Search

Christen Lykkegaard Andersen,1,2 Volkert Dirk Siersma,1 Willy Karlslund,1 Hans Carl Hasselbalch,2 Peter Felding,3 Ole Weis Bjerrum,4 Niels de Fine Olivarius11The Research Unit for General Practice and Section of General Practice, Department of Public Health, University of Copenhagen, 2Department of Hematology, Roskilde University Hospital, 3The Elective Laboratory of the Capital Region, 4Department of Hematology, Copenhagen University Hospital, Copenhagen, DenmarkBackground: The differential blood cell count provides valuable information about a person's state of health. Together with a variety of biochemical variables, these analyses describe important physiological and pathophysiological relations. There is a need for research databases to explore associations between these parameters, concurrent comorbidities, and future disease outcomes.Methods and results: The Copenhagen General Practitioners’ Laboratory is the only laboratory serving general practitioners in the Copenhagen area, covering approximately 1.2 million inhabitants. The Copenhagen General Practitioners’ Laboratory has registered all analytical results since July 1, 2000. The Copenhagen Primary Care Differential Count database contains all differential blood cell count results (n=1,308,022) from July 1, 2000 to January 25, 2010 requested by general practitioners, along with results from analysis of various other blood components. This data set is merged with detailed data at a person level from The Danish Cancer Registry, The Danish National Patient Register, The Danish Civil Registration System, and The Danish Register of Causes of Death.Conclusion: This paper reviews methodological issues behind the construction of the Copenhagen Primary Care Differential Count database as well as the distribution of characteristics of the population it covers and the variables that are recorded. Finally, it gives examples of its use as an inspiration to peers for collaboration.Keywords: differential leukocyte count, research, nationwide health registers

Abstract: Aims: To investigate whether long-term mortality or clinical outcomes differed between patients diagnosed with type 2 diabetes mellitus and presenting with HbA1c within or above normal range at time of diagnosis. Methods: Data were from a population-based sample of 1136 individuals with newly diagnosed type 2 diabetes mellitus. The diagnosis was confirmed with a single fasting whole blood/plasma glucose ≥7.0/8.0mmol/l. The median time from day of diagnosis until end of follow up was 18.8years. Patients were grouped according to normal HbA1c and elevated HbA1c at diagnosis. The effect of elevated HbA1c on a number of clinical outcomes and all-cause mortality was assessed in Cox regression models. Results: At diagnosis, 97 patients (8.5%) had an HbA1c level within normal range. Age (mean (SD)) at diagnosis was 64.5 (11.5) years. Both unadjusted and adjusted hazard ratios for the effect of HbA1c on mortality and other outcomes were not statistically significant. Conclusions: Patients who are diagnosed with type 2 diabetes mellitus by means of elevated fasting whole blood/plasma glucose but have HbA1c within reference range at diagnosis do not seem to have a relatively benign long-term clinical course. Therefore new diagnostic procedures should preferably be able to identify these individuals. [Copyright &y& Elsevier]

OBJECTIVE: Diabetic men and women differ in lifestyle and attitudes toward diabetes and may benefit differently from interventions to improve glycemic control. We explored the relation between HbA1c (A1C), sex, treatment allocation, and their interactions with behavioral and attitudinal characteristics in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Six years after their diabetes diagnosis, a population-based sample of 874 primary care patients cluster-randomized to receive structured personal care or routine care reported lifestyle, medication, social support, diabetes-related consultations, and attitudes toward diabetes. Multivariate analyses were applied, split by sex. RESULTS: A marked intervention effect on A1C was confined to the structured personal care women. The median A1C was 8.4% in structured personal care women and 9.2% in routine care women (P < 0.0001) and 8.5% in structured personal care men and 8.9% in routine care men (P = 0.052). Routine care women had a 1.10 times higher A1C than structured personal care women, (P < 0.0001, adjusted analysis). Structured personal care women had relatively more consultations than routine care women, but neither number of consultations nor other covariates helped to explain the sex difference in A1C. Irrespective of treatment allocation, women had more adaptive attitudes toward diabetes but lacked support compared with men. CONCLUSIONS: In this study, the observed effect of structured personal care on A1C was present only among women, possibly because they were more inclined to comply with regular follow-up and had a tendency to have a more adaptive attitude toward diabetes. [ABSTRACT FROM AUTHOR]

Haemoglobin A1c (HbA1c) is now the key component for monitoring glycaemic control in diabetes mellitus (DM), especially for its close relation to diabetes complications. However, treatment goals in terms of HbA1c concentrations have been difficult to define and compare because of lack of international standardization and lack of common reference values of HbA1c concentrations. The aims of our study were to document our HbA1c analysis and make it traceable to international reference laboratories with the aid of current reference preparations, to establish a reference interval based on a low-risk population, and to evaluate the analytical quality specifications, which could meet clinical needs. The s(analytical) of our method (Tosoh) was < 0.3 HbA1c%, and the mean bias as estimated from Dr Cas Weykamp's reference preparation was below 0.3 HbA1c. This was the same as that for participating Scandinavian and international reference laboratories. The concentrations were made traceable to results from the Diabetes Control and Complication Trial (DCCT) and the UK Prospective Diabetes Study (UKPDS). Risk groups for DM were ruled out from a randomly selected population in Vejle County, which isolated a "low-risk" reference population. The 97.5 reference interval in this population (N=430) was from 5.07 HbA1c% (95% CI: 5.02-5.11) to 6.24 HbA1c% (95% CI: 6.19-6.30), and the 99.9 centile was 6.62 HbA1c% (95%) CI 6.55-6.71). Body mass index, age and gender contributed marginally to the level of HbA1c concentrations. A 10% delta risk estimate of DM complications was detectable with a probability of Type I error of 40%, while adoption of a significance level of 95% and consideration to biological variation needed a risk difference of at least 33% to be detected. The critical difference was 11% for changes in either direction at s(analytical) < or = 0.2 HbA1c% and a s(biological) of 0.3 HbA1c%. Based on criteria for sharing common reference intervals and clinical utility, we accepted that the bias and s(analytical) should both be < 0.3 HbA1c% at the level of 7.0 HbA1c%. [ABSTRACT FROM AUTHOR]

According to new proposals from the American Diabetes Association (ADA) and WHO, venous peripheral plasma is the preferred system for measuring glucose for diagnosing diabetes mellitus. Owing to the instability of glucose in plasma after blood sampling, strict well-defined and standardized preanalytical conditions are essential to ensure that glucose concentration measured in plasma reflects real blood glucose in the patient. This is in contrast to the capillary whole blood measurements, which are easy to perform and well established. We investigated whether it is possible to perform analysis on capillary whole blood but express the results as plasma glucose values and hence obtain comparable results and the same predictive values for diagnosis in the individual patient? The conclusion of our investigations is that these two systems are not interchangeable and that conversion should not be done for diagnostic purposes where plasma determinations are recommended. [ABSTRACT FROM AUTHOR]

The new diagnostic criteria for type 2 diabetes from the American Diabetes Association (ADA) and World Health Organization (WHO) recommend measurements on plasma and a lowering of the glucose threshold for diabetes by 0.8 mmol/L. This narrows the distance between the upper end of the reference limit and the discriminatory level to a degree where analytical quality becomes critical. The quality demands for the preanalytical and analytical phase and their consequences on diagnostic performance have to be established in the new technical system, measuring in plasma rather than in capillary whole blood. Because of the instability of glucose in blood samples it is necessary to clarify the influence of different preanalytical and analytical factors on the number of false-positive and false-negative classifications. Thus the aim of the present study was to find optimal conditions for sampling, additives, storage, transport and analysis of plasma glucose combining feasibility with an analytical bias close to zero and a within-imprecision around 1%. We have documented the analytical performance of the method itself and its traceability to an international standard. The preanalytical conditions, such as influence of antiglycolytic agent NaF, conditions for plasma separation, storage temperature and storage time before and after plasma separation were investigated. In conclusion, we recommend that blood should be drawn in tubes containing heparin and NaF and kept on ice water for not more than 1 h until centrifugation at minimum 1000 x g for 10 min. The plasma is then stable for at least 48 h at room temperature. [ABSTRACT FROM AUTHOR]

The aim of the study was to establish a reference interval of fasting venous plasma glucose (FPG) from healthy individuals. A prospective modified cross-sectional population-based study was made with random selection of 2100 persons in age-stratified groups > or = 18 years identified from the local Personal Identification Register. The invitation was accepted by 755 persons, of which 726 aged 18-92 years were eligible. They did not have a diabetes diagnosis, were non-pregnant and capable of fasting for 8 h. All participants filled in a questionnaire on medical risk factors. Blood for the FPG and haemoglobin Alc (HbAlc) measurements was drawn in accordance with a standardized procedure. A total of 302 participants carried diabetes risk indicators and were ruled out. The FPG concentrations in the remaining low-risk population (n=424) was ln Gaussian distributed. The FPG 97.50 centile in this group was 6.4 mmol/L (95% CI: 6.3-6.5 mmol/L), in contrast to the WHO and ADA theoretical limit of 6.1 mmol/L. Their diagnostic decision limit of 7.0 mmol/L FPG corresponded to the 99.86 centile of the FPG reference distribution (95% CI: 6.8-7.1). Subclassification of the reference population showed increasing FPG with increasing BMI and age and was higher in men than in women. The study determined the FPG 95% interfractile reference interval in a healthy population. The interval in glucose concentration between the 97.5 centile of the reference interval and the ADA-WHO diagnostic limit is very narrow. The clinical application of the diagnostic discriminator and the interpretation of the WHO-ADA grey zone from 6.1 to 7.0 mmol/L FPG may consequently be biased because of poorly defined limits and influence from BMI, age and gender. [ABSTRACT FROM AUTHOR]

Presents summaries of symposiums on Nordic reference intervals in clinical chemistry in Scandinavia. Elements of analytical quality; Goal to produce common Nordic reference intervals; Design of the Nordic Reference Intervals Project.

Objective: We analyzed data from a cohort of 1,381 newly diagnosed type 2 diabetic patients to test the hypothesis that urinary markers of nucleic acid oxidation are independent predictors of mortality.Research Design and Methods: We examined the relationship between urinary excretion of markers of DNA oxidation (8-oxo-7,8-dihydro-2'-deoxyguanosine [8-oxodG]) and RNA oxidation (8-oxo-7,8-dihydroguanosine [8-oxoGuo]) and long-term mortality using Cox proportional hazards regression.Results: After multivariate adjustment, the hazard ratios for all-cause and diabetes-related mortality of patients with 8-oxoGuo levels in the highest quartile compared with those in the lowest quartile were 1.44 (1.12-1.85) and 1.54 (1.13-2.10), respectively. Conversely, no significant associations between 8-oxodG and mortality were found in the adjusted analyses.Conclusions: Urinary excretion of the RNA oxidation marker 8-oxoGuo measured shortly after diagnosis of type 2 diabetes predicts long-term mortality independently of conventional risk factors. This finding suggests that 8-oxoGuo could serve as a new clinical biomarker in diabetes. [ABSTRACT FROM AUTHOR]

Abstract Background Many diabetic patients fear visual loss as the worst consequence of diabetes. In most studies the main eye pathology is assigned as the cause of visual impairment. This study analysed a broad range of possible ocular and non-ocular predictors of visual impairment prospectively in patients newly diagnosed with clinical type 2 diabetes. Methods Data were from a population-based cohort of 1,241 persons newly diagnosed with clinical, often symptomatic type 2 diabetes aged ≥ 40 years. After 6 years, 807 patients were followed up. Standard eye examinations were done by practising ophthalmologists. Results At diabetes diagnosis median age was 65.5 years. Over 6 years, the prevalence of blindness (visual acuity of best seeing eye ≤ 0.1) rose from 0.9% (11/1,241) to 2.4% (19/807) and the prevalence of moderate visual impairment (> 0.1; < 0.5) rose from 5.4% (67/1,241) to 6.7% (54/807). The incidence (95% confidence interval) of blindness was 40.2 (25.3-63.8) per 10,000 patient-years. Baseline predictors of level of visual acuity (age, age-related macular degeneration (AMD), cataract, living alone, low self-rated health, and sedentary life-style) and speed of continued visual loss (age, AMD, diabetic retinopathy (DR), cataract, living alone, and high fasting triglycerides) were identified. Conclusions In a comprehensive assessment of predictors of visual impairment, even in a health care system allowing self-referral to free eye examinations, treatable eye pathologies such as DR and cataract emerge together with age as the most notable predictors of continued visual loss after diabetes diagnosis. Our results underline the importance of eliminating barriers to efficient eye care by increasing patients' and primary care practitioners' awareness of the necessity of regular eye examinations and timely surgical treatment.

Abstract Background At diabetes diagnosis major decisions about life-style changes and treatments are made based on characteristics measured shortly after diagnosis. The predictive value for mortality of these early characteristics is widely unknown. We examined the predictive value of patient characteristics measured shortly after diabetes diagnosis for 5-year all-cause and cardiovascular mortality with special reference to self-rated general health. Methods Data were from a population-based sample of 1,323 persons newly diagnosed with clinical diabetes and aged 40 years or over. Possible predictors of mortality were investigated in Cox regression models. Results Multivariately patients who rated their health less than excellent experienced increased all-cause and cardiovascular mortality. These end-points also increased with sedentary life-style, relatively young age at diagnosis and presence of cardiovascular disease (CVD) at diagnosis. Further predictors of all-cause mortality were male sex, low body mass index and cancer, while cardiovascular mortality increased with urinary albumin concentration. Conclusions We found that patients who rated their health as less than excellent had increased 5-year mortality, similar to that of patients with prevalent CVD, even when biochemical, clinical and life-style variables were controlled for. This finding could motivate doctors to discuss perceptions of health with newly diagnosed diabetic patients and be attentive to patients with suboptimal health ratings. Our findings also confirm that life-style changes and optimizing treatment are particularly relevant for relatively young and inactive patients and those who already have CVD or (micro)albuminuria at the time of diabetes diagnosis.

Abstract Background Studies have shown that type 2 diabetic patients have higher all-cause mortality than people without diabetes, but it is less clear how diabetes affects mortality in elderly patients and to what degree mortality differs between diabetic men and women. The aim of the present study is to investigate the age- and sex-specific all-cause mortality pattern in patients with type 2 diabetes in comparison with the Danish background population. Methods Population-based cohort study of 1323 patients, diagnosed with clinical type 2 diabetes in 1989-92 and followed for 16 years. Median (interquartile range) age at diagnosis was 65.3 (55.8-73.6) years. The age- and sex-specific hazard rates were estimated for the cohort using the life table method and compared with the expected hazard rates calculated with Danish register data from the general population. Results In comparison with the general population, diabetic patients had a 1.5-2.5 fold higher risk of dying depending on age. The over-mortality was higher for men than for women. It decreased with age in both sexes, and among patients over 80 years at diagnosis the difference between the observed and the expected survival was small. Conclusion We found an excess mortality of type 2 diabetic patients compared with the background population in all age groups. The excess mortality was most pronounced in men and in young patients.

Background: Survival from many cancer types is steadily increasing, and as a result, a growing number of cancer patients will live with other chronic diseases, of which diabetes is one of the most prevalent. This study aims to describe the impact of cancer on health outcomes in patients with type 2 diabetes and to compare the effectiveness of a multifactorial intervention in diabetes patients with and without cancer., Methods: The randomized controlled trial Diabetes Care in General Practice (DCGP) included 1381 patients newly diagnosed with type 2 diabetes. Patients were randomized to either six years of structured personal diabetes care or routine care. In a post hoc analysis, we followed patients for 19 years in Danish national registries for the occurrence of diabetes-related outcomes. We used Cox regression models to estimate hazard ratios for outcomes., Results: At diagnosis 48 patients had cancer, and 243 patients were diagnosed with cancer during follow up. Patients with diabetes and cancer had excess all-cause mortality (HR 3.33; 95%CI 2.72-4.06), as well as an increased incidence of myocardial infarction (HR 1.76; 95%CI 1.29-2.39) and any diabetes-related outcome (HR 1.36; 95%CI 1.07-1.71). The intervention reduced the risk of both these endpoints in patients without cancer. Furthermore, there was no statistically significant difference in the effectiveness of the intervention among patients with and without cancer., Conclusions: Diabetes patients with cancer had an increased risk of myocardial infarction and any diabetes-related outcome. The observed positive effect of structured personal diabetes care on clinical outcomes did not differ between patients with and without cancer. Attention to and prevention of diabetes complications in patients with both type 2 diabetes and cancer is warranted., Trial Registration: ClinicalTrials.gov NCT01074762 (February 24, 2010).

Aims: The urinary marker of RNA oxidation, 8‑oxo‑7,8‑dihydroguanosine (8-oxoGuo), but not the corresponding marker of DNA oxidation, 8‑oxo‑7,8‑dihydro‑2'‑deoxyguanosine (8-oxodG), is a prognostic biomarker in patients with type 2 diabetes (T2D). The aim of the present study was to investigate the effect of structured personal care (individualized multifactorial treatment) versus standard care on RNA oxidation level in patients with T2D and to assess if the effect of structured personal care on all-cause and diabetes-related mortality was modified by RNA oxidation level., Methods: Urine samples were analyzed for 8-oxoGuo/8-oxodG from 1381 newly diagnosed T2D patients from the cluster randomized trial Diabetes Care in General Practice cohort, and 970 patients were reexamined after six years of intervention., Results: The yearly variation in RNA oxidation levels were not significantly different between the structured personal care group and standard care group. The effect of treatment on all-cause and diabetes-related mortality was not modified by the level of RNA oxidation. No changes in DNA oxidation were seen., Conclusions: Structured personal care does not influence RNA oxidation level nor is it better for patients with high RNA oxidation level. Thus, structured personal care may not impact the disease-related aspects identified by RNA oxidation level in T2D patients., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Measurement of B-type natriuretic peptide (BNP) in plasma may have its greatest potential in primary care, as general practitioners need to rapidly identify patients who warrant further medical review. The aim of the present study was to examine the prognostic information of BNP measurement on all-cause mortality in a large Danish primary care cohort., Methods: This study covered a cohort of Danish primary care patients (n = 61665) with a median follow-up period of 4.36 years (interquartile range, 2.29-6.62 years). BNP was measured in plasma using the ADVIA Centaur/CentaurXP platform. The association of BNP with mortality was assessed with a hazard ratio for all-cause mortality from a multivariable Cox proportional hazards model., Results: Kaplan-Meier curves showed decreasing survival probability with increasing BNP ( P < 0.001). Each doubling of BNP increased mortality by 32.3% (95% CI, 30.8-33.8) when adjusted for sex and age, and by 25.3% (95% CI, 23.8-26.8) when further adjusted for Charlson comorbidity index, hemoglobin, estimated glomerular filtration rate, glycohemoglobin, and thyroid-stimulating hormone. Also, in a subcohort (n = 10824) without biochemical signs of severe kidney failure, anemia, polycythemia, hypothyroidism or hyperthyroidism, or dysregulated diabetes, each doubling of BNP increased mortality by 28.6% (95% CI, 22.8-34.7)., Conclusions: Our results show that even in a primary care population, BNP measurements contain prognostic information regarding all-cause mortality., (© 2018 American Association for Clinical Chemistry.)

Aims: To investigate, in a large population in primary care, the relationship between fasting plasma glucose and HbA 1c measurements, as well as the clinical implications of anaemia or chronic kidney disease for the interpretation of HbA 1c values., Methods: From a primary care resource, we examined HbA 1c and fasting plasma glucose as well as haemoglobin and estimated GFR. We stratified observations by chronic kidney disease stage and anaemia level. The estimation of the mean fasting plasma glucose level from HbA 1c alone, and from HbA 1c , haemoglobin and estimated GFR, respectively, was evaluated., Results: In 198 346 individuals, the fasting plasma glucose-HbA 1c relationship mimicked the regression described in the A1c-Derived Average Glucose (ADAG) study, which was based on average capillary and interstitial glucose. The fasting plasma glucose-HbA 1c relationship was unaffected in mild to moderate chronic kidney disease and in mild to moderate anaemia. The correlation changed only in severe hyperglycaemia and concurrent severe anaemia or when estimated GFR was <45 ml/min/1.73m², so that glucose concentration was underestimated by HbA 1c in anaemia and overestimated in chronic kidney disease. The prevalence of estimated GFR <30 ml/min/1.73m² was 0.82%, while the prevalence of haemoglobin <81 g/l (5.0 mmol/l) was 0.11%., Conclusions: The relationship between fasting plasma glucose and HbA 1c mimics that of the people with diabetes included in the ADAG study. Mild to moderate anaemia and CKD do not have a significant impact on the interpretation of HbA 1c as a marker of retrograde glycaemia. Hence, it seems justified to use HbA 1c without adjustment in primary care., (© 2018 Diabetes UK.)

Aims: To explore the effect of structured personal care on diabetes symptoms and self-rated health over 14 years after diabetes diagnosis while patients are gradually diagnosed with other chronic conditions (multimorbidity)., Methods: Post hoc analysis of the Danish randomized controlled trial Diabetes Care in General Practice including 1381 patients newly diagnosed with type 2 diabetes. The effect of structured personal care compared with routine care on diabetes symptoms and self-rated health was analysed 6 and 14 years after diagnosis with a generalized multilevel Rasch model., Results: Structured personal care reduced the overall likelihood of reporting diabetes symptoms at the end of the intervention (OR 0.79; 95% CI: 0.64-0.97), but this effect was not explained by glycaemic control or multimorbidity. There was no effect of the intervention on diabetes symptoms after 14 years or on self-rated health after 6 years or 14 years., Conclusions: Structured personal care had a beneficial effect on diabetes symptoms 6 years after diagnosis, but not on self-rated health at either follow up point. To optimally manage patients over time it is important to supplement clinical information by information provided by the patients., (Copyright © 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Background: We investigated how four aspects of socio-demography influence the effectiveness of an intervention with structured personal diabetes care on long-term outcomes., Methods: The Diabetes Care in General Practice (DCGP) study is a cluster-randomized trial involving a population-based sample of 1381 patients with newly diagnosed type 2-diabetes mellitus. We investigated how education, employment, cohabitation status and residence influenced the effectiveness of 6 years of intervention with structured personal diabetes care, resembling present day recommendations. Outcomes were incidence of any diabetes-related endpoint and death during 19 years after diagnosis, and cardiovascular risk factors, behaviour, attitudes and process-of-care variables 6 years after diagnosis., Results: Structured personal care reduced the risk of any diabetes-related endpoint and the effect of the intervention was modified by geographical area (interaction p = 0.034) with HR of 0.71 (95%CI: 0.60-0.85) and of 1.07 (95%CI: 0.77-1.48), for patients in urban and rural areas, respectively. Otherwise, there was no effect modification of education, employment and civil status on the intervention for the final endpoints. There were no noticeable socio-demographic differences in the effect of the intervention on cardiovascular risk factors, behaviour, attitudes, and process-of-care., Conclusion: Structured personal care reduced the aggregate outcome of any diabetes-related endpoint and independent of socio-demographic factors similar effect on cardiovascular risk factors, behaviour, attitudes and process of care, but the intervention did not change the existing inequity in mortality and morbidity. Residence modified the uptake of the intervention with patients living in urban areas having more to gain of the intervention than rural patients, further investigations is warranted., Trial Registration: ClinicalTrials.gov registration no. NCT01074762 (February 24, 2010).

Urinary albumin is an important biomarker used to identify high risk patients with diabetes, but there is a need for new biomarkers that alone or in combination with urinary albumin could give an even better prediction of clinical patient outcomes. One promising biomarker is 8-oxo-7,8-dihydroguanosine (8-oxoGuo) that represents intracellular oxidative stress. We investigated the ability of microalbuminuria (MA) and urinary 8-oxoGuo, alone and in combination, to predict mortality and cardiovascular disease (CVD) in patients with type 2 diabetes. We used data from 1381 newly diagnosed diabetes patients, and urinary albumin and 8-oxoGuo were assessed in morning urine collected at the time of diabetes diagnosis and at a follow-up visit 6 years later. Associations between the urinary markers and mortality and CVD were assessed in Cox proportional hazards regression models. Test performance was assessed using sensitivity, specificity, positive predictive value and negative predictive value for 10-year mortality and 10-year incidence of CVD. Both 8-oxoGuo and urinary albumin were statistically significantly associated with all-cause mortality at diagnosis as well as at 6-year follow-up. At diagnosis only urinary albumin was associated with CVD. In contrast, only 8-oxoGuo was associated with CVD at 6-year follow-up. When investigating test performance, we found that by combining information from MA and 8-oxoGuo the ability to correctly identify patients at risk could be improved. The findings suggest that measurement of urinary 8-oxoGuo provides additional information about risk to that obtained from urinary albumin, and that the combined use of 8-oxoGuo and urinary albumin could be useful for a better identification of patients at risk of CVD and death., (Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims/hypothesis: The aim of this study was to assess gender differences in mortality and morbidity during 13 follow-up years after 6 years of structured personal care in patients with type 2 diabetes mellitus., Methods: In the Diabetes Care in General Practice (DCGP) multicentre, cluster-randomised, controlled trial (ClinicalTrials.gov registration no. NCT01074762), 1,381 patients newly diagnosed with type 2 diabetes were randomised to receive 6 years of either structured personal care or routine care. The intervention included regular follow-up, individualised goal setting and continuing medical education of general practitioners participating in the intervention. Patients were re-examined at the end of intervention. This observational analysis followed 970 patients for 13 years thereafter using national registries. Outcomes were all-cause mortality, incidence of diabetes-related death, any diabetes-related endpoint, myocardial infarction, stroke, peripheral vascular disease and microvascular disease., Results: In women, but not men, a lower HR for structured personal care vs routine care emerged for any diabetes-related endpoint (0.65, p = 0.004, adjusted; 73.4 vs 107.7 events per 1,000 patient-years), diabetes-related death (0.70, p = 0.031; 34.6 vs 45.7), all-cause mortality (0.74, p = 0.028; 55.5 vs 68.5) and stroke (0.59, p = 0.038; 15.6 vs 28.9). This effect was different between men and women for diabetes-related death (interaction p = 0.015) and all-cause mortality (interaction p = 0.005)., Conclusions/interpretation: Compared with routine care, structured personal diabetes care reduced all-cause mortality and diabetes-related death in women but not in men. This gender difference was also observed for any diabetes-related outcome and stroke but was not statistically significant after extensive multivariate adjustment. These observational results from a post hoc analysis of a randomised controlled trial cannot be explained by intermediate outcomes like HbA1c alone, but involves complex social and cultural issues of gender. There is a need to rethink treatment schemes for both men and women to gain benefit from intensified treatment efforts.

Objective: This study examined the influence of weight loss on long-term morbidity and mortality in overweight (BMI≥25 kg/m2) patients with type 2 diabetes, and tested the hypothesis that therapeutic intentional weight loss supervised by a medical doctor prolongs life and reduces the risk for cardiovascular disease in these patients., Methods: This is a 19 year cohort study of patients in the intervention arm of the randomized clinical trial Diabetes Care in General Practice. Weight and prospective intentions for weight loss were monitored every third month for six years in 761 consecutive patients (≥40 years) newly diagnosed with diabetes in general practices throughout Denmark in 1989-92. Multivariable Cox regression was used to estimate the association between weight change during the monitoring period (year 0 to 6) and the outcomes during the succeeding 13 years (year 6 to 19) in 444 patients who were overweight at diagnosis and alive at the end of the monitoring period (year 6). The analysis was adjusted for age, sex, education, BMI at diagnosis, change in smoking, change in physical activity, change in medication, and the Charlson comorbidity 6-year score. Outcomes were from national registers., Results: Overall, weight loss regardless of intention was an independent risk factor for increased all-cause mortality (P<0.01). The adjusted hazard ratio for all-cause mortality, cardiovascular mortality, and cardiovascular morbidity attributable to an intentional weight loss of 1 kg/year was 1.20 (95%CI 0.97-1.50, P = 0.10), 1.26 (0.93-1.72, P = 0.14), and 1.06 (0.79-1.42, P = 0.71), respectively. Limiting the analysis to include only those patients who survived the first 2 years after the monitoring period did not substantially change these estimates. A non-linear spline estimate indicated a V-like association between weight change and all-cause mortality, suggesting the best prognosis for those who maintained their weight., Conclusions: In this population-based cohort of overweight patients with type 2 diabetes, successful therapeutic intentional weight loss, supervised by a doctor over six years, was not associated with reduced all-cause mortality or cardiovascular morbidity/mortality during the succeeding 13 years.

Objective: To assess the effectiveness of an intervention in Type 2 diabetic patients with concurrent psychiatric illness (PI) and compare this with the effectiveness in patients without PI., Method: In the Diabetes Care in General Practice trial, 1381 patients newly diagnosed with Type 2 diabetes were randomized to 6 years of structured personal diabetes care or routine diabetes care (ClinicalTrials.gov NCT01074762). In this observational post-hoc analysis, the effectiveness of the intervention for diabetes in 179 patients with concurrent PI was analyzed., Results: During the 19-year follow-up period, patients with PI in the structured personal care group experienced a lower risk for all-cause mortality [105.3 vs. 140.4 events per 1000 patient-years; hazard ratio (HR): 0.63, P=0.023, multivariably adjusted], diabetes-related death (66.0 vs. 95.1; HR: 0.57, P=0.015), any diabetes-related endpoint (169.5 vs. 417.5; HR: 0.47, P=0.0009) and myocardial infarction (54.1 vs. 104.4; HR: 0.48, P=0.013), compared to patients with PI in the routine care group. This translates into a number needed to treat over 10 years of three or lower for these outcomes., Conclusion: These findings suggest that in primary care, structured diabetes care allowing for individualization was highly effective among diabetic patients with co-occurring PI., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: To examine the impact of smoking cessation on body weight compared with normal long-term weight development., Methods: Of 1970 adults (20-69 years) in a rural town in Denmark invited to take part in the study in 1998-2000, 1374 (70%) participated. After 9 years, 1121 participated in the follow-up study. Weight changes were compared using multivariable regression models., Results: The mean baseline weight of never-smokers was 76.4 kg (SD 16.0). The adjusted weight of smokers and ex-smokers differed by -4.2 kg (95% CI: -5.9, -2.6), and -0.7 kg (95% CI: -2.5, 1.1), respectively. The adjusted weight gain rate (kg/year) of never-smokers, smokers, and ex-smokers was 0.213, 0.127, and 0.105, respectively. The absolute post cessation weight gain (PCWG) was 5.0 kg (SD 7.0), and the adjusted PCWG was 2.8 kg (95% CI: 1.7, 3.9) compared with never-smokers, and 3.5 kg (95% CI: 2.3, 4.8) compared with smokers. The follow-up weight did not differ between quitters and never-smokers (0.1 kg; 95% CI: -2.4, 2.6)., Conclusion: Smokers weigh less than never-smokers. By quitting, they gain weight and end up weighing the same as comparable never-smokers. Weight gain rates differ by smoking status. Consequently, PCWG depends on the length of follow-up. Our graphical model indicates that smoking cessation results in a return to normal weight development., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: Standard portions or substitution of missing portion sizes with medians may generate bias when quantifying the dietary intake from FFQ. The present study compared four different methods to include portion sizes in FFQ., Design: We evaluated three stochastic methods for imputation of portion sizes based on information about anthropometry, sex, physical activity and age. Energy intakes computed with standard portion sizes, defined as sex-specific medians (median), or with portion sizes estimated with multinomial logistic regression (MLR), 'comparable categories' (Coca) or k-nearest neighbours (KNN) were compared with a reference based on self-reported portion sizes (quantified by a photographic food atlas embedded in the FFQ)., Setting: The Danish Health Examination Survey 2007-2008., Subjects: The study included 3728 adults with complete portion size data., Results: Compared with the reference, the root-mean-square errors of the mean daily total energy intake (in kJ) computed with portion sizes estimated by the four methods were (men; women): median (1118; 1061), MLR (1060; 1051), Coca (1230; 1146), KNN (1281; 1181). The equivalent biases (mean error) were (in kJ): median (579; 469), MLR (248; 178), Coca (234; 188), KNN (-340; 218)., Conclusions: The methods MLR and Coca provided the best agreement with the reference. The stochastic methods allowed for estimation of meaningful portion sizes by conditioning on information about physiology and they were suitable for multiple imputation. We propose to use MLR or Coca to substitute missing portion size values or when portion sizes needs to be included in FFQ without portion size data.

Aims: The association between recent and more distant weight changes before and after the diagnosis of type 2 diabetes has been little researched. The aim of this study is to determine the influence of patients' weight history before diabetes diagnosis on the observed 6-year weight changes after diagnosis., Methods: A clinical cohort study combined with self-reported past weight history. In total 885 patients aged ≥40 years and newly diagnosed with clinical type 2 diabetes were included. Body weight was measured immediately after diabetes diagnosis and again at the 6-year follow up examination (median, 5.7 years). At diagnosis patients reported their weight 1 year and 10 years previously, and also at the age of 20. Multivariate linear regression analyses controlled for 20 baseline patient characteristics., Results: The median (interquartile range) age at diagnosis was 63.2 (53.9; 71.4) years. Median body weight was 80.0 (72.0; 90.0) kg 10 years before diagnosis, 85.0 (75.0; 95.0) kg 1 year before diagnosis, 82.4 (72.0; 94.0) kg at diagnosis, and 80.0 (70.0; 91.1) kg at 6-year follow up. Each kg of weight gain during the year preceding the diagnosis was associated with a weight change (95% CI) of -0.20 (-0.28; -0.13) kg during the follow up period. In all models age and body mass index at diagnosis predicted future weight changes, while the weight at age 20 (-0.01 (-0.06; 0.03) kg/kg), and the weight change from 10 years to 1 year before diagnosis (-0.01 (-0.06; 0.04) kg/kg), did not predict weight change after diagnosis., Conclusions: During the first on average 5.7 years after diagnosis of type 2 diabetes, patients generally follow a course of declining average weight, and these weight developments are related primarily to recent weight changes, body mass index, and age, but not to the more distant weight history.

Objective: This study explored the impact of involvement in cooking on long-term morbidity and mortality among patients newly diagnosed with type 2 diabetes mellitus (T2DM)., Design and Subjects: Data are from the population-based study Diabetes Care in General Practice. In baseline questionnaires, 1348 patients newly diagnosed with T2DM gave information on how frequently they consumed a warm main meal and how often they cooked it themselves. The selected patients were followed up for 19 years in the Danish National Patient Registry and the Danish Register of Causes of Death., Main Outcome Measures: This study analysed the association between involvement in cooking and each of seven pre-specified outcomes was analysed in Cox regression models with stepwise adjustment for possible confounders and mediators., Results: 92% of the patients with T2DM consumed a warm main meal ≥ five times per week. Among these, women who cooked for themselves less than once a week had a higher risk of diabetes-related deaths (HR 1.86 [95% CI 1.03-3.35], p = 0.039) and stroke (HR 2.47 [95% CI 1.08-5.65], p = 0.033), after adjustment for confounders. For men, infrequent cooking was not related to increased risk for the outcomes investigated., Conclusions: In patients newly diagnosed with T2DM and with a regular intake of warm main meals, infrequent involvement in cooking was associated with an increased risk of diabetes-related death and stroke for women, but not for men. General practitioners should pay special attention to managing diabetes treatment in female patients newly diagnosed with T2DM who report infrequent involvement in cooking.

Aims/hypothesis: We investigated whether urinary markers of nucleic acid oxidation are associated with an increased risk of cancer in type 2 diabetes patients., Methods: Urine samples from 1381 newly diagnosed diabetes patients were assayed for the oxidatively modified guanine nucleosides 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo). Cox proportional hazards regression was used to examine the relationship between the urinary markers and cancer incidence., Results: The crude analyses showed an association between overall cancer and urinary excretion of the RNA oxidation marker 8-oxoGuo (unadjusted hazard ratio for cancer per natural log increase in 8-oxoGuo 1.35 [95% CI, 1.01-1.81]), however, in the adjusted analyses, no significant associations between 8-oxodG or 8-oxoGuo and overall cancer were found. For site-specific cancers 8-oxodG was associated with breast cancer in the crude analyses (unadjusted hazard ratio for breast cancer per natural log increase in 8-oxodG was 2.37 [95% CI, 1.07-5.26]), although the association was attenuated in the adjusted analyses (sex- and age-adjusted hazard ratio 2.15 [95% CI, 0.92-5.02] and multivariate adjusted hazard ratio1.98 [95% CI, 0.95-4.10])., Conclusions: Urinary excretion of the nucleic acid oxidation markers 8-oxodG and 8-oxoGuo at the time of diagnosis was not associated with cancer overall in type 2 diabetes patients. For site-specific cancers, risk elevations were seen for breast cancer (8-oxodG). These findings should be examined in future and larger studies., (Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Eosinophilia may represent an early paraclinical sign of malignant disease and a host anti-tumor effect. The association between eosinophilia and the development of solid tumors has never before been examined in an epidemiological setting. The aim of the present study was to investigate eosinophilia in routine blood samples as a potential biomarker of solid tumor development in a prospective design., Material and Methods: From the Copenhagen Primary Care Differential Count (CopDiff) Database, we identified 356 196 individuals with at least one differential cell count (DIFF) encompassing the eosinophil count during 2000-2007. From these, one DIFF was randomly chosen and categorized according to no (< 0.5 × 10(9)/l), mild (≥ 0.5-1.0 × 10(9)/l) or severe (≥ 1.0 × 10(9)/l) eosinophilia. From the Danish Civil Registration System and the Danish Cancer Registry we ascertained all-cause death and solid tumors within the first three years following the DIFF. Using multivariable logistic regression, odds ratios (OR) were calculated and adjusted for previous eosinophilia, sex, age, year, month, C-reactive protein, previous cancer and Charlson's Comorbidity Index., Results: The risk of bladder cancer was increased with mild eosinophilia [OR 1.93 (CI 1.29-2.89), p = 0.0013]. No associations with eosinophilia were observed for the remaining solid cancers., Conclusion: We demonstrate that eosinophilia in routine blood samples associates with an increased risk of bladder cancer. Our data emphasize that additional preclinical studies are needed in order to shed further light on the role of eosinophils in carcinogenesis, where it is still unknown whether the cells contribute to tumor immune surveillance or neoplastic evolution.