1. Biochemistry and Chemical Biology
  2. Computational and Systems Biology

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

  1. Yongjin Xu
  2. Richard M Bergenstal
  3. Timothy C Dunn
  4. Ramzi A Ajjan  Is a corresponding author
  1. Abbott Diabetes Care, United States
  2. International Diabetes Center, Park Nicollet, HealthPartners, United States
  3. Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, United Kingdom
https://doi.org/10.7554/eLife.69456
Share this article
Cite this article
  1. Yongjin Xu
  2. Richard M Bergenstal
  3. Timothy C Dunn
  4. Ramzi A Ajjan
(2021)
Addressing shortfalls of laboratory HbA1c using a model that incorporates red cell lifespan
eLife 10:e69456.
https://doi.org/10.7554/eLife.69456
  2. Download BibTeX
  3. Download .RIS
2 figures, 3 tables and 1 additional file

Figures

Figure 1
Download asset Open asset
Individual red blood cell (RBC) lifespan can affect HbA1c and diabetes treatment.

In some individuals, laboratory HbA1c can be misleading and resulting in undertreatment, thus increasing the risk of complications, or overtreatment, predisposing to hypoglycaemia.

Figure 2
Download asset Open asset
Distribution of red blood cell (RBC) lifespan for type 1 (n = 51) and type 2 (n = 80) diabetes and adjustment to laboratory HbA1c by RBC lifespan.

The number (percentage) of individuals having HbA1c adjustments < 1 % (<11 mmol/mol), 1–2% (11–22 mmol/mol), 2–3% (22–33 mmol/mol), and >3% (>33 mmol/mol) were 90 (68%), 21 (16%), 12 (9%), and 8 (6%), respectively.

Tables

Table 1
Main characteristics of the cohort studied.
N131
Age [years; mean ± SD (range)]53.5 ± 13.7 (18, 77)
Gender, male [number (percentage)]86 (66%)
T1D [number (percentage)]T2D [number (percentage)]BMI [kg/m2; mean ± SD (range)]51 (39%)80 (61%)29.8 ± 5.9 (18.8, 54.1)
Duration of diabetes (years)17.7 ± 8.7 (2, 46)
Hypoglycaemic therapyMultiple daily injections of insulin
Data are presented as mean ± SD (min, max) or n (%)
Appendix 1—table 1
Summary of kinetic model validation studies.

The mean absolute deviation differences between calculated HbA1c (cHbA1c) and glucose management indicator (GMI) are statically significant with p < 0.0001.

StudyT1D SAP [22]DPV T1D [23]Replace/mpact [9]
CountryJapanGermanyEurope
Subject count (male)51 (14)352 (171)120 (79) [TID 54 (37), T2D 66 (42)]
Age median (range)42 (6–73)12.5 (3–19)52 (18–77)
HbA1c testCentral labPOC+ central labCentral lab
CGM deviceMedtronicAbbottAbbott
MethodcHbA1cGMI (14-day AG)cHbA1cGMI (14-day AG)cHbA1cGMI (14-day AG)
Abs. dev.% (mmol/mol)Mean0.11 (1.2)0.47 (5.1)0.32 (3.5)0.57 (6.2)0.31 (3.4)0.66 (7.2)
SD0.06 (0.7)0.46 (5.0)0.28 (3.0)0.55 (6.0)0.22 (2.4)0.46 (5.0)
Median0.10 (1.1)0.36 (3.9)0.26 (2.8)0.46 (5.0)0.27 (3.0)0.5 (5.5)
Average bias% (mmol/mol)0 (0)–0.3 (–3.3)0 (0)0.4 (4.4)0 (0)–0.6 (–6.6)
R20.910.650.790.520.880.63
Appendix 1—table 2
Main characteristics of markers assessing average glycaemic control.
Intracellular (I) or extracellular (E) glucoseAffected by mean red blood cell (RBC) lifespanAdvantagesDisadvantages
CGM-derivedAverage glucoseENo

  • Can reflect both long- (weeks/months) and short-term (minutes, hours) glucose control

  • Extracellular measurements

  • Lack of large-scale longitudinal studies demonstrating a direct association with long-term complications

Time in range
Average fasting plasma glucoseENo
Glycated albuminENo

  • Mid-term (weeks) average glucose

HbA1cIYes

  • Long-term (months) intracellular average glucose exposure

  • Longitudinal studies demonstrating associations with long-term complications

  • Affected by variation in RBC lifespan

  • Lacks accuracy in the presence of other conditions (anaemias, renal failure, haemoglobin variants, etc.)

Adjusted HbA1cINo

  • Long-term intracellular average glucose

  • Exposure normalised for RBC lifespan, providing a personalised glycaemic marker

  • Requires RBC lifespan determination

  • Longitudinal studies linking with outcome are lacking

Intracellular glucoseINo

  • Reflects both long- and short-term intracellular glucose control

Additional files

Transparent reporting form
https://cdn.elifesciences.org/articles/69456/elife-69456-transrepform1-v2.docx

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Yongjin Xu
  2. Richard M Bergenstal
  3. Timothy C Dunn
  4. Ramzi A Ajjan
(2021)
Addressing shortfalls of laboratory HbA1c using a model that incorporates red cell lifespan
eLife 10:e69456.
https://doi.org/10.7554/eLife.69456