Plasma disappearance of glycated and non-glycated albumin in Type 1 (insulin-dependent) diabetes mellitus: evidence for charge dependent alterations of the plasma to lymph pathway

Abstract

The fractional plasma escape rates of glycated and non-glycated albumin have earlier been measured in groups of Type 1 (insulin-dependent) diabetic patients and control subjects. The escape of non-glycated albumin was similar in control subjects and normoalbuminuric patients, but elevated in patients with micro or macroalbuminuria. In all groups the escape rate of glycated albumin was lower than that of non-glycated albumin. Glycation increases the anionic charge of albumin. To assay for charge-dependent alterations of transport a selectivity index (non-glycated albumin/glycated albumin transport ratio) was determined from the disappearance data. The index was high in control subjects (1.021 +/- 0.0057 (SEM)). This reflects a mean difference between the two escape rates of 2.1% per hour (for comparison the mean of the fractional escape rate of non-glycated albumin of the normal control subjects was 4.7% per hour). The index was numerically even higher in normoalbuminuric patients (1.031 +/- 0.0047 (SEM)), but reached significantly lower levels in patients with microalbuminuria (1.013 +/- 0.0030 (SEM), p < 0.02). Patients with clinical nephropathy had very low levels indicating loss of selectivity (1.002 +/- 0.0068 (SEM), p < 0.001). This pattern accords well with measurements of renal clearance selectivity indices, suggesting a general, progressive deterioration of anionic perivascular barrier components in diabetic microangiopathy. The structural target for these changes is likely to be the glycosaminoglycans of the glomerular basal membrane and the interstitial matrix.

Discordance Between HbA1c and Fructosamine

“…Patients with a high GG and high risk of nephropathy have a low FA in relationship to the HbA 1c . This would be the direction anticipated if albumin has a shorter survival time in the circulation, upon loss of glomerular selectivity (18,19). However, the lack of significant difference in FA by nephropathy stage is itself an argument that the findings are not explained by reduced FA in the group with urinary protein loss.…”

“…There is evidence that glycated albumin is no more likely to be lost in the urine than nonglycated albumin (17)(18)(19). At total body albumin daily synthesis of 13.9 g/person reported in patients with type 1 diabetes and nephropathy (20), GG would be altered by 0.1% for each 213 mg/24 h of urinary albumin at the group mean FA of 386.…”

Macro-microangiopathy and endothelial dysfunction in NIDDM patients with and without diabetic nephropathy

“…Changes in the size and charge selectiveproperties of the microvasculature may occur due to structural lesions [23] and/or biochemical abnormalities, e. g. in heparan sulphate proteoglycan [15]. Recent findings signal that loss of charge selectivity contributes to the elevated TER alb in IDDM patients with diabetic nephropathy [44]. The mechanisms involved in the raised TER alb seem to differ between our patients with and without nephropathy.…”

The promise of nanotechnology for separation devices – from a top‐down approach to nature‐inspired separation devices

“…The sieving mechanism would then be quite akin to that occurring, e.g. in the basal membrane of the kidney, where the negatively charged albumin is prevented from passing from the blood to the primary urine by a combination of size filtering and co-ion exclusion by the negatively charged matrix [21]. The larg- Figure 2.…”