Linking glycemic dysregulation in diabetes to symptoms, comorbidities, and genetics through EHR data mining.

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.

Effect of population screening for type 2 diabetes and cardiovascular risk factors on mortality rate and cardiovascular events: a controlled trial among 1,912,392 Danish adults.

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.

Does training of general practitioners for intensive treatment of people with screen-detected diabetes have a spillover effect on mortality and cardiovascular morbidity in 'at risk' individuals with normoglycaemia? Results from the ADDITION-Denmark cluster-randomised controlled trial.

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.

Drug safety and the impact of drug warnings: An interrupted time series analysis of diabetes drug prescriptions in Germany and Denmark.

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.

A randomised trial of the effect and cost-effectiveness of early intensive multifactorial therapy on 5-year cardiovascular outcomes in individuals with screen-detected type 2 diabetes: the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care (ADDITION-Europe) study.

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.

Incidence of register-based diabetes 10 years after a stepwise diabetes screening programme: the ADDITION-Denmark study.

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.

Hemoglobin levels and blood pressure are associated in rural black africans.

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.

Cardiovascular risk factors in rural Kenyans are associated with differential age gradients, but not modified by sex or ethnicity.

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.

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).

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.

[General practice plays a role in health check screening].

A Cochrane review has recently challenged the benefit of health checks. Included studies, screening procedures and treatments were however very heterogeneous and did not fulfil present days standards and most studies were done outside primary care. This review concentrates on research from health checks in Danish general practices focusing on early detection and treatment of risk factors for cardiovascular disease and diabetes.

A common Greenlandic TBC1D4 variant confers muscle insulin resistance and type 2 diabetes.

The Greenlandic population, a small and historically isolated founder population comprising about 57,000 inhabitants, has experienced a dramatic increase in type 2 diabetes (T2D) prevalence during the past 25 years. Motivated by this, we performed association mapping of T2D-related quantitative traits in up to 2,575 Greenlandic individuals without known diabetes. Using array-based genotyping and exome sequencing, we discovered a nonsense p.

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.

Objective: To determine the benefit of multifactorial treatment on microvascular complications among people with type 2 diabetes detected by screening.

Research Design And Methods: 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.

Change in cardiovascular risk factors following early diagnosis of type 2 diabetes: a cohort analysis of a cluster-randomised trial.

Background: There is little evidence to inform the targeted treatment of individuals found early in the diabetes disease trajectory.

Aim: 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.

Design And Setting: Cohort analysis of a cluster-randomised trial (ADDITION-Europe) in general practices in Denmark, England, and the Netherlands.

Socioeconomic position and cardiovascular risk factors among people with screen-detected Type 2 DM: six-year follow-up of the ADDITION-Denmark trial.

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.

Psychological distress, cardiovascular complications and mortality among people with screen-detected type 2 diabetes: follow-up of the ADDITION-Denmark trial.

Aims/hypothesis: The aim of this study was to examine the association between psychological distress and the risk of cardiovascular disease (CVD) events and all-cause mortality in patients with screen-detected type 2 diabetes mellitus. In addition, we explored whether or not metabolic control and medication adherence could explain part of this association.

Methods: A follow-up study was performed including 1,533 patients aged 40-69 years with screen-detected type 2 diabetes mellitus identified in general practice during 2001-2006 in the Denmark arm of the ADDITION (Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care) study.

HbA1c, fasting and 2 h plasma glucose in current, ex- and never-smokers: a meta-analysis.

Aims/hypothesis: The relationships between smoking and glycaemic variables have not been well explored. We compared HbA1c, fasting plasma glucose (FPG) and 2 h plasma glucose (2H-PG) in current, ex- and never-smokers.

Methods: This meta-analysis used individual data from 16,886 men and 18,539 women without known diabetes in 12 DETECT-2 consortium studies and in the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) and Telecom studies.

Effect of early intensive multifactorial therapy compared with routine care on self-reported health status, general well-being, diabetes-specific quality of life and treatment satisfaction in screen-detected type 2 diabetes mellitus patients (ADDITION-Europe): a cluster-randomised trial.

Aims/hypothesis: The study aimed to examine the effects of intensive treatment (IT) vs routine care (RC) on patient-reported outcomes after 5 years in screen-detected diabetic patients.

Methods: In a pragmatic, cluster-randomised, parallel-group trial, 343 general practices in Denmark, Cambridge and Leicester (UK) and the Netherlands were randomised to screening for type 2 diabetes mellitus plus IT of multiple risk factors in people 40-69 years without known diabetes (n = 1,678 patients) or screening plus RC (n = 1,379 patients). Practices were randomised in a 1:1 ratio according to a computer-generated list.

Fat distribution and glucose intolerance among Greenland Inuit.

Objective: A high amount of subcutaneous fat is suggested to explain the observation of lower obesity-associated metabolic risk among Inuit than among Europeans. We examined the association between measures of obesity (visceral adipose tissue [VAT], subcutaneous adipose tissue [SAT], BMI, waist circumference [WC], and percentage of body fat) and the indices of glucose metabolism (fasting and 2-h glucose levels, insulin resistance per homeostasis model assessment [HOMA-IR], and the insulin sensitivity index [ISI0,120]) among Greenland Inuit.

Research Design And Methods: A total of 3,108 adult Inuit participated in a population-based study.

Abdominal obesity has the highest impact on metabolic profile in an overweight African population.

Aim: The aim of this study was to determine the association between different anthropometric parameters and metabolic profile in an overweight, adult, black Kenyan population.

Methods: An opportunity sample of 245 overweight adult Kenyans (body mass index (BMI) ≥ 25 kg/m(2)) was analysed. A score of metabolic profile (metabolic Z-score) was constructed on the basis of levels of plasma lipids, blood pressure, blood glucose and serum insulin.

Effect of intensive multifactorial treatment compared with routine care on aortic stiffness and central blood pressure among individuals with screen-detected type 2 diabetes: the ADDITION-Denmark study.

Objective: Diabetes is associated with increased brachial and central blood pressure and aortic stiffness. We examined the effect of intensive multifactorial treatment in general practice on indices of peripheral and central hemodynamics among patients with screen-detected diabetes.

Research Design And Methods: As part of a population-based screening and intervention study in general practice, 1,533 Danes aged 40-69 years were clinically diagnosed with screen-detected diabetes.

All-cause mortality and pharmacological treatment intensity following a high risk screening program for diabetes. A 6.6 year follow-up of the ADDITION study, Denmark.

Aim: To study all-cause mortality and pharmacological treatment intensity in relation to baseline glucose metabolism and HbA1c following high risk screening for diabetes in primary care.

Methods: Persons aged 40-69 years (N=163,185) received mailed diabetes risk questionnaires. 20,916 persons without diabetes but with high risk of diabetes were stratified by glucose metabolism (normal glucose tolerance (NGT), dysglycemia (IFG or IGT) or diabetes) and by HbA1c at screening (<6%, 6.