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Query: UMLS:C0011849 (diabetes)
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Microalbuminuria is thought to be rare in people with insulin-dependent diabetes mellitus (IDDM) for less than 5 years. We measured its prevalence in 733 clinic-attending IDDM patients with diabetes duration of 1-5 years in two large multicenter studies [EURODIAB IDDM Complications Study and the World Health Organization (WHO) Multinational Study]. We also compared characteristics of microalbuminuric patients with IDDM for 1-5 years versus more than 5 years' duration. Albumin excretion rate was measured from a timed 24-h urine collection in the EURODIAB Study. Proteinuria was measured by the salicylsulphonic acid test in the WHO Study. The prevalence of microalbuminuria (20-200 micrograms/min, EURODIAB) was 18% [95% confidence interval (CI) 13%-22%)]. The prevalence of light proteinuria was 15% (9%-20%, WHO study). Raised protein excretion was a consistent finding in 34 of the 36 centers. The increased cardiovascular risk (raised blood pressure and total cholesterol) associated with microalbuminuria in patients with IDDM for more than 5 years was also apparent in those with diabetes for 1-5 years. However, repeat urine testing suggested that microalbuminuria before 5 years was more likely to be transient or reversible. In conclusion, these two studies in 36 centers, which used different methods more than 10 years apart, show consistently that raised urinary albumin excretion occurs before 5 years of IDDM. The clinical significance of this needs to be examined by prospective observation.
J Diabetes Complications
PMID:Microalbuminuria is not rare before 5 years of IDDM. EURODIAB IDDM Complications Study Group and the WHO Multinational Study of Vascular Disease in Diabetes Study Group. 808 53

Microalbuminuria and its association with vascular disease has previously been reported in nondiabetic individuals. The aims of this study were to determine whether there is a cross-sectional relationship between urinary albumin excretion rate and cardiovascular disease in nondiabetic subjects and to investigate hereditary predisposition to microalbuminuria by studying offspring of the main study population. Europid patients, aged 40-70 years, were randomly selected from a large inner-city general practice; there was a 62.6% attendance rate, and a study population of 959 remained after exclusions. Blood pressure, ankle systolic pressure, height, and weight were measured. Albumin excretion rate was calculated from overnight and morning urine collections. Venous blood was taken for lipids, fibrinogen, and factor VII; and resting electrocardiograms were carried out. Offspring (aged 15-40 years) of those found to be microalbuminuric were invited to attend for the same tests, and controls were selected by age and sex matching the parents. There was no association between parents' albumin excretion rate with that of their offspring, and there were no significant differences in albumin excretion rate between offspring subjects and their controls. There were no statistically significant associations of prevalent coronary heart disease (CHD) with albumin excretion rate or microalbuminuria in either sex [CHD in women: odds ratio (OR) 1.85; 95% confidence interval (CI) 0.19,9.0] [CHD in men: OR 2.13; 95% CI (0.64, 6.59)]. In women, there were significant associations between albumin excretion rate and peripheral vascular disease (positive) and fibrinogen (negative). Because established risk factors may not be as strongly associated with CHD in cross-sectional studies, we intend to follow this group prospectively.
J Diabetes Complications
PMID:Associations of urinary albumin excretion rate with vascular disease in europid nondiabetic subjects. 808 57

Less than 30% of chronic dialysis patients are employed, but little is known about the factors affecting the employment status of these patients. Some conflicting reports about an improvement in vocational status with the use of erythropoietin and the lack of information about the contribution of dialysis adequacy (as assessed by KT/Vurea) to employment status prompted us to examine demographic and biochemical factors associated with employment status in chronic in-center hemodialysis (n = 46) and continuous peritoneal dialysis (n = 31) patients who were < or = 55 years of age. Thirty-three of the 77 patients (43%) were either working or attending school full-time. The working patients were noted to be better educated (20 of 33 working v 12 of 44 nonworking patients had > 12 years of education; P = 0.005) and on dialysis for a shorter mean time (44 +/- 52 months for the working patients v 77 +/- 78 months for the nonworking patients; P = 0.03). Sex, race, diabetes mellitus, mode of dialysis, and prior transplant were not associated with employment status. Similarly, mean hematocrit (30.2% +/- 5% in the working patients v 30.5% +/- 4% in the nonworking patients) and mean weekly delivered KT/V (1.4 +/- 0.7 v 1.3 +/- 0.6 for hemodialysis and 2.3 +/- 0.7 v 2.3 +/- 0.6 for peritoneal dialysis in the working and nonworking patients, respectively) were not different among the working and nonworking patients. Albumin was also not significantly different among the working and nonworking patients (4 +/- 0.3 v 3.9 +/- 0.4, respectively; P = 0.27).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:An analysis of factors affecting employment of chronic dialysis patients. 817 10

An inherited predisposition to hypertension may increase susceptibility to nephropathy in type I diabetes. We evaluated the influence of a family history of essential hypertension on albuminuria in normotensive, normoalbuminuric type I diabetic patients. Forty-two diabetics (12.9 +/- 2.04 years) were divided into three groups according to tertiles of albumin excretion rate (group 1, 1.27 +/- 0.35; group 2, 2.43 +/- 0.49; group 3, 6.37 +/- 3.43 micrograms/min; P < .001). Familial hypertension was considered to be present if the patient had one parent or grandparent on antihypertensive therapy. The three groups did not differ concerning age, diabetes duration, insulin requirement, body mass index, blood pressure, and urinary glucose excretion. Albumin excretion rate did not correlate with any parameter studied. The frequency of hypertension was significantly lower among the relatives of the patients from group 1 compared with those from groups 2 and 3 (28.6% versus 64.3% versus 78.6%, P < .03). Our data suggest that a familial antecedent of hypertension in normoalbuminuric type I diabetic patients is associated with a high normal albumin excretion rate not related to increases in blood pressure. Early changes in renal hemodynamics, seen in patients with a predisposition to hypertension, may contribute to increments in albuminuria even within the normal range.
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PMID:Familial hypertension and albuminuria in normotensive type I diabetic patients. 828 70

Decreased glomerular heparan sulfate synthesis could account for the increased albuminuria observed in experimental diabetes. A similar albuminuria has been observed in galactose-fed animals. To test whether heparan sulfate synthesis is also decreased in galactosemic animals we measured the heparan sulfate synthesis in isolated renal glomeruli from streptozotocin diabetic and normal rats fed regular diets or 30% galactose diets for 11-12 weeks. Albumin excretion and glomerular heparan sulfate synthesis were determined at the time of sacrifice. As predicted by this hypothesis glomerular heparan sulfate synthesis was significantly lower in the diabetic group than in normals given regular diets (309 +/- 23 vs 487 +/- 56 dpm/mg glomerular wt.; P < 0.01), and albumin excretion greater in these diabetics than in the normals (20 +/- 4.3 vs 2.0 +/- 0.7 mg/24 hr; P < 0.002). Albumin excretion and glomerular heparan sulfate synthesis were also consistent with the hypothesis, but unpredictably reversed, in the galactose-fed diabetic group. Glomerular heparan sulfate synthesis was significantly increased in this group (713 +/- 67 dpm/mg glomerular wt.) and albumin excretion decreased (10.7 +/- 3.6 mg/24 hr) compared to the diabetic on regular diet. Some possible explanations are discussed, but the galactose effect described here remains phenomenological.
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PMID:Effect of galactose regimen on glomerular heparan sulfate synthesis and albumin excretion in diabetic rats. 832 19

In an in-depth examination to better define the renal effects of mild hypertension, we used urinary proteins to indicate damage to the glomerulus (albumin), tubular reabsorption capability (retinol-binding protein), and turnover of tubular tissue (alanine aminopeptidase and N-acetyl-beta-D-glucosaminidase) in a group of 18 people with mild hypertension not associated with diabetes and a control group (n = 12). The participants' activity was controlled on a high normal salt diet for 3 days followed by a low salt diet for 4 days. Two distinct patterns of albumin excretion were evident in the hypertensive group: 22% had elevated, highly variable excretion patterns, and the rest had tightly grouped values below 16 mg/g creatinine, 16 micrograms/min, or 16 mg/L, with the lowest within-person biological variability given by albumin calculated as a ratio to creatinine. Albumin and NAG excretion primarily correlated with systolic blood pressure and the best correlations were given by ratios to creatinine. A marked decrease in salt excretion of 71% (to 50.8 mEq/day) resulted in significant (P < .0005) decreases in systolic (13.9 mm Hg), diastolic (6.4 mm Hg), and mean arterial pressures (8.9 mm Hg) only in the group with mild hypertension. However, albumin excretion did not decrease when dietary salt content was lowered. The group with hypertension also had higher urinary excretion of lysosomal N-acetyl-beta-D-glucosaminidase (P < .01), and whites in the group had a higher excretion of retinol-binding protein than did whites in the control group (P < .02). Retinol-binding protein values, however, were within the normal range, indicating that the elevated albumin values were the result of changes in selectivity of the glomerulus.
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PMID:An in-depth examination of the excretion of albumin and other sensitive markers of renal damage in mild hypertension. 855 30

Microalbuminuria in both insulin-dependent (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) is a marker for insulin resistance. Microalbuminuria is also associated with hypertension, itself an insulin-resistant state. Therefore, in order to examine the independent relationships of microalbuminuria with blood pressure and insulin resistance, we measured ambulatory blood pressure (Takeda TM-2420), insulin resistance (modified Harano method), and urinary albumin excretion rate (overnight urine collection) in 36 subjects with NIDDM. Albumin excretion correlated with 24-h systolic blood pressure (r = 0.49, p = 0.003), and insulin sensitivity (r = -0.39, p = 0.007). Microalbuminuric subjects had reduced insulin sensitivity compared with normoalbuminuric subjects [Mean (SD) 2.95 (0.33) versus 4.67 (0.56) ml.kg-1.min-1; p = 0.013]. In multivariate analysis including ambulatory blood pressure and insulin resistance, urinary albumin excretion was associated primarily with insulin resistance, with smaller contributions from glycated hemoglobin and male gender. These data suggest that microalbuminuria in NIDDM, although associated with hypertension, is also independently associated with insulin resistance.
J Diabetes Complications
PMID:Insulin resistance in non-insulin-dependent diabetes mellitus is associated with microalbuminuria independently of ambulatory blood pressure. 857 34

The direct relationship between elevated glucose concentrations and accelerated protein glycation has implicated increased glycation as a potential mechanistic link between hyperglycemia and the pathogenesis of diabetic nephropathy. Albumin modified by Amadori glucose adducts has been shown to stimulate collagen secretion by mesangial cells in vitro, and to contribute to the overproduction of glomerular mesangial matrix in vivo. To delineate mechanisms responsible for these effects, we examined the influence of glycated albumin on transcriptional activation of the alpha 1 (IV) collagen gene in renal glomerular mesangial cells. These experiments used a stably transfected reporter mesangial cell line that exhibits responses to media manipulations that are directionally parallel with those of non-transformed mesangial cells, and that expresses luciferase driven by 5'-flanking and first intron regions of the alpha 1 (IV) collagen gene. In these cells, purified glycated albumin stimulated collagen IV gene transcription, whereas glucose-free albumin did not. Further, glycated albumin induced a significant increase in mesangial cell collagen IV mRNA, assessed by Northern blot analysis and quantified by calculation of the ratio of collagen IV mRNA to 18S ribosomal RNA after densitometric scanning. The stimulation of collagen gene transcription and mRNA expression were both prevented by monoclonal antibodies known to specifically recognize Amadori-modified albumin. The findings indicate that glycated albumin promotes mesangial cell transcriptional activation and mRNA expression of the alpha 1 (IV) collagen gene and further implicate increased glycated albumin in diabetes in the pathogenesis of diabetic nephropathy.
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PMID:Albumin modified by Amadori glucose adducts activates mesangial cell type IV collagen gene transcription. 858 15

Familial clustering of diabetic nephropathy points to genetic susceptibility. The observation that in non-diabetic subjects microalbuminuria occurs more frequently in the presence of a parental history of diabetes supports this hypothesis. However, the role of inherited factors in poorly understood in non-insulin dependent diabetes mellitus (NIDDM). This study investigated the albumin excretion rate in non-diabetic offspring of NIDDM patients with increased albumin excretion rate (> 20 micrograms/min) or normal albumin excretion rate (< 20 micrograms/min). We recruited 20 offspring of NIDDM patients with increased albumin excretion rate (A-off) and 20 offspring rate (N-off), matched for age, sex, body mass index, blood pressure and estimated protein intake. All offspring were normotensive, had normal creatinine clearance, normal glucose tolerance and sterile urine collection. Albumin excretion rate was measured on three sterile overnight urine collections and median values were used for calculations. Albumin excretion rate was significantly higher in A-off than in N-off (7.7 +/- 1.2 vs 3.4 +/- 0.6 micrograms/min p<0.01) and significantly related to parents' albumin excretion rate (p<0.01, r=0.53). These results suggest that an increased glomerular permeability is present in non-diabetic offspring of NIDDM patients with increased albumin excretion rate.
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PMID:Albumin excretion rate levels in non-diabetic offspring of NIDDM patients with and without nephropathy. 869 Jan 75

In insulin-dependent diabetes mellitus (IDDM), microalbuminuria predicts renal and cardiovascular disease. We report a combined analysis of 235 normotensive IDDM patients with microalbuminuria who participated in two 24-month double-blind, randomised, placebo-controlled trials to assess the effects of captopril 50 mg twice daily on the progression to overt clinical albuminuria. Of the 225 patients who were evaluable on an intent to treat basis, 25 of 114 placebo-treated patients (21.9%) and 8 or 111 captopril-treated patients (7.2%) progressed to persistent clinical albuminuria. The risk of progression over 24 months was significantly reduced by captopril (p = 0.004) with a risk reduction of 69.2% (95% confidence interval (CI):31.7 to 86.1%). This degree of risk reduction remained at the same level (62.9% [16.1-83.6%], p = 0.017) after adjustment for differences in time-varying mean arterial blood pressure. Albumin excretion rate increased by an average of 14.2% [3.1-26.5%] per year in the placebo-treated group compared with a reduction of 9.6% [-18.6-0.4%] per year in the captopril-treated group (p = 0.002). The rate of fall of creatinine clearance tended to be faster in the placebo-treated group than in the captopril-treated group (-6.4 [-10.2- -2.5] vs -1.4 [-5.3-2.6] ml.min-1.1.73m-2, p = 0.07). Baseline albumin excretion rate (p < 0.0001) and glycated haemoglobin (p = 0.03) were independent predictors of progression to clinical albuminuria and changes in mean arterial blood pressure (p = 0.02) and serum cholesterol level (p = 0.003) were significantly associated with percentage changes in albumin excretion rate. Captopril reduces the risk of progression to overt nephropathy in IDDM patients with microalbuminuria, an effect partly independent of its blood pressure-lowering effects.
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PMID:Captopril reduces the risk of nephropathy in IDDM patients with microalbuminuria. The Microalbuminuria Captopril Study Group. 873 19


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