations were statistically significant for i-IGT and NDD (i-IGT OR 1.23; NDD OR 1.41). However, in non-hypertensive persons, all associations between serum potassium levels and each of the categories of impaired glucose regulation were non-significant. CONCLUSIONS/INTERPRETATION: Serum potassium levels were independently associated with prediabetes and NDD in hypertensive adults from the general population.

Long-term exposure to traffic-related air pollution and insulin resistance in children: results from the GINIplus and LISAplus birth cohorts.

AIMS/HYPOTHESIS: Epidemiological studies that have examined associations between long-term exposure to traffic-related air pollution and type 2 diabetes mellitus in adults are inconsistent, and studies on insulin resistance are scarce. We aimed to assess the association between traffic-related air pollution and insulin resistance in children. METHODS: Fasting blood samples were collected from 397 10-year-old children in two prospective German birth cohort studies. Individual-level exposures to traffic-related air pollutants at the birth address were estimated by land use regression models. The association between air pollution and HOMA of insulin resistance (HOMA-IR) was analysed using a linear model adjusted for several covariates including birthweight, pubertal status and BMI. Models were also further adjusted for second-hand smoke exposure at home. Sensitivity analyses that assessed the impact of relocating, study design and sex were performed. RESULTS: In all crude and adjusted models, levels of insulin resistance were greater in children with higher exposure to air pollution. Insulin resistance increased by 17.0% (95% CI 5.0, 30.3) and 18.7% (95% CI 2.9, 36.9) for every 2SDs increase in ambient NO2 and particulate matter ≤10 µm in diameter, respectively. Proximity to the nearest major road increased insulin resistance by 7.2% (95% CI 0.8, 14.0) per 500 m. CONCLUSIONS/INTERPRETATION: Traffic-related air pollution may increase the risk of insulin resistance. Given the ubiquitous nature of air pollution and the high incidence of insulin resistance in the general population, the associations examined here may have potentially important public health effects despite the small/moderate effect sizes observed.