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Genome-Wide Association Study of Serum Fructosamine and Glycated Albumin in Adults Without Diagnosed Diabetes: Results From the Atherosclerosis Risk in Communities Study.

ABSTRACT: Fructosamine and glycated albumin are potentially useful alternatives to hemoglobin A1c (HbA1c) as diabetes biomarkers. The genetic determinants of fructosamine and glycated albumin, however, are unknown. We performed genome-wide association studies of fructosamine and glycated albumin among 2,104 black and 7,647 white participants without diabetes in the Atherosclerosis Risk in Communities (ARIC) Study and replicated findings in the Coronary Artery Risk Development in Young Adults (CARDIA) study. Among whites, rs34459162, a novel missense single nucleotide polymorphism (SNP) in RCN3, was associated with fructosamine (P = 5.3 × 10-9) and rs1260236, a known diabetes-related missense mutation in GCKR, was associated with percent glycated albumin (P = 5.9 × 10-9) and replicated in CARDIA. We also found two novel associations among blacks: an intergenic SNP, rs2438321, associated with fructosamine (P = 6.2 × 10-9), and an intronic variant in PRKCA, rs59443763, associated with percent glycated albumin (P = 4.1 × 10-9), but these results did not replicate. Few established fasting glucose or HbA1c SNPs were also associated with fructosamine or glycated albumin. Overall, we found genetic variants associated with the glycemic information captured by fructosamine and glycated albumin as well as with their nonglycemic component. This highlights the importance of examining the genetics of hyperglycemia biomarkers to understand the information they capture, including potential glucose-independent factors.

SUBMITTER: Loomis SJ

PROVIDER: S-EPMC6054442 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Genome-Wide Association Study of Serum Fructosamine and Glycated Albumin in Adults Without Diagnosed Diabetes: Results From the Atherosclerosis Risk in Communities Study.

Loomis Stephanie J SJ Li Man M Maruthur Nisa M NM Baldridge Abigail S AS North Kari E KE Mei Hao H Morrison Alanna A Carson April P AP Pankow James S JS Boerwinkle Eric E Scharpf Robert R Rasmussen-Torvik Laura J LJ Coresh Josef J Duggal Priya P Köttgen Anna A Selvin Elizabeth E

Diabetes 20180529 8

Fructosamine and glycated albumin are potentially useful alternatives to hemoglobin A<sub>1c</sub> (HbA<sub>1c</sub>) as diabetes biomarkers. The genetic determinants of fructosamine and glycated albumin, however, are unknown. We performed genome-wide association studies of fructosamine and glycated albumin among 2,104 black and 7,647 white participants without diabetes in the Atherosclerosis Risk in Communities (ARIC) Study and replicated findings in the Coronary Artery Risk Development in Youn ...[more]

PMID: 29844224

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Project description:BackgroundHbA1c 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.MethodsWe 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.FindingsThe 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.InterpretationFructosamine and glycated albumin were strongly associated with incident diabetes and its microvascular complications, with prognostic value comparable to HbA1c.FundingNational Heart, Lung, and Blood Institute.

Dataset Information

Genome-Wide Association Study of Serum Fructosamine and Glycated Albumin in Adults Without Diagnosed Diabetes: Results From the Atherosclerosis Risk in Communities Study.

Publications

Genome-Wide Association Study of Serum Fructosamine and Glycated Albumin in Adults Without Diagnosed Diabetes: Results From the Atherosclerosis Risk in Communities Study.

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