Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Diabetes. Jan 15, 2019; 10(1): 1-15
Published online Jan 15, 2019. doi: 10.4239/wjd.v10.i1.1
Update on biomarkers of glycemic control
Maja Krhač, Marijana Vučić Lovrenčić
Maja Krhač, Marijana Vučić Lovrenčić, Division of Laboratory Medicine, Department of Medical Biochemistry and Laboratory Medicine, Merkur University Hospital, Zagreb 10000, Croatia
Author contributions: The authors equally contributed to this paper in the conception, literature review and analysis, drafting and editing, and final approval of the submission.
Conflict-of-interest statement: No potential conflicts of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Marijana Vučić Lovrenčić, PhD, Senior Scientist, Division of Laboratory Medicine, Department of Medical Biochemistry and Laboratory Medicine, Merkur University Hospital, Zajčeva 19, Zagreb 10000, Croatia. vucic@idb.hr
Telephone: +385-1-2353861 Fax: +385-1-2353847
Received: August 29, 2018
Peer-review started: August 29, 2018
First decision: October 16, 2018
Revised: November 14, 2018
Accepted: December 5, 2018
Article in press: December 5, 2018
Published online: January 15, 2019
Processing time: 140 Days and 20.2 Hours
Abstract

Attaining and maintaining good glycemic control is a cornerstone of diabetes care. The monitoring of glycemic control is currently based on the self-monitoring of blood glucose (SMBG) and laboratory testing for hemoglobin A1c (HbA1c), which is a surrogate biochemical marker of the average glycemia level over the previous 2-3 mo period. Although hyperglycemia is a key biochemical feature of diabetes, both the level of and exposure to high glucose, as well as glycemic variability, contribute to the pathogenesis of diabetic complications and follow different patterns in type 1 and type 2 diabetes. HbA1c provides a valuable, standardized and evidence-based parameter that is relevant for clinical decision making, but several biological and analytical confounders limit its accuracy in reflecting true glycemia. It has become apparent in recent years that other glycated proteins such as fructosamine, glycated albumin, and the nutritional monosaccharide 1,5-anhydroglucitol, as well as integrated measures from direct glucose testing by an SMBG/continuous glucose monitoring system, may provide valuable complementary data, particularly in circumstances when HbA1c results may be unreliable or are insufficient to assess the risk of adverse outcomes. Long-term associations of these alternative biomarkers of glycemia with the risk of complications need to be investigated in order to provide clinically relevant cut-off values and to validate their utility in diverse populations of diabetes patients.

Keywords: Diabetes mellitus; Hemoglobin A1c; Fructosamine; Glycated albumin; 1,5-anhydroglucitol; Plasma glucose; Glucose variability; Diabetic complications

Core tip: Monitoring of glycemic control is currently based on the self-monitoring of blood glucose and laboratory testing for hemoglobin A1c (HbA1c), which is a surrogate marker of the average glycemia level over the past 2-3 mo. The severity of hyperglycemia and glycemic variability contribute to the pathogenesis of complications, but the HbA1c measurement reflects only a piece of these important variables. In this review, we provide a critical update on the use of HbA1c and alternative biomarkers of glycemic control, with particular emphasis on the need for a personalized approach in utilizing and interpreting different tests in a clinically meaningful manner.