The impact of intensive multifactorial treatment on perceptions of chronic care among individuals with screen-detected diabetes: results from the ADDITION-Denmark trial.

OBJECTIVES: To describe perceptions of chronic care among diabetes patients 6 years after diagnosis by screening and to examine the impact of intensive treatment on patients' perceptions of chronic care. METHODS: The ADDITION-Denmark (2001-2006) trial compared the effects of intensive multifactorial therapy (IT) with routine care (RC) among individuals with screen-detected diabetes. Perceptions of chronic care were assessed using the Patient Assessment of Chronic Illness Care (PACIC) measure after 6-year follow-up (n = 937). Analysis was by intention-to-treat, accounting for clustering by general practice. RESULTS: The mean (SD) summary PACIC score was 2.4 (0.79) in the RC and 2.4 (0.82) in the IT group. The highest mean (SD) PACIC subscale score was for Delivery System Design/Decision Support [RC: 3.2 (0.95), IT: 3.3 (0.91)] and the lowest was for Follow-up/Coordination [RC: 2.1 (0.84), IT: 2.1 (0.87)]. Perceptions of chronic care did not differ between trial groups. CONCLUSIONS: Compared to RC, an intensive multifactorial intervention was not associated with differences in perceptions of chronic care among patients with screen-detected diabetes after 6 years. Intensive treatment does not adversely affect perceptions of chronic care early in the course of the disease. However, there is potentially room for improvement in some aspects of chronic care.The ADDITION-Denmark trial was funded by the National Health Services in the counties of Copenhagen, Aarhus, Ringkøbing, Ribe and South Jutland in Denmark, the Danish Council for Strategic Research, the Danish Research Foundation for General Practice, Novo Nordisk Foundation, the Danish Centre for Evaluation and Health Technology Assessment, the diabetes fund of the National Board of Health, the Danish Medical Research Council, the Aarhus University Research Foundation. The trial has been given unrestricted grants from Novo Nordisk AS, Novo Nordisk Scandinavia AB, Novo Nordisk UK, ASTRA Denmark, Pfizer Denmark, GlaxoSmithKline Pharma Denmark, Servier Denmark A/S and HemoCue Denmark A/S. Parts of the grants from Novo Nordisk Foundation, Danish Council for Strategic Research and Novo Nordisk were transferred to the other centres. LK was supported by the German Research Foundation (DFG) Grant KU 3056/1-1.This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1111/ijcp.1257

Effectiveness of the population-based Check your health preventive programme conducted in primary care with 4 years follow-up [the CORE trial]: study protocol for a randomised controlled trial

BACKGROUND: The periodic health check-up has been a fundamental part of routine medical practice for decades, despite a lack of consensus regarding its value in health promotion and disease prevention. A large-scale Danish population-based preventive programme ‘Check your health’ was developed based on available evidence of screening and successive accepted treatment, prevention for diseases and health promotion, and is closely aligned with the current health care system. The objective of the ‘Check your health’ [CORE] trial is to investigate effectiveness on health outcomes of a preventive health check offered at a population-level to all individuals aged 30–49 years, and to establish the cost-effectiveness. METHODS/DESIGN: The trial will be conducted as a pragmatic household-cluster randomised controlled trial involving 10,505 individuals. All individuals within a well-defined geographical area in the Central Denmark Region, Denmark (DK) were randomised to be offered a preventive health check (Intervention group, n = 5250) or to maintain routine access to healthcare until a delayed intervention (Comparison group, n = 5255). The programme consists of a health examination which yields an individual risk profile, and according to this participants are assigned to one of the following interventions: (a) referral to a health promoting consultation in general practice, (b) behavioural programmes at the local Health Centre, or (c) no need for follow-up. The primary outcomes at 4 years follow-up are: ten-year-risk of fatal cardiovascular event (Heart-SCORE model), physical activity level (self-report and cardiorespiratory fitness), quality of life (SF12), sick leave and labour market attachment. Cost-effectiveness will be evaluated according to life years gained, direct costs and total health costs. Intention to treat analysis will be performed. DISCUSSION: Results from the largest Danish health check programme conducted within the current healthcare system, spanning the sectors which share responsibility for the individual, will provide a scientific basis to be used in the development of systems to optimise population health in the 21st century. TRIAL REGISTRATION: The trial has registered at ClinicalTrials.gov with an ID: NCT02028195 (7. March 2014)

Impact of early detection and treatment of diabetes on the 6-year prevalence of cardiac autonomic neuropathy in people with screen-detected diabetes: ADDITION-Denmark, a cluster-randomised study

Aims/hypothesis: There is limited evidence on how multifactorial treatment improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in routine clinical practice. Cardiac autonomic neuropathy (CAN) in people with diabetes indicates widespread damage to the autonomic nervous system, which may severely affect health and quality of life. We examined effects of early detection and subsequent intensive treatment of type 2 diabetes in primary care on the prevalence of CAN at the 6-year follow-up examination in a pragmatic cluster-randomised parallel group trial. Methods: One hundred and ninety general practices were randomised to deliver either intensive multifactorial treatment (IT) or routine care (RC) as recommended by national guidelines to patients with type 2 diabetes, identified through a stepwise screening programme in the primary care setting. 1533 people (IT, n = 910; RC, n = 623) were identified and included. At the 6-year follow-up examination, measures of CAN were applied in an unselected subsample of 777 participants using heart rate variability analysis and standard tests of CAN. Results: At the 6-year follow-up examination, the prevalence of early CAN was 15.1% in the RC group and 15.5% in the IT group, while manifest CAN was present in 7.1% and 7.3%, respectively. We found no statistically significant effect of intensive treatment on the prevalence of CAN compared with routine care. Conclusions/interpretation: In the Danish arm of the ADDITION Study, signs of CAN were highly prevalent 6 years after a screening-based diagnosis of type 2 diabetes. Intensive multifactorial treatment did not significantly affect the prevalence of CAN compared with routine care. However, at follow-up the level of medication was also high in the RC group.</p

Does Training and Support of General Practitioners in Intensive Treatment of People with Screen-Detected Diabetes Improve Medication, Morbidity and Mortality in People with Clinically-Diagnosed Diabetes? Investigation of a Spill-Over Effect in a Cluster RCT

$\textbf{Introduction}$ Very few studies have examined the potential spill-over effect of a trial intervention in general practice. We investigated whether training and support of general practitioners in the intensive treatment of people with screen-detected diabetes improved rates of redeemed medication, morbidity and mortality in people with clinically-diagnosed diabetes. $\textbf{Methods}$ This is a secondary, post-hoc, register-based analysis linked to a cluster randomised trial. In the $\textit{ADDITION-Denmark}$ trial, 175 general practices were cluster randomised (i) to routine care, or (ii) to receive training and support in intensive multifactorial treatment of individuals with screen-detected diabetes (2001 to 2009). Using national registers we identified all individuals who were diagnosed with clinically incident diabetes in the same practices over the same time period. (Patients participating in the ADDITION trial were excluded). We compared rates of redeemed medication, a cardiovascular composite endpoint, and all-cause mortality between the routine care and intensive treatment groups. $\textbf{Results}$ In total, 4,107 individuals were diagnosed with clinically incident diabetes in $\textit{ADDITION-Denmark}$ practices between 2001 and 2009 (2,051 in the routine care group and 2,056 in the intensive treatment group). There were large and significant increases in the proportion of patients redeeming cardio-protective medication in both treatment groups during follow- up. After a median of seven years of follow-up, there was no difference in the incidence of a composite cardiovascular endpoint (HR 1.15, 95% CI 0.95 to 1.38) or all-cause mortality between the two groups (HR 1.08, 95% CI 0.94 to 1.23). $\textbf{Discussion}$ There was no evidence of a spill-over effect from an intervention promoting intensive treatment of people with screen-detected diabetes to those with clinically-diagnosed diabetes. Overall, the proportion of patients redeeming cardio-protective medication during follow-up was similar in both groups. $\textbf{Trial Registration}$ ClinicalTrials.gov NCT00237549Novo Nordisk Foundation (Grant ID: NNF14OC0008981

Prevalence of Neuropathy and Peripheral Arterial Disease and the Impact of Treatment in People With Screen-Detected Type 2 Diabetes

OBJECTIVE: There is limited evidence on how intensive multifactorial treatment (IT) improves outcomes of diabetes when initiated in the lead time between detection by screening and diagnosis in routine clinical practice. We examined the effects of early detection and IT of type 2 diabetes in primary care on the prevalence of diabetic peripheral neuropathy (DPN) and peripheral arterial disease (PAD) 6 years later in a pragmatic, cluster-randomized parallel group trial. RESEARCH DESIGN AND METHODS: A stepwise screening program in 190 general practices in Denmark was used to identify 1,533 people with type 2 diabetes. General practices were randomized to deliver either IT or routine care (RC) as recommended through national guidelines. Participants were followed for 6 years and measures of DPN and PAD were applied. RESULTS: We found no statistically significant effect of IT on the prevalence of DPN and PAD compared with RC. The prevalence of an ankle brachial index ≤0.9 was 9.1% (95% CI 6.0–12.2) in the RC arm and 7.3% (5.0–9.6) in the IT arm. In participants tested for vibration detection threshold and light touch sensation, the prevalence of a least one abnormal test was 34.8% (26.7–43.0) in the RC arm and 30.1% (24.1–36.1) in the IT arm. CONCLUSIONS: In a population with screen-detected type 2 diabetes, we did not find that screening followed by IT led to a statistically significant difference in the prevalence of DPN and PAD 6 years after diagnosis. However, treatment levels were high in both groups

Combined analysis of 19 common validated type 2 diabetes susceptibility gene variants shows moderate discriminative value and no evidence of gene-gene interaction

Udgivelsesdato: 2009-JulAIMS/HYPOTHESIS: The list of validated type 2 diabetes susceptibility variants has recently been expanded from three to 19. The variants identified are common and have low penetrance in the general population. The aim of the study is to investigate the combined effect of the 19 variants by applying receiver operating characteristics (ROC) to demonstrate the discriminatory value between glucose-tolerant individuals and type 2 diabetes patients in a cross-sectional population of Danes. METHODS: The 19 variants were genotyped in three study populations: the population-based Inter99 study; the ADDITION study; and additional type 2 diabetic patients and glucose-tolerant individuals. The case-control studies involved 4,093 type 2 diabetic patients and 5,302 glucose-tolerant individuals. RESULTS: Single-variant analyses demonstrated allelic odds ratios ranging from 1.04 (95% CI 0.98-1.11) to 1.33 (95% CI 1.22-1.45). When combining the 19 variants, subgroups with extreme risk profiles showed a threefold difference in the risk of type 2 diabetes (lower 10% carriers with &lt; or =15 risk alleles vs upper 10% carriers with &gt; or =22 risk alleles, OR 2.93 (95% CI 2.38-3.62, p = 1.6 x 10(-25)). We calculated the area under a ROC curve to estimate the discrimination rate between glucose-tolerant individuals and type 2 diabetes patients based on the 19 variants. We found an area under the ROC curve of 0.60. Two-way gene-gene interaction showed few nominal interaction effects. CONCLUSIONS/INTERPRETATION: Combined analysis of the 19 validated variants enables detection of subgroups at substantially increased risk of type 2 diabetes; however, the discrimination between glucose-tolerant and type 2 diabetes individuals is still too inaccurate to achieve clinical value

Homozygous carriers of the G allele of rs4664447 of the glucagon gene (GCG) are characterised by decreased fasting and stimulated levels of insulin, glucagon and glucagon-like peptide (GLP)-1

The glucagon gene (GCG) encodes several hormones important for energy metabolism: glucagon, oxyntomodulin and glucagon-like peptide (GLP)-1 and -2. Variants in GCG may associate with type 2 diabetes, obesity and/or related metabolic traits

Trends in cause-specific mortality among people with type 2 and type 1 diabetes from 2002 to 2019:A Danish population-based study

BackgroundDespite advances in primary and secondary prevention of cardiovascular disease,excess mortality persists within the diabetes population. This study explores thecomponents of this excess mortality and their interaction with sex.MethodsUsing Danish registries (2002-2019), we identified residents aged 18-99 years, theirdiabetes status, and recorded causes of death. Applying Lexis-based methods, wecomputed age-standardized mortality rates (asMRs), mortality relative risks (asMRRs),and log-linear trends for cause-specific mortality.FindingsFrom 2002-2019, 958,278 individuals died in Denmark (T2D: 148,620; T1D: 7,830)during 84.4M person-years. During the study period, overall asMRs declined, driven byreducing cardiovascular mortality, notably in men with T2D. Conversely, cancermortality remained high, making cancer the leading cause of death in individuals withT2D. Individuals with T2D faced an elevated mortality risk from nearly all cancer types,ranging from 9% to 257% compared to their non-diabetic counterparts. Notably,obesity-related cancers exhibited the highest relative risks: liver cancer (Men: asMRR3·58(3·28;3·91); Women: asMRR 2·49(2·14;2·89)), pancreatic cancer (Men: asMRR3·50(3·25;3·77); Women: asMRR 3·57(3·31;3·85)), and kidney cancer (Men: asMRR2·10(1·84;2·40); Women: asMRR 2·31(1·92;2·79)). In men with type 2 diabetes, excessmortality remained stable, except for dementia. In women, diabetes-related excessmortality increased by 6-17% per decade across all causes of death, exceptcardiovascular disease.InterpretationIn the last decade, cancer has emerged as the leading cause of death amongindividuals with T2D in Denmark, emphasizing the need for diabetes managementstrategies incorporating cancer prevention. A sex-specific approach is crucial toaddress persistently higher relative mortality in women with diabetes.FundingSupported by Steno Diabetes Center Aarhus, which is partially funded by anunrestricted donation from the Novo Nordisk Foundation, and by The Danish DiabetesAcademy.<br/

Patient-reported outcomes after 10-year follow-up of intensive, multifactorial treatment in individuals with screen-detected type 2 diabetes: the ADDITION-Europe trial.

AIMS: To present the longer-term impact of multifactorial treatment of type 2 diabetes on self-reported health status, diabetes-specific quality of life, and diabetes treatment satisfaction at 10-year follow up of the ADDITION-Europe trial. METHODS: The ADDITION-Europe trial enrolled 3057 individuals with screen-detected type 2 diabetes from four centres [Denmark, the UK (Cambridge and Leicester) and the Netherlands], between 2001 and 2006. Participants were randomized at general practice level to intensive treatment or to routine care . The trial ended in 2009 and a 10-year follow-up was performed at the end of 2014. We measured self-reported health status (36-item Short-Form Health Survey and EQ-5D), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life questionnaire), and diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire) at different time points during the study period. A mixed-effects model was applied to estimate the effect of intensive treatment (intention-to-treat analyses) on patient-reported outcome measures for each centre. Centre-specific estimates were pooled using a fixed effects meta-analysis. RESULTS: There was no difference in patient-reported outcome measures between the routine care and intensive treatment arms in this 10-year follow-up study [EQ-5D: -0.01 (95% CI -0.03, 0.01); Physical Composite Score (36-item Short-Form Health Survey): -0.27 (95% CI -1.11, 0.57), Audit of Diabetes-Dependent Quality of Life questionnaire: -0.01 (95% CI -0.11, 0.10); and Diabetes Treatment Satisfaction Questionnaire: -0.20 (95% CI -0.70, 0.29)]. CONCLUSIONS: Intensive, multifactorial treatment of individuals with screen-detected type 2 diabetes did not affect self-reported health status, diabetes-specific quality of life, or diabetes treatment satisfaction at 10-year follow-up compared to routine care

Preschool weight and body mass index in relation to central obesity and metabolic syndrome in adulthood.

BACKGROUND: If preschool measures of body size routinely collected at preventive health examinations are associated with adult central obesity and metabolic syndrome, a focused use of these data for the identification of high risk children is possible. The aim of this study was to test the associations between preschool weight and body mass index (BMI) and adult BMI, central obesity and metabolic alterations. METHODS: The Northern Finland Birth Cohort 1966 (NFBC1966) (N = 4111) is a population-based cohort. Preschool weight (age 5 months and 1 year) and BMI (age 2-5 years) were studied in relation to metabolic syndrome as well as BMI, waist circumference, lipoproteins, blood pressure, and fasting glucose at the age of 31 years. Linear regression models and generalized linear regression models with log link were used. RESULTS: Throughout preschool ages, weight and BMI were significantly linearly associated with adult BMI and waist circumference. Preschool BMI was inversely associated with high-density lipoprotein levels from the age of 3 years. Compared with children in the lower half of the BMI range, the group of children with the 5% highest BMI at the age of 5 years had a relative risk of adult obesity of 6.2(95% CI:4.2-9.3), of adult central obesity of 2.4(95% CI:2.0-2.9), and of early onset adult metabolic syndrome of 2.5(95% CI:1.7-3.8). CONCLUSIONS: High preschool BMI is consistently associated with adult obesity, central obesity and early onset metabolic syndrome. Routinely collected measures of body size in preschool ages can help to identify children in need of focused prevention due to their increased risk of adverse metabolic alterations in adulthood