Figures and data in Addressing shortfalls of laboratory HbA1c using a model that incorporates red cell lifespan

Version of Record: October 5, 2021
Version of Record: September 13, 2021

Download
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)
- Article PDF
Open citations (links to open the citations from this article in various online reference manager services)
- Mendeley
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Yongjin Xu

Richard M Bergenstal

Timothy C Dunn

Ramzi A Ajjan

(2021)
Addressing shortfalls of laboratory HbA_1c using a model that incorporates red cell lifespan

eLife 10:e69456.

https://doi.org/10.7554/eLife.69456
- Download BibTeX
- Download .RIS
Cite
Share
CommentOpen annotations (there are currently 0 annotations on this page).

Figures
Tables
Additional files

2 figures, 3 tables and 1 additional file

Figures

Figure 1

Download asset Open asset

Individual red blood cell (RBC) lifespan can affect HbA_1c and diabetes treatment.

In some individuals, laboratory HbA_1c 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 HbA_1c by RBC lifespan.

The number (percentage) of individuals having HbA_1c 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 …

Tables

Table 1

Main characteristics of the cohort studied.

N	131
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 therapy	Multiple 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 HbA_1c (cHbA_1c) and glucose management indicator (GMI) are statically significant with p < 0.0001.

Study		T1D SAP ^[22]		DPV T1D ^[23]		Replace/mpact ^[9]
Country		Japan		Germany		Europe
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)
HbA_1c test		Central lab		POC+ central lab		Central lab
CGM device		Medtronic		Abbott		Abbott
Method		cHbA_1c	GMI (14-day AG)	cHbA_1c	GMI (14-day AG)	cHbA_1c	GMI (14-day AG)
Abs. dev.% (mmol/mol)	Mean	0.11 (1.2)	0.47 (5.1)	0.32 (3.5)	0.57 (6.2)	0.31 (3.4)	0.66 (7.2)
	SD	0.06 (0.7)	0.46 (5.0)	0.28 (3.0)	0.55 (6.0)	0.22 (2.4)	0.46 (5.0)
	Median	0.10 (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)
R²		0.91	0.65	0.79	0.52	0.88	0.63

Appendix 1—table 2

Main characteristics of markers assessing average glycaemic control.

		Intracellular (I) or extracellular (E) glucose	Affected by mean red blood cell (RBC) lifespan	Advantages	Disadvantages
CGM-derived	Average glucose	E	No	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
CGM-derived	Time in range	E	No
Average fasting plasma glucose		E	No
Glycated albumin		E	No	Mid-term (weeks) average glucose
HbA_1c		I	Yes	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 HbA_1c		I	No	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 glucose		I	No	Reflects both long- and short-term intracellular glucose control	No direct measurement available Requires RBC glucose uptake rate determination (Ladyzynski et al., 2011; Kameyama et al., 2021), which is not feasible in routine clinical practice