Search

Background: It is unclear whether cardiovascular risk factor modification influences the development of renal disease in people with type 2 diabetes identified through screening. We determined predictors of albuminuria 5 years after a diagnosis of screen-detected diabetes within the ADDITION-Europe study, a pragmatic cardiovascular outcome trial of multifactorial cardiovascular risk management.Methods: In 1826 participants with newly diagnosed, screen-detected diabetes without albuminuria, we explored associations between risk of new albuminuria (≥2.5 mg mmol-1 for males and ≥3.5 mg mmol-1 for females) and (1) baseline cardio-metabolic risk factors and (2) changes from baseline to 1 year in systolic blood pressure (ΔSBP) and glycated haemoglobin (ΔHbA1c ) using logistic regression.Results: Albuminuria developed in 268 (15%) participants; baseline body mass index and active smoking were independently associated with new onset albuminuria in 5 years after detection of diabetes. In a model adjusted for age, gender, baseline HbA1c and blood pressure, a 1% decrease in HbA1c and 5-mm Hg decrease in SBP during the first year were independently associated with lower risks of albuminuria (odds ratio), 95% confidence interval: 0.76, 0.62 to 0.91 and 0.94, 0.88 to 1.01, respectively. Further adjustment did not materially change these estimates. There was no interaction between ΔSBP and ΔHbA1c in relation to albuminuria risk, suggesting likely additive effects on renal microvascular disease.Conclusions: Baseline measurements and changes in HbA1c and SBP a year after diagnosis of diabetes through screening independently associate with new onset albuminuria 4 years later. Established multifactorial treatment for diabetes applies to cases identified through screening. [ABSTRACT FROM AUTHOR]

Diabetes is a diverse and complex disease, with considerable variation in phenotypic manifestation and severity. This variation hampers the study of etiological differences and reduces the statistical power of analyses of associations to genetics, treatment outcomes, and complications. We address these issues through deep, fine-grained phenotypic stratification of a diabetes cohort. Text mining the electronic health records of 14,017 patients, we matched two controlled vocabularies (ICD-10 and a custom vocabulary developed at the clinical center Steno Diabetes Center Copenhagen) to clinical narratives spanning a 19 year period. The two matched vocabularies comprise over 20,000 medical terms describing symptoms, other diagnoses, and lifestyle factors. The cohort is genetically homogeneous (Caucasian diabetes patients from Denmark) so the resulting stratification is not driven by ethnic differences, but rather by inherently dissimilar progression patterns and lifestyle related risk factors. Using unsupervised Markov clustering, we defined 71 clusters of at least 50 individuals within the diabetes spectrum. The clusters display both distinct and shared longitudinal glycemic dysregulation patterns, temporal co-occurrences of comorbidities, and associations to single nucleotide polymorphisms in or near genes relevant for diabetes comorbidities., Competing Interests: IK, CS, KB, PH, AH, PJ, LJ, CR, MP, RE, HA, TA, JB, NG, KB, OP, FP, TH, RB, PR, SB No competing interests declared, (© 2019, Kirk et al.)

Aims/hypothesis: 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., Methods: 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., Results: 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)., Conclusions/interpretation: 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.

Aims/hypothesis: Within a trial of intensive treatment of people with screen-detected diabetes, we aimed to assess a potential spillover effect of the trial intervention on incident cardiovascular disease (CVD) and all-cause mortality among people who screened positive on a diabetes risk questionnaire but who were normoglycaemic., Methods: In the Anglo-Danish-Dutch Study of Intensive Treatment In People with Screen-Detected Diabetes in Primary Care (ADDITION)-Denmark trial, 175 general practices were cluster-randomised into: (1) screening plus routine care of individuals with screen-detected diabetes (control group); or (2) screening plus training and support in intensive multifactorial treatment of individuals with screen-detected diabetes (intervention group). We identified all individuals who screened positive on a diabetes risk questionnaire in ADDITION-Denmark but were normoglycaemic following biochemical testing for use in this secondary analysis. After a median 8.9 years follow-up, we used data from national registers to compare rates of first CVD events and all-cause mortality in individuals in the routine care group with those in the intensive treatment group., Results: In total, 21,513 individuals screened positive for high risk of diabetes but were normoglycaemic on biochemical testing in ADDITION-Denmark practices between 2001 and 2006 (10,289 in the routine care group and 11,224 in the intensive treatment group). During 9 years of follow-up, there were 3784 first CVD events and 1748 deaths. The incidence of CVD was lower among the intensive treatment group compared with the routine care group (HR 0.92 [95% CI 0.85, 0.99]). This association was stronger among individuals at highest CVD risk (heart SCORE ≥ 10; HR 0.85 [95% CI 0.75, 0.96]). There was no difference in mortality between the two treatment groups (HR 1.02 [95% CI 0.92, 1.14])., Conclusions/interpretation: Training of general practitioners to provide target-driven intensive management of blood glucose levels and other cardiovascular risk factors showed some evidence of a spillover effect on the risk of CVD over a 9 year period among individuals at high risk of diabetes. The effect was particularly pronounced among those at highest risk of CVD. There was no effect on mortality., Trial Registration: ClinicalTrials.gov NCT00237549.

Objective: To analyse the impact of drug safety warnings from the European Medicines Agency (EMA) on drug utilisation and their interaction with information released through national reimbursement bodies., Methods: Insurance claims data on anti-diabetic drug prescriptions in primary care in Germany and Denmark were analysed using interrupted time series analysis, with EMA drug warnings for thiazolidinediones (TZDs) in 2007 and 2011 as the intervention. Monthly drug utilisation data per substance in defined daily dosages (DDD) consumed per 1000 insurees were retrieved from the Danish national drug prescriptions register and one large statutory sickness fund in Germany., Results: TZDs were generally reimbursed in Germany but restricted to individual reimbursement in Denmark. Consequently, utilisation of TZDs was much higher in Germany in 2007 compared with Denmark. For rosiglitazone, the drug warning had a significant impact on utilisation, reducing the number of DDD per 1000 insurees per day by -0.0105 in Denmark and -0.0312 in Germany (p-values<0.05). For pioglitazone, neither of the drug warnings had a significant effect on utilisation., Conclusion: The impact of EMA drug warnings differed across countries and might be mediated by information released through national reimbursement bodies and physician associations. Increasing complexity of new drugs and modified approval procedures require a strengthening of information exchange between drug regulation bodies and physicians to ensure patient safety., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Intensive treatment (IT) of cardiovascular risk factors can halve mortality among people with established type 2 diabetes but the effects of treatment earlier in the disease trajectory are uncertain., Objective: To quantify the cost-effectiveness of intensive multifactorial treatment of screen-detected diabetes., Design: Pragmatic, multicentre, cluster-randomised, parallel-group trial., Setting: Three hundred and forty-three general practices in Denmark, the Netherlands, and Cambridge and Leicester, UK., Participants: Individuals aged 40-69 years with screen-detected diabetes., Interventions: Screening plus routine care (RC) according to national guidelines or IT comprising screening and promotion of target-driven intensive management (medication and promotion of healthy lifestyles) of hyperglycaemia, blood pressure and cholesterol., Main Outcome Measures: The primary end point was a composite of first cardiovascular event (cardiovascular mortality/morbidity, revascularisation and non-traumatic amputation) during a mean [standard deviation (SD)] follow-up of 5.3 (1.6) years. Secondary end points were (1) all-cause mortality; (2) microvascular outcomes (kidney function, retinopathy and peripheral neuropathy); and (3) patient-reported outcomes (health status, well-being, quality of life, treatment satisfaction). Economic analyses estimated mean costs (UK 2009/10 prices) and quality-adjusted life-years from an NHS perspective. We extrapolated data to 30 years using the UK Prospective Diabetes Study outcomes model [version 1.3; (©) Isis Innovation Ltd 2010; see www.dtu.ox.ac.uk/outcomesmodel (accessed 27 January 2016)]., Results: We included 3055 (RC, n = 1377; IT, n = 1678) of the 3057 recruited patients [mean (SD) age 60.3 (6.9) years] in intention-to-treat analyses. Prescription of glucose-lowering, antihypertensive and lipid-lowering medication increased in both groups, more so in the IT group than in the RC group. There were clinically important improvements in cardiovascular risk factors in both study groups. Modest but statistically significant differences between groups in reduction in glycated haemoglobin (HbA1c) levels, blood pressure and cholesterol favoured the IT group. The incidence of first cardiovascular event [IT 7.2%, 13.5 per 1000 person-years; RC 8.5%, 15.9 per 1000 person-years; hazard ratio 0.83, 95% confidence interval (CI) 0.65 to 1.05] and all-cause mortality (IT 6.2%, 11.6 per 1000 person-years; RC 6.7%, 12.5 per 1000 person-years; hazard ratio 0.91, 95% CI 0.69 to 1.21) did not differ between groups. At 5 years, albuminuria was present in 22.7% and 24.4% of participants in the IT and RC groups, respectively [odds ratio (OR) 0.87, 95% CI 0.72 to 1.07), retinopathy in 10.2% and 12.1%, respectively (OR 0.84, 95% CI 0.64 to 1.10), and neuropathy in 4.9% and 5.9% (OR 0.95, 95% CI 0.68 to 1.34), respectively. The estimated glomerular filtration rate increased between baseline and follow-up in both groups (IT 4.31 ml/minute; RC 6.44 ml/minute). Health status, well-being, diabetes-specific quality of life and treatment satisfaction did not differ between the groups. The intervention cost £981 per patient and was not cost-effective at costs ≥ £631 per patient., Conclusions: Compared with RC, IT was associated with modest increases in prescribed treatment, reduced levels of risk factors and non-significant reductions in cardiovascular events, microvascular complications and death over 5 years. IT did not adversely affect patient-reported outcomes. IT was not cost-effective but might be if delivered at a reduced cost. The lower than expected event rate, heterogeneity of intervention delivery between centres and improvements in general practice diabetes care limited the achievable differences in treatment between groups. Further follow-up to assess the legacy effects of early IT is warranted., Trial Registration: ClinicalTrials.gov NCT00237549., Funding Details: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 20, No. 64. See the NIHR Journals Library website for further project information.

Aims/hypothesis: Screening programmes for type 2 diabetes inevitably find more people at high risk of developing diabetes than people with undiagnosed prevalent diabetes. We describe the incidence of diabetes for risk groups according to advancement in a screening process., Methods: In 2001-2006, a diabetes screening programme based on the Danish diabetes risk score and measures of HbA1c and glucose was carried out in Danish general practices. The present study includes 13,249 individuals with low diabetes risk scores and 22,726 with high diabetes risk scores but no diabetes according to WHO 1999 criteria. Seven incremental levels of diabetes risk were defined and followed for incident diabetes recorded in the Danish National Diabetes Register until December 2012. For each group, cumulative diabetes incidence was calculated. Incidence rates and rate ratios were estimated by Poisson regression analyses., Results: After 10 years of follow-up 1,164 new diabetes cases were registered. Incidence rates were 1.0, 4.2, 14.5, 28.8 and 52.6 per 1,000 person-years in individuals at low risk and in those with normal glucose tolerance, impaired fasting glucose, impaired glucose tolerance and one diabetic glucose value, respectively. For each step in the screening algorithm, the risk of developing diabetes was higher than in the previous step., Conclusions/interpretation: The risk of developing clinical diabetes in people who screen negative for diabetes depends on the level of risk stratification at screening, even at lower risk levels. This risk increases markedly in the presence of impaired glucose regulation. These results can inform policy recommendations concerning prevention strategies following screening.

Background: The relationship between metabolic disease and the non-modifiable risk factors sex, age and ethnicity in Africans is not well-established., Aim: This study aimed to describe sex, age and ethnicity differences in blood pressure (BP) and lipid status in rural Kenyans., Subjects and Methods: A cross-sectional study was undertaken among rural Kenyans. BP and pulse rate (PR) were measured while sitting and fasting blood samples were taken for analysis of standard lipid profile. Standard anthropometric measurements were collected. Physical activity energy expenditure was obtained objectively and lifestyle data were obtained using questionnaires., Results: In total, 1139 individuals (61.0% women) participated aged 17-68 years. Age was positively associated with BP and plasma cholesterol levels. Sitting PR was negatively associated with age in women only (sex-interaction p < 0.001). Ethnicity did not modify any of the age-associations with haemodynamic or lipid outcomes. Differences in intercept between women and men were found in all parameters except for diastolic BP (p = 0.154), with men having lower HDL-C but higher values in all other cardiovascular risk factors., Conclusion: BP and plasma cholesterol levels increase with age at a similar gradient in men and women, but absolute levels of the majority of the risk factors were higher in men.

Objectives: The association between blood levels of hemoglobin (B-hgb) and blood pressure (BP) has been widely investigated in Caucasians and Asians but there is a paucity of data in rural black Africans. The objective was to investigate the association between B-hgb and BP in a rural black African population., Methods: A cross-sectional study was conducted in three districts in Kenya (Bondo, Kitui, and Transmara) with the inclusion of participants aged ≥17 years. Background information, anthropometry, BP, B-hgb, hepatic insulin resistance (HOMA2-IR), standard lipid profile, and oral glucose tolerance test were obtained in each participant., Results: Background characteristics among 1,167 participants showed that anemic and non-anemic participants differed significantly from each other as there were more women, lower body mass index and waist circumference (WC), lower degree of hepatic insulin resistance and plasma cholesterols among the anemic participants. Furthermore, anemic participants had significantly lower systolic and diastolic BP (P < 0.01) but not a significantly different prevalence of hypertension (P = 0.08). Multivariate linear regression models adjusted for-age, sex, plasma total-cholesterol, WC, Log2(HOMA2-IR), ethnicity, and smoking status-revealed that B-hgb (per mmol/l increment) was significantly associated with systolic BP (estimate: 1.18 (0.37-1.98)) and diastolic BP (estimate: 1.06 (0.54-1.57)) (P < 0.01)., Conclusions: B-hgb is associated with BP in rural black Africans., (© 2015 Wiley Periodicals, Inc.)

Objective: 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., Research Design and Methods: 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., Results: 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., Conclusions: 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., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Aims: To examine whether socioeconomic position (SEP) was associated with change in cardiovascular risk factors and meeting treatment targets for cardiovascular risk factors among individuals with screen-detected Type 2 DM at six-year follow-up., Methods: The study population was 1533 people with Type 2 DM identified from at stepwise diabetes screening programme in general practice during 2001-2006 in the ADDITION-Denmark study. The ADDITION-study was performed as a randomised trial but the two randomisation groups were analysed as one cohort in this study. Cardiovascular risk factors were measured at baseline and repeated at follow-up (mean: 5.9 [1.4] years). Information on SEP, redeemed antihypertensive and lipid-lowering treatment were obtained from Danish registers. Multivariate analyses were performed to estimate change in cardiovascular risk factors and difference in meeting treatment targets., Results: The change in HbA1c, cholesterol, blood pressure and BMI were virtually the same across educational level, income level, occupational status or cohabiting status. Overall, the ability to meet treatment targets for HbA1c, cholesterol and blood pressure was not modified by SEP-group. A higher proportion of people with lower educational level or lower income level in the intensive care redeemed anti-hypertensive treatment compared to people with higher educational or income levels., Conclusion: Screen-detection and early treatment onset did not introduce socioeconomic inequality in metabolic control in people with screen-detected Type 2 DM at six-year follow-up., (Copyright © 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)