Nurses' descriptions of person-centred care for older people in an acute medical ward-On the individual, team and organisational levels'.

AIM AND OBJECTIVES: To describe nurses' experiences of providing person-centred care for older people on an acute medical ward. BACKGROUND: There is evidence that person-centred care for older people contributes to a higher quality care and increased satisfaction with care. However, there is a shortness of studies providing concrete examples of what facilitates nurses providing person-centred care for older people in acute care. DESIGN: An interview study with qualitative content analysis. COREQ guidelines have been applied. METHOD: Fourteen registered nurses and enrolled nurses from an acute care ward participated in semi structured research interviews. The interviews were conducted during 2016 and interpreted using qualitative content analyses. RESULTS: Person-centred care was described at different levels in care; at the individual nurse level, person-centred care was described as involving person-centred assessing, relating and spacing which involved personalising assessments, relationships as well as the physical environment. At the team level, person-centred care was described in terms of person-centred goal setting, team responsibilities and team support, and involved having shared and personalised goals, different team responsibilities and a climate of support and collaboration. At the organisational level, person-centred care was described in terms of having person-centred routines, workloads and staff roles that all contributed to put the person at the core of the organisation and build routines to support this. CONCLUSIONS: The current study emphasises that, rather than confining person-centred care to specific moments or relationships, a systematic, multilevel organisational approach seems needed to enable nurses as individuals and teams to provide person-centred care consistently and continuously to older people in acute care settings. RELEVANCE TO CLINICAL PRACTICE: The results of this study should inspire nurses and managers to expedite implementation of person-centred care for older care recipients hospitalised in acute care wards. Examples of person-centred care are presented herein at clearly identified sites, namely, the "individual," "team" and "organisational levels."

A threat to our integrity--Meanings of providing nursing care for older patients with cognitive impairment in acute care settings.

BACKGROUND: Older people with cognitive impairment represent a large group of patients in acute care settings. Research show that these acute care environments can be unsafe and even unfriendly for frail older patients. Research and clinical experience show that being a nurse in acute/specialised medical facilities means to work in a high-speed, technologically complex and demanding environment. When caring for older patients with cognitive impairment, nurses' workload and responsibilities have been shown to increase. This is largely dependent on how easily it is to connect with and help patients understand what to do, and what is best for them. AIM: This study aimed to illuminate meanings of caring for older patients with cognitive impairment in acute care settings as experienced by nursing staff. METHOD: A purposeful sample of thirteen nurses experienced in caring for older people with cognitive impairment in acute care settings participated in the study. Narrative interviews were conducted during autumn 2012 and interpreted using a phenomenological hermeneutic method. FINDINGS: Caring for older, acutely ill cognitively impaired patients was found to be very complex. The meanings of caring for these older patients seemed to change depending on the nurses' perceptions of the patients and the gap between what they could do (real) and wanted to do (ideal) in providing care for them. The greater this gap was felt to be and the more care was perceived as meaningless, the more serious was the threat to nurses' personal-professional integrity which could be at risk, compromised or harmed. CONCLUSION: The comprehensive understanding indicates that being a nurse and having to care for older patients in acute care settings means providing nursing care in an environment that does not support possibilities to protect and develop nurses' personal-professional integrity.

Reconciling concepts of time and person-centred care of the older person with cognitive impairment in the acute care setting.

The aim of this analysis was to examine the concept of time to rejuvenate and extend existing narratives of time within the nursing literature. In particular, we hope to promote a new trajectory in nursing research and practice which focuses on time and person-centred care, specifically of older people with cognitive impairment hospitalized in the acute care setting. We consider the explanatory power of concepts such as clock time, process time, fast care, slow care and time debt for elucidating the relationship between 'good care' and 'time use'. We conclude by offering two additional concepts of time, plurotemporality and person-centred time (PCT) which we propose will help advance of nursing knowledge and practice. Nurse clinicians and researchers can use these alternative concepts of time to explore and describe different temporal structures that honour the patient's values and preferences using experiential, observation-based nursing research approaches.

Guthrie card methylomics identifies temporally stable epialleles that are present at birth in humans.

A major concern in common disease epigenomics is distinguishing causal from consequential epigenetic variation. One means of addressing this issue is to identify the temporal origins of epigenetic variants via longitudinal analyses. However, prospective birth-cohort studies are expensive and time consuming. Here, we report DNA methylomics of archived Guthrie cards for the retrospective longitudinal analyses of in-utero-derived DNA methylation variation. We first validate two methodologies for generating comprehensive DNA methylomes from Guthrie cards. Then, using an integrated epigenomic/genomic analysis of Guthrie cards and follow-up samplings, we identify interindividual DNA methylation variation that is present both at birth and 3 yr later. These findings suggest that disease-relevant epigenetic variation could be detected at birth, i.e., before overt clinical disease. Guthrie card methylomics offers a potentially powerful and cost-effective strategy for studying the dynamics of interindividual epigenomic variation in a range of common human diseases.

Measuring levels of person-centeredness in acute care of older people with cognitive impairment: evaluation of the POPAC scale.

BACKGROUND: Person-centeredness is increasingly advocated in the literature as a gold-standard, best practice concept in health services for older people. This concept describes care that incorporates individual and multidimensional needs, personal biography, subjectivity and interpersonal relationships. However, acute in-patient hospital services have a long-standing biomedical tradition that may contrast with person-centred care. Since few tools exist that enable measurements of the extent to which acute in-patient hospital services are perceived as being person-centred, this study aimed to translate the English version of the Person-centred care of older people with cognitive impairment in acute care scale (POPAC) to Swedish, and evaluate its psychometric properties in a sample of acute hospital staff. METHODS: The 15-item POPAC was translated, back-translated and culturally adjusted, and distributed to a cross-sectional sample of Swedish acute care staff (n = 293). Item performance was evaluated through assessment of item means, internal consistency by Cronbach's alpha on total and on subscale levels; temporal stability was assessed through Pearson's product correlation and intra-class correlation between test and retest scores. Confirmatory factor analysis was used to explore model fit. RESULTS: The results indicate that the Swedish version POPAC provides a tentatively construct-valid and reliable contribution to measuring the extent to which acute in-patient hospital services have processes and procedures that can facilitate person-centred care of older patients with cognitive impairment. However, some questions remain regarding the dimensionality of POPAC. CONCLUSIONS: POPAC provides a valuable contribution to the quest of improving acute care for older patients with cognitive impairment by enabling measures and subsequent accumulation of internationally comparable data for research and practice development purposes. POPAC can be used to highlight strengths and areas for improvements in care practice for older patients, and to illuminate aspects that risk being overlooked in busy acute hospital settings.

Falling behind: a substantive theory of care for older people with cognitive impairment in acute settings.

AIMS AND OBJECTIVES: To develop a theoretical understanding of the processes hindering person-centred care of older people with cognitive impairment in acute care settings. BACKGROUND: Although person-centred care with its holistic focus on the biopsychosocial needs of patients is commonly considered the gold standard care for older people with cognitive impairment, the extent to which care is person-centred can increase in acute care settings generally. DESIGN: Grounded theory inspired by Strauss and Corbin. METHOD: The study used a grounded theory approach to generate and analyse data from a Swedish sample of acute care staff, patients and family members. RESULTS: The substantive theory postulates that staff risks 'falling behind' in meeting the needs of older patients with cognitive impairment if working without consensus about the care of these patients, if the organisation is disease-oriented and efficiency-driven, and if the environment is busy and inflexible. This facilitated 'falling behind' in relation to meeting the multifaceted needs of older patients with cognitive impairment and contributed to patient suffering, family exclusion and staff frustration. CONCLUSIONS: The theory highlights aspects of importance in the provision of person-centred care of older people with cognitive impairment in acute settings and suggests areas to consider in the development of caring environments in which the place, pace and space can meet the needs of the older person. RELEVANCE TO CLINICAL PRACTICE: The proposed substantive theory can be used to critically examine current ward practices and routines, and the extent to which these support or inhibit high-quality person-centred care for older patients with known or unknown cognitive impairments.

The person-centred care of older people with cognitive impairment in acute care scale (POPAC).

AIM: To construct and evaluate psychometric properties of the person-centred care of older people with cognitive impairment in acute care settings (POPAC) scale. BACKGROUND: Older people with cognitive impairment are admitted frequently to acute care, with needs not always met through standard practice. Best practice models have been suggested, but few assessment scales exist. METHODS: Psychometric evaluation using statistical estimates of validity and reliability based on an Australian sample of acute care nursing staff (n = 212). RESULTS: The final 15-item questionnaire consists of three subscales, 'using cognitive assessments and care interventions', 'using evidence and cognitive expertise' and 'individualizing care'. Estimates of validity and reliability were highly satisfactory. CONCLUSION: The POPAC scale makes a valuable contribution by providing valid and reliable measures of the extent to which acute nursing staff report using best practice care processes to identify and consider cognitive impairment and to employ nursing interventions to meet the needs associated with old age and cognitive impairment. IMPLICATIONS FOR NURSING MANAGEMENT: The POPAC scale is short, easy to administer and not time consuming to complete, but still provides clinically relevant information. It can be used as a conceptual fundament in developing best practice nursing care in the acute clinical setting, as well as for nursing research.

The influence of a person-centred psychosocial unit climate on satisfaction with care and work.

AIM: To describe nurses' satisfaction with care and work and to explore the extent to which a person-centred unit climate influenced this satisfaction. BACKGROUND: Although the concept of person-centred care is used to describe high-quality care, there is a shortage of studies exploring the relationship between person-centredness and nurses' satisfaction with care and work in acute care settings. METHODS: Registered nurses within a university hospital in Sweden (n = 206) completed the Satisfaction with Nursing Care and Work Assessment Scale and the Person-centred Climate Questionnaire. The data collected was analysed using descriptive and analytical statistics. DESIGN: Cross-sectional explorative study. RESULTS: The majority of respondents were satisfied with the care and work situation. Nurses with more than 9 years of work experience were more satisfied with care and work, and there were a significant association between a person-centred psychosocial climate of units and nurses' satisfaction with care and work. CONCLUSIONS: This study provided evidence for a significant association between person-centredness and the satisfaction with care and work of nurses in acute care environments. IMPLICATIONS FOR NURSING MANAGEMENT: Promoting and implementing a person-centred philosophy of care can be one way to improve nurses' satisfaction with care and work.

Staff attitudes towards older patients with cognitive impairment: need for improvements in acute care.

AIM: To explore the attitudes held by staff working in acute care units towards patients aged 70 years or older with cognitive impairment, and to explore factors associated with negative attitudes. BACKGROUND: Hospital staff attitudes towards older patients with cognitive impairment are of concern as older people are the main hospital users, and because staff attitudes influence care quality and uptake of evidence-based care. METHOD: A cross-sectional survey design was used to collect data from staff (n = 391). RESULTS: Staff attitudes were not explicitly negative. However, higher perceived strain in caring for older patients with cognitive impairment, higher perceived prevalence of these patients in the ward, being younger and working as an assistant nurse were associated with negative attitudes. A majority of staff reported that these patients received the best possible care, but few reported formally assessing cognitive status or working with evidence-based care protocols. CONCLUSION: Staff characteristics associated with negative attitudes were described and staff perception that patients received best hospital care, despite limited cognitive assessments and care guidelines, indicate areas for improvement. IMPLICATIONS FOR NURSING MANAGEMENT: Supporting young staff and assistant nurses, and implementing cognitive assessments and evidence-based guidelines can promote positive attitudes and best practice.

Two insulin gene single nucleotide polymorphisms associated with type 1 diabetes risk in the Finnish and Swedish populations.

We have developed high-throughput tests for the detection of the insulin gene region SNPs -23HphI and -2221MspI. The potential of these markers to enhance the efficiency of type 1 diabetes risk screening was then evaluated by analyzing them in Finnish and Swedish populations. Blood spots on filter paper were analyzed using PCR followed by sequence-specific hybridization and time-resolved fluorometry reading. Distribution of the genotypes at both positions differed significantly among the affected children compared to the controls. The risk genotypes (CC, AA) were significantly more common in Finland than in Sweden, both among patients and controls. The VNTR genotype homozygous for the protective class III alleles showed a significantly stronger protective effect than the heterozygote (p=0.02). Analyzing both SNPs enabled the detection of VNTR class III subclasses IIIA and IIIB. The observed significance between effects of the protective genotypes was due to the strong protective effect of the IIIA/IIIA genotype. IIIA/IIIA was the only genotype with significant discrepancy between protective effects compared to the other class III genotypes. These observations suggest that heterogeneity between the protective IDDM2 lineages could exist, and analyzing both -23HphI and -2221MspI would thus potentially enhance the sensitivity and specificity of type 1 diabetes risk estimation.

A combination of human leukocyte antigen DQB1*02 and the tumor necrosis factor alpha promoter G308A polymorphism predisposes to an insulin-deficient phenotype in patients with type 2 diabetes.

Our previous results have suggested that genes outside the human leukocyte antigen (HLA) class II locus may affect the phenotype of type 2 diabetic patients from families with both type 1 and type 2 diabetes (mixed type 1/2). To study whether the TNF alpha gene could be such a modifying gene, we studied TNF alpha promoter polymorphisms (G-->A substitution at positions -308 and -238) in relation to HLA-DQB1 genotypes in type 2 patients from mixed type 1/2 families or common type 2 diabetes families as well as in patients with adult-onset type 1 diabetes and control subjects. The TNF alpha(308) AA/AG genotype frequency was increased in adult onset type 1 patients (55%, 69 of 126), but it was similar in type 2 patients from type 1/2 families (35%, 33/93) or common type 2 families (31%, 122 of 395), compared with controls (33%, 95/284; P < 0.0001 vs. type 1). The TNF alpha(308) A and DQB1*02 alleles were in linkage disequilibrium in type 1 patients (Ds = 0.81; P < 0.001 vs. Ds = 0.25 in controls) and type 2 patients from type 1/2 families (Ds = 0.59, P < 0.05 vs. controls) but not in common type 2 patients (Ds = 0.39). The polymorphism was associated with an insulin-deficient phenotype in the type 2 patients from type 1/2 families only together with DQB*02, whereas the common type 2 patients with AA/AG had lower waist to hip ratio [0.92 (0.12) vs. 0.94 (0.11), P = 0.008] and lower fasting C-peptide concentration [0.48 (0.47) vs. 0.62 (0.46) nmol/liter, P = 0.020] than those with GG, independently of the presence of DQB1*02. In conclusion, TNF alpha is unlikely to be the second gene in the HLA area responsible for our previous findings in type 1/2 patients. However, we could show an association between TNF alpha(308) polymorphism and the phenotype of common type 2 diabetes.

Few differences in cytokines between patients newly diagnosed with type 1 diabetes and their healthy siblings.

The cause of the worldwide increase in type 1 diabetes (T1D) is largely unknown. T cells are thought to play a role in disease progression. In contemporary research over the last decade, age- and gender-specific serum levels as well as changes of Th1 and Th2-related cytokines are not well described. From a population-based register of children diagnosed from 1997 to 2005 this study explores eight different cytokines at time of diagnosis. Only TGF-ß and IL-18 showed higher levels in patients compared to siblings in an adjusted model (p<0.01); whereas the other seven cytokines were not significantly different. IL-1ß, IL-18, IL-12, IL-10 and IL-4 were significantly higher among the youngest children and males had significantly lower levels of IL-10 and IL-12 but higher levels of TNF-α. During the nine-year study all of the cytokines increased except TGF-ß, which showed a slight decrease over time. The cytokine levels tended to be highest during summer and were most pronounced for IL-1ß and TNF-α. In conclusion, serum levels of known ß-cell cytotoxic cytokines were indifferent in patients and siblings, while gender, age and season appear to exert some influence on the serum level and need to be explored further. The influence of time on systemic levels cannot be ignored and may reflect decay or environmental impact on the immune system.

High levels of immunoglobulin E and a continuous increase in immunoglobulin G and immunoglobulin M by age in children with newly diagnosed type 1 diabetes.

The incidence of type 1 diabetes (T1D) is increasing, either because of environmental factors accelerating onset of the disease or because of inducement of autoimmune diabetes in children who previously were at lower risk. High levels of immunoglobulin (Ig), specifically, IgM and IgA, and a low level of IgG were reported in adult patients; however no studies have analyzed the increasing incidence in relation to Ig levels. Our aim was to describe Ig in children newly diagnosed with diabetes and in their healthy siblings. Children with T1D expressed significantly lower IgG (p < 0.01) and higher IgA levels (p = 0.045), whereas no differences in IgE or IgM (p > 0.5) levels were found. Age-specific levels were unchanged over a 9-year period. In patients and siblings IgG, IgA and IgE increased by age (p < 0.001); which was in contrast to IgM (p > 0.05). The continued increase in IgG levels by age indicates that adult levels are reached later than in previously studied cohorts, thereby indicating a slower maturation of the immune system.

A new PCR-SSP method for HLA DR-DQ risk assessment for celiac disease.

BACKGROUND: Susceptibility to celiac disease is essentially restricted to carriers of specific HLA DQA1 and DQB1 alleles. We have developed a semi-automated sequence specific primer (SSP) PCR method for clinical HLA typing and compared the test results with those from a commercial method. METHODS: Primers for each DQA1 and DQB1 allele group were included in our PCR-SSP reaction to allow differentiation of homozygous from heterozygous carriers of risk alleles. Primers detecting the tightly linked DRB1*04, *03, *07 and *09 alleles were included to resolve potentially ambiguous results. Fluorescently labeled PCR products of 119 clinical samples were analyzed by capillary electrophoresis, and results were compared to those previously obtained from the DELFIA® Type 1 Diabetes Genetic Predisposition assay. RESULTS: The risk assessment derived from the two methods was 100% concordant. One previously unreported haplotype was detected and haplotype assignments in two of the 119 samples were improved from previous reports. CONCLUSIONS: The use of three PCR reactions and a single electrophoretic step for DQA1, DQB1 and DRB1 typing provides distinction of celiac disease associated alleles and their homo- or heterozygous status. This multiplex analysis reduces reagent costs, personnel and instrument time, while enabling improved allelic assignment through HLA-DR-DQ haplotype association.

Correlations between islet autoantibody specificity and the SLC30A8 genotype with HLA-DQB1 and metabolic control in new onset type 1 diabetes.

We hypothesised that the correlation between autoantibody specificity for the ZnT8 Arg325Trp isoforms and the type 2 diabetes-associated rs13266634 may affect ß-cell function at type 1 diabetes (T1D) onset. To study this, we tested 482 newly diagnosed diabetic probands and 478 healthy siblings from the Danish population-based T1D registry for autoantibodies to ZnT8 (ZnT8A) in addition to GAD65 and IA-2. The prevalence and titres of autoantibodies were correlated with genotypes for rs13266634 and HLA-DQB1, age at diagnosis (AAD) and insulin dose-adjusted HbA1c (IDAA1c), as a proxy for residual ß-cell function. We replicated the correlation between rs13266634 genotypes and specificity for the ZnT8-Argenine (ZnT8R) and ZnT8-Tryptophan (ZnT8W) isoforms previously reported. ZnT8A overlapped substantially with autoantibodies to glutamate decarboxylase 65 (GADA) and IA-2 (IA-2A) and correlated significantly with IA-2A prevalence (p < 2e-16). No effect on IDAA1c was demonstrated for ZnT8A or rs13266634. We found a correlation between ZnT8R positivity and HLA-DQB1*0302 genotypes (p = 0.016), which has not been shown previously. Furthermore, significantly lower ZnT8R and GADA prevalence and titres was found among probands with AAD < 5 years (prevalence: p = 0.004 and p = 0.0001; titres: p = 0.002 and p = 0.001, respectively). The same trend was observed for IA-2A and ZnT8W; however, the difference was non-significant. Our study confirms ZnT8 as a major target for autoantibodies at disease onset in our Danish T1D cohort of children and adolescents, and we have further characterised the relationship between autoantibody specificity for the ZnT8 Arg325Trp epitopes and rs13266634 in relation to established autoantibodies, AAD, measures of ß-cell function and HLA-DQB1 genotypes in T1D.

Danish children born with glutamic acid decarboxylase-65 and islet antigen-2 autoantibodies at birth had an increased risk to develop type 1 diabetes.

OBJECTIVE: A large, population-based case-control cohort was used to test the hypothesis that glutamic acid decarboxylase-65 (GAD65) and islet antigen-2 autoantibodies (IA-2A) at birth predict type 1 diabetes. DESIGN AND METHODS: The design was an individually matched case-control study of all Danish type 1 diabetes patients born between 1981 and 2002 and diagnosed before May 1 2004 (median age at diagnosis was 8.8 years). Dried blood spot samples collected 5 days after birth in the 1981-2002 birth cohorts and stored at -25 °C were identified from 2023 patients and from two matched controls (n = 4042). Birth data and information on parental age and diabetes were obtained from Danish registers. GAD65A and IA-2A were determined in a radiobinding assay. HLA-DQB1 alleles were analyzed by PCR using time-resolved fluorescence. RESULTS: GAD65A and IA-2A were found in 70/2023 (3.5%) patients compared to 21/4042 (0.5%) controls resulting in a hazard ratio (HR) of 7.49 (P < 0.0001). The HR decreased to 4.55 but remained significant (P < 0.0003) after controlling for parental diabetes and HLA-DQB1 alleles. Conditional logistic regression analysis showed a HR of 2.55 (P < 0.0001) for every tenfold increase in the levels of GAD65A and IA-2A. This HR decreased to 1.93 but remained significant (P < 0.001) after controlling for parental diabetes and HLA-DQB1 alleles. CONCLUSION: These data suggest that GAD65A and IA-2A positivity at birth are associated with an increased risk of developing type 1 diabetes in Danish children diagnosed between 1981 and 2004.

Comparison of measurements of autoantibodies to glutamic acid decarboxylase and islet antigen-2 in whole blood eluates from dried blood spots using the RSR-enzyme linked immunosorbent assay kits and in-house radioimmunoassays.

To evaluate the performance of dried blood spots (DBSs) with subsequent analyses of glutamic acid decarboxylase (GADA) and islet antigen-2 (IA-2A) with the RSR-ELISAs, we selected 80 children newly diagnosed with type 1 diabetes and 120 healthy women. DBSs from patients and controls were used for RSR-ELISAs while patients samples were analysed also with in-house RIAs. The RSR-ELISA-GADA performed well with a specificity of 100%, albeit sensitivity (46%) was lower compared to in RIA (56%; P = .008). No prozone effect was observed after dilution of discrepant samples. RSR-ELISA-IA-2A achieved specificity of 69% and sensitivity was lower (59%) compared with RIA (66%; P < .001). Negative or low positive patients and control samples in the RSR-ELISA-IA-2A increased after dilution. Eluates from DBS can readily be used to analyse GADA with the RSR-ELISA, even if low levels of autoantibodies were not detected. Some factor could disturb RSR-ELISA-IA-2A analyses.

Atherogenic vascular and lipid phenotypes in young patients with Type 1 diabetes are associated with diabetes high-risk HLA genotype.

Expression of human leukocyte antigen (HLA) class II molecules on islet endothelial cells is a central vascular event in the pathogenesis of Type 1 diabetes. Previous studies demonstrated the ability of other vascular endothelial cells to express HLA and thereby to process islet autoantigens on their surface. We investigated whether the HLA-DQ2/8 genotype, which confers the highest risk for Type 1 diabetes, is associated with early atherosclerosis in youths with this disease. Brachial artery endothelium-dependent, flow-mediated dilation (BA-FMD) and carotid artery intima-media thickness (CA-IMT), as well as markers of systemic inflammation [C-reactive protein (CRP), fibrinogen, and orosomucoid], HbA(1C), LDL, HDL, and total cholesterol, were assessed in 86 children and adolescents with Type 1 diabetes (mean age and diabetes duration, 15 and 7 yr, respectively) between 2004 and 2006. HLA genotypes were determined in dried blood spots by an oligoblot hybridization method. As a result, HLA-DQ2/8 was detected in 34 patients (DQ2/8). When this group was compared with the remaining patients (non-DQ2/8, n = 52), there were no differences in age, diabetes duration, HbA(1C), body mass index, inflammatory markers, and IMT (P > or = 0.4). In the DQ2/8 group, LDL-to-HDL ratio was elevated compared with that in the non-DQ2/8 group (1.8 vs. 1.3, respectively; P = 0.001), whereas FMD did not significantly differ between the groups (5.3% vs. 6.7%, respectively; P = 0.08). When patients were further categorized in relation to CRP (cut-off value, 1 mg/l), BA-FMD was significantly lower (3%, P < 0.01), whereas LDL-to-HDL ratio increased further (2.2, P < 0.001) in the subgroup of DQ2/8 and CRP > or = 1 patients compared with the remaining three subgroups. These associations remained significant after adjustment for age, diabetes duration, and HbA(1C) by analysis of covariance. The brachial artery responses to nitroglycerine were similar in all subgroups. In conclusion, the diabetes-predisposing HLA-DQ2/8 genotype in children and adolescents with Type 1 diabetes interferes with endothelial and lipid-related mechanisms of early atherosclerosis, possibly in part through inflammatory pathways.

Type 1 diabetes risk analysis on dried blood spot samples from population-based newborns: design and feasibility of an unselected case-control study.

Development of type 1 diabetes mellitus (T1D) may be triggered pre- or perinatally by multiple factors. Identifying new predisposing T1D markers or combinations of markers in a large, well-characterised case-control collection may be important for future T1D prevention. The present work describes the design and feasibility of a large and unselected case-control study, which will define and evaluate prediction criteria for T1D at the time of birth. Danish registries (Biological Specimen Bank for Neonatal Screening, and the National Discharge Registry) made it possible to identify and collect dried blood spots (DBS) from newborns who later developed T1D (cases) born 1981-2002. DBS samples from 2086 cases and two matching control subjects per case were analysed for genetic and immune factors that are associated with T1D: (a) candidate genes (HLA, INS and CTLA4), (b) cytokines and inflammatory markers, (c) islet auto-antibodies (GAD65A, IA-2A). The objective of the study was to define reliable prediction tools for T1D using samples available at the time of birth. In a unique approach, the study linked a large unselected and population-based sample resource to well-ascertained clinical databases and advanced technology. It combined genetic, immunological and demographic data to develop prediction algorithms. It also provided a resource for future studies in which new genetic markers can be included as they are identified.