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.
BACKGROUND
HbA1c is the standard measure by which to monitor long-term (2-3 months) glucose control in people with diabetes and is now used for diagnosis of diabetes. Fructosamine and glycated albumin are markers of short-term (2-4 weeks) glycaemic control that might add complementary prognostic information to HbA1c. Our aim was to clarify the performance of fructosamine and glycated albumin measurements for identifying people at risk of incident diabetes or diabetic complications.


METHODS
We measured glycated albumin and fructosamine in blood samples from 11 348 adults without diabetes and 958 adults diagnosed with diabetes mellitus (both type 1 and 2) who attended the second examination of the Atherosclerosis Risk in Communities (ARIC) study in 1990-92 (baseline). We assessed the associations of fructosamine and glycated albumin with risk of incident diabetes, retinopathy, and risk of incident chronic kidney disease (CKD), during two decades of follow-up. We compared these associations with those of HbA1c with incident diabetes, retinopathy, and CKD. For analyses of associations with incident diabetes and CKD, adjusted hazard ratios (HRs) and their corresponding 95% CIs were estimated using Cox proportional hazards models. Model discrimination was assessed using Harrell's C statistic.


RESULTS
The HRs for incident diabetes were 4·96 (4·36-5·64) for fructosamine above the 95th percentile and 6·17 (5·45-6·99) for glycated albumin above the 95th percentile. Associations were attenuated but persisted after adjustment for HbA1c. Fructosamine and glycated albumin were strongly associated with retinopathy (p<0·0001 for trend). The multivariable-adjusted HRs for CKD for people with fructosamine and glycated albumin above the 95th percentile were 1·50 (95% CI 1·22-1·85) and 1·48 (1·20-1·83), respectively, when compared with people with no diabetes and fructosamine or glycated albumin below the 75th percentile. Prediction of incident CKD by fructosamine (C statistic 0·717) and glycated albumin (0·717) were nearly as strong as by HbA1c (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.


CONCLUSIONS
Fructosamine and glycated albumin were strongly associated with incident diabetes and its microvascular complications, with prognostic value comparable to HbA1c.


BACKGROUND
National Heart, Lung, and Blood Institute.
Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Division of General Internal Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA. Electronic address: lselvin@jhsph.edu.
Elizabeth
E
Selvin
Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Division of General Internal Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Andreea M
AM
Rawlings
Division of Nephrology, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Morgan
M
Grams
Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Ronald
R
Klein
Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
A Richey
AR
Sharrett
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MD, USA.
Michael
M
Steffes
Department of Epidemiology and the Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; Division of General Internal Medicine, Department of Medicine, Johns Hopkins University, Baltimore, MD, USA.
Josef
J
Coresh
D000368:Aged; D050197:Atherosclerosis / Q000150:complications / Q000175:diagnosis*; D015331:Cohort Studies; D048909:Diabetes Complications / Q000175:diagnosis*; D003920:Diabetes Mellitus / Q000175:diagnosis*; D003925:Diabetic Angiopathies / Q000175:diagnosis*; D005260:Female; D019270:Fructosamine; D006442:Glycated Hemoglobin / Q000032:analysis; D017127:Glycation End Products, Advanced; D006801:Humans; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018570:Risk Assessment / Q000379:methods; D012709:Serum Albumin; D000093423:Glycated Serum Albumin
D019270:Fructosamine; D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced; D012709:Serum Albumin; D000093423:Glycated Serum Albumin