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: 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.

Findings: 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.

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

Funding: National Heart, Lung, and Blood Institute.

Figure 1. Adjusted Hazard Ratios (95% Confidence Intervals) for baseline Fructosamine, Glycated Albumin, and Hemoglobin A1c with incident Chronic Kidney Disease and Incident Diabetes

Legend: Adjusted hazard ratios are from Cox proportional hazards models with adjustment for age (years), race-center, sex (male, female), body mass index (kg/m²), (body mass index)². Baseline fructosamine, glycated albumin, and hemoglobin A1c were modeled using restricted cubic splines (solid lines) with knots at the 5^th, 35^th, 65^th, and 95^th percentiles. All models are centered at the 50^th percentile (fructosamine: 228 umol/L, glycated albumin: 12.7%, hemoglobin A1c: 5.4%). The shaded areas are the confidence intervals for the restricted cubic spline models. Models are truncated at the 5^th and 95^th percentile of each marker, histograms are truncated at the 1^st and 99^th percentile. For incident chronic kidney disease, baseline study population was limited to persons with normal kidney function (estimated glomerular filtration rate ≥60 ml/min/1.73 m²), N=11,932. For incident diabetes, baseline study population was limited to persons without a history of diabetes, N=10,946.