Fructosamine and glycated albumin for risk stratification and prediction of incident diabetes and microvascular complications: a prospective cohort analysis of the Atherosclerosis Risk in Communities (ARIC) study

Abstract

Background Hemoglobin A1c (HbA1c) is the standard measure to monitor long-term glucose control in diabetes management and is now used for diagnosis. Fructosamine and glycated albumin are markers of short-term glycemic control that may add complementary information to HbA1c. However, the performance of fructosamine and glycated albumin to identify people at risk of complications is unclear. Methods We measured glycated albumin and fructosamine in 11348 adults without diabetes and 958 adults with diagnosed diabetes who attended the second examination of the Atherosclerosis Risk in Communities (ARIC) Study in 1990–1992 (baseline). We evaluated the associations of fructosamine and glycated albumin with retinopathy and risk of incident chronic kidney disease and incident diabetes during two decades of follow-up. We compared these associations to those for HbA1c. Findings Fructosamine and glycated albumin were strongly associated with retinopathy and these associations were very similar to that observed for HbA1c. Fructosamine and glycated albumin were also significantly associated with risk of incident chronic kidney disease and incident diabetes. Compared to persons with no diabetes and fructosamine or glycated albumin levels <75th percentile, the multivariable-adjusted hazard ratios (95%CIs) for chronic kidney disease for persons with fructosamine and glycated albumin levels >95th percentile were 1.50 (1.22, 1.85) and 1.48 (1.20, 1.83), respectively. The HRs for incident diabetes were 4.96 (4.36, 5.64) for fructosamine >95th percentile and 6.17 (5.45, 6.99) for glycated albumin >95th percentile. Associations were attenuated but persisted after adjustment for HbA1c. Prediction of incident chronic kidney disease by fructosamine (C-statistic, 0.717) and glycated albumin (C-statistic, 0.717) were nearly as strong as by HbA1c (C-statistic, 0.726) but HbA1c outperformed fructosamine and glycated albumin for prediction of incident diabetes with C-statistics of 0.760, 0.706, and 0.703, respectively. Interpretation Fructosamine and glycated albumin were strongly associated with diabetes and its microvascular complications and complemented the prognostic utility of HbA1c.

The ratio of glycated albumin to hemoglobin A1c measured in IFCC units accurately represents the glycation gap

“…The G-gap is also reported to be an indicator with biological variation [5,31], and Nayak et al [6] reported that the G-gap has consistent biological variability in individuals. Recently, as mentioned above, fructosamine or GA and G-gap have been reported as predictive indicators for diabetic complications independent of A1C [16,17,32]. If the GA/A1C-SI ratio reflected the difference in biological variability of glycation between GA in the circulation and A1C within the cell, the GA/ A1C-SI ratio might be a predictive indicator of diabetic complications accurately representing the G-gap.…”

“…GA is not affected by other glycated proteins in serum, compared with fructosamine which is including glycated proteins other than albumin. Selvin et al reported the prediction of incident diabetes and microvascular complications by both fructosamine and GA [17]. Thus, GA is considered to be almost biologically equal to fructosamine for calculating G-gap.…”

“…The GA/A1C ratio may not be derivable from HbA1c by any simple conversion formula. Recently Cohen [32] pointed out an unexplained finding in the analyses by Selvin et al [17] that there was a proportionately greater increase in GA and fructosamine concentrations than of A1C concentrations in the range of 5.4-5.8% in non-diabetic participants, apparent in the plots of GA and fructosamine versus A1C fitted with a nonlinear curve. By contrast, the relationships between A1C and both GA and fructosamine were linear within the diabetic population.…”

“…Furthermore, Selvin et al reported the prediction of incident diabetes and microvascular complications by both fructosamine and GA [17]. The prediction power differed little between fructosamine and GA.…”

Association between direct measurement of active serum calcium and risk of type 2 diabetes mellitus: A prospective study

“…Similarly, higher levels of plasma lactate are associated with incident T2DM (31) and could modify calcium fractions (28). Lastly, it is worth noting that adjustment for albumin concentration has been proposed for another biomarker associated with incident T2DM (fructosamine) (32,33), although it is still unclear the appropriateness of such adjustment given (34). Interestingly, our results are in line with a previous study showing no difference in direct iCa measurement comparing subjects with and without diabetes (11); notably, the Authors speculated that 'correction' of total calcium for serum albumin would not be appropriate because of an increased serum free fatty acids concentrations.…”