Diabetic Retinopathy Predicts Risk of Alzheimer's Disease: A Danish Registry-Based Nationwide Cohort Study.

BACKGROUND: Retinal neurodegeneration is evident in early diabetic retinopathy (DR) which may be associated with other neurodegenerative diseases like Alzheimer's disease (AD). OBJECTIVE: To investigate diabetes and DR as a risk marker of present and incident AD. METHODS: A register-based cohort study was performed. We included 134,327 persons with diabetes above 60 years of age, who had attended DR screening, and 651,936 age- and gender-matched persons without diabetes. RESULTS: At baseline, the prevalence of AD was 0.7% and 1.3% among patients with and without diabetes, respectively. In a multivariable regression model, patients with diabetes were less likely to have AD at baseline (adjusted OR 0.63, 95% CI 0.59-0.68). During follow-up, incident AD was registered for 1473 (0.35%) and 6,899 (0.34%) persons with and without diabetes, respectively. Compared to persons without diabetes, persons with diabetes and no DR had a lower risk to develop AD (adjusted HR 0.87, 95% CI 0.81-0.93), while persons with diabetes and DR had higher risk of AD (adjusted HR 1.24, 95% CI 1.08-1.43). When persons with diabetes and no DR were used as references, a higher risk of incident AD was observed in persons with DR (adjusted HR 1.34, 95% CI 1.18-1.53). CONCLUSION: Individuals with diabetes without DR were less likely to develop AD compared to persons without diabetes. However, individuals with DR had a 34% higher risk of incident AD, which raise the question whether screening for cognitive impairment should be done among individuals with DR.

Interactions between ocular and systemic disease using national register-based data in the Danish Excellence Centre in Ophthalmic Epidemiology (DECODE-EYE): study perspective.

PURPOSE: The Danish Excellence Centre in Ophthalmic Epidemiology (DECODE-EYE) is a national research collaboration formed in order to study the real-life interaction between ocular and systemic disease based on the entire Danish population. Here, we aim to describe the study design and the methodology, which will be used. METHODS: We will extract data from various healthcare registers and databases including the Danish Civil Registration System (unique personal identifier), the Danish National Patient Register (inpatient and outpatient visits), the Danish National Prescription Registry (redeemed prescription drugs), the National Health Service Register (data on health services in primary health care), the Danish Register of Cause of Death (data on cause of death), Statistics Denmark (demographic and socioeconomic data), the Danish Registry of Diabetic Retinopathy (level of diabetic retinopathy (DR) in diabetes patients) and the database of the Danish Association of the Blind (date and cause of blindness). Relevant registers will be linked by the unique personal identifier, and associations will be examined cross-sectional and/or longitudinally, in principle in 1:5 age- and gender-matched case-control cohort studies. CONCLUSION: Denmark has a strong tradition in register-based healthcare research, given a high number of validated national registers and databases. DECODE-EYE will provide Danish, large-scale data on associations between ocular and systemic disease. With a target population of 5.8 million individuals, twelve separate studies (Protocols A-L) have initially been designed to be studied in the upcoming years. These will provide novel data on interactions between systemic disease and relevant ophthalmological end-points like blindness, DR, glaucoma, corneal disease, retinal vascular disease, cataract and intravitreal angiostatic treatment.

Stratification by smoking status reveals an association of CHRNA5-A3-B4 genotype with body mass index in never smokers.

We previously used a single nucleotide polymorphism (SNP) in the CHRNA5-A3-B4 gene cluster associated with heaviness of smoking within smokers to confirm the causal effect of smoking in reducing body mass index (BMI) in a Mendelian randomisation analysis. While seeking to extend these findings in a larger sample we found that this SNP is associated with 0.74% lower body mass index (BMI) per minor allele in current smokers (95% CI -0.97 to -0.51, P = 2.00 × 10(-10)), but also unexpectedly found that it was associated with 0.35% higher BMI in never smokers (95% CI +0.18 to +0.52, P = 6.38 × 10(-5)). An interaction test confirmed that these estimates differed from each other (P = 4.95 × 10(-13)). This difference in effects suggests the variant influences BMI both via pathways unrelated to smoking, and via the weight-reducing effects of smoking. It would therefore be essentially undetectable in an unstratified genome-wide association study of BMI, given the opposite association with BMI in never and current smokers. This demonstrates that novel associations may be obscured by hidden population sub-structure. Stratification on well-characterized environmental factors known to impact on health outcomes may therefore reveal novel genetic associations.

Genome-wide linkage and association scans for pulse pressure in Chinese twins.

Elevated pulse pressure (PP) is associated with cardiovascular disorders and mortality in various populations. The genetic influence on PP has been confirmed by heritability estimates using related individuals. Recently, efforts have been made by mapping genes that are linked to the phenotype. We report the results of our gene mapping studies conducted in the Chinese population in mainland China. The genome-wide linkage and association scans were carried out on 63 middle-aged dizygotic twin pairs using high-density markers. The linkage analysis identified three significant linkage peaks (all with a single point P<1e(-05)) on chromosome 11 (LOD core 4.06 at 30.5 cM), chromosome 12 (LOD score 3.97 at 100.7 cM) and chromosome 18 (LOD score 4.01 at 70.7 cM), with the last two peaks closely overlapping with linkage peaks reported by two American studies. Multiple regions with suggestive linkages were identified, with many of the peaks overlapping with published linkage regions. The genome-wide association analysis detected a suggestive association on chromosome 4 (rs17031508, P<8.34e(-08)) located within a wide region of suggestive linkage. Our results provide some evidence for genetic linkages and associations with PP in the Chinese population. Further investigation is warranted to replicate the findings and to explore the susceptibility loci or genes for PP.

Impact of common variation in bone-related genes on type 2 diabetes and related traits.

Exploring genetic pleiotropy can provide clues to a mechanism underlying the observed epidemiological association between type 2 diabetes and heightened fracture risk. We examined genetic variants associated with bone mineral density (BMD) for association with type 2 diabetes and glycemic traits in large well-phenotyped and -genotyped consortia. We undertook follow-up analysis in ∼19,000 individuals and assessed gene expression. We queried single nucleotide polymorphisms (SNPs) associated with BMD at levels of genome-wide significance, variants in linkage disequilibrium (r(2) > 0.5), and BMD candidate genes. SNP rs6867040, at the ITGA1 locus, was associated with a 0.0166 mmol/L (0.004) increase in fasting glucose per C allele in the combined analysis. Genetic variants in the ITGA1 locus were associated with its expression in the liver but not in adipose tissue. ITGA1 variants appeared among the top loci associated with type 2 diabetes, fasting insulin, ß-cell function by homeostasis model assessment, and 2-h post-oral glucose tolerance test glucose and insulin levels. ITGA1 has demonstrated genetic pleiotropy in prior studies, and its suggested role in liver fibrosis, insulin secretion, and bone healing lends credence to its contribution to both osteoporosis and type 2 diabetes. These findings further underscore the link between skeletal and glucose metabolism and highlight a locus to direct future investigations.

Communication skills training increases self-efficacy of health care professionals.

INTRODUCTION: Despite the knowledge of good communication as a precondition for optimal care and treatment in health care, serious communication problems are still experienced by patients as well as by health care professionals. An orthopedic surgery department initiated a 3-day communication skills training course for all staff members expecting an increase in patient-centeredness in communication and more respectful intercollegial communication. The aim of this study was to investigate the impact of this training course on participants' self-efficacy with a focus on communication with both colleagues and patients. METHODS: The study was designed as an effectiveness study with the training course implemented in a real-world context. The staff members attended a 3-day training course in patient-centered communication and communication with colleagues. The effect of the training was evaluated by means of a questionnaire filled out before, immediately after, and 6 months after the course. RESULTS: Of the 181 participants, 177 answered the questionnaire before, 165 immediately after, and 150 six months after the course. The mean score for self-efficacy in communication with patients increased from 6.68 to 7.88 (p < .001) and in communication with colleagues from 6.85 to 7.84 (p < .001) immediately following the training course. The effect was still present 6 months after the course was completed. DISCUSSION: Although the study was conducted in a real-world setting with many competing demands, a communication course produced an increase in self-efficacy. This result was observed for doctors, nurses, nursing assistants, and medical secretaries.

Communication skills training for health care professionals improves the adult orthopaedic patient's experience of quality of care.

RATIONALE: Despite the fact that communication has become a core topic in health care, patients still experience the information provided as insufficient or incorrect and a lack of involvement. OBJECTIVE: To investigate whether adult orthopaedic patients' evaluation of the quality of care had improved after a communication skills training course for healthcare professionals. DESIGN AND METHODS: The study was designed as an intervention study offering professionals training in communicating with patients and colleagues. The outcome was measured by assessing patients' experience of quality of care. Data were collected by means of a questionnaire and analysed using a linear regression model. Approval was obtained from the Danish Data Protection Agency. RESULTS: A total of 3133 patients answered the questionnaire, 1279 before staff had attended courses and 1854 in the postcourse period, with response rates of 67.8 and 77.8%, respectively. After the course period, significant increases in responses indicating 'considerable' improvement were recorded for 15/19 questions, nonsignificant increases were registered for 3/19 questions and a statistically significant decrease for one question. STUDY LIMITATIONS: This being an effectiveness study, it is deemed that the organizational changes taking place during the study period constitute no serious limitation. Response rates were comparable to those of other studies. CONCLUSION: Patients show increased satisfaction with the quality of health care after professionals have attended a communication skills training course, even when implemented in an entire department. PRACTICE IMPLICATIONS: We recommend that healthcare professionals are trained in patient-centred communication and that training is extended to the entire organization.

Genetic and environmental contributions to weight, height, and BMI from birth to 19 years of age: an international study of over 12,000 twin pairs.

OBJECTIVE: To examine the genetic and environmental influences on variances in weight, height, and BMI, from birth through 19 years of age, in boys and girls from three continents. DESIGN AND SETTINGS: Cross-sectional twin study. Data obtained from a total of 23 twin birth-cohorts from four countries: Canada, Sweden, Denmark, and Australia. Participants were Monozygotic (MZ) and dizygotic (DZ) (same- and opposite-sex) twin pairs with data available for both height and weight at a given age, from birth through 19 years of age. Approximately 24,036 children were included in the analyses. RESULTS: Heritability for body weight, height, and BMI was low at birth (between 6.4 and 8.7% for boys, and between 4.8 and 7.9% for girls) but increased over time, accounting for close to half or more of the variance in body weight and BMI after 5 months of age in both sexes. Common environmental influences on all body measures were high at birth (between 74.1-85.9% in all measures for boys, and between 74.2 and 87.3% in all measures for girls) and markedly reduced over time. For body height, the effect of the common environment remained significant for a longer period during early childhood (up through 12 years of age). Sex-limitation of genetic and shared environmental effects was observed. CONCLUSION: Genetics appear to play an increasingly important role in explaining the variation in weight, height, and BMI from early childhood to late adolescence, particularly in boys. Common environmental factors exert their strongest and most independent influence specifically in pre-adolescent years and more significantly in girls. These findings emphasize the need to target family and social environmental interventions in early childhood years, especially for females. As gene-environment correlation and interaction is likely, it is also necessary to identify the genetic variants that may predispose individuals to obesity.

Dissecting complex phenotypes using the genomics of twins.

Genetics in the post-genomic period is shifting from structural to functional genetics or genomics. Meanwhile, the use of twins is largely expanding from traditional heritability estimation for disease phenotypes to the study of both diseases and various molecular phenotypes, such as the regulatory phenotypes in functional genomics concerning gene expression and regulation, by engaging both classical twin design and marker-based gene mapping techniques in genetic epidemiology. New research designs have been proposed for making novel uses of twins in studying the molecular basis in the epigenetics of human diseases. Besides, twins not only serve as ideal samples for disease gene mapping using conventional genetic markers but also represent an excellent model for associating DNA copy number variations, a structural genetic marker, with human diseases. It is believed that, with the rapid development in biotechniques and new advances in bioinformatics, the unique samples of twins will make new contributions to our understanding of the nature and nurture in complex disease development and in human health. This paper aims at summarizing the new uses of twins in current genetic studies and suggesting novel proposes together with useful design and analytical strategies.

Data collection on multiple births -- establishing twin registers and determining zygosity.

Twins are a valuable resource not only for studies on multiple births themselves, but on the etiology of diseases and other phenotypes. The method of ascertainment and selection of twins can be crucial for such studies and population based twin registries are thus of great importance as tools of research. Accurate determination of zygosity and chorionicity is essential in all studies of multiple births and in their professional care. The parents and the multiples ask for it. It is of pre-and postnatal medical importance and now considered as a prerequisite in several domains of twin research. It is also important for educational reasons as it helps the multiples and their parents and teachers to ascertain identity. The methods are briefly described and a plea is made to the obstetricians and pediatricians to use them systematically at birth. The distribution of zygosity and chorionicity types among spontaneous and induced twin births are illustrated.