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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: Estimation of the accuracy of 1, 5 and 10 y body weight recall. DESIGN: Comparison of information on body weight history from a patient questionnaire with measured body weights retrieved in general practitioners' records. SUBJECTS: Among 729 newly diagnosed diabetic patients record information on measured body weight was found for 86, 141 and 122 patients recalling their body weight 1, 5 and 10 y ago, respectively. Median age was 63.6 y. Median body mass index was 31.1 kg/m². RESULTS: No average deviation between I y body weight recall and the corresponding measured weights is observed, but 5 and 10 y recall underestimates the measured weights by 1.89 kg and 1.98 kg on an average, respectively. On the individual level the agreement is less satisfactory with increasing variability the further back in time you go. The recall does not vary with age and sex and it is independent of weight status, marital status, smoking habits and self-reported health status in this obese group of individuals. CONCLUSIONS: The findings suggest that data from three standard questions may contribute with useful information on near weight history, independent of age, sex and current body weight. [ABSTRACT FROM AUTHOR]

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.