Comparison of annual variability in HbA1c and glycated albumin in patients with type 1 vs. type 2 diabetes mellitus

doi:10.1016/j.jdiacomp.2012.12.001

Journal of Diabetes and its Complications

Volume 27, Issue 3, May–June 2013, Pages 211-213

https://doi.org/10.1016/j.jdiacomp.2012.12.001 Get rights and content

Abstract

Objective

It has been suggested that plasma glucose (PG) levels per se and long-term variations in PG levels are associated with diabetic vascular complications. Glycated albumin (GA) reflects shorter-term glycemic control, as well as postprandial PG levels, as compared to HbA1c. In this study, we hypothesized that GA more strongly reflects long-term variations in PG levels than HbA1c, and compared the variability of HbA1c and that of GA in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).

Methods

This study included 8 T1DM patients and 48 T2DM patients. Over a 1-year period, HbA1c and GA were measured every month and the mean values and coefficients of variation (CV) for each patient were calculated.

Results

In both T1DM and T2DM patients, the CV of GA was significantly higher than the CV of HbA1c. Both the CV of HbA1c and the CV of GA were significantly higher in the T1DM patients than in the T2DM patients.

Conclusion

The annual variability in GA was greater than that in HbA1c. In addition, the annual variability in HbA1c and that in GA in the T1DM patients were greater than in the T2DM patients. Our findings suggest that GA more accurately reflects long-term variations in PG levels than HbA1c.

Introduction

HbA1c reflects the glycemic control status of the previous 2–3 months and is widely used as an indicator for plasma glucose (PG) levels (Bunn et al., 1978, Koenig et al., 1976). Glycated albumin (GA) has also been used as a glycemic control indicator (Koga & Kasayama, 2010). GA reflects PG levels over a shorter period (Tahara & Shima, 1995) and has been shown to more accurately reflect postprandial PG levels than HbA1c (Saisho et al., 2011, Sakuma et al., 2011, Suwa et al., 2010).

In patients with type 1 diabetes mellitus (T1DM) with greater long-term variability in HbA1c, the risk of diabetic microangiopathies and macroangiopathies has been shown to be elevated (Kilpatrick et al., 2008, Wadén et al., 2009). Recently, the risk of cardiovascular diseases has also been shown to be elevated in patients with type 2 diabetes mellitus (T2DM) with increased fluctuations in HbA1c (Bouchi et al., 2012). These results suggest that not only PG levels per se, but also long-term variations in PG levels are associated with diabetic vascular complications.

We hypothesized that GA is more sensitive than HbA1c with regard to reflecting long-term variations in PG levels. This study aimed to compare the variability in HbA1c and that in GA over a 1-year period in T1DM and T2DM patients.

Section snippets

Subjects

This study included 8 T1DM patients and 48 T2DM patients (Table 1). All T1DM patients had been undergoing intensive insulin therapy. The T2DM patients included one patient on dietary therapy alone, 32 patients receiving oral hypoglycemic agents, and 15 patients receiving insulin therapy. In these patients, HbA1c and GA were measured every month over 1 year (12 times/year), and their mean values and coefficients of variation (CV) were calculated. Patients with major changes in treatment, such as

Results

Table 1 shows the clinical characteristics of the study patients. There was a greater proportion of females among the T1DM patients than among the T2DM patients. BMI was significantly lower in the T1DM patients than in the T2DM patients. Both HbA1c and GA in the T1DM patients were significantly higher than in the T2DM patients. In addition, the ratio of GA to HbA1c in the T1DM patients was significantly higher than in the T2DM patients.

In the T1DM patients, the CV of GA was significantly higher

Discussion

In both T1DM and T2DM patients, the CV of GA was significantly greater than the CV of HbA1c. This is thought to be because GA reflects shorter-term control of plasma glucose levels than HbA1c. For example, in patients with repetitive worsening and improvement of glycemic control status in the shorter term, changes in HbA1c levels are small, whereas GA levels fluctuate dynamically. Thus, short-term glycemic excursions can be assessed by serial measurements in GA levels.

It has been suggested that

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Cited by (29)

Association between visit-to-visit variability of glycated albumin and diabetic retinopathy among patients with type 2 diabetes – A prospective cohort study
2021, Journal of Diabetes and its Complications
Citation Excerpt :
At present, the variability of glycated hemoglobin A1c (HbA1c) is commonly used to assess long-term glycemic variability, but the conclusions of HbA1c variability are inconsistent in certain studies in terms of diabetes-related complications.1–3 In addition to HbA1c variability, glycated albumin (GA) variability can also assess long-term blood glucose fluctuations, and it may have potential advantages.4–6 GA is not affected by hemoglobin levels, and can identify rapid changes or deterioration of blood sugar in a shorter period of time to improve the alternation.
There is a paucity of studies regarding the association between long-term glycemic variability with the risk of diabetic retinopathy (DR) in patients with type 2 diabetes. Therefore, the purpose of this study is to explore the association of glycated albumin (GA) variability and HbA1c variability with the risk of DR in patients with type 2 diabetes.
This prospective cohort study included 315 inpatients with type 2 diabetes (191 males and 124 females) with at least 3 measurements of GA and HbA1c within 2 years prior to the baseline investigation. Different GA and HbA1c variability markers were calculated, including CV, variability independent of the mean (VIM), and the average real variability (ARV). Cox proportional hazard regression models were used to explore the association between visit-to-visit variability of GA and HbA1c and the risk of DR.
After an average follow-up of 3.42 years, 81 patients developed incident DR. Multivariable-adjusted (diabetes duration, smoking status, systolic blood pressure, albumin to creatinine ratio, triglycerides, using fibrates, and mean HbA1c) hazard ratios of DR associated with each unit increase in GA-CV, GA-VIM, and GA-ARV were 1.05 (95% CI 1.02–1.09), 1.69 (95% CI 1.24–2.32), and 1.13 (95%CI 1.04–1.23), respectively. However, there was no significant association between visit-to-visit HbA1c variability and the risk of DR.
The present study indicated that visit-to-visit variability of GA can predict the risk of incident DR in patients with type 2 diabetes, and the prediction ability is independent of the average HbA1c levels.
Glycated albumin and its variability: Clinical significance, research progress and overall review
2020, Obesity Medicine
Citation Excerpt :
Several studies have used GA variability as the long-term glycemic variability parameter as well. In a 12 months follow-up study by Koga et al., HbA1c and GA were measured every month and the variability of two parameters were calculated (Koga et al., 2013). The study found that the CV of GA was significantly higher than that of HbA1c in both type 1 and type 2 diabetes, suggesting that GA variability might provide more information in terms of reflecting long-term glycemic variability.
Glycated albumin (GA) and the variation of consecutive GA measurements are demonstrated to be associated with chronic diabetic complications. Compared to hemoglobin A1c, GA can provide more accurate glycemic information in patients with specific clinical conditions such as hemoglobin diseases, end-stage renal diseases on dialysis, or in patients who experience drastic changes in glucose level. Meanwhile, the use of GA is limited in several clinical situations such as obesity, autoimmune diseases, and predicting adverse pregnancy outcomes and arterial stiffness. This review summarized the clinical significance and research progress of GA and its variability.
Association of glycated albumin to HbA1c ratio with diabetic retinopathy but not diabetic nephropathy in patients with type 2 diabetes
2017, Clinical Biochemistry
Citation Excerpt :
While the present study is cross-sectional and uses one measurement of GA and HbA1c once per year, the same results were obtained as our previous study [20]. Since the fluctuations of GA and HbA1c values are smaller in patients with type 2 diabetes than in those with type 1 diabetes [29], the values reflected glycemic control for a year even when we used GA and HbA1c measurements once per year, resulting in the GA/HbA1c ratio being the participation factor for diabetic retinopathy. In the ARIC study Selvin et al. investigated whether glycemic control indicators could be a predictor of the progression of diabetic complications [30].
The ratio of glycated albumin to HbA1c (GA/HbA1c ratio) is a known indicator that reflects fluctuations in plasma glucose. In this study, the association of the GA/HbA1c ratio to diabetic nephropathy and diabetic retinopathy in patients with type 2 diabetes was investigated.
Among patients with type 2 diabetes, 613 patients (364 males and 249 females, aged 63.2 ± 12.5, body mass index (BMI) 25.4 ± 4.8 kg/m²) were enrolled. Patients with overt proteinuria, reduced renal function, or anemia were excluded.
In a comparison between patients with and without diabetic nephropathy, significance was observed in insulin therapy, HbA1c, and GA. In addition, in a comparison between patients with and without diabetic retinopathy, the GA/HbA1c ratio along with insulin therapy, HbA1c, and GA showed significant differences. When the GA/HbA1c ratios were divided into three groups and compared, the rates of diabetic nephropathy did not show any significance, while the rate of diabetic retinopathy increased significantly as the GA/HbA1c ratio increased. In multivariable analyses, while insulin therapy and BMI were the significant independent variables for diabetic nephropathy, insulin therapy and the GA/HbA1c ratios were the significant independent variable for diabetic retinopathy.
The GA/HbA1c ratio was associated with diabetic retinopathy, but not with diabetic nephropathy in patients with type 2 diabetes. These results suggest that the development and progression of diabetic retinopathy is associated with plasma glucose fluctuations.
Distinct biomarker roles for HbA<inf>1c</inf> and glycated albumin in patients with type 2 diabetes on hemodialysis
2016, Journal of Diabetes and its Complications
Citation Excerpt :
Because it is known that high glycemic variability is related to higher cardiovascular events, glycemic variability must be also monitored and controlled. Former studies revealed that GA reflects glucose excursion (Yoshiuchi et al., 2008) and long-term variation more accurately in non-complicated diabetes when daily glucose profiles were used as reference (Koga, Murai, Morita, Saito, & Kasayama, 2013). We reported previously that GA/HbA1c ratio serves as a good glycemic variability indicator in participants with type 1 and 2 diabetes without complications (Ogawa et al., 2012).
HbA_1c and glycated albumin (GA) are used to monitor glycemia, but their accuracy to represent glycemic profiles in hemodialysis remains controversial.
Continuous glucose monitoring in 97 patients with type 2 diabetes (41 on hemodialysis [HD] and 56 without nephropathy) was analyzed to evaluate whether HbA_1c and/or GA serve as appropriate glycemic profile markers.
The average glucose significantly correlated with HbA_1c in both HD group and group without nephropathy (r = 0.59, P < 0.0001; r = 0.40, P < 0.005). The slopes of linear regression lines were statistically indistinguishable (F = 0.30, P = 0.744), while the y-intercepts were significantly different (F = 57.86, P < 0.0001). GA showed strong correlation with the glycemic standard deviation (r = 0.68, P < 0.0001), and with the average glucose (r = 0.42, P < 0.001). Least square analysis revealed that only HbA_1c, but not GA, was significantly associated with the average glucose (F = 10.20, P < 0.0005; F = 0.38, P = 0.5427), while only GA was significantly associated with the glycemic variability in HD group.
In HD participants, HbA_1c correlates with the average glucose more than GA, but underestimates it, and a correction formula of HbA1c can be developed as an appreciable marker. GA value itself reflects the average glucose, but less accurately than HbA_1c, while it could serve as an indicator for hyperglycemia/hypoglycemia excursion.
Glycated albumin; clinical usefulness
2014, Clinica Chimica Acta
Citation Excerpt :
These findings suggest that not only high mean plasma glucose levels but also long-term glycemic excursion contribute to the development of diabetic vascular complications. We suspected that GA can capture medium- to long-term glycemic excursion with higher sensitivity than HbA1c, and compared fluctuations of HbA1c and GA in diabetic patients in whom HbA1c and GA were measured every other month [76]. As a result, it was found that the annual fluctuations of GA were significantly greater than those of HbA1c.
The main purpose of treating diabetes is to prevent the onset and progression of diabetic chronic complications. Since the mechanism of onset of chronic complications is still not well understood, the main strategy to achieve this purpose is to bring plasma glucose levels as close as possible to those in healthy subjects and maintain good glycemic control over the long term. Since glycation among various proteins is increased in diabetic patients compared with non-diabetic subjects, glycated protein can be used as a glycemic control indicator. Currently, among these glycated proteins, HbA1c is used as the gold standard of glycemic control indicators. However, HbA1c does not accurately reflect the actual status of glycemic control in some conditions with rapid changes in glycemic control and in patients with anemia (hemolytic anemia, iron deficiency anemia, etc.) and variant hemoglobin. In comparison, glycated albumin (GA) more accurately reflects changes in plasma glucose during the short term and postprandial plasma glucose. GA also reflects glycemic control in patients with hematologic disorders whereas GA does not reflect glycemic control in patients with disorder of albumin metabolism. GA is a glycemic control indicator which overcomes most of the disadvantages of HbA1c, and could be therefore expected to replace HbA1c as the standard glycemic control indicator in the near future. However, it is necessary to accumulate more evidences from large research studies on the effective directions for measuring GA.
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2023, Archives of Plastic Surgery

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^☆: Conflicts of interest: The authors declare no conflict of interest relevant to this manuscript.

View full text

Comparison of annual variability in HbA1c and glycated albumin in patients with type 1 vs. type 2 diabetes mellitus☆

Abstract

Objective

Methods

Results

Conclusion

Introduction

Section snippets

Subjects

Results

Discussion

Clinica Chimica Acta

Fluctuations in HbA1c are associated with a higher incidence of cardiovascular disease in Japanese patients with type 2 diabetes

Journal of Diabetes Investigation

The glycosylation of hemoglobin: Relevance to diabetes mellitus

Science

Glucose tolerance and mortality: Comparison of WHO and American Diabetes Association diagnostic criteria

Lancet

International clinical harmonization of glycated hemoglobin in Japan: From Japan Diabetes Society to National Glycohemoglobin Standardization Program values

J Diab Invest

A1C variability and the risk of microvascular complications in type 1 diabetes: Data from the Diabetes Control and Complications Trial

Diabetes Care

Correlation of glucose regulation and hemoglobin AIc in diabetes mellitus

The New England Journal of Medicine