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  • 1
    ISSN: 1432-0428
    Keywords: Key words Insulin-dependent diabetes mellitus ; arterial hypertension ; borderline hypertension ; microalbuminuria ; diabetic nephropathy.
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Arterial hypertension and poor glycaemic control are central to the development of microalbuminuria in insulin-dependent diabetes mellitus (IDDM). Recent consensus has established sensitive criteria for their detection and treatment, although the proportion of patients who may benefit is unclear. Between 1988 and 1990, we measured urinary albumin to creatinine concentration ratio (A/C) in 3,636 adult out-patients with IDDM of more than 3 years duration, serum creatinine under 133 μmol/l and who were not undergoing antihypertensive treatment. A/C indicating microalbuminuria (≥ 2.38/2.96 mg/mmol, male/female) was found in 620 of 3,451 patients without proteinuria, and associated with hypertension (blood pressure ≥ 140 and/or 90 mm Hg; p = 0.0016; rate: 39.6 %), independent of diabetes duration (p = 0.0082) and male gender (p = 0.0350; relative risk = 1.16; 95 % confidence interval: 1.01–1.32). Hypertension was less common among those with normal A/C (27.5 %, p 〈 0.0001) but was positively related with diabetes duration. Of the 1,015 patients with A/C ≥ 2.0 mg/mmol 529 were reexamined. Glycated haemoglobin levels exceeded 3 SD above the mean of normal in 84.3 % of the 198 microalbuminuric patients (AER = 20–200 μg/min), but were comparably poor (79.2 %) in normoalbuminuria. Duration of diabetes was inversely related to glycated haemoglobin only in microalbuminuria (0.05 〈 p 〈 0.1). Intervention to lower blood pressure remains mainly restricted to those patients with long-term diabetes and slower development of kidney disease. Near-normalisation of glycaemia remains the priority for the majority of patients with microalbuminuria. [Diabetologia (1994) 37: 1015–1024]
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Insulin-dependent diabetes mellitus ; arterial hypertension ; borderline hypertension ; microalbuminuria ; diabetic nephropathy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Arterial hypertension and poor glycaemic control are central to the development of microalbuminuria in insulin-dependent diabetes mellitus (IDDM). Recent consensus has established sensitive criteria for their detection and treatment, although the proportion of patients who may benefit is unclear. Between 1988 and 1990, we measured urinary albumin to creatinine concentration ratio (A/C) in 3,636 adult out-patients with IDDM of more than 3 years duration, serum creatinine under 133 Μmol/l and who were not undergoing antihypertensive treatment. A/C indicating microalbuminuria (≥2.38/ 2.96 mg/mmol, male/female) was found in 620 of 3,451 patients without proteinuria, and associated with hypertension (blood pressure ≥140 and/or 90 mm Hg; p=0.0016; rate: 39.6%), independent of diabetes duration (p=0.0082) and male gender (p=0.0350; relative risk=1.16; 95% confidence interval: 1.01–1.32). Hypertension was less common among those with normal A/C (27.5%, p〈0.0001) but was positively related with diabetes duration. Of the 1,015 patients with A/C〉2.0 mg/mmol 529 were reexamined. Glycated haemoglobin levels exceeded 3 SD above the mean of normal in 84.3% of the 198 microalbuminuric patients (AER=20–200 Μg/min), but were comparably poor (79.2%) in normoalbuminuria. Duration of diabetes was inversely related to glycated haemoglobin only in microalbuminuria (0.05〈p〈0.1). Intervention to lower blood pressure remains mainly restricted to those patients with long-term diabetes and slower development of kidney disease. Near-normalisation of glycaemia remains the priority for the majority of patients with microalbuminuria.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0009-9120
    Keywords: AER ; diabetes mellitus ; diabetic nephropathy ; microalbuminuria ; radioimmunoassay ; urinary albumin
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 0009-9120
    Keywords: AER ; diabetes mellitus ; diabetic nephropathy ; microalbuminuria ; radioimmunoassay ; urinary albumin
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
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  • 5
    ISSN: 1432-5233
    Keywords: Key words Urinary albumin ; Immunonephelometry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Measurement of the urinary albumin excretion rate (UAER) is essential for the early diagnosis and monitoring of diabetic nephropathy; immunonephelometry is a procedure used worldwide for routine screening of diabetic patients. Since we have met with occasional inconsistent values of UAER in serial urine collections, we searched for possible sources of analytic error. To assess the best working conditions of the instrument in use, the stability of urine samples during storage and the need for previous urine centrifugation, we assayed repeatedly the six automatically diluted points of the standard curve (55.6 to 1.7 mg/l), four control samples of human albumin in saline (100 to 1 mg/l) and 24-h urine collections from outpatient diabetic subjects. The last were also assayed with and without previous centrifugation, and both immediately after collection as well as after storage at –20°C for 7, 42, 79, 97, 128 and 161 days. We concluded that: (1) pre-analytic centrifugation of urine samples is unnecessary; (2) the intra-assay coefficient of variation (CV) of the standard curve changed from 2.4% to 9.3% when moving from the highest to the lowest concentration; the inter-assay CV changed from 4.1% to 14.4%, respectively; (3) the intra-assay CV of the control samples (manually prepared) changed from 5.7% to 10.2% and the inter-assay CV from 7.7% to 22.9%; there was a constant and significant (P〈0.01) underestimation (from –9% to –30%) of the obtained values compared with the expected concentrations; (4) a progressive decrease in recovered albumin by multiple freezing and thawing of urine samples did occur, which became significant after 161 days of storage. In the BNA workbook (menu 7.1, assay protocols), a 7-day validity of the reference curve is reported. Moreover, to economize, pre-dilution cuvettes were often recycled in our hospital central laboratory. We observed that: the intra-assay CV for urine samples was 79.4% with recycled cuvettes and stored standard curve, 11.3% with new cuvettes and stored standard curve, 4.9% with both new cuvettes and newly performed standard curve; the inter-assay CV was 32.6%, 10.5% and 6.4%, respectively. These data emphasize, from the laboratory viewpoint, the need for both accurate calibration of BNA and use of native urines; in addition, they stress the importance of careful supervision of laboratory routine and interpreting analytic results in the clinical setting.
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  • 6
    ISSN: 1432-5233
    Keywords: Key words Glycated hemoglobin (HbA1c) ; High-performance liquid chromatography ; Quality control
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The clinical usefulness of glycated hemoglobin (HbA1c) depends crucially on the accuracy and precision of its assay. When we compared an immunological bench-top analyzer (DCA 2000, Bayer Diagnostici, Milan) to the high-performance liquid chromatography (HPLC) reference method used in a routine hospital laboratory (Diamat and Fast Diamat, Bio-Rad Lab., Milan) by assaying multiple control sera, we found so many sources of systematic analytical errors in the routine use of HPLC as to compromise between-assay precision. DCA 2000 showed intra- and interassay coefficients of variation (CV) of 1.1% and 2.3% with the normal standard serum, 1.0% and 4.2% with the pathological one; Diamat yielded CVs of 1.3% and 7.0%, 1.3% and 5.7%, respectively. Although the measurement of 161 blood samples showed that Diamat usually overestimated HbA1c (paired t-test, P〈0.001), a great variability of Diamat performance became evident when the relationship Diamat vs DCA was evaluated day by day over 17 days of observation (analysis of variance, ANOVA, P〈0.001). Intra- and interassay CVs of Fast Diamat initially (new instrument still on approval) were 0.6% and 2.5% (normal standard serum), 0.3% and 1.9% (high standard serum), yet after 6 months of routine laboratory use, they became 3.1% and 3.2%, 1% and 12.3%, respectively. Main sources of error were: inaccurate autodilution, unsuitable parameter settings, disregard of the maintenance schedule. We conclude that the tendency to overlook major critical aspects in the routine use of HPLC is detrimental to the quality of HbA1c determination and implies the loss of HbA1c value in clinical practice. Both carefully supervising laboratory quality and checking the likelihood of the analytical result with the clinical setting appear even more important.
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  • 7
    ISSN: 1432-5233
    Keywords: Diabetic nephropathy ; Microalbuminuria ; Type 1 (insulin0dependent) diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The prevalence of microalbuminuria and arterial hypertension among type 1 (insulin-dependent) diabetic patients is poorly known in Italy. In the preliminary phase of a large outpatient screening programme, we addressed the possibility of using non-time urine samples to predit the chance of detecting albumin excretion rate (AER) in the range of microalbuminuria. We therefore measured urinary albumin and creatinine concentration in timed overnight collections from 641 type 1 diabetic patients with serum creatinine levels lower than 133 μmol/l. AER was strongly and comparably predicted both by urinary albumin concentration (UAlb;r 2=0.754) and by the urinary albumin to creatinine concentration ratio (A/C;r 2=0.773). After exploring several independent cut-off levels for UAlb and A/C, AER in the range 20–200 μg/min (n=91) was found to be predicted with 90% sensitivity and specificity either by UAlb≧20 mg/l or by A/C≧2.0 mg/mmol. UAlb was negatively associated with diuresis, and false negative outcomes were explained by polyuria when screening by this variable. A/C was positively associated with female gender among normoalbuminuric patients, in line with the lower urinary excretion of creatinine in women (7.2±0.25 vs 10.2±0.35 μmol/min,P〈0.00001). A significant excess of false positive outcomes in women compared with men was found when screening by any A/C cut-off level equal to or less than 2.5 mg/mmol. Simplified screening techniques seem to remain, however, a practicable option for the detection of microalbuminuria both in epidemiology and in clinical practice.
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  • 8
    ISSN: 1432-5233
    Keywords: Key words Sodium-hydrogen antiporter ; Echocardiography ; type 1 diabetes mellitus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We assessed the relationship between erythrocyte Na+/H+ antiport activity and myocardial anatomical-functional parameters (by Doppler echocardiography) in normotensive IDDM patients, with and without microalbuminuria. We studied 33 normotensive IDDM subjects and 14 matched healthy controls (group 4). Based on urinary albumin excretion rate (UAER), 23 diabetics were normoalbuminuric, 10 microalbuminuric (group 3). Normoalbuminurics were divided up for normal (group 1, n = 13) or high (group 2, n = 10) antiport activity. We evaluated fasting glycaemia and 24-h urine glucose output, HbA1c, plasma lipids, urea, creatinine and electrolyte clearances, UAER, erythrocyte Na+/H+ countertransport, M-Mode and 2D echocardiograms with Doppler analysis. Antiport, which was higher in diabetics than controls, was significantly overactive in groups 2 and 3 vs group 4, independently from UAER. Diabetics showed left ventricular volume, cardiac mass and systolic function within the control range. In left ventricular diastolic filling, while peak E was similar in diabetic and healthy people, the late peak transmitral flow velocity (peak A) was significantly higher in diabetics than controls, and this was also true in groups 2 and 3 vs group 4. Antiport activity was positively related to peak A (p〈0.03). These observations suggest that (a) the Na+/H+ antiport may be overactive in diabetes, apart from microalbuminuria; (b) increased Na+/H+ antiport activity, in normotensive IDDM people, may be associated with preclinical diastolic myocardial dysfunction (``incipient diabetic cardiomyopathy''?).
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  • 9
    ISSN: 1432-5233
    Keywords: Key words Pregnancy ; Glucose tolerance ; Insulin response ; Fetal growth
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Fetal growth is dependent on transplacental supply of fuels. We aimed to assess the effect of serial changes in maternal glucose tolerance and insulin secretion with advancing pregnancy on maternal-fetal outcomes. Sixty-nine healthy pregnant women were studied over the course of gestation for glucose tolerance, by oral glucose tolerance test (OGTT), and hemoglobin A1c (HbA1c), fetal intrauterine growth (by ultrasound) and pregnancy outcome. Seven women had an abnormal OGTT in the third trimester developing gestational diabetes mellitus (GDM), but none of the 12 mothers of large babies (〉 3.9 kg) had GDM: the former had the highest post-load glycemic increment, despite an apparently ‘normal’ insulin secretory response, the latter showed the lowest post-load glucose increase in the face of the lowest insulinemic response. Neonatal body weight correlated with maternal gestational weight gain, placental weight, third trimester ratio of incremental plasma insulin and glucose integrated areas under the curve and first and second trimester HbA1c levels. Fetal growth indices (femur length, biparietal diameter and abdominal circumference) were correlated with both HbA1c and 2h OGTT. Fetal growth rate is confirmed as being associated with maternal glycemic equilibrium, but one of the main determinants of high infant birthweight seems to be an enhanced maternal insulin sensitivity, accompanied by remarkable gestational weight gain.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1432-5233
    Keywords: Diabetic nephropathy ; Non-insulin-dependent diabetes mellitus ; Microalbuminuria ; Atherosclerosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Supranormal urinary albumin excretion (microalbuminuria) is an early indicator of microangiopathy, i.e. diabetic nephropathy, and is associated with higher cardiovascular mortality in both type 1 and type 2 diabetes. The relationship between the presence of microalbuminuria and some atherosclerotic risk factors has been evaluated in 318 (170 male, 148 female) type 2 (non-insulin-dependent) diabetic subjects [age 63±10 years; known duration of diabetes 10.9±8.8 years; age at diabetes diagnosis 52±11 years; systolic blood pressure (BP) 150±23 mmHg; diastolic BP 86±11 mmHg (mean±SD)]. In “early morning” urine samples, albumin (immunonephelometry) and creatinine were assayed. On the basis of the albumin/creatinine ratio (A/C, mg/mmol), patients were categorized as normoalbuminuric (Na; A/C〈2.0;n=159, 50%), microalbuminuric (ma; A/C 2–20;n=135, 42.5%) or macroalbuminuric (Ma; A/C 〉20;n=24, 7.5%). The three groups were closely matched for age, age at diagnosis, duration of diabetes, and fasting plasma and urinary glucose levels. Systolic and diastolic BP rose progressively with increasing urinary A/C ratio levels. While high-density lipoprotein (HDL) cholesterol was unaffected by albuminuria, total cholesterol (218±45 vs 198±43 mg/dl,P〈0.001) and low-density lipoprotein (LDL) cholesterol (145±42 vs 131±38 mg/dl,P〈0.05) levels were higher in microalbuminuric than in normoalbuminuric patients. Further, a significant correlation (r=0.16,P〈0.01) existed between albuminuria and triglyceride concentrations. Prevalence of arterial hypertension, defined as BP≥160/95 mmHg and/or drug treatment (Na, 51%; ma, 65%; Ma, 78%;P〈0.001) and obesity, defined as body mass index (BMI)〉30 (Na, 15%; ma, 26%; Ma, 32%;P〈0.05) rose with increasing A/C ratios. Both coronary heart disease (30% vs 15%) and intermittent claudication (18% vs 7%) were more frequent in microalbuminuric than in normoalbuminuric subjects. Finally, multiple stepwise regression analysis showed that urinary albumin excretion is significantly and independently associated with coronary heart disease and intermittent claudication, also taking into account hypertension and other established cardiovascular risk factors. In type 2 diabetes microalbuminuria tends to aggregate with risk factors for atherosclerotic vascular disease, e.g. increased prevalence of hypertension and obesity, elevated total and LDL cholesterol, and raised triglycerides levels. These abnormalities may only explain the excess of cardiovascular morbidity and mortality in part. Microalbuminuria per se may be an important and independent cardiovascular risk factor.
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