There is little evidence to inform the targeted treatment of individuals found early in the diabetes disease trajectory.
To describe cardiovascular disease (CVD) risk profiles and treatment of individual CVD risk factors by modelled CVD risk at diagnosis; changes in treatment, modelled CVD risk, and CVD risk factors in the 5 years following diagnosis; and how these are patterned by socioeconomic status.
Cohort analysis of a cluster-randomised trial (ADDITION-Europe) in general practices in Denmark, England, and the Netherlands.
A total of 2418 individuals with screen-detected diabetes were divided into quartiles of modelled 10-year CVD risk at diagnosis. Changes in treatment, modelled CVD risk, and CVD risk factors were assessed at 5 years.
The largest reductions in risk factors and modelled CVD risk were seen in participants who were in the highest quartile of modelled risk at baseline, suggesting that treatment was offered appropriately. Participants in the lowest quartile of risk at baseline had very similar levels of modelled CVD risk at 5 years and showed the least variation in change in modelled risk. No association was found between socioeconomic status and changes in CVD risk factors, suggesting that treatment was equitable.
Diabetes management requires setting of individualised attainable targets. This analysis provides a reference point for patients, clinicians, and policymakers when considering goals for changes in risk factors early in the course of the disease that account for the diverse cardiometabolic profile present in individuals who are newly diagnosed with type 2 diabetes.
Cites: BMJ. 1998 Sep 12;317(7160):703-139732337
Cites: BMJ. 1998 Jan 10;316(7125):100-59462313
Cites: Lancet. 1999 Feb 20;353(9153):617-2210030326
Promoting positive changes in lifestyle behavior in the whole population may be a feasible and effective approach to reducing type 2 diabetes burden, but the impact of population shifts of modifiable risk factors remains unclear. Currently most of the evidence on modifiable lifestyle behavior and type 2 diabetes risk on a population level comes from studies of between-individual differences. The objective of the study was to investigate the association and potential impact on disease burden for within-individual change in lifestyle behavior and diabetes risk.
Population-based prospective cohort study of 35,680 participants aged 30-50 at baseline in 1990-2003 in Västerbotten County, Sweden (follow-up until 2013). Five self-reported modifiable lifestyle behaviors (tobacco use, physical activity, alcohol intake, dietary fiber intake and dietary fat intake) were measured at baseline and 10 year follow-up. Lifestyle behaviors were studied separately, and combined in a score. Incident diabetes was detected by oral glucose tolerance tests. Multivariate logistic regression models and population attributable fractions (PAF) were used to analyze the association between change in lifestyle behavior between baseline and 10 year follow-up, and risk of incident diabetes.
Incident diabetes was detected in 1,184 (3.3%) participants at 10 year follow-up. There was a reduced diabetes risk associated with increase in dietary fiber intake, odds ratio (OR) 0.79 (95% confidence interval (CI) 0.66, 0.96) for increase of at least one unit standard deviation (3.0 g/1,000 kcal) of the baseline distribution, PAF 16.0% (95% CI 4.2, 26.4%). Increase in the lifestyle behavior score was associated with reduced diabetes risk, OR 0.92 (95% CI 0.85, 0.99) per unit increase of the score.
These results support a causal link between lifestyle behavior and type 2 diabetes incidence. A small shift in lifestyle behaviors, in particular intake of dietary fiber, has the potential to reduce diabetes burden in the population and might be a suitable target for public health intervention.
Early Detection and Treatment of Type 2 Diabetes Reduce Cardiovascular Morbidity and Mortality: A Simulation of the Results of the Anglo-Danish-Dutch Study of Intensive Treatment in People With Screen-Detected Diabetes in Primary Care (ADDITION-Europe).
To estimate the benefits of screening and early treatment of type 2 diabetes compared with no screening and late treatment using a simulation model with data from the ADDITION-Europe study.
We used the Michigan Model, a validated computer simulation model, and data from the ADDITION-Europe study to estimate the absolute risk of cardiovascular outcomes and the relative risk reduction associated with screening and intensive treatment, screening and routine treatment, and no screening with a 3- or 6-year delay in the diagnosis and routine treatment of diabetes and cardiovascular risk factors.
When the computer simulation model was programmed with the baseline demographic and clinical characteristics of the ADDITION-Europe population, it accurately predicted the empiric results of the trial. The simulated absolute risk reduction and relative risk reduction were substantially greater at 5 years with screening, early diagnosis, and routine treatment compared with scenarios in which there was a 3-year (3.3% absolute risk reduction [ARR], 29% relative risk reduction [RRR]) or a 6-year (4.9% ARR, 38% RRR) delay in diagnosis and routine treatment of diabetes and cardiovascular risk factors.
Major benefits are likely to accrue from the early diagnosis and treatment of glycemia and cardiovascular risk factors in type 2 diabetes. The intensity of glucose, blood pressure, and cholesterol treatment after diagnosis is less important than the time of its initiation. Screening for type 2 diabetes to reduce the lead time between diabetes onset and clinical diagnosis and to allow for prompt multifactorial treatment is warranted.
Intensive treatment of multiple cardiovascular risk factors can halve mortality among people with established type 2 diabetes. We investigated the effect of early multifactorial treatment after diagnosis by screening.
In a pragmatic, cluster-randomised, parallel-group trial done in Denmark, the Netherlands, and the UK, 343 general practices were randomly assigned screening of registered patients aged 40-69 years without known diabetes followed by routine care of diabetes or screening followed by intensive treatment of multiple risk factors. The primary endpoint was first cardiovascular event, including cardiovascular mortality and morbidity, revascularisation, and non-traumatic amputation within 5 years. Patients and staff assessing outcomes were unaware of the practice's study group assignment. Analysis was done by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00237549.
Primary endpoint data were available for 3055 (99
9%) of 3057 screen-detected patients. The mean age was 60
3 (SD 6
9) years and the mean duration of follow-up was 5
3 (SD 1
6) years. Improvements in cardiovascular risk factors (HbA(1c) and cholesterol concentrations and blood pressure) were slightly but significantly better in the intensive treatment group. The incidence of first cardiovascular event was 7
5 per 1000 person-years) in the intensive treatment group and 8
9 per 1000 person-years) in the routine care group (hazard ratio 0
83, 95% CI 0
05), and of all-cause mortality 6
6 per 1000 person-years) and 6
5 per 1000 person-years; 0
An intervention to promote early intensive management of patients with type 2 diabetes was associated with a small, non-significant reduction in the incidence of cardiovascular events and death.
National Health Service Denmark, Danish Council for Strategic Research, Danish Research Foundation for General Practice, Danish Centre for Evaluation and Health Technology Assessment, Danish National Board of Health, Danish Medical Research Council, Aarhus University Research Foundation, Wellcome Trust, UK Medical Research Council, UK NIHR Health Technology Assessment Programme, UK National Health Service R&D, UK National Institute for Health Research, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Novo Nordisk, Astra, Pfizer, GlaxoSmithKline, Servier, HemoCue, Merck.
Effect of early multifactorial therapy compared with routine care on microvascular outcomes at 5 years in people with screen-detected diabetes: a randomized controlled trial: the ADDITION-Europe Study.
To determine the benefit of multifactorial treatment on microvascular complications among people with type 2 diabetes detected by screening.
This study was a multicenter cluster randomized controlled trial in primary care with randomization at the practice level. In four centers in Denmark; Cambridge, U.K.; the Netherlands; and Leicester, U.K., 343 general practices participated in the trial. Eligible for follow-up were 2,861 of the 3,057 people with diabetes detected by screening included in the original trial. Biomedical data on nephropathy were collected in 2,710 (94.7%) participants, retinal photos in 2,190 (76.6%), and questionnaire data on peripheral neuropathy in 2,312 (80.9%). The prespecified microvascular end points were analyzed by intention to treat. Results from the four centers were pooled using fixed-effects meta-analysis.
Five years after diagnosis, any kind of albuminuria was present in 22.7% of participants in the intensive treatment (IT) group and in 24.4% in the routine care (RC) group (odds ratio 0.87 [95% CI 0.72-1.07]). Retinopathy was present in 10.2% of the IT group and 12.1% of the RC group (0.84 [0.64-1.10]), and severe retinopathy was present in one patient in the IT group and seven in the RC group. Neuropathy was present in 4.9% and 5.9% (0.95 [0.68-1.34]), respectively. Estimated glomerular filtration rate increased between baseline and follow-up in both groups (4.31 and 6.44 mL/min, respectively).
Compared with RC, an intervention to promote target-driven, intensive management of patients with type 2 diabetes detected by screening was not associated with significant reductions in the frequency of microvascular events at 5 years.
Health check programmes for chronic disease have been introduced in a number of countries. However, there are few trials assessing the benefits and harms of these screening programmes at the population level. In a post hoc analysis, we evaluated the effect of population-based screening for type 2 diabetes and cardiovascular risk factors on mortality rates and cardiovascular events.
This register-based, non-randomised, controlled trial included men and women aged 40-69 years without known diabetes who were registered with a general practice in Denmark (n = 1,912,392). Between 2001 and 2006, 153,107 individuals registered with 181 practices participating in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Denmark study were sent a diabetes risk score questionnaire. Individuals at moderate-to-high risk were invited to visit their GP for assessment of diabetes status and cardiovascular risk (screening group). The 1,759,285 individuals registered with all other general practices in Denmark constituted the retrospectively constructed no-screening (control) group. Outcomes were mortality rate and cardiovascular events (cardiovascular disease death, non-fatal ischaemic heart disease or stroke). The analysis was performed according to the intention-to-screen principle.
Among the screening group, 27,177 (18%) individuals attended for assessment of diabetes status and cardiovascular risk. Of these, 1,533 were diagnosed with diabetes. During a median follow-up of 9.5 years, there were 11,826 deaths in the screening group and 141,719 in the no-screening group (HR 0.99 [95% CI 0.96, 1.02], p = 0.66). There were 17,941 cardiovascular events in the screening group and 208,476 in the no-screening group (HR 0.99 [0.96, 1.02], p = 0.49).
A population-based stepwise screening programme for type 2 diabetes and cardiovascular risk factors among all middle-aged adults in Denmark was not associated with a reduction in rate of mortality or cardiovascular events between 2001 and 2012.
Cites: Ann Intern Med. 2015 Dec 1;163(11):861-8 PMID 26501513
There is continuing debate about the net benefits of population screening for type 2 diabetes. We compared the risk of cardiovascular disease (CVD) and mortality among incident cases of type 2 diabetes in a screened group with those in an unscreened group.
In this register-based non-randomised controlled trial, eligible individuals were all men and women aged 40-69 years without known diabetes, registered with a general practice in Denmark (n = 1,912,392). Between 2001 and 2006, 153,107 individuals registered with 181 practices participating in the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION)-Denmark study were sent a diabetes-risk-score questionnaire. Individuals at moderate-to-high risk were invited to visit their family doctor for assessment of diabetes status and cardiovascular risk (screening group). The 1,759,285 individuals registered with all other practices in Denmark constituted the retrospectively constructed no-screening (control) group. In this post hoc analysis, we identified individuals from the screening and no-screening groups who were diagnosed with diabetes between 2001 and 2009 (n = 139,075), and compared risk of CVD and mortality in these groups between 2001 and 2012.
In the screening group, 27,177/153,107 (18%) individuals attended for screening, of whom 1533 were diagnosed with diabetes. Between 2001 and 2009, 13,992 people were newly diagnosed with diabetes in the screening group (including those diagnosed by screening) and 125,083 in the no-screening group. Between 2001 and 2012, the risks of CVD and mortality were lower among individuals with diabetes in the screening group compared with individuals with diabetes in the no-screening (control) group (CVD HR 0.84, 95% CI 0.80, 0.89; mortality HR 0.79, 95% CI 0.74, 0.84).
A single round of diabetes screening and cardiovascular risk assessment in middle-aged Danish adults in general practice was associated with a significant reduction in risk of all-cause mortality and CVD events in those diagnosed with diabetes.
Cites: Ann Intern Med. 2015 Dec 1;163(11):861-8 PMID 26501513
Weight loss in individuals at high risk of diabetes is an effective prevention method and a major component of the currently prevailing diabetes prevention strategies. The aim of the present study was to investigate the public health potential for diabetes prevention of weight maintenance or moderate weight loss on a population level in an observational cohort with repeated measurements of weight and diabetes status.
Height, weight and diabetes status were objectively measured at baseline and 10 year follow-up in a population-based cohort of 33,184 participants aged 30-60 years between 1990 and 2013 in Västerbotten County, Sweden. The association between risk of incident diabetes and change in BMI or relative weight was modelled using multivariate logistic regression. Population attributable fractions (PAF) were used to assess population impact of shift in weight.
Mean (SD) BMI at baseline was 25.0 (3.6) kg/m(2). Increase in relative weight between baseline and follow-up was linearly associated with incident diabetes risk, odds ratio (OR) 1.05 (95% confidence interval (CI) 1.04-1.06) per 1% change in weight. Compared to weight maintenance (±1.0 kg/m(2)), weight gain of?>?+1.0 kg/m(2) was associated with an increased risk of incident diabetes, OR 1.52 (95% CI 1.32, 1.74), representing a PAF of 21.9% (95% CI 15.8, 27.6%). For moderate weight loss (-1.0 to -2.0 kg/m(2)) the OR was 0.72 (95% CI 0.52, 0.99).
Weight maintenance in adulthood is strongly associated with reduced incident diabetes risk and there is considerable potential for diabetes prevention in promoting this as a whole population strategy.
Cites: Am J Epidemiol. 1998 May 1;147(9):826-339583712
Cross-sectional associations between sociocultural factors and objectively-measured physical activity in a sample of 397 children (aged 9) and 213 adolescents (aged 15) were investigated. Associations with children's physical activity were found for mothers' physical activity (Beta = 80, p
Complementary strategies to shift risk factor population distributions and target high-risk individuals are required to reduce the burden of type 2 diabetes and cardiovascular disease (CVD).
To examine secular changes in glucose and CVD risk factors over 20 years during an individual and population-based CVD prevention program in Västerbotten County, Sweden.
Population-based health promotion intervention was conducted and annual invitation for individuals turning 40, 50, and 60 years to attend a health assessment, including an oral glucose tolerance test, biochemical measures, and a questionnaire. Data were collected between 1991 and 2010, analyzed in 2012 and available for 120,929 individuals. Linear regression modeling examined age-adjusted differences in CVD risk factor means over time. Data were direct-age-standardized to compare disease prevalence.
Between 1991-1995 and 2006-2010, mean age-adjusted cholesterol (men=-0.53, 95% CI=-0.55, -0.50 mmol/L; women=-0.48, 95% CI=-0.50, -0.45 mmol/L) and systolic blood pressure declined (men=-3.06, 95% CI=-3.43, -2.70 mm Hg; women=-5.27, 95% CI=-5.64, -4.90 mm Hg), with corresponding decreases in the age-standardized prevalence of hypertension and hyperlipidemia. Mean age-adjusted 2-hour plasma glucose (men=0.19, 95% CI=0.15, 0.23 mmol/L; women=0.08, 95% CI=0.04, 0.11 mmol/L) and BMI increased (men=1.12, 95% CI=1.04, 1.21; women=0.65, 95% CI=0.55, 0.75), with increases in the age-standardized prevalence of diabetes and obesity.
These data demonstrate the potential of combined individual- and population-based approaches to CVD risk factor control and highlight the need for additional strategies addressing hyperglycemia and obesity.