Effectiveness of a supportive telephone counseling intervention in type 2 diabetes patients: randomized controlled study.

OBJECTIVES: This randomized controlled trial investigated whether a patient-centered supportive counseling intervention comprising monthly telephone-based counseling sessions by practice nurses over 12 months improved diabetes-related medical and psycho-social outcomes above usual care in type 2 diabetes patients with poor glycemic control at baseline (HbA1c >7.5%) in a primary care setting. RESEARCH DESIGN: Patients were individually randomized into intervention (n = 103) and usual care group (n = 101). The primary outcome was change in HbA1c-concentration after 12 and 18 months. Secondary outcomes were lipid levels, blood pressure, health-related quality of life and symptoms of depression. Follow-up-measurements were carried out after 6, 12 and 18 months to assess potential immediate and maintained effects of the intervention. For the multivariate analysis, hierarchical linear models were computed for each outcome to assess within-group changes in outcomes over time and between-group differences in patterns of change. RESULTS: HbA1c (in %) decreased significantly from baseline to 12-month follow-up measurement both in the intervention (-0.44) and the usual care group (-0.51), but there was no significant between-group intervention effect. Significant improvements in the intervention group along with significant between-group differences were seen for health-related quality of life and, transiently, for systolic blood pressure and depression. CONCLUSIONS: Although we found no beneficial effect of the supportive telephone counseling in terms of a reduction of HbA1c above usual care, our findings suggest some beneficial effects on cardiovascular risk factors, quality of life and depression. Continuous efforts might be needed to sustain improvements in patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00742547.

Genetic variations in the vitamin D binding protein and season-specific levels of vitamin D among older adults.

BACKGROUND: Vitamin D insufficiency is common among older adults. Genome-wide association studies have found an association between variants in the vitamin D binding protein and serum levels of vitamin D. The quantification of this association among older women and men and its potential variation by season remain unexplored. METHODS: Serum levels of 25-hydroxyvitamin D [25(OH)D] and genetic variants in the vitamin D binding protein were analyzed in 2160 women and 1581 men age 50 to 74 years participating in a large population-based cohort study (ESTHER study-epidemiologic study assessing chances of prevention and early detection of various chronic diseases, including cancer among older adults) in Germany. Serum levels of 25(OH)D were assessed in relation to four single nucleotide polymorphisms (SNPs; rs4588, rs2282679, rs1155563, and rs12512631) by descriptive and multivariate analysis. RESULTS: Both heterozygous and homozygous women and men carrying the rare allele with SNPs rs4588, rs2282679, or rs1155563 had lower levels of 25(OH)D in summer months than those homozygous for the wild-type alleles. Adjusted differences ranged from 5.1 to 5.4 nmol/l among heterozygous carriers of the rare alleles and from 8.8 to 9.6 nmol/l among homozygous carriers of the rare alleles. During winter months, 25(OH)D differences by genotype were smaller among women and not apparent among men. CONCLUSIONS: Older women and men living in a high-latitude region and carrying the rare alleles of SNPs rs4588, rs2282679, or rs1155563 seem to benefit less from higher levels of ultraviolet radiation during the summer season.

Development and evaluation of a modification of the Fried frailty criteria using population-independent cutpoints.

OBJECTIVES: To develop and evaluate a modification of the Fried frailty assessment using population-independent cutpoints and to determine frailty prevalence of community-dwelling elderly people in a German population. DESIGN: Cross-sectional analysis of 8-year follow-up data of a large German cohort study. SETTING: Saarland, Germany. PARTICIPANTS: Three thousand one hundred twelve community-dwelling adults aged 59 and older. MEASUREMENTS: Frailty was operationalized using modified Fried frailty criteria. Criteria were categorized according to quintiles (lowest-quintile approach) or using population-independent cutpoints derived from the literature (population-independent approach). Agreement and construct validity of frailty classification according to both approaches were evaluated according to weighted kappa (κ) and Spearman rank correlation (r(Sp) ). Associations between frailty and covariates were assessed using multiple logistic regression models. RESULTS: Although more participants were identified as frail according to the population-independent index (8.9%) than the lowest-quintile index (6.5%), agreement and correlation of frailty classification using both approaches was high (κ = 0.75 and r(Sp) = 0.84). Sex differences in frailty prevalence were more pronounced when the population-independent approach was used (women 11.4%; men 6.1%). Similarly strong significant associations with sociodemographic, lifestyle, and medical factors such as older age, female sex, smoking, and obesity were seen for both approaches. CONCLUSION: The modified Fried index using literature-derived cutpoints independent from the frailty criteria distributions in the underlying study population showed good correlation with the lowest-quintile approach and enables prevalence estimates that are directly comparable between different populations.

The importance of social support for people with type 2 diabetes - a qualitative study with general practitioners, practice nurses and patients.

OBJECTIVE: Social support is an important element of family medicine within a primary care setting, delivered by general practitioners and practice nurses in addition to usual clinical care. The aim of the study was to explore general practitioner's, practice nurse's and people with type 2 diabetes' views, experiences and perspectives of the importance of social support in caring for people with type 2 diabetes and their role in providing social support. METHODS: Interviews with general practitioners (n=10) and focus groups with practice nurses (n=10) and people with diabetes (n=9). All data were audio-recorded, fully transcribed and thematically analysed using qualitative content analysis by Mayring. RESULTS: All participants emphasized the importance of the concept of social support and its impacts on well-being of people with type 2 diabetes. Social support is perceived helpful for people with diabetes in order to improve diabetes control and give support for changes in lifestyle habits (physical activity and dietary changes). General practitioners identified a lack of information about facilities in the community like sports or self-help groups. Practice nurses emphasized that they need more training, such as in dietary counselling. CONCLUSIONS: Social support given by general practitioners and practice nurses plays a crucial role for people with type 2 diabetes and is an additional component of social care. However there is a need for an increased awareness by general practitioners and practice nurses about the influence social support could have on the individual's diabetes management.

Gender disparities in diabetes and coronary heart disease medication among patients with type 2 diabetes: results from the DIANA study.

BACKGROUND: Coronary heart disease (CHD) is one of the most common long-term complications in people with type 2 diabetes. We analyzed whether or not gender differences exist in diabetes and CHD medication among people with type 2 diabetes. METHODS: The study was based on data from the baseline examination of the DIANA study, a prospective cohort study of 1,146 patients with type 2 diabetes conducted in South-West Germany. Information on diabetes and CHD medication was obtained from the physician questionnaires. Bivariate and multivariate analyses using logistic regression were employed in order to assess associations between gender and prescribed drug classes. RESULTS: In total, 624 men and 522 women with type 2 diabetes with a mean age of 67.2 and 69.7 years, respectively, were included in this analysis. Compared to women, men had more angiopathic risk factors, including smoking, alcohol consumption and worse glycemic control, and had more often a diagnosed CHD. Bivariate analyses showed higher prescription of thiazolidinediones and oral combination drugs as well as of angiotensin-converting enzyme (ACE) inhibitors, calcium channel blockers and aspirin in men than in women. After full adjustment, differences between men and women remained significant only for ACE inhibitors (OR=1.44; 95%-confidence interval (CI): 1.11-1.88) and calcium channel blockers (OR=1.42, 95%-CI: 1.05-1.91). CONCLUSIONS: These findings contribute to current discussions on gender differences in diabetes care. Men with diabetes are significantly more likely to receive oral combination drugs, ACE inhibitors and calcium channel blockers in the presence of coronary heart disease, respectively. Our results suggest, that diabetic men might be more thoroughly treated compared to women. Further research is needed to focus on reasons for these differences mainly in treatment of cardiovascular diseases to improve quality of care.

Gender differences in healthcare utilization of patients with diabetes.

OBJECTIVES: To examine gender differences in healthcare utilization including outpatient and inpatient medical care for patients with type 2 diabetes mellitus (T2DM), despite participation in T2DM-specific disease management programs (DMP-DM). STUDY DESIGN: Baseline data from a cohort study in southwest Germany including 1146 patients with T2DM recruited between October 2008 and March 2010 were used. METHODS: After bivariate analyses, multivariate Poisson and logistic regression models were used to estimate the effect of sex on the number of general practitioner (GP) and medical specialist appointments, prescribed medications, hospitalizations, and inpatient rehabilitations, with additional consideration of glycemic control levels. Poor glycemic control (PGC) was defined as glycated hemoglobin ≥7.5%. RESULTS: In total, 905 participants had acceptable glycemic control and 237 participants had poor glycemic control. PGC was more prevalent in men than in women (23% vs 18%). Bivariate analyses among participants with PGC showed significantly fewer GP and medical specialist appointments, a lower number of medications, and longer rehabilitation stays in men than in women. Multivariate regression analyses among participants with PGC confirmed statistically significant gender differences for GP appointments and number of prescribed medications (P <.05) for men compared with women. Gender differences regarding inpatient care were less evident. CONCLUSIONS: Our data disclosed major gender differences in healthcare utilization of diabetes patients in Germany despite a high DMP-DM rate. Future research should focus attention on gender-specific approaches to healthcare delivery to improve quality and access to care.

Medication non-adherence and poor glycaemic control in patients with type 2 diabetes mellitus.

AIMS: Our main aim was to analyse gender differences in the association of adherence and poor glycaemic control (PGC) in a cohort of patients with type 2 diabetes mellitus in Germany. METHODS: Baseline data of the DIANA-study, a prospective cohort study of type 2 diabetes mellitus patients in South-West Germany, were analysed. Information on medication adherence and factors related to PGC was obtained by self-administered questionnaire. PGC was defined as HbA(1c)≥7.5%. Bivariate and multivariate analyses using log-binomial regression were employed to assess overall and gender-specific associations of non-adherence and PGC. RESULTS: 624 men and 518 women were included in the analyses. In total, 147 men (24%) and 114 women (23%) reported non-adherence to medication. In men, PGC was found in 37% of the participants reporting non-adherence and in 19% reporting adherence (adjusted prevalence ratio (PR)=1.90, 95%-CI: 1.46-2.49). In women, PGC was found in 19% of the participants reporting non-adherence and in 18% reporting adherence (adjusted PR=0.97, 95%-CI: 0.65-1.46). CONCLUSIONS: Our results show gender-specific differences in the association of adherence and PGC. This underlines the need for efforts to improve glycaemic control in patients with type 2 diabetes mellitus with a particular focus on men.

Public health implications of standardized 25-hydroxyvitamin D levels: a decrease in the prevalence of vitamin D deficiency among older women in Germany.

OBJECTIVE: To compare the public health implications of using unstandardized immunoassay measurements of serum 25-hydroxyvitamin D [25(OH)D] concentrations versus using measurements standardized by liquid chromatography tandem-mass spectrometry (LC-MS/MS) when assessing the prevalence of 25(OH)D insufficiency and deficiency in various subgroups of individuals. METHOD: We standardized immunoassay-based measurements of 25(OH)D with LC-MS/MS in a population-based sample of 5386 women aged 50-74 recruited in 2000-2002 in Germany. We used multivariate regression to assess 25(OH)D determinants and the association of vitamin D deficiency with health status. RESULTS: Prevalences of 25(OH)D levels <50 nmol/L (insufficiency) and <30 nmol/L (deficiency) decreased considerably by standardization. The decrease in vitamin D deficiency (from 64.4% to 17.9%) was particularly strong in March-May among women aged ≥ 65. Independent of season of blood draw and standardization, women ≥ 70 years, obese, or currently smoking had an increased risk of having 25(OH)D levels <30 nmol/L. CONCLUSION: The proportion of older women with vitamin D deficiency in Germany is much lower than previously reported, but prevalence of vitamin D insufficiency is high. Standardization of 25(OH)D values by immunoassay methods to LC-MS/MS equivalent values or direct measurement by LC-MS/MS is indispensable in drawing valid conclusions about the health implications of vitamin D deficiency or insufficiency.

Type 2 diabetes mellitus and gender-specific risk for colorectal neoplasia.

Although a positive association between type 2 diabetes mellitus (T2DM) and colorectal cancer is well established, uncertainty exists about risk differences in diabetic men and women when considering colorectal neoplasia (CN). The main objective was to examine gender-specific associations of T2DM with CN in a population-based cohort study of adults in Germany. This analysis is based on participants of the ESTHER-study, a population-based cohort study. Participants were 50-74 years old at baseline and underwent colonoscopy during 5 year follow-up. CN detected at colonoscopy were validated by medical records review. Total and gender-specific associations of T2DM at baseline and CN were estimated using log-binomial regression. Overall, 55 cases of CN were detected in 166 participants with T2DM and 328 cases in 1,360 participants without T2DM. In women, CN was found in 32 % of participants with T2DM and in 18 % without T2DM (adjusted prevalence ratio (PR): 1.66 95 % CI 1.04-2.64). In men, prevalence for CN was 35 % for those with T2DM and 33 % for those without T2DM (adjusted PR = 1.01; 95 % CI 0.71-1.43). T2DM might have a stronger impact on CN among women than among men. Further research should examine possible reasons for these differences.

Gender specific temporal and cross-sectional associations between BMI-class and symptoms of depression in the elderly.

OBJECTIVE: The aim of the study was the gender specific analysis of cross-sectional and longitudinal associations between body mass index class (BMI-class) and symptoms of depression in a representative sample of elderly German people. METHODS: At the baseline of the ESTHER study (2000-2002), 9953 participants completed a comprehensive questionnaire including items regarding weight, height, and depression history. After five years, 7808 participants again completed the questionnaire and the 15-item geriatric depression scale (GDS-15). BMI was classified into five classes: normal weight, 18.5≤BMI<25; overweight, 25≤BMI<30; obesity class I, 30≤BMI<35; obesity class II, 35≤BMI<40; obesity class III, BMI≥40. RESULTS: Logistic regression analysis for the cross-sectional data at five-year follow-up, adjusted for age, education, marital status, smoking, multimorbidity, physical activity, self-perceived cognitive impairment, and use of antidepressants, showed that the odds for depression were significantly elevated for women in obesity class II and significantly decreased for overweight men. The longitudinal analysis showed a similar pattern: Women in obesity classes II and III at baseline had significantly higher odds for being depressive five years later than women with normal weight at baseline (class II: OR=1.67; 95%CI=[1.06; 2.64]; class III: OR=2.93; 95%CI=[1.37; 6.26]; overweight men had lower odds than normal-weight men (OR=0.69; 95%CI=[0.51;0.92]). CONCLUSION: The relationship between obesity and symptoms of depression appears to be heterogeneous across BMI-classes. Women are more affected than men by obesity class II and III; overweight appears to be associated with reduced risk of depression in elderly men.

Temporal predictors of health-related quality of life in elderly people with diabetes: results of a German cohort study.

BACKGROUND: The aim of the study was to determine predictors that influence health-related quality of life (HRQOL) in a large cohort of elderly diabetes patients from primary care over a follow-up period of five years. METHODS AND RESULTS: At the baseline measurement of the ESTHER cohort study (2000-2002), 1375 out of 9953 participants suffered from diabetes (13.8%). 1057 of these diabetes patients responded to the second-follow up (2005-2007). HRQOL at baseline and follow-up was measured using the SF-12; mental component scores (MCS) and physical component scores (PCS) were calculated; multiple linear regression models were used to determine predictors of HRQOL at follow-up. As possible predictors for HRQOL, the following baseline variables were examined: treatment with insulin, glycated hemoglobin (HbA1c), number of diabetes related complications, number of comorbid diseases, Body-Mass-Index (BMI), depression and HRQOL. Regression analyses were adjusted for sociodemographic variables and smoking status. 1034 patients (97.8%) responded to the SF-12 both at baseline and after five years and were therefore included in the study. Regression analyses indicated that significant predictors of decreased MCS were a lower HRQOL, a higher number of diabetes related complications and a reported history of depression at baseline. Complications, BMI, smoking and HRQOL at baseline significantly predicted PCS at the five year follow-up. CONCLUSIONS: Our findings expand evidence from previous cross-sectional data indicating that in elderly diabetes patients, depression, diabetes related complications, smoking and BMI are temporally predictive for HRQOL.

Association between the prevalence of depression and age in a large representative German sample of people aged 53 to 80 years.

OBJECTIVE: The aim of the study was to determine the association between the prevalence of clinically significant depression and age in a large representative sample of elderly German people. METHODS: In the second follow-up (2005-2007) of the ESTHER cohort study, the 15-item geriatric depression scale (GDS-15) as well as a sociodemographic and clinical questionnaire were administered to a representative sample of 8270 people of ages 53 to 80 years. The prevalence of clinically significant depression was estimated using a GDS cut-off score of 5/6. Prevalence rates were estimated for the different age categories. Association between depression and age was analyzed using logistic regression, adjusted for gender, co-morbid medical disorders, education, marital status, physical activity, smoking, self-perceived cognitive impairment, and anti-depressive medication. RESULTS: Of the participants, 7878 (95.3%) completed more than twelve GDS items and were included in the study. The prevalence of clinically significant depression was 16.0% (95%CI = [15.2; 16.6]). The function of depression prevalence dependent on age group showed a U-shaped pattern (53-59: 21.0%, CI = [18.9; 23.3]; 60-64: 17.7%, CI = [15.7; 19.7]; 65-69: 12.6%, CI = [11.2; 14.0]; 70-74: 14.4%, CI = [12.6; 16.0]; 75-80: 17.1%, CI = [14.9; 19.4]). Adjusted odds ratios showed that the chances of being depressive decrease with the age category but remain relatively stable for people aged 65 and over. CONCLUSIONS: The prevalence of depression in the elderly seems to be associated with the age category. Adjusted odds ratios showed that people aged 60 and older had lower chances of being depressive than people aged 53 to 59 years.

Polymorphisms in MUC1, MUC2, MUC5B and MUC6 genes are not associated with the risk of chronic atrophic gastritis.

Mucins represent major components of the mucous layer in the stomach, protecting the underlying epithelium from acid, mechanical trauma, proteases and pathogenic bacteria. Previous studies have shown an association of neoplastic transformation in the stomach with aberrant mucin levels, suggesting a potential role of genetic variation in mucin genes in the development of gastric cancer (GC). We assessed the association of genetic variation in candidate single nucleotide polymorphisms (SNPs) in mucin genes with the risk of chronic atrophic gastritis (CAG), a well-established precursor of GC in the German population-based ESTHER study. We genotyped MUC1 T31T, MUC2 L58P, MUC2 V116M, MUC5B E34G, MUC5B R51W, MUC5B rs2014486 (intronic) and MUC6 V619M for 533 serologically defined CAG cases and 1054 age- and sex-matched controls. None of the analysed SNPs was associated with CAG. However, large studies are needed to disclose or exclude potential weak associations of these SNPs with CAG risk.

Vitamin D and cognitive functioning in the elderly population in Germany.

OBJECTIVES: To examine the relationship of serum 25-hydroxy vitamin D3 with cognitive functioning in higher age, using an instrument covering multiple cognitive domains in a population-based study. DESIGN: Follow-up study with measurement of vitamin D levels at baseline and assessment of cognitive functioning at year 5 follow-up. SETTING AND PARTICIPANTS: A subgroup of 1639 participants of the ongoing epidemiological ESTHER study of the elderly general population in Saarland State, Germany, aged 65+ years at baseline (2000-2002). INTERVENTION: Observational study. MEASUREMENTS: Cognitive functioning was assessed by the COGTEL phone interview developed by Kliegel et al., which was administered 5 years after ESTHER baseline. Vitamin D in baseline samples was measured by chemiluminescence methods. Additional information was obtained by standardised questionnaires. RESULTS: In multiple linear regression adjusted for important confounders, women in the lowest sex-specific quintile of vitamin D showed an on average 2.1 (95% confidence interval: 0.4 to 3.9) units lower COGTEL score than women in the highest quintile. A similar, albeit slightly weaker, association was seen in males (difference of 1.7 [-0.4 to 3.8] units). Spline regression suggested non-linearity with a distinct decline in cognitive performance in the lower range of vitamin D levels. CONCLUSIONS: Our findings support suggestions that low levels of vitamin D may be associated with reduced cognitive functioning in the elderly.

Type 2 diabetes mellitus and colorectal cancer: meta-analysis on sex-specific differences.

Although there is consent concerning a higher risk for colorectal cancer (CRC) amongst patients with type 2 diabetes mellitus (T2DM), there remains uncertainty regarding potential sex differences in the strength of this association. We reviewed and summarised epidemiological studies assessing the sex-specific association of T2DM with the risk for CRC. All relevant studies published until 14th February 2011 were identified by a systematic search of MEDLINE, EMBASE, BIOSIS Previews and ISI Web of Knowledge databases and cross-referencing. We included observational studies that reported relative risk (RR) or odds ratio (OR) estimates with 95% confidence intervals (CIs) for the association between T2DM and CRC. Two authors independently extracted data and assessed study quality of each study in a standardised manner. Study-specific estimates were pooled for both sexes separately using random-effects models. A total of 29 eligible studies were used for meta-analysis. Overall estimates of relative risk (RR) were very similar amongst men (RR=1.29; 95%-confidence interval (CI): 1.19-1.140) and women (RR=1.34; 95%-CI: 1.22-1.47). In both men and women, risk estimates from case-control studies were slightly higher than those from cohort studies. Overall, T2DM is associated with a moderate increase in CRC risk in both men and women.

DNA repair gene polymorphisms and risk of chronic atrophic gastritis: a case-control study.

BACKGROUND: Recent studies have reported associations of DNA repair pathway gene variants and risk of various cancers and precancerous lesions, such as chronic atrophic gastritis (CAG). METHODS: A nested case-control study within the German population-based ESTHER cohort was conducted, including 533 CAG cases and 1054 controls. Polymorphisms in eleven DNA repair genes (APEX1, ERCC1, ERCC2/XPD, PARP1 and XRCC1), in CD3EAP/ASE-1 and PPP1R13L were analysed. RESULTS: No association was disclosed for any of the analysed polymorphisms. Nor did stratified analyses according to ages < 65 and ≥ 65 years show any significant association with CAG risk. CONCLUSIONS: The results of this large German case-control study do not reveal associations of DNA repair pathway polymorphisms and risk of CAG. On the basis of a large number of CAG cases, they do not support associations of DNA repair pathway SNPs with CAG risk, but suggest the need of larger studies to disclose or exclude potential weak associations, or of studies with full coverage of candidate genes.

Prognostic value of haemoglobin A1c and fasting plasma glucose for incident diabetes and implications for screening.

The aim of this analysis is to compare screening strategies with haemoglobin A(1c) (HbA(1c)), fasting plasma glucose (FPG) or combined measures in the identification of individuals at high risk for diabetes. Applying American Diabetes Association thresholds for FPG and HbA(1c) screening, 6,803 subjects free of diabetes were classified as non-diabetic, pre-diabetic and possibly diabetic by FPG (<100, 100-125 and >125 mg/dl) and HbA(1c) (<5.7, 5.7-6.4 and >6.4%). Hazard ratios, sensitivity and specificity were estimated for individuals with pre-diabetes with respect to incident diabetes in the following 5 years. Areas under the receiver operating characteristic curves (AUC) were estimated for levels of FPG ≤ 125 mg/dl and HbA(1c) ≤ 6.4% in diabetes prediction. Although FPG and HbA(1c) screenings poorly agreed in classifying individuals as pre-diabetic, hazard ratios [95% confidence interval] for incident diabetes were similarly increased in univariate models in the two pre-diabetic groups: FPG 100-125 mg/dl, 4.72 [3.69; 6.05]; HbA(1c) 5.7-6.4%, 3.97 [3.05; 5.23]. HbA(1c) and FPG had comparable AUCs (FPG, 0.732; HbA(1c), 0.725) and consequently similar 5-year sensitivities and specificities for their pre-diabetes definitions (when the lower cut-off for HbA(1c)-defined pre-diabetes was increased to a level between 5.8 and 5.9%). Combining HbA(1c) and FPG increased the AUC to 0.778, and a further increase to 0.817 was seen with additional inclusion of conventional risk factors. FPG and HbA(1c) have comparable (yet insufficient) abilities in identifying individuals at high risk for diabetes. Effectiveness of a diabetes screening program could be improved by a risk score including FPG and HbA(1c).

Dopamine-related genes and spontaneous smoking cessation in ever-heavy smokers.

UNLABELLED: Several studies have provided evidence for associations of polymorphisms located in and near dopamine-related genes and nicotine dependence and other smoking-related phenotypes, including pharmacogenetic interactions. AIM: The purpose of the present work was to examine the association of SNPs in the DOPA decarboxylase (DDC), dopamine receptor D2 (DRD2) and dopamine transporter (SLC6A3) genes with smoking cessation in a large retrospective study featuring approximately 900 cessation events. MATERIALS & METHODS: Data originated from the enrollment questionnaire of the epidemiological ESTHER study of community-dwelling adults aged 50-74 years, conducted in the German state of Saarland between July 2000 and December 2002. Restricting the analyses to subjects who reported to have regularly smoked > 20 cigarettes per day at some point in their life, we used survival analysis methods to model the time from initiation of regular smoking to cessation (defined as quitting with abstinence lasting until enrollment) and its relation with eight polymorphisms in the aforementioned genes (five in DDC, two in DRD2 and one in SLC6A3) in 1446 participants. RESULTS: Neither individual variants nor DDC haplotypes were associated with the probability of overcoming nicotine dependence in this cohort. CONCLUSION: The repeated suggestion of associations between the variants examined and nicotine dependence in previous reports seems to contrast the negative results in the present study. This would appear consistent with the hypothesis that the establishment of regular heavy smoking might abolish associations between genetic determinants of nicotine dependence and nicotine dependence-related phenotypes, in particular the probability of successful smoking cessation.

Meta-analysis: Serum vitamin D and colorectal adenoma risk.

OBJECTIVE: To perform a systematic review and meta-analysis of human studies on the association between serum 25 hydroxyvitamin D (25(OH)D) and incident, sporadic colorectal adenoma (CRA) and CRA recurrence. METHODS: Relevant studies among humans were identified by systematically searching Ovid Medline, EMBASE, and ISI Web of Knowledge databases and by cross-referencing. Due to the heterogeneity across studies in categorizing serum vitamin D levels, all results were recalculated for an increase of serum 25(OH)D by 20 ng/ml. Summary odds ratios (ORs) were calculated using meta-analysis methods. RESULTS: Overall, 10 original studies were included. Specific results for incident CRA according to serum 25(OH)D were reported in 8 studies, and for CRA recurrence in 2 studies, respectively. In meta-analyses, summary ORs (95% confidence intervals) regarding incident and recurrent CRA, and both outcomes combined were 0.82 (0.69-0.97), 0.87 (0.56-1.35), and 0.84 (0.72-0.97), respectively, for an increase of 25(OH)D by 20 ng/ml. No publication bias was found. CONCLUSION: Our results support suggestions that serum 25(OH)D levels are inversely associated with CRA risk.

Tobacco smoke exposure before, during, and after pregnancy and risk of overweight at age 6.

Maternal smoking during pregnancy has been associated with overweight and obesity in childhood and is strongly correlated with children's tobacco smoke exposure before and after pregnancy. We investigated the independent association of tobacco smoke exposure at various pre- and postnatal periods and overweight at age 6. A total of 1,954 children attending the 2001-2002 school entrance health examination in the city of Aachen, Germany, were included into this study. Height and weight were measured, BMI was calculated. Tobacco smoke exposure at various periods, other lifestyle and sociodemographic factors were ascertained by questionnaire. Multiple logistic regression models were used to assess the association between tobacco smoke exposure and overweight. Prevalence of overweight was 8.9%. Significant positive associations were found with maternal smoking before and during pregnancy and during the first and sixth year of life. When all smoking periods were included into one logistic model simultaneously, secondhand smoke exposure after birth remained positively associated with overweight at age 6 at either one of the two time periods (first year only: odds ratio (OR) (95% confidence interval (CI)): 2.94 (1.30-6.67), sixth year only: 2.57 (1.64-4.04), respectively) or at both (4.43 (2.24-8.76)). Exposure to tobacco smoke during the first years of life appears to be a key risk factor for development of childhood overweight.