Correction to: Soluble CD163, adiponectin, C-reactive protein and progression of dysglycaemia in individuals at high risk of type 2 diabetes mellitus: the ADDITION-PRO cohort.

The authors have discovered a coding error in the statistical analysis syntax file used for the mixed-effect model analyses in this paper. The error has led to differences (first decimal) in the estimates for the main results.

Soluble CD163, adiponectin, C-reactive protein and progression of dysglycaemia in individuals at high risk of type 2 diabetes mellitus: the ADDITION-PRO cohort.

AIM/HYPOTHESIS: Our aim was to investigate the association between the macrophage-activation marker soluble CD163 (sCD163), adiponectin, C-reactive protein (CRP) and changes in glycaemia, insulin resistance and insulin secretion in individuals at high risk of type 2 diabetes mellitus. METHODS: This prospective study included 1014 individuals at high risk of type 2 diabetes mellitus participating in the Danish arm of the Anglo-Danish-Dutch study of Intensive Treatment In PeOple with ScreeN-detected Diabetes in Primary Care (ADDITION-Europe trial) baseline examination in 2001-2006 and follow-up examination (ADDITION-Progression [ADDITION-PRO]) in 2009-2011. Baseline serum samples were analysed for sCD163, adiponectin and CRP. The associations between sCD163, adiponectin and CRP per doubling of concentration, and changes per year in HbA1c, fasting plasma glucose, 2 h glucose, fasting insulin, HOMA-IR and HOMA-ß were assessed using a mixed-effects model. RESULTS: A doubling of sCD163 concentration was positively associated with changes in fasting insulin (ß = 1.078 per year, 95% CI 0.454, 1.702) and HOMA-ß (ß = 1.313 per year, 95% CI 0.537, 2.089), and a doubling of CRP concentration was positively associated with HbA 1c (ß = 0.004 per year, 95% CI 0.001, 0.007) and fasting insulin (ß = 0.267 per year, 95% CI 0.029, 0.504) after adjustment for age and sex. A doubling of adiponectin was inversely associated with changes in fasting glucose (ß = −0.017 per year, 95% CI −0.028, −0.005), 2 h glucose (ß = −0.063 per year, 95% CI −0.107, −0.019), fasting insulin (ß = −1.558 per year, 95% CI −2.020, −1.096), HOMA-IR (ß = −0.040 per year, 95% CI −0.062, −0.019) and HOMA-ß (ß = −1.009 per year, 95% CI −1.589, −0.429) after adjustment for age and sex. The associations were robust to adjustment for baseline waist circumference and smoking. Adjustment for CRP did not change the associations for sCD163 or adiponectin. CONCLUSIONS/INTERPRETATION: Our findings indicate that mechanisms related to inflammation, including macrophage activation and adipocyte metabolism, may play a role in changes in glucose homeostasis in individuals at high risk of type 2 diabetes mellitus.

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. Mental health was measured at baseline with the Mental Health Inventory 5 (MHI-5). Psychological distress was defined as an MHI-5 score of ≤ 68 (18.2% of the population). CVD risk factors were measured at baseline and repeated at the follow-up examination. Information on death, hospital discharge diagnosis, and antihypertensive and lipid-lowering drug treatment was obtained from national registers. Cox proportional regression was used to estimate HRs for the association between psychological distress, CVD events and all-cause mortality. Age- and sex-adjusted risk difference analyses were performed to estimate differences in meeting treatment targets. RESULTS: Patients with psychological distress had a 1.8-fold higher mortality rate (HR 1.76, 95% CI 1.23, 2.53) and a 1.7-fold higher risk of having a CVD event (HR: 1.69, 95% CI 1.05, 2.70) compared with those with an MHI-5 score of >68. Overall, psychological distress was not associated with the ability to meet treatment targets for HbA1c levels, cholesterol levels or BP, or to redeem antihypertensive or lipid-lowering drug treatment. CONCLUSIONS/INTERPRETATION: In people detected and treated early in the diabetes disease trajectory, those with psychological distress at the time of diagnosis had a higher risk of CVD events and death than those without psychological distress.

Understanding Educational and Psychosocial Factors Associated with Alcohol Use among Adolescents in Denmark; Implications for Health Literacy Interventions.

Background. Alcohol misuse is a global public health priority, with a variation in prevalence and impact between countries. Alcohol misuse in adolescence is associated with adverse psychological, social and physical health. Adolescents in Denmark have higher alcohol consumption and problematic alcohol use than adolescents in other European countries. Associations between social determinants of health (SDH), psycho-social factors and alcohol consumption are complex and influenced by national context and cultures. This study explored these associations in Danish adolescents. Method. The European School Survey Project on Alcohol and Other Drugs (ESPAD) survey collects data on alcohol and substance use among 15⁻16-year-old European students. Data contributed by Danish students to the 2011 survey were analyzed. The outcomes of interest were alcohol consumption (any, intoxication and problematic). Health literacy was not directly measured, so self-described educational performance and knowledge about alcohol were used as proxies for health literacy. Exploratory factors thus included socio-demographic, health literacy-related (knowledge about alcohol, educational performance) and psycho-social factors, as well as expectancies of the effect of alcohol (both positive and negative) and self-reported health. Univariate and multivariate logistic regression analyses were undertaken. Results. Of the 2768 adolescents who participated in the survey, 2026 (80%) consumed alcohol during the last 30 days, 978 (38%) were intoxicated at least once during the last 30 days, and 1050 (41%) experienced at least one problem because of alcohol use during the last 12 months. Multivariable analysis showed that the factors associated with higher alcohol intake were gender, poor relationships with parents, expectancies of the impact of alcohol (both positive and negative), and the influence of peers and their alcohol use. Higher school performance was related to lower alcohol consumption. Low socio-demographic status was not associated with higher alcohol consumption. Conclusions. This study confirmed the high levels of alcohol intake, intoxication, and problem drinking amongst the Danish students in the survey and the complexity of the socio-demographic, psychosocial, health literacy-related, and environmental factors associated with alcohol behaviours. Approaches to addressing the issue of alcohol use in Danish adolescents will need to be multi-factorial, including supporting students to develop alcohol-related health literacy skills to enable them to make informed choices.

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.

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. METHODS: This is a secondary, post-hoc, register-based analysis linked to a cluster randomised trial. In the 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. RESULTS: In total, 4,107 individuals were diagnosed with clinically incident diabetes in 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). 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00237549.

Relationship of HbA1c variability, absolute changes in HbA1c, and all-cause mortality in type 2 diabetes: a Danish population-based prospective observational study.

OBJECTIVE: We assessed the relationship of mortality with glycated hemoglobin (HbA1c) variability and with absolute change in HbA1c. DESIGN: A population-based prospective observational study with a median follow-up time of 6 years. METHODS: Based on a validated algorithm, 11 205 Danish individuals with type 2 diabetes during 2001-2006 were identified from public data files, with at least three HbA1c measurements: one index measure, one closing measure 22-26 months later, and one measurement in-between. Medium index HbA1c was 7.3%, median age was 63.9 years, and 48% were women. HbA1c variability was defined as the mean absolute residual around the line connecting index value with closing value. Cox proportional hazard models with restricted cubic splines were used, with all-cause mortality as the outcome. RESULTS: Variability between 0 and 0.5 HbA1c percentage point was not associated with mortality, but for index HbA1c ≤8% (64 mmol/mol), a variability above 0.5 was associated with increased mortality (HR of 1 HbA1c percentage point variability was 1.3 (95% CI 1.1 to 1.5) for index HbA1c 6.6-7.4%). For index HbA1c≤8%, mortality increased when HbA1c declined, but was stable when HbA1c rose. For index HbA1c>8%, change in HbA1c was associated with mortality, with the lowest mortality for greatest decline (HR=0.9 (95% CI 0.80 to 0.98) for a 2-percentage point decrease). CONCLUSIONS: For individuals with an index HbA1c below 8%, both high HbA1c variability and a decline in HbA1c were associated with increased mortality. For individuals with index HbA1c above 8%, change in HbA1c was associated with mortality, whereas variability was not.

Socioeconomic position, type 2 diabetes and long-term risk of death.

BACKGROUND: Both socioeconomic position (SEP) and type 2 diabetes have previously been found to be associated with mortality; however, little is known about the association between SEP, type 2 diabetes and long-term mortality when comorbidity is taken into account. METHODS: We conducted a population-based cohort study of all Danish citizens aged 40-69 years with no history of diabetes during 2001-2006 (N=2,330,206). The cohort was identified using nationwide registers, and it was followed for up to 11 years (mean follow-up was 9.5 years (SD: 2.6)). We estimated the age-standardised mortality rate (MR) and performed Poisson regression to estimate the mortality-rate-ratio (MRR) by educational level, income and cohabiting status among people with and without type 2 diabetes. RESULTS: We followed 2,330,206 people for 22,971,026 person-years at risk and identified 139,681 individuals with type 2 diabetes. In total, 195,661 people died during the study period; 19,959 of these had type 2 diabetes. The age-standardised MR increased with decreasing SEP both for people with and without diabetes. Type 2 diabetes and SEP both had a strong impact on the overall mortality; the combined effect of type 2 diabetes and SEP on mortality was additive rather than multiplicative. Compared to women without diabetes and in the highest income quintile, the MRR's were 2.8 (95%CI 2.6, 3.0) higher for women with type 2 diabetes in the lowest income quintile, while diabetes alone increased the risk of mortality 2.0 (95%CI 1.9, 2.2) times and being in the lowest income quintile without diabetes 1.8 (95%CI 1.7,1.9) times after adjusting for comorbidity. For men, the MRR's were 2.7 (95%CI 2.5,2.9), 1.9 (95%CI 1.8,2.0) and 1.8 (95%CI 1.8,1.9), respectively. CONCLUSION: Both Type 2 diabetes and SEP were associated with the overall mortality. The relation between type 2 diabetes, SEP, and all-cause mortality was only partly explained by comorbidity.

Survival after colorectal cancer in patients with Crohn's disease: A nationwide population-based Danish follow-up study.

BACKGROUND AND AIMS: Patients with Crohn's disease (CD) are at increased risk of colorectal cancer (CRC), but little is known about the impact of CD on CRC prognosis. Based on nationwide population-based registries, we compared survival among CRC patients with CD and CRC patients without CD. METHODS: We used the Danish Cancer Registry and the Danish Hospital Discharge Registry to identify all patients diagnosed with CRC, with and without CD, in Denmark between 1977 and 1999. We ascertained the stage distribution at the time of CRC diagnosis and 1- and 5-yr survival both for patients with Crohn-associated CRC and patients with non-Crohn CRC. Cox regression was used to compute hazard ratios (HRs), adjusting for gender, age, calendar year, and stage. RESULTS: We identified 100 CRC patients with CD and 71,438 CRC patients without CD. At the time of diagnosis, patients with CD were younger, but stage distributions were similar in the two groups. The overall HR for CRC with CD compared to CRC without CD was 1.82 (95% CI 1.36-2.43) after 1 yr of follow-up, and 1.57 (95% CI 1.24-1.99) after 5 yr of follow-up. Subanalyses showed that the effect of CD on CRC survival was more pronounced in the youngest patients (0-59 yr), in men, and in patients whose tumors had regional spread. CONCLUSIONS: We found that CD worsens the prognosis of CRC, particularly CRC with regional spread.

Survival after colorectal cancer in patients with ulcerative colitis: a nationwide population-based Danish study.

OBJECTIVES: Patients with ulcerative colitis (UC) are at increased risk of colorectal cancer (CRC). Little is known about how UC impacts CRC prognosis. In a nationwide population-based study we examined the CRC prognosis in UC patients compared to CRC patients without UC. METHODS: From the Danish Cancer Registry and the Danish Hospital Discharge Registry, we identified all CRC patients and all patients with UC in Denmark from 1977 to 1999. We compared survival in 279 UC patients with CRC to all other 71,259 CRC patients and computed mortality rate ratios (MRR). We also compared stage distribution at time of cancer diagnosis. RESULTS: The mean age at time of CRC diagnosis was 62.6 yr in UC patients and 71.2 yr in patients without UC. Cancer stage distribution for localized cancer, regional spread, and distant metastasis were 46.6%, 30.1%, and 16.5% in UC patients compared to 44.0%, 28.3%, and 19.4% in CRC patients without UC. The overall MRR for UC patients with CRC compared with all other CRC patients were 1.24 (95% CI 1.02-1.51) in the first year and 1.17 (95% CI 1.01-1.36) after 5 yr of follow-up. CONCLUSION: UC patients with CRC have a stage distribution similar to patients with CRC without UC. The prognosis of CRC is poorer for UC patients than for patients without UC.

Aspirin use during early pregnancy and the risk of congenital abnormalities: a population-based case-control study.

It is still controversial whether aspirin use during pregnancy increases the risk of certain congenital abnormalities (in particular, neural tube defects, gastroschisis, and cleft lip +/- palate). We examined the risk of selected congenital abnormalities in a large case-control dataset from Hungary and found no increased risk of such congenital abnormalities.

A population-based study of maternal use of amoxicillin and pregnancy outcome in Denmark.

AIMS: Amoxicillin is a widely used penicillin, but data on its safety in pregnancy are limited. We examined the association between amoxicillin exposure during pregnancy and birth weight, preterm delivery, congenital malformations, perinatal death, and spontaneous abortion. METHODS: We identified all primiparous women with a live birth, or a stillbirth after the 28th gestational week, from 1 January 1991-31 December 2000 in the County of North Jutland, Denmark. Data on prescriptions for amoxicillin and outcome were obtained from population-based registries. Using a follow-up and a case-control design, we compared pregnancy outcomes between women who had been prescribed amoxicillin during pregnancy and those who had not, adjusting for available potentially confounding factors. RESULTS: We identified 401 primiparous women who redeemed a prescription for amoxicillin during their pregnancy. The control group consisted of 10 237 primiparous women who did not redeem any prescriptions from 3 months before pregnancy until the end of pregnancy. The adjusted mean birth weight of children born to amoxicillin-exposed mothers was 57 g [95% confidence interval (CI) 9, 105] higher than that of children born to controls. Odds ratios among amoxicillin-exposed relative to controls were: low birth weight 0.63 (95% CI 0.26, 1.53), preterm delivery 0.77 (95% CI 0.49, 1.21), congenital malformation 1.16 (95% CI 0.54, 2.50), and spontaneous abortion 0.89 (95% CI 0.66, 1.18). We did not observe any cases of perinatal death in the amoxicillin-exposed women. CONCLUSIONS: We did not find any increased risk of adverse pregnancy outcome associated with amoxicillin exposure during pregnancy, but additional studies are warranted.