Formation of immunochemical advanced glycosylation end products precedes and correlates with early manifestations of renal and retinal disease in diabetes.
Elevated levels of advanced glycosylation end products (AGEs) have been found in multiple tissues in association with diabetic vascular complications and during the microalbuminuric phase of diabetic nephropathy. In this study, we have used an AGE-specific enzyme-linked immunosorbent assay (ELISA) to measure skin AGEs to determine whether elevated levels can be detected before the onset of overt microangiopathy. Subjects with type I diabetes (n = 48) were graded for the degree of nephropathy (normal [23], microalbuminuria [12], or macroalbuminuria [12]) and retinopathy (none [13], background [20], or proliferative [15]). Subgroups with a premicroalbuminuric phase of albumin excretion (< or = 28 mg/24 h, n = 27) or with the earliest stages of retinopathy (n = 27) were identified. A significant increase in tissue AGEs was found as urinary albumin increased during the premicroalbuminuric phase of nephropathy even when the data were adjusted for age and duration of diabetes (P = 0.005). Immunoreactive AGEs also increased as normal renal status advanced to microalbuminuria and macroalbuminuria (P = 0.0001 across groups). Significant elevation of AGEs was also found in association with the earliest stages of clinically evident retinopathy (early background versus minimal grades). In addition, higher AGE levels were found in subjects with proliferative retinopathy when compared with those with less severe retinopathy (P < 0.004 across groups). In contrast, no significant differences were found in tissue AGE levels between groups with or without early retinopathy based on pentosidine or fluorescent AGE measurements, although fluorescent AGEs correlated with albumin excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
Beisswenger
P J
PJ
Department of Medicine, Dartmouth Medical School, Hanover, New Hampshire, USA.
Makita
Z
Z
Curphey
T J
TJ
Moore
L L
LL
Jean
S
S
Brinck-Johnsen
T
T
Bucala
R
R
Vlassara
H
H
D000328:Adult; D000419:Albuminuria; D000704:Analysis of Variance; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000032:analysis; D003094:Collagen / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D003928:Diabetic Nephropathies / Q000378:metabolism / Q000473:pathology* / Q000652:urine; D003930:Diabetic Retinopathy / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D017127:Glycation End Products, Advanced / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D012044:Regression Analysis; D012867:Skin / Q000378:metabolism / Q000473:pathology*
D015415:Biomarkers; D001786:Blood Glucose; D017127:Glycation End Products, Advanced; D003094:Collagen