Margit Heier

The prevalence of celiac disease in Europe: Results of a centralized, international mass screening project

Abstract Introduction. Although the prevalence of celiac disease (CD) has been extensively investigated in recent years, an accurate estimate of CD frequency in the European population is still lacking. The aims of this study were: 1) to establish accurately the prevalence of CD in a large sample of the European population (Finland, Germany, Italy, and UK), including both children and adults; and 2) to investigate whether the prevalence of CD significantly varies between different areas of the European continent. Materials and methods. Samples were drawn from the four populations. All 29,212 participants were tested for CD by tissue transglutaminase (tTG) antibody test. Positive and border-line findings were further tested for serum endomysial antibodies (EMA). All serological determinations were centrally performed. Small-bowel biopsies were recommended to autoantibody-positive individuals. Previously diagnosed cases were identified. Results. The overall CD prevalence (previously diagnosed plus anti-tTG and EMA positives) was 1.0% (95% CI 0.9–1.1). In subjects aged 30–64 years CD prevalence was 2.4% in Finland (2.0–2.8), 0.3% in Germany (0.1–0.4), and 0.7% in Italy (0.4–1.0). Sixty-eight percent of antibody-positive individuals showed small-bowel mucosal changes typical for CD (Marsh II/III lesion). Conclusions. CD is common in Europe. CD prevalence shows large unexplained differences in adult age across different European countries.

Sleep disturbance as a predictor of type 2 diabetes mellitus in men and women from the general population

Aims/hypothesisTo examine gender specific associations between sleep disturbance and incident type 2 diabetes mellitus in a representative population sample in Germany.MethodsThe study was based on 4,140 men and 4,129 women (aged 25–74 years) who participated in one of the three MONICA Augsburg surveys between 1984 and 1995, and who were free of diabetes at baseline. Incident cases of type 2 diabetes were assessed using a follow-up questionnaire in 1998. Gender specific hazard ratios were estimated from Cox proportional hazard models.ResultsA total of 119 cases of incident type 2 diabetes among men and 69 among women were registered during the mean follow-up period of 7.5 years. In both sexes, difficulty maintaining sleep was associated with a higher risk of type 2 diabetes. After adjustment for age, survey, hypertension, dyslipidemia, parental history of diabetes, history of angina pectoris, regular smoking, physical activity, alcohol intake, body mass index and education, the hazard ratio in men was 1.60 (95% CI: 1.05–2.45) and the hazard ratio in women was 1.98 (95% CI: 1.20–3.29). In contrast, difficulty initiating sleep was not associated with a significantly increased risk of developing type 2 diabetes mellitus after multivariable adjustment in both sexes in the present study.Conclusions/interpretationDifficulty maintaining sleep was associated with an increased risk of type 2 diabetes in men and women from the general population. Although, the causal pathway is not entirely clear, it seems that both insulin resistance and chronic low-grade systemic inflammation may be involved.

Long term exposure to ambient air pollution and incidence of acute coronary events: prospective cohort study and meta-analysis in 11 European cohorts from the ESCAPE Project

Objectives To study the effect of long term exposure to airborne pollutants on the incidence of acute coronary events in 11 cohorts participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Design Prospective cohort studies and meta-analysis of the results. Setting Cohorts in Finland, Sweden, Denmark, Germany, and Italy. Participants 100 166 people were enrolled from 1997 to 2007 and followed for an average of 11.5 years. Participants were free from previous coronary events at baseline. Main outcome measures Modelled concentrations of particulate matter <2.5 μm (PM2.5), 2.5-10 μm (PMcoarse), and <10 μm (PM10) in aerodynamic diameter, soot (PM2.5 absorbance), nitrogen oxides, and traffic exposure at the home address based on measurements of air pollution conducted in 2008-12. Cohort specific hazard ratios for incidence of acute coronary events (myocardial infarction and unstable angina) per fixed increments of the pollutants with adjustment for sociodemographic and lifestyle risk factors, and pooled random effects meta-analytic hazard ratios. Results 5157 participants experienced incident events. A 5 μg/m3 increase in estimated annual mean PM2.5 was associated with a 13% increased risk of coronary events (hazard ratio 1.13, 95% confidence interval 0.98 to 1.30), and a 10 μg/m3 increase in estimated annual mean PM10 was associated with a 12% increased risk of coronary events (1.12, 1.01 to 1.25) with no evidence of heterogeneity between cohorts. Positive associations were detected below the current annual European limit value of 25 μg/m3 for PM2.5 (1.18, 1.01 to 1.39, for 5 μg/m3 increase in PM2.5) and below 40 μg/m3 for PM10 (1.12, 1.00 to 1.27, for 10 μg/m3 increase in PM10). Positive but non-significant associations were found with other pollutants. Conclusions Long term exposure to particulate matter is associated with incidence of coronary events, and this association persists at levels of exposure below the current European limit values.

Regional disparities of hypertension prevalence and management within Germany.

Objective To investigate regional variations in the prevalence and management of hypertension in two communities in the north-east and the south-west of Germany. Study setting Two population-based surveys of men and women aged 25–74 years, using a common standardized protocol: the Study of Health in Pomerania (SHIP; 3744 participants) and the Kooperative Gesundheitsforschung in der Region Augsburg (KORA; 4224 participants). Main outcome measures Comparison of SHIP and KORA with regard to mean systolic (SBP) and diastolic blood pressure (DBP), prevalence of hypertension, percentage of awareness, treatment and control of hypertension in the community, by age and sex. Results The overall age-standardized prevalence of hypertension for men was 60.1% in SHIP and 41.4% in KORA; the corresponding values for women were 38.5 and 28.6%. Mean blood pressure differences were present in each 10-year age group and sex. The overall SBP difference between SHIP and KORA was 8.2 mmHg (95% confidence interval 7.2–9.3) in men and 6.3 mmHg (5.3–7.3) in women, the respective DBP differences were 3.8 mmHg (3.2–4.5) and 3.6 mmHg (3.0–4.2). Nevertheless, the percentage of awareness, treatment and control of hypertension was strikingly similar in the two studies (women, P = 0.858; and men, P = 0.564). Conclusions The entire distribution of diastolic and systolic blood pressure values was shifted upwards in the north-eastern as compared to the south-western German population samples and the prevalences of hypertension differed accordingly. Despite such substantial epidemiologic differences, the community management of hypertension was of almost identical quality.

Incidence of Type 2 diabetes in the elderly German population and the effect of clinical and lifestyle risk factors: KORA S4/F4 cohort study

Aims  To determine the incidence of Type 2 diabetes in an elderly population in Germany and its association with clinical and lifestyle factors.

Official statistics and claims data records indicate non-response and recall bias within survey-based estimates of health care utilization in the older population

BackgroundThe validity of survey-based health care utilization estimates in the older population has been poorly researched. Owing to data protection legislation and a great number of different health care insurance providers, the assessment of recall and non-response bias is challenging to impossible in many countries. The objective of our study was to compare estimates from a population-based study in older German adults with external secondary data.MethodsWe used data from the German KORA-Age study, which included 4,127 people aged 65–94 years. Self-report questions covered the utilization of long-term care services, inpatient services, outpatient services, and pharmaceuticals. We calculated age- and sex-standardized mean utilization rates in each domain and compared them with the corresponding estimates derived from official statistics and independent statutory health insurance data.ResultsThe KORA-Age study underestimated the use of long-term care services (−52%), in-hospital days (−21%) and physician visits (−70%). In contrast, the assessment of drug consumption by postal self-report questionnaires yielded similar estimates to the analysis of insurance claims data (−9%).ConclusionSurvey estimates based on self-report tend to underestimate true health care utilization in the older population. Direct validation studies are needed to disentangle the impact of recall and non-response bias.

Genetic Determinants of Serum Testosterone Concentrations in Men

Testosterone concentrations in men are associated with cardiovascular morbidity, osteoporosis, and mortality and are affected by age, smoking, and obesity. Because of serum testosterones high heritability, we performed a meta-analysis of genome-wide association data in 8,938 men from seven cohorts and followed up the genome-wide significant findings in one in silico (n = 871) and two de novo replication cohorts (n = 4,620) to identify genetic loci significantly associated with serum testosterone concentration in men. All these loci were also associated with low serum testosterone concentration defined as <300 ng/dl. Two single-nucleotide polymorphisms at the sex hormone-binding globulin (SHBG) locus (17p13-p12) were identified as independently associated with serum testosterone concentration (rs12150660, p = 1.2×10−41 and rs6258, p = 2.3×10−22). Subjects with ≥3 risk alleles of these variants had 6.5-fold higher risk of having low serum testosterone than subjects with no risk allele. The rs5934505 polymorphism near FAM9B on the X chromosome was also associated with testosterone concentrations (p = 5.6×10−16). The rs6258 polymorphism in exon 4 of SHBG affected SHBGs affinity for binding testosterone and the measured free testosterone fraction (p<0.01). Genetic variants in the SHBG locus and on the X chromosome are associated with a substantial variation in testosterone concentrations and increased risk of low testosterone. rs6258 is the first reported SHBG polymorphism, which affects testosterone binding to SHBG and the free testosterone fraction and could therefore influence the calculation of free testosterone using law-of-mass-action equation.

Patterns of Multimorbidity in the Aged Population. Results from the KORA-Age Study.

Multimorbidity is a common problem in aged populations with a wide range of individual and societal consequences. The objective of the study was to explore patterns of comorbidity and multimorbidity in an elderly population using different analytical approaches. Data were gathered from the population-based KORA-Age project, which included 4,127 persons aged 65–94 years living in the city of Augsburg and its two surrounding counties in Southern Germany. Information on the presence of 13 chronic conditions was collected in a standardized telephone interview and a self-administered questionnaire. Patterns of comorbidity and multimorbidity were analyzed using prevalence figures, logistic regression models and exploratory tetrachoric factor analysis. The prevalence of multimorbidity (≥2 diseases) was 58.6% in the total sample. Hypertension and diabetes (Odds Ratio [OR] 2.95, 99.58% confidence interval [CI] [2.19–3.96]), as well as hypertension and stroke (OR 2.00, 99.58% CI [1.26–3.16]) most often occurred in combination. This association was independent of age, sex and the presence of other conditions. Using factor analysis, we identified four patterns of multimorbidity: the first pattern includes cardiovascular and metabolic diseases, the second includes joint, liver, lung and eye diseases, the third covers mental and neurologic diseases and the fourth pattern includes gastrointestinal diseases and cancer. 44% of the persons were assigned to at least one of the four multimorbidity patterns; 14% could be assigned to both the cardiovascular/metabolic and the joint/liver/lung/eye pattern. Further common pairs were the mental/neurologic pattern combined with the cardiovascular/metabolic pattern (7.2%) or the joint/liver/lung/eye pattern (5.3%), respectively. Our results confirmed the existence of co-occurrence of certain diseases in elderly persons, which is not caused by chance. Some of the identified patterns of multimorbidity and their overlap may indicate common underlying pathological mechanisms.

Serum γ-glutamyltransferase and risk of type 2 diabetes mellitus in men and women from the general population

Objectives.  To examine gender‐specific associations between γ‐glutamyltransferase (GGT) and incident type 2 diabetes mellitus in a representative population‐based sample in Germany.

Prevalence of undiagnosed diabetes and impaired glucose regulation in 35-59-year-old individuals in Southern Germany: the KORA F4 Study.

Diabet. Med. 27, 360–362 (2010)