Relationship of Prospective GHb to Glycated Serum Proteins in Incident Diabetic Retinopathy
Implications of the glycation gap for mechanism of risk prediction
- Robert M. Cohen, MD12,
- Tamara J. LeCaire, MS3,
- Christopher J. Lindsell, PHD4,
- Eric P. Smith, MD1 and
- Donn J. D'Alessio, MD3
- 1Division of Endocrinology, Metabolism and Diabetes, University of Cincinnati Medical Center, Cincinnati, Ohio
- 2General Clinical Research Center, University of Cincinnati Medical Center, Cincinnati, Ohio
- 3Department of Population Health Sciences, University of Wisconsin, Madison, Wisconsin
- 4Department of Emergency Medicine, University of Cincinnati Medical Center, Cincinnati, Ohio
- Address correspondence and reprint requests to Robert M. Cohen, MD, University of Cincinnati, P.O. Box 670547, Cincinnati, OH 45267-0547. E-mail: robert.cohen{at}uc.edu
When estimating long-term glycemic control, A1C is considered the gold standard (1–3), but patients with seemingly equivalent A1C differ in their risk for microvascular complications (4,5). Recently, the “glycation gap,” defined as the difference between the measured A1C and that which would be predicted from another measure of glycemic control, fructosamine, has been proposed as a means of identifying sources of variance in the apparent risk (6). Because hemoglobin is an intracellular protein and fructosamine reflects extracellular proteins, the glycation gap could result from differences between the ambient glucose concentrations or rates of glycation in the intracellular and extracellular compartments or interindividual differences in the turnover/metabolism of underlying proteins (6). In this study, we sought to determine whether there are differences in the relationship of GHb to fructosamine in diabetic subjects who do or do not develop retinopathy.
RESEARCH DESIGN AND METHODS—
The present study was completed in collaboration with the Wisconsin Diabetes Registry Study (WDRS), an incident type 1 diabetes cohort followed for complications over 4–14 years’ duration. The WDRS has been described previously (7). New fructosamine testing was completed in 86 subjects who were identified among 290 with fundus photographs at 9 years. Patients with retinopathy (n = 13), patients with missing photographs indicating no retinopathy (n = 38) at 4 years or missing GHb or random glucose at 4 and/or 9 years (n = 118), and patients having insufficient plasma for testing fructosamine at the 4-year exam (n = 35) were excluded. Of the 86 eligible patients, 2 with fructosamine concentrations >1,000 μmol/l were omitted. …
