Raised serum sialic acid concentration precedes onset of microalbuminuria in IDDM. A 10-year follow-up study.
OBJECTIVE
Elevated concentrations of serum sialic acid, a potent cardiovascular risk factor in the general population, have been found in patients with IDDM and microalbuminuria. We investigated whether a coincidence exists between the increase of sialic acid concentrations and albuminuria in the transition from normoalbuminuria to microalbuminuria. Furthermore, the predictability of increased sialic acid as well as von Willebrand factor (vWF) and total and HDL cholesterol concentrations in development of persistent microalbuminuria in IDDM was investigated.


METHODS
This 10-year prospective study was carried out in a cohort of 209 IDDM patients with normoalbuminuria at baseline.


RESULTS
Of the cohort, 198 patients completed the follow-up period and 27 developed persistent microalbuminuria (urinary albumin excretion rate [UAER] > or = 30 mg/24 h). A coincident increase of UAER and serum sialic acid concentration was seen before persistent microalbuminuria was diagnosed. Elevation of serum sialic acid concentrations in those who later developed microalbuminuria occurred 3 years before the diagnosis of persistent microalbuminuria. Baseline serum sialic acid concentrations were significantly higher in the group of patients who later developed microalbuminuria than in the group who remained normoalbuminuric (2.02 +/- 0.41 vs. 1.85 +/- 0.31 mmol/l [means +/- SD], P < 0.05). Baseline serum sialic acid concentration correlated significantly with HbA1c, UAER, blood pressure, total cholesterol, HDL cholesterol, and vWF and was significantly predictive for development of microalbuminuria (hazards ratio [95% CI], 3.1 [1.2-8.1]; P = 0.02) after adjustments for sex, duration of diabetes, smoking, blood pressure, vWF, total cholesterol, and HDL cholesterol. Adjustment for the effects of HbA1c and UAER, however, canceled out the predictive effect of serum sialic acid.


CONCLUSIONS
UAER and serum sialic acid concentration increase coincidentally before the onset of persistent microalbuminuria. An increased serum sialic acid concentration is predictive for the onset of microalbuminuria independent of age, sex, diabetes duration, smoking, blood pressure, vWF, and total HDL cholesterol.
Yokoyama
H
H
Steno Diabetes Center, Gentofte, Denmark.
Jensen
J S
JS
Myrup
B
B
Mathiesen
E R
ER
Rønn
B
B
Deckert
T
T
D000328:Adult; D000419:Albuminuria / Q000453:epidemiology; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000503:physiopathology / Q000652:urine; D003928:Diabetic Nephropathies / Q000097:blood / Q000175:diagnosis* / Q000652:urine; D005260:Female; D005500:Follow-Up Studies; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D019158:N-Acetylneuraminic Acid; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012794:Sialic Acids / Q000097:blood*; D013997:Time Factors; D014841:von Willebrand Factor / Q000032:analysis
D015415:Biomarkers; D002784:Cholesterol; D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D019158:N-Acetylneuraminic Acid; D012794:Sialic Acids; D014841:von Willebrand Factor