Abstract Body

This presentation attempts to compare and contrast two key glycaemic markers: the old and the new, represented by glycated haemoglobin (HbA1c) and time in range (TIR), respectively.
HbA1c has been used as the gold standard for assessing glycaemic control in diabetes, given the wealth of data linking this glycaemic marker to future vascular complications. While HbA1c served us well, this glycaemic marker is not without limitations as accuracy can be affected by factors that influence red blood cell lifespan. Moreover, HbA1c fails to provide information on hypoglycaemic exposure and glycaemic variability, which are both associated with adverse outcome. HbA1c is also slow at assessing response to new glycaemic therapies, which can delay optimisation of glucose levels.

These were accepted limitations for HbA1c in the absence of a credible alternative. However, with the increased use of continuous glucose monitoring, additional glycaemic markers have surfaced that can address the shortcomings of HbA1c.

One of these modern glycaemic markers is TIR, depicting the time spent in glucose levels between 3.9 and 10 mmol/l (70-180 mg/dl) each day, and showing an inverse relationship with the risk of diabetes complications. While use of TIR is not as widespread as HbA1c, it is easy to understand and well accepted by health care professionals as well as individuals with diabetes. Importantly, TIR gives an unbiased account of glucose levels, and, unlike HbA1c, is not affected by red blood cells changes, while rapidly assessing response to the introduction of new glycaemic therapies.

Despite the clear advantages of TIR, HbA1c will continue to serve the diabetes community for a while. However, this old friend will need help from the new generation of glycaemic markers for optimal glucose management in people with diabetes.

Background and Aims

HbA1c and time in range (TIR) are important glycemic markers but they can be discordant, creating clinical management difficulties. Our aims were to improve HbA1c accuracy at reflecting glucose exposure by adjusting for personal glycation factors and to investigate the effects of glycaemic variability (GV) on HbA1c accuracy.

Methods

Three months of continuous glucose monitoring (CGM) preceding HbA1c values were obtained from 758 individuals with type 1 diabetes (T1D) from 7 clinical trials. A total of 1,636 periods had glycemic metrics of average glucose (AG), time in range (TIR) 70-180 mg/dL, and HbA1c. Apparent glycation ratio (AGR) was calculated as: , where AG is average glucose and K_M is 472 mg/dL, thus allowing personalized HbA1C (pHbA1c):

where AGR_ref is assumed at 65.1 ml/g. Due to the known effect of glucose variability on the TIR-HbA1c relationship, the paired metrics were grouped by quartiles of glucose CV, and agreements were evaluated by linear regression.

Results

The agreement between pHbA1c and TIR was greater than that of TIR and HbA1c (R² = 0.45 v. 0.82, Figure 1A-B). GV was divided by CV quartile groups (30.9+2.5, 35.4+0.9, 38.4+0.9 and 43.2+2.7%) with linear regression correlations demonstrating that increasing CV is associated with worsening HbA1c-TIR correlations (R² ranging between 0.33-0.53; Figure 1C). Accuracy for the correlations improved substantially with the use of pHbA1c (R² ranging between 0.76-0.89; Figure 1D).

Conclusions

Accounting for a personal glycation factor improves the accuracy of HbA1c at reflecting average glucose even in the presence of high GV.

Abstract Body

This presentation attempts to compare and contrast two key glycaemic markers: the old and the new, represented by glycated haemoglobin (HbA1c) and time in range (TIR), respectively.
HbA1c has been used as the gold standard for assessing glycaemic control in diabetes, given the wealth of data linking this glycaemic marker to future vascular complications. While HbA1c served us well, this glycaemic marker is not without limitations as accuracy can be affected by factors that influence red blood cell lifespan. Moreover, HbA1c fails to provide information on hypoglycaemic exposure and glycaemic variability, which are both associated with adverse outcome. HbA1c is also slow at assessing response to new glycaemic therapies, which can delay optimisation of glucose levels.

These were accepted limitations for HbA1c in the absence of a credible alternative. However, with the increased use of continuous glucose monitoring, additional glycaemic markers have surfaced that can address the shortcomings of HbA1c.

One of these modern glycaemic markers is TIR, depicting the time spent in glucose levels between 3.9 and 10 mmol/l (70-180 mg/dl) each day, and showing an inverse relationship with the risk of diabetes complications. While use of TIR is not as widespread as HbA1c, it is easy to understand and well accepted by health care professionals as well as individuals with diabetes. Importantly, TIR gives an unbiased account of glucose levels, and, unlike HbA1c, is not affected by red blood cells changes, while rapidly assessing response to the introduction of new glycaemic therapies.

Despite the clear advantages of TIR, HbA1c will continue to serve the diabetes community for a while. However, this old friend will need help from the new generation of glycaemic markers for optimal glucose management in people with diabetes.