Discordance between HbA1c and fructosamine: evidence for a glycosylation gap and its relation to diabetic nephropathy.
OBJECTIVE
Discordances between HbA1c and other measures of glycemic control are common in clinical practice and remain unexplained. We developed a measure of discordance between HbA1c and fructosamine (FA) (glycosylated serum proteins) to conduct a systematic evaluation. We termed this the glycosylation gap (GG) and sought to determine its relationship to diabetic nephropathy.


METHODS
Measurements of HbA1c and FA on the same sample in 153 people were used to calculate GG, defined as the difference between measured HbA1c and HbA1c predicted from FA based on the population regression of HbA1c on FA.


RESULTS
GG had a broad distribution (range, -3.2% to 5.5%); 40% of samples had values indicating major differences in prediction of complications risk by the measured versus predicted HbA1c. GG was highly correlated (r = 0.81) between measurements repeated in 65 patients 23 +/- 2 weeks apart, indicating that the discordances are reliable and not explained by differences in turnover of underlying proteins. In 40 patients with type 1 diabetes of >or = 15 years' duration, an increase in GG by 1% was associated with a 2.9-fold greater frequency of increasing nephropathy stage (P = 0.0014). GG was -0.8 +/- 0.2% in subjects with no nephropathy, -0.3 +/- 0.2% with microalbuminuria/hypertension, and 0.7 +/- 0.3% in subjects with proteinuria or renal dysfunction (P < 0.05). GG correlated better with nephropathy than did either HbA1c or FA alone in this population.


CONCLUSIONS
The glycosylation gap may be a useful clinical research tool for evaluating physiologic sources of variation in diabetic complications beyond glycemic control.
Cohen
Robert M
RM
Division of Endocrinology, Department of Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio 45267-0547, USA. robert.cohen@uc.edu
Holmes
Yancey R
YR
Chenier
Thomas C
TC
Joiner
Clinton H
CH
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000453:epidemiology / Q000378:metabolism*; D005260:Female; D019270:Fructosamine / Q000097:blood*; D006442:Glycated Hemoglobin / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011237:Predictive Value of Tests; D012044:Regression Analysis; D015203:Reproducibility of Results; D012307:Risk Factors
D019270:Fructosamine; D006442:Glycated Hemoglobin