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Progressive renal vascular sclerosis is a key feature of chronic kidney disease (CKD). Adiponectin, an adipokine with potent anti-inflammatory and antiatherosclerotic properties, is associated with insulin resistance, type II diabetes and cardiovascular disease. In this study, we evaluated the predictive value of adiponectin for the progression of CKD in patients enrolled in the Mild to Moderate Kidney Disease Study. The primary end point was defined as a doubling of the baseline serum creatinine and/or terminal renal failure in 177 patients who completed a prospective follow-up of 7 years. Patients who reached a progression endpoint (n=65) were significantly older, had higher baseline serum creatinine, proteinuria and adiponectin concentrations and more components of the metabolic syndrome. A gender-stratified Cox model revealed adiponectin in men as a significant predictor of progression after adjustment for age, glomerular filtration rate, and proteinuria. Male patients with adiponectin levels above their ROC analysis-derived optimal cutoff of 4μg/ml had a significantly faster progression than patients below this point. This prospective long-term study in patients with CKD indicates high adiponectin as a novel independent predictor of disease progression in men but not in women. Our observation may be relevant for other conditions of progressive vascular sclerosis and diabetic nephropathy.

Abstract Objective To determine the risk of lung cancer associated with exposure at home to the radioactive disintegration products of naturally occurring radon gas Design Collaborative analysis of individual data from 13 case-control studies of residential radon and lung cancer. Setting Nine European countries. Subjects 7148 cases of lung cancer and 14 208 controls. Main outcome measures Relative risks of lung cancer and radon gas concentrations in homes inhabited during the previous 5-34 years measured in becquerels (radon disintegrations per second) per cubic metre (Bq/m3) of household air. Results The mean measured radon concentration in homes of people in the control group was 97 Bq/m3, with 11% measuring > 200 and 4% measuring > 400 Bq/m3. For cases of lung cancer the mean concentration was 104 Bq/m3. The risk of lung cancer increased by 8.4% (95% confidence interval 3.0% to 15.8%) per 100 Bq/m3 increase in measured radon (P = 0.0007). This corresponds to an increase of 16% (5% to 31%) per 100 Bq/m3 increase in usual radon—that is, after correction for the dilution caused by random uncertainties in measuring radon concentrations. The dose-response relation seemed to be linear with no threshold and remained significant (P = 0.04) in analyses limited to individuals from homes with measured radon < 200 Bq/m3. The proportionate excess risk did not differ significantly with study, age, sex, or smoking. In the absence of other causes of death, the absolute risks of lung cancer by age 75 years at usual radon concentrations of 0, 100, and 400 Bq/m3 would be about 0.4%, 0.5%, and 0.7%, respectively, for lifelong non-smokers, and about 25 times greater (10%, 12%, and 16%) for cigarette smokers. Conclusions Collectively, though not separately, these studies show appreciable hazards from residential radon, particularly for smokers and recent ex-smokers, and indicate that it is responsible for about 2% of all deaths from cancer in Europe.

Recent advances in molecular subtyping of Pancreatic Ductal Adenocarcinoma (PDAC) support individualization of therapeutic strategies in this most aggressive disease. With the emergence of various novel therapeutic strategies and neoadjuvant approaches in this quickly deteriorating disease, robust approaches for fast evaluation of therapy response are urgently needed. To this aim, we designed a preclinical imaging-guided therapy trial where genetically engineered mice harboring endogenous aggressive PDAC were treated with the MEK targeting drug refametinib, which induces rapid and profound tumor regression in this model system. Multi-parametric non-invasive imaging was used for therapy response monitoring. A significant increase in the Diffusion-Weighted Magnetic Resonance Imaging derived Apparent Diffusion Coefficient (ADC) was noted already 24 hours after treatment onset. Histopathological analyses showed increased apoptosis and matrix remodeling at this time point. Our findings suggest the ADC parameter as an early predictor of therapy response in PDAC.

In patients with type 2 diabetes, sleep-disordered breathing is a widespread cause of deteriorated quality of life. However, robust prevalence estimates for sleep-disordered breathing in patients with type 2 diabetes are limited due to scarce data. We investigated sex differences in sleep-disordered breathing prevalence and its modulators in the DIACORE SDB substudy, a sample of outpatient type 2 diabetes. 721 participants were tested for sleep-disordered breathing using a two-channel sleep apnoea monitoring device. Patients were stratified according to the severity of sleep-disordered breathing, defined as an apnoea-hypopnoea index < 15, ≥15 to 29, and ≥30 events per hour as no/mild, moderate, and severe sleep-disordered breathing, respectively. In the 679 analysed patients (39% women, age 66 ± 9 years, body mass index 31.0 ± 5.4 kg/m2), the prevalence of sleep-disordered breathing was 34%. The prevalence of sleep-disordered breathing was higher in men than in women (41% versus 22%, p<0.001) and increased with age (15%, 21%, and 30% in women and 35%, 40%, and 47% in men in those aged 18–59, 60–69, or ≥70, respectively; age trend p=0.064 in women and p=0.15 in men). In linear regression analysis, age, BMI, and waist-hip ratio were associated with apnoea-hypopnoea index. Modulators for higher apnoea-hypopnoea index seem to be similar in men and women.

Purpose Despite the health benefits of full breastfeeding for both infants and mothers, less than 50% of mothers in Germany practice this method for at least 4 months after childbirth. Because of the growing importance of health literacy to improve public health, we investigated the role of maternal health literacy in breastfeeding behavior. Methods We analyzed the data of 1172 mother–child dyads of the KUNO-Kids health study of the University Children’s and Maternity Hospital Regensburg. Maternal health literacy was assessed with the HLS-EU-Q47 questionnaire (sub-index health care) up to 48 h after childbirth. Outcome was analyzed 6 months after childbirth and categorized into full breastfeeding for less than 4 months or for at least 4 months. The association between breastfeeding and maternal health literacy was calculated with univariable and multivariable logistic regression analyses. Results 38.8% of mothers showed inadequate or limited health literacy. 75.9% of mothers had fully breastfed their child for at least 4 months. Univariable logistic regression analysis showed that health literacy and full breastfeeding for at least 4 months were not associated (OR = 0.995 [CI 0.977–1.015], p  = 0.60). After adjusting for all potentially confounding variables with a significant association ( p  ≤ 0.05) on both health literacy and breastfeeding, the multivariable model showed no association between health literacy and breastfeeding (OR = 0.984 [CI 0.963–1.007], p  = 0.170). Conclusion Surprisingly, we found no association between health literacy and breastfeeding behavior in our study. Therefore, future research with comparable measurements of health literacy and breastfeeding is required to validate this result and to identify reasons for early breastfeeding cessation.

Background. Metabolic syndrome (MS) and sleep-disordered breathing (SDB) are highly prevalent in patients with diabetes mellitus type 2 (DM2). The present study examined whether there is an independent association between SDB and MS in a sample of outpatients with DM2. Methods. MS was determined in 679 patients of the DIACORE-SDB substudy, a study of outpatients with DM2. According to the National Cholesterol Education Program (NCEP) criteria, MS is defined by at least three of the following five criteria: waist circumference of >102 cm (men)/>88 cm (women), blood pressure of ≥130/85 mmHg, a fasting triglyceride level of >150 mg/dl, high-density lipoprotein (HDL) of <40 mg/dl (men)/<50 mg/dl (women), and a fasting glucose level of ≥110 mg/dl. The apnea-hypopnea index (AHI) was assessed with a 2-channel ambulatory monitoring device and used to define the severity of SDB (AHI<15.0: no/mild SDB; AHI 15.0-29.9: moderate SDB; AHI≥30.0: severe SDB). Results. 228 (34%) of the 679 participants (mean age 66 years, mean body mass index (BMI) 31.2 kg/m2, and mean AHI 14/hour) had SDB. MS was significantly more frequent in patients with more severe SDB (no/mild SDB vs. moderate SDB vs. severe SDB: 72% vs. 79% vs. 85%, respectively, p=0.038). Logistic regression analysis adjusted for sex, age, obesity (BMI≥30 kg/m2), and the HOMA index showed a significant association between the AHI and the presence of MS (OR 95%CI=1.039 (1.011; 1.068); p=0.007). Further, male sex, obesity, and the HOMA index were significantly associated with MS. Conclusion. SDB is significantly and independently associated with MS in outpatients with DM2.

Background: Data from meta-analyses of genome-wide association studies provided evidence for an association of polymorphisms with body mass index (BMI), and gene expression results indicated a role of these variants in the hypothalamus. It was consecutively hypothesized that these associations might be evoked by a modulation of nutritional intake or energy expenditure. Objective: It was our aim to investigate the association of these genetic factors with BMI in a large homogenous population-based sample to explore the association of these polymorphisms with lifestyle factors related to nutritional intake or energy expenditure, and whether such lifestyle factors could be mediators of the detected single-nucleotide polymorphism (SNP)-association with BMI. It was a further aim to compare the proportion of BMI explained by genetic factors with the one explained by lifestyle factors. Design: The association of seven polymorphisms in or near the genes NEGR1, TMEM18, MTCH2, FTO, MC4R, SH2B1 and KCTD15 was analyzed in 12 462 subjects from the population-based MONICA/KORA Augsburg study. Information on lifestyle factors was based on standardized questionnaires. For statistical analysis, regression-based models were used. Results: The minor allele of polymorphism rs6548238 C>T (TMEM18) was associated with lower BMI (−0.418 kg m−2, P=1.22 × 10(-8)), and of polymorphisms rs9935401 G>A (FTO) and rs7498665 A>G (SH2B1) with increased BMI (0.290 kg m−2, P=2.85 × 10(-7) and 0.145 kg m−2, P=9.83 × 10(-3)). The other polymorphisms were not significantly associated. Lifestyle factors were correlated with BMI and explained 0.037% of the BMI variance as compared with 0.006% of explained variance by the associated genetic factors. The genetic variants associated with BMI were not significantly associated with lifestyle factors and there was no evidence of lifestyle factors mediating the SNP–BMI association. Conclusions: Our data first confirm the findings for TMEM18 with BMI in a single study on adults and also confirm the findings for FTO and SH2B1. There was no evidence for a direct SNP–lifestyle association.

Background: The melanocortin-4-receptor gene (MC4R) is part of the melanocortinergic pathway that controls energy homeostasis. In a recent meta-analysis, the MC4R V103I (rs2229616) polymorphism was shown to be associated with body weight regulation. Although no functional differences between the isoleucine comprising receptor and the wild type receptor have been detected as yet, this meta-analysis of 14 case–control studies reported a mild negative association with obesity (odds ratio (OR) 0.69, p = 0.03). However, evidence in a large population based study in a homogeneous population and a significant estimate of the change in quantitative measures of obesity is still lacking. Methods: We analysed the data of two surveys of a white population with the same high quality study protocol, giving a total of 7937 participants. Results: By linear regression, we found a significant decrease of 0.52 body mass index (BMI) units (95% confidence interval (CI) −0.02 to −1.03, p = 0.043) for carriers of the heterozygote rs2229616G/A genotype, which was observed in 3.7% of the participants. Logistic regression yielded a significantly negative association of the MC4R variant with “above average weight” (BMI ⩾ median BMI) yielding an OR of 0.75 (95% CI 0.59 to 0.95 p = 0.017). We obtained similar results comparing obese (BMI ⩾30 kg/m2, World Health Organization results for 1997) with non-obese (BMI <30 kg/m2) participants. The results were found for both sexes and each survey separately, and did not depend on the modelling of age, sex, or survey effects. Conclusions: Our study confirms previous findings of a meta-analysis that the relatively infrequent G/A genotype of the V103I MC4R polymorphism is negatively associated with above average weight and obesity in population based original data of 7937 participants, and extends previous findings by showing for the first time a significantly lower BMI in individuals carrying the infrequent allele of this MC4R variant.

Measurement error in exposure assessment is unavoidable. Statistical methods to correct for such errors rely upon a valid error model, particularly regarding the classification of classical and Berkson error, the structure and the size of the error. We provide a detailed list of sources of error in residential radon exposure assessment, stressing the importance of (a) the differentiation between classical and Berkson error and (b) the clear definitions of predictors and operationally defined predictors using the example of two German case-control studies on lung cancer and residential radon exposure. We give intuitive measures of error size and present evidence on both the error size and the multiplicative structure of the error from three data sets with repeated measurements of radon concentration. We conclude that modern exposure assessment should not only aim to be as accurate and precise as possible, but should also provide a model of the remaining measurement errors with clear differentiation of classical and Berkson components.