Non-enzymatic glycosylation of urinary proteins in Type 1 (insulin-dependent) diabetes: correlation with metabolic control and the degree of proteinuria

G, Gragnoli; Signorini, A. M.; Tanganelli, I

doi:10.1007/bf00262211

Cited by 20 publications

(4 citation statements)

References 17 publications

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“…The increased selectivity index found in normoalbuminuric patients is hardly explained by increased tubular reabsorption of the more anionically charged glycated albumin, since an increased tubular reabsorption of cationic albumin has been demonstrated in rats [17]. Our results disagree with previous observations of a preferential urinary excretion of glycated protein in diabetic patients [19,20]. The method used by these authors for determination of glycated proteins was, however, less specific [5] and unreliable in our hands [6].…”

Section: Discussioncontrasting

confidence: 95%

Evidence of changes in renal charge selectivity in patients with Type 1 (insulin-dependent) diabetes mellitus

Kverneland¹,

Feldt‐Rasmussen²,

Vidal

et al. 1986

Diabetologia

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Altered filtration of macromolecules due to decreased electrical charge of the glomerular basement membrane might be the initial step in the development of albuminuria in patients with Type 1 (insulin-dependent) diabetes mellitus. We therefore investigated the selectivity index, i.e. renal clearance of non-glycated plasma albumin/clearance of glycated plasma albumin in 38 patients with Type 1 diabetes mellitus. The two albumin molecules differed slightly in charge, non-enzymatic glycated albumin being more anionic at physiological pH compared with unmodified plasma albumin. Glycated albumin in plasma and urine was determined by a specific, sensitive and highly reproducible chromatographic procedure. In diabetic patients with normal urinary albumin excretion, the selectivity index was increased three-fold compared with that of non-diabetic subjects (2 p less than 0.01). A significant correlation (r = 0.53, 2 p less than 0.01) between haemoglobin A1c and selectivity index was demonstrated in these patients, indicating a change in charge-dependent renal filtration could possibly be attributed to non-enzymatic glycation of components in the glomerular basement membrane and tubuli. Diabetic patients with increased albumin excretion rate had a significantly lower selectivity index compared with patients with normal albumin excretion (2 p less than 0.01). A significant negative correlation (r = 0.85, 2 p less than 0.001, exponential curve fit) was seen between urinary albumin excretion and selectivity index in the diabetic patients, indicating that the capability of differentiating between macromolecules of different charges is again lost with increasing urinary albumin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

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Section: Discussioncontrasting

confidence: 95%

Evidence of changes in renal charge selectivity in patients with Type 1 (insulin-dependent) diabetes mellitus

Kverneland¹,

Feldt‐Rasmussen²,

Vidal

et al. 1986

Diabetologia

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“…This finding indicates that in normoalbuminuric diabetic patients the renal excretion of glycated albumin is relatively lower than that of non-glycated albumin, as previously documented by Kverneland et al [7,8] on 24-h urine collection during normal physical activity. On the other hand, our results and those of Kverneland et al disagree with the preferential urinary excretion of glycated proteins reported by others [5,6] using a method considered as poorly specific for glycated albumin [17].…”

Section: Discussioncontrasting

confidence: 99%

The increase in albuminuria induced by exercise is not associated with preferential excretion of glycated albumin in Type 1 (insulin-dependent) diabetic patients

et al. 1991

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The increase in urinary albumin excretion induced by acute exercise in Type 1 (insulin-dependent) diabetic patients is associated with the urinary excretion of cationic proteins. To test whether the renal excretion of glycated albumin (more anionic than non-glycated albumin) is affected by exercise, we submitted seven normoalbuminuric (albumin excretion rate less than 30 mg/24 h) Type 1 diabetic patients and six well-matched healthy subjects to an exercise test (600 kpm/min for 20 min) on a bicycle ergometer, preceded and followed by a 1-h resting period. The selectivity index (renal clearance of non-glycated/glycated albumin) was not significantly different among the pre-exercise, exercise and post-exercise periods, either in the normal subjects (1.01 +/- 0.03 vs 1.08 +/- 0.06 vs 1.08 +/- 0.05) or in the diabetic patients (1.25 +/- 0.09 vs 1.20 +/- 0.07 vs 1.20 +/- 0.06), whereas it was significantly higher (p less than 0.05) in diabetic patients compared to healthy subjects during pre-exercise. These results are not consistent with the hypothesis that acute exercise may induce a preferential excretion of glycated albumin.

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“…Administration of anti-glycated albumin antibody in animal models reduces plasma levels of glycated albumin, reduces AER, and reverses glomerular pathology (22). Human studies have been conflicting, perhaps in part because of small numbers and confounding by other risk factors, but one of the largest previous studies clearly indicated that Amadori albumin levels were elevated in individuals with nephropathy compared with individuals without nephropathy (15,(23)(24)(25).…”

Section: Discussionmentioning

confidence: 99%

Circulating and Urinary Transforming Growth Factor β1, Amadori Albumin, and Complications of Type 1 Diabetes

Chaturvedi¹,

Schalkwijk

Abrahamian

et al. 2002

Diabetes Care

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OBJECTIVE -Transforming growth factor (TGF)-␤1 is overexpressed in diabetes as a consequence of hyperglycemia and the creation of early glycated end products and may be responsible for the characteristic structural renal changes associated with diabetes. We sought to examine the role of both urinary and circulating TGF-␤1 and its promoter Amadori albumin in the vascular complications of type 1 diabetes. RESEARCH DESIGN AND METHODS -The present article reports on a nested casecontrol study from the EURODIAB Prospective Complications Study of Europeans with type 1 diabetes. Case subjects (n ϭ 356) were all individuals with one or more complications of diabetes; control subjects (n ϭ 185) were all individuals with no evidence of complications.RESULTS -Urinary TGF-␤1 and Amadori albumin were elevated in patients with micro-or macroalbuminuria. Standardized regression effects (SREs) for macroalbuminuria versus normoalbuminuria were 2.45 (95% CI 1.88 -3.18, P ϭ 0.0001 for urinary TGF-␤1) and 1.67 (1.34 -2.07, P ϭ 0.001 for Amadori albumin). The SRE for urinary TGF-␤1 remained statistically significant when adjusted for HbA 1c , Amadori albumin, and blood pressure. Circulating TGF-␤1 was elevated in individuals with proliferative retinopathy compared with individuals without retinopathy (SRE 1.29 [1.07-1.550], P ϭ 0.007). This result was attenuated to 1.16 (0.95-1.43, P ϭ 0.2) in the multivariate model, largely because of HbA 1c .CONCLUSIONS -Elevated levels of urinary TGF-␤1 in macroalbuminuria were associated with elevations in Amadori albumin and HbA 1c and also in blood pressure. In contrast, only circulating TGF-␤1 was related to proliferative retinopathy, and HbA 1c largely accounted for this. These findings may indicate novel pathways for understanding mechanisms and therapeutic interventions. Diabetes Care 25:2320 -2327, 2002I mprovements in glycemic control and the greater use of antihypertensive therapy should eventually have a beneficial impact on the incidence of severe nephropathy in type 1 diabetes. However, early disease, such as microalbuminuria and macroalbuminuria, will continue to occur because glycemic control cannot wholly prevent the progression of albuminuria, and there is currently little evidence that antihypertensive use in normotensive normoalbuminuric patients is of clinical value (1). Both microalbuminuria and macroalbuminuria significantly increase the risk of morbidity and mortality from coronary heart disease and are strong predictors of subsequent severe renal disease (2). Prevention of the early stages of diabetic renal disease and reduction in progression should now be priorities, but these steps require a more complete understanding of the etiology to identify suitable targets for intervention.Diabetic nephropathy is characterized by hypertrophy of the glomerular and tubuloepithelial structures and thickening of the glomerular and tubular basement membrane, due largely to the effects of hyperglycemia (3). The cytokine transforming growth factor (TGF)-␤1 appears to be a key mediator f...

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Non-enzymatic glycosylation of urinary proteins in Type 1 (insulin-dependent) diabetes: correlation with metabolic control and the degree of proteinuria

Cited by 20 publications

References 17 publications

Evidence of changes in renal charge selectivity in patients with Type 1 (insulin-dependent) diabetes mellitus

Evidence of changes in renal charge selectivity in patients with Type 1 (insulin-dependent) diabetes mellitus

The increase in albuminuria induced by exercise is not associated with preferential excretion of glycated albumin in Type 1 (insulin-dependent) diabetic patients

Circulating and Urinary Transforming Growth Factor β1, Amadori Albumin, and Complications of Type 1 Diabetes

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