Addressing shortfalls of laboratory HbA1c using a model that incorporates red cell lifespan

Abstract

Laboratory HbA1c does not always predict diabetes complications and our aim was to establish a glycaemic measure that better reflects intracellular glucose exposure in organs susceptible to complications. Six months of continuous glucose monitoring data and concurrent laboratory HbA1c were evaluated from 51 type 1 diabetes (T1D) and 80 type 2 diabetes (T2D) patients. Red blood cell (RBC) lifespan was estimated using a kinetic model of glucose and HbA1c, allowing the calculation of person-specific adjusted HbA1c (aHbA1c). Median (IQR) RBC lifespan was 100 (86–102) and 100 (83–101) days in T1D and T2D, respectively. The median (IQR) absolute difference between aHbA1c and laboratory HbA1c was 3.9 (3.0–14.3) mmol/mol [0.4 (0.3–1.3%)] in T1D and 5.3 (4.1–22.5) mmol/mol [0.5 (0.4–2.0%)] in T2D. aHbA1c and laboratory HbA1c showed clinically relevant differences. This suggests that the widely used measurement of HbA1c can underestimate or overestimate diabetes complication risks, which may have future clinical implications.

The relative contribution of diurnal and nocturnal glucose exposures to HbA1c in type 1 diabetes males: a pooled analysis

“…Another important consideration is that HbA1c is modulated by intracellular glucose levels and that glucose uptake and erythrocyte lifespan is inter-individual [ 47 , 48 ]. As such we cannot categorically rule out a role for these erythrocyte-related variables and their potential mediating impact on our study findings, Recently, our group has proposed a model which, incorporating erythrocyte lifespan, attempts to address limitations in laboratory HbA1c [ 49 – 52 ]. However, the method used provides only an approximate measure and therefore the interaction between fluctuations in daily glucose levels and erythrocyte parameters remains an area for future work.…”

Interindividual variability in average glucose‐glycated haemoglobin relationship in type 1 diabetes and implications for clinical practice

“…A recent glucose-HbA1c kinetic model has been described accounting for individual RBC glucose uptake and cellular lifespan, [22][23][24][25] which can be represented by an individual-specific apparent glycation ratio (AGR). In this model, AGR dictates the individual relationship between HbA1c and average glucose.…”

Type 1 diabetes iron‐deficiency anaemia case report and the clinical relevance of red blood cell lifespan‐adjusted glycated haemoglobin

“…Laboratory glycated haemoglobin (HbA1c) measurement does not precisely reflect glycaemic control in those with altered red blood cell lifespan (RBCls) and our aim was to evaluate the glycaemic measure aA1c (Equation 1) 1 which adjusts HbA1c to a reference RBCls (RBCls ref ). By removing the individual RBCls variation, this glycaemic measure better reflects intracellular glucose exposure in red blood cells (RBCs) and perhaps other cells susceptible to complications.…”

“…With our kinetic model, gap‐free continuous glucose monitoring (CGM) and repeated HbA1c measurements over weeks or months are required. 2 Under steady‐state conditions, an individual's apparent glycation ratio (AGR) dictates the glucose‐HbA1c relationship, and AGR can be easily estimated from average glucose and HbA1c (Equation 2, derived from Equation 6 in 2 and Equation a5 in Xu et al 1 ). AGR is the product of RBCls and apparent haemoglobin glycation rate constant ( k gly ), which is mostly driven by RBC glucose uptake.…”

“…Assays for red cell distribution width (RDW), haematocrit, haemoglobin and ferritin were performed in some monthly visits.The data processing steps are shown in Figure1. Using the kinetic model,1,2 one or more data sections are required to estimate k gly and RBCls. A data section consists of two HbA1c values and CGM measures in between.…”