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N de Fine Olivarius

Publications and source records attributed to N de Fine Olivarius.

At least 19 recordsLinked to original sources

Changes in patient weight and the impact of antidiabetic therapy during the first 5 years after diagnosis of diabetes mellitus.

AIMS/HYPOTHESIS: It is generally thought difficult for type 2 diabetic patients to lose weight. We monitored changes in patients' weight during the first 5 years after diabetes diagnosis in relation to initiation of antidiabetic treatment. SUBJECTS AND METHODS: Data from 711 newly diagnosed diabetic patients aged 40 or over were analysed with a random-effect linear-regression model. Patients were included consecutively from a well-defined patient list in general practice. RESULTS: In 245 patients whose only treatment was advice on diet, an initial weight loss of 6 to 7 kg was largely maintained over 5 years. Patients receiving metformin (n=86) or sulfonylureas (n=330) maintained an average weight loss of 2 to 4 kg that was dependent on age and sex. Patients' weight did not change on initiation of treatment with sulfonylureas or metformin. Over 5 years, median HbA(1c) increased from 7.0 to 7.8% (reference range 5.4-7.4%) in the diet-alone group. HbA(1c) was approximately 1 percentage point higher for most of the other treatment groups. CONCLUSIONS/INTERPRETATION: In newly diagnosed type 2 diabetic patients, long-term weight loss was common and weight loss was not affected by sulfonylurea treatment. The measurements in the study are taken from treatment results achieved in the general population of diabetic patients, who are rarely treated in secondary care and seldom the subject of research; the results thus indicate that weight reduction is a practicable treatment in diabetic patients.

Age Factors↗

Symptoms, signs and complications in newly diagnosed type 2 diabetic patients, and their relationship to glycaemia, blood pressure and weight.

AIMS/HYPOTHESIS: To document the prevalence of typical diabetic symptoms, signs and complications in the diagnosis of type 2 diabetes mellitus, examine their pre-diagnostic duration, and analyse associations with glycaemic level, blood pressure (BP), and weight. METHODS: An epidemiological population-based study of 1137 Danish patients with type 2 diabetes newly diagnosed by general practitioners (GPs). GPs and patients together filled in a questionnaire about typical symptoms, signs and complications preceding the diagnosis. RESULTS: Abnormal thirst, frequent urination, weight loss, genital itching, stomatitis, visual disturbances, fatigue, confusion and (in men) balanitis were associated with glycaemic level irrespective of age, sex, BMI, BP, complications and antihypertensive treatment. Eighty-nine percent of the patients presented with one or more of these hyperglycaemic symptoms and signs, and the pre-diagnostic duration was typically less than 3 months. Only a few symptoms, signs and complications were associated with weight and BP. CONCLUSIONS/INTERPRETATION: In patients newly diagnosed with type 2 diabetes in family practice, typical diabetic symptoms, signs and complications are common. Typical diabetic symptoms and signs are associated with hyperglycaemia. The pre-diagnostic duration of hyperglycaemic symptoms and signs were typically short, thus questioning the feasibility of early detection relying on increased anticipatory care by GPs. In contrast, elevated levels of cardiovascular risk factors and longer pre-diagnostic duration of cardiovascular complications suggest these might have a central role in an early diagnosis of type 2 diabetes.

Aged↗

Peripheral vascular disease is associated with reduced glycosuria in newly diagnosed type 2 diabetic patients.

OBJECTIVES: We examined whether the finding of glycosuria and its level in themselves give information of clinical relevance, apart from being an unreliable indicator of glycemic control. METHODS: Subjects were a population-based sample of 1,284 newly diagnosed type 2 diabetic patients. Median age was 65.2 years. Urinary glucose concentration (UGC) was determined quantitatively in a freshly voided morning urine specimen. RESULTS: The over-all prevalence of peripheral vascular disease (PVD) was 16.5%. Bivariately, high values of UGC were associated with low prevalence of PVD (p<0.001, chi2-test). The predictive value of PVD--together with HbA1c, glomerular filtration rate (GFR) and 10 other possible predictors--was confirmed in a logistic regression analysis with glycosuria (Y/N) as outcome variable (p=0.0004). CONCLUSION: Surprisingly, type 2 diabetic patients with PVD tend not to have glycosuria as compared to patients without PVD. PVD may be indicative of generalized atherosclerotic lesions in the major vessels, including the renal arteries. This could lead to a lowering of GFR and thereby of the amount of glucose filtered. Assuming no, or only a minor direct effect of PVD on tubular function, this would lead to an increased renal threshold for glucose in patients with PVD.

Aged↗

Can capillary whole blood glucose and venous plasma glucose measurements be used interchangeably in diagnosis of diabetes mellitus?

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.

Algorithms↗

Upper reference limit, analytical quality specifications and clinical use of haemoglobin A1C.

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%.

Bias↗

[Randomized controlled trial of structured, individualized treatment of type 2 diabetes mellitus. The project of Diabetes Care in General Practice].

INTRODUCTION: We assessed the effect of a multifaceted intervention directed at general practitioners to improve type 2 diabetes care. MATERIALS AND METHODS: Three hundred and eleven Danish practices with 474 general practitioners were randomised to structured personal care (intervention group) or routine care (comparison group). Of 970 surviving patients (aged 40+ years) diagnosed with diabetes in 1989-1991, 874 (90.1%) were assessed after 6 years. Intervention comprised regular follow-up and individualized goal-setting, supported by reminders to doctors, clinical guidelines, feed-back, and continuing medical education. RESULTS: Predefined non-fatal outcomes and mortality were the same in both groups. The following risk factor levels were lower in the intervention patients than in the comparison patients: fasting plasma glucose (7.9 vs 8.7 mmol/l, medians, P = 0.0007), haemoglobin A1c (8.5 vs 9.0%, P < 0.0001, normal range 5.4-7.4%), systolic blood pressure (145 vs 150 mmHg, P = 0.0004), and cholesterols (6.0 vs 6.1 mmol/l, P = 0.029, baseline-adjusted). Both groups had sustained a weight loss since diagnosis (2.6 vs 2.0 kg). Metformin was the only drug used more frequently in the intervention group (24 vs 15%). Intervention doctors arranged more follow-up consultations, referred fewer patients to diabetes clinics, and were more optimistic in their goal-setting. DISCUSSION: In primary care, individualized goal-setting with educational and surveillance support may for at least six years bring risk factors of patients with type 2 diabetes to a level that in other trials has been shown to reduce diabetic complications, but without adverse weight gain.

Denmark↗

[Screening for alcohol overconsumption in general practice. Experiences of general practitioners with a patient questionnaire].

INTRODUCTION: We investigated to which degree a sample of 143 general practitioners in the County of Copenhagen would screen their patients for problem drinking by using The Alcohol Use Disorders Identification Test (AUDIT). Furthermore, among users of AUDIT, we aimed to describe the doctors' perception of using it. METHODS: Eighty-one out of the 143 doctors requested AUDIT. However, after they had had the possibility of using AUDIT, only 38 had handed an AUDIT to at least one patient. These 38 doctors were asked to answer a questionnaire on which this study is based. RESULTS: Thirty-two percent (12/38) of the doctors handed out an AUDIT in more than 14 days, and 21% (8/38) gave at least 100 patients an AUDIT. The general practitioners worked a median of 20 days in their practice during the study period. Only 14% (5/36) would screen all their patients in the future, and 42% (15/36) only when they suspected problem drinking. Sixty-four percent (22/34) of the doctors stated that handing all patients an AUDIT was much too time-consuming, 50% (17/34) stated that financial incentives are necessary, and 53% (18/34) questioned whether the patients wanted an AUDIT. Sixty-six percent (23/35) of the doctors judged that they had improved in detecting patients with alcohol related problems. CONCLUSION: The participating general practitioners were not interested in handing all patients an AUDIT. Major barriers were lack of time and financial incentives and furthermore the doctors questioned whether the patients wanted an AUDIT. However, half of the doctors would use AUDIT for certain patients, especially when they suspected problem drinking.

Adult↗

Diabetic retinopathy in newly diagnosed middle-aged and elderly diabetic patients. Prevalence and interrelationship with microalbuminuria and triglycerides.

BACKGROUND: The exact role of factors such as serum lipids, body mass index and (micro-)albuminuria as possible determinants of diabetic retinopathy remains to be determined. We have scrutinized the prevalence of diabetic retinopathy and its concomitants in terms of risk factors and other diabetic complications in newly diagnosed diabetic patients. METHODS: A population-based sample of 1,251 newly diagnosed diabetic patients aged 40 years or over was established in general practice. Median age was 65.3 years. Funduscopy was performed by practising ophthalmologists. Blood and urine analyses were centralised. RESULTS: The overall prevalence of diabetic retinopathy was 5.0%. Only three patients had proliferative diabetic retinopathy. As expected, diabetic retinopathy and renal involvement, as expressed by the urinary albumin/creatinine ratio. were strongly positively associated. An intriguing finding was that of an inverse relationship between fasting triglycerides and diabetic retinopathy, an association that proved to be confined to microalbuminuric patients. An inverse association between body mass index and diabetic retinopathy was found only univariately. CONCLUSION: The low prevalence of diabetic retinopathy cannot be explained by the screening method alone, but rather by early detection of diabetes in a non-selective patient sample. It seems that renal involvement modifies the expected relationship between diabetic retinopathy and triglycerides, but a pathophysiological mechanism is not available.

Aged↗

Optimization of preanalytical conditions and analysis of plasma glucose. 1. Impact of the new WHO and ADA recommendations on diagnosis of diabetes mellitus.

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.

Anticoagulants↗

Plasma glucose reference interval in a low-risk population. 2. Impact of the new WHO and ADA recommendations on the diagnosis of diabetes mellitus.

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.

Adolescent↗

Evaluation of systematic and random factors in measurements of fasting plasma glucose as the basis for analytical quality specifications in the diagnosis of diabetes. 3. Impact of the new WHO and ADA recommendations on diagnosis of diabetes mellitus.

On behalf of the Danish Society of Clinical Endocrinology and the Danish Society of Clinical Chemistry we were commissioned to evaluate the influence of analytical and pre-analytical systematic and random factors on the diagnosis of diabetes, in order to provide a tool for conclusions on the analytical quality specifications needed to diagnose diabetes. A systems analysis was performed in accordance with the principles for evaluation of analytical quality specifications. The clinical setting was defined--diagnosis of diabetes in accordance with the WHO and ADA criteria with determination of fasting plasma glucose concentration (FPG) > or =7.0 mmol/L in two independent samples--with well-documented data on In (loge)-Gaussian distribution of reference values from a low-risk population and values for within-subject biological variation taken from the literature. An investigation was made of the consequences for the clinical setting of assumed errors related to the measurement of FPG. Four approaches were investigated for a single sampling and measurement and also for two independent samples: one showing the percentage of healthy individuals who had values > or = 7.0 mmol/L, one illustrating the origin of biological set-points for results > or = 7.0 mmol/L, one showing the risk of being measured > or =7.0 mmol/L when the biological set-point is known, and one showing the combined bias and imprecision for assumed percentages of false-positive (FP), defined as measurements > or = 7.0 mmol/L for the low-risk population and false-negative (FN), defined as measurements <6.4 mmol/L (the upper reference limit) for diabetics. This leaves a "grey zone" which includes the upper part of low-risk individuals, and defined by ADA and WHO as "impaired fasting glucose" (IFG). In the analysis, increasing systematic and random errors (combined analytical and pre-analytical) were assumed, and for each error condition the fractions of FP and FN were calculated. This gave plots from which the combined allowable systematic and random errors could be read off for pre-determined clinically acceptable fractions of FP and FN. The analysis does not distinguish between pre-analytical and analytical errors, as specified information on one of these is needed for specification of the other. The investigation provides a reliable basis for estimation of the needed analytical quality, and thereby for decisions about analytical quality specifications for analysis of FPG in relation to diagnosis of diabetes under optimized pre-analytical and analytical conditions. Consequences of deviations from these ideal conditions are illustrated in the figures, and should be considered for the different approaches with different performance conditions.

Blood Glucose↗

Discrepancy in HbA1c measurements performed at different local laboratories and at a selected central reference laboratory.

As participants in a general practice intervention study, 66 patients had their HbA1c measured both at a local and at a selected central reference laboratory. A discrepancy in the results was observed, as 97% of the results measured locally were lower than the centrally determined results. Bias (as calculated from mean value of measured HbA1c) between local laboratories and the central laboratory was measured to -1.47% HbA1c. A bias of this magnitude gave "problems" both to the general practitioners, patients and laboratories. To reduce the "problems" a bias of 0.5% HbA1c is estimated to be acceptable. But, to avoid these "problems" totally, a bias of 0.25% HbA1c is estimated to be the highest allowed bias. For HbA1c, a control system for both control of method standardisation and for specificity is described.

Evaluation Studies as Topic↗

Microalbuminuria in non-insulin-dependent diabetes.

According to international consensus, microalbuminuria is defined as an elevated urinary albumin excretion rate (UAER) of 20-200 micrograms/min, which is below the proteinuric range. Nephropathy is a major complication in IDDM, seen in about 30% of patients after many years of diabetes. Increasing microalbuminuria is an excellent marker of subsequent nephropathy in these patients. End-stage diabetic nephropathy is also important in NIDDM, but in most Western countries this serious complication eventually develops in only 5 to 10% of cases, whereas the majority of patients die before this from cardiovascular disease. In completely healthy individuals there is no clear correlation between age and UAER, at least up to about 70 years of age. The mean excretion rate is around 5 micrograms/min, with a considerable range, but excretion only rarely exceeds 15 micrograms/min. In population studies among middle-aged and elderly individuals, higher values are seen. In newly diagnosed NIDDM about 40% of patients show an excretion rate above 15-20 micrograms/min. There is a significant but not precise correlation between albumin excretion rate and glycemic control, and usually UAER is reduced by standard antidiabetic treatment. In a considerable number of patients, high values cannot be reduced. In the course of NIDDM about 20-30% of patients show microalbuminuria. In patients with known diabetes, microalbuminuria is related not only to subsequent diabetic proteinuria, but even more strongly to early death, mainly from cardiovascular disease. Even slight microalbuminuria (15-40 mg/l in early morning urines) is clearly associated with increased mortality. In subjects with newly detected elevated blood glucose (by screening) microalbuminuria also predicts early mortality. The mechanisms are not established, but several arteriosclerosis-related risk factors are seen more frequently in patients with microalbuminuria, e.g. lipid abnormalities, elevated systolic blood pressure (BP), hemostatic measures, as well other markers of cardiovascular disease. Usually there is a significant but not precise correlation between BP and UAER in groups of patients throughout the course of diabetes. New studies document that also in the elderly background population microalbuminuria is a significant risk factor for early death, maybe even stronger than the established risk markers, which thus may be confounded with the presence of microalbuminuria.

Adult↗