3-Deoxyfructose concentrations are increased in human plasma and urine in diabetes.
3-Deoxyglucosone (3-DG) is a reactive dicarbonyl sugar thought to be a key intermediate in the nonenzymatic polymerization and browning of proteins by glucose. 3-DG may be formed in vivo from fructose, fructose 3-phosphate, or Amadori adducts to protein, such as N epsilon-fructoselysine (FL), all of which are known to be elevated in body fluids or tissues in diabetes. Modification of proteins by 3-DG formed in vivo is thought to be limited by enzymatic reduction of 3-DG to less reactive species, such as 3-deoxyfructose (3-DF). In this study, we have measured 3-DF, as a metabolic fingerprint of 3-DG, in plasma and urine from a group of diabetic patients and control subjects. Plasma and urinary 3-DF concentrations were significantly increased in the diabetic compared with the control population (0.853 +/- 0.189 vs. 0.494 +/- 0.072 microM, P < 0.001, and 69.9 +/- 44.2 vs. 38.7 +/- 16.1 nmol/mg creatinine, P < 0.001, respectively). Plasma and urinary 3-DF concentrations correlated strongly with one another, with HbA1c (P < 0.005 in all cases), and with urinary FL (P < 0.02 and P = 0.005, respectively). The overall increase in 3-DF concentrations in plasma and urine in diabetes and their correlation with other indexes of glycemic control suggest that increased amounts of 3-DG are formed in the body during hyperglycemia in diabetes and then metabolized to 3-DF. These observations are consistent with a role for increased formation of the dicarbonyl sugar 3-DG in the accelerated browning of tissue proteins in diabetes.
Wells-Knecht
K J
KJ
Department of Chemistry and Biochemistry, University of South Carolina, Columbia 29208.
Lyons
T J
TJ
McCance
D R
DR
Thorpe
S R
SR
Feather
M S
MS
Baynes
J W
JW
D000293:Adolescent; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood / Q000652:urine; D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus / Q000097:blood* / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000652:urine; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000652:urine; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007661:Ketoses / Q000097:blood* / Q000652:urine*; D008239:Lysine / Q000031:analogs & derivatives / Q000652:urine; D008875:Middle Aged; D012016:Reference Values; D012044:Regression Analysis
D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D007661:Ketoses; D008239:Lysine; C033186:fructosyl-lysine; C068286:3-deoxyhexulose