Transferrinuria in Type 2 Diabetes: The Effect of Glycaemic Control

Abstract

SUMMARY. Urinary excretion rates of transferrin, albumin. N-acetyl-8-Dglucosaminidase (NAG) and a-I-microglobulin (A1 M) were measured in type 2 (non-insulin-dependent) diabetic patients at diagnosis and after 6 and 12 weeks treatment. Initially 21 (53%) patients had elevated transferrin excretion rates. The proportion of patients with raised transferrin excrction rates fcll to 30% at 6 wccks and 20% at 12 wecks with treatment of diabetcs. At diagnosis I 1 (28%) paticnts had elevated albumin excretion rates and 10 of these had clevatcd transferrin excrction rates. After 6 weeks treatment only six ( 1 So/,) had elevatcd albumin excrction ratcs and by 12 wecks this number had fallen to four (IOYO). NAG and A I M lcvcls also fcll with treatment of diabetes. There were correlations betwccn the transfcrrin cxcrction rate and albumin excretion rate ( r = 0436. P < 0.OOOl). transfcrrin excrction ratc and NAG ( r = 0.46, P < O.OOOl), and transferrin excrction ratc and A I M ( r = 0.55, P < 0.00Ol) at each visit. Therc were weaker correlations between thc albumin excretion rate and A I M and NAG at each visit. The correlations between the transfcrrin excretion ratc and markers of tubular function (NAG and AIM) suggest that tubular dysfunction may play a part in rcnal loss of transfcrrin in diabetes mellitus. There were no differences in transferrin excretion rates between patients with and without evidence of complications. Additional key phrases: alhuminuria; alpha-I-mi~~ro,~lohulin~ N-acetyl-hero-Dglucosamin idase

Urinary α1-Microglobulin as a Marker of Nephropathy in Type 2 Diabetic Asian Subjects in Singapore

“…Urinary ␣ 1 -microglobulin was also directly related to poorer control of diabetes, as measured by HbA 1c , fasting plasma glucose, and 2-h postprandial glucose, which is similar to findings in Caucasian populations (17,18). A study in Japan found that the development or progression of early diabetic nephropathy was inhibited by good glucose control (28).…”

“…Urinary ␣ 1 -microglobulin has been found to be higher, when compared with normal control subjects, in both type 1 (12) and type 2 diabetic subjects (13) and present even without clinical nephropathy (14,15). In type 2 diabetic subjects, ␣ 1 -microglobulin excretion was directly correlated with albuminuria (16) and HbA 1c levels (17) and decreased with improved glycemic control (17,18). These studies, however, were conducted on Caucasian populations, and the number of subjects was small (Ͻ100).…”

Urinary transferrin as an early biomarker of diabetic nephropathy

“…Similarly to our results, O'Donnell et al 23 found no correlation between urinary transferrin levels and glycemic control in the group of 40 DM2 patients at first day of the disease diagnosis and after 6 and 12 weeks of treatment. Urinary excretion rates of transferrin were measured, and they showed that urinary transferrin was not correlated with glycemic control.…”

Urinary Markers of Glomerular Injury in Diabetic Nephropathy

“…Nevertheless, glycemic control in newly diagnosed type 2 diabetic patients can effectively decrease transferrinuria [59]. Further evidence of transferrinuria as a marker of diabetic microvascular complications is the fact that urinary transferrin excretion is higher in type 2 diabetic patients with retinopathy [42, 44].…”

“…It is known that reabsorption of transferrin results in release of reactive iron [57], which can produce oxidative stress on the tubular epithelium. Several studies have shown that markers of proximal tubule damage (i.e., alpha-1-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG)) and urinary transferrin excretion are associated in diabetic patients [40, 43, 44, 53, 59]. It is not clear if transferrinuria is secondary to decreased tubular reabsorption, or transferrin is the cause of tubular damage.…”