Influences of Anemia,Kidney Disease,Thyroid Dysfunction,and Liver Disease on the Ratio of Glycated Albumin to Hemoglobin A1c

Glycated albumin (GA) is used as an intermediate glycemic control marker for patients with diabetes, and would be a good complement measurement of hemoglobin A1c (HbA1c). Basically, there is a very strong relationship between HbA1c and GA, but it has been known that some discrepancies between these markers exist under certain physiological and pathologic conditions.

Calculating the ratio of GA to HbA1c (GA/HbA1c ratio) is a useful method to evaluate such discrepancies. GA/HbA1c ratios are reported to change depending on a variety of factors, including in the case of a rapid deterioration of glycemic control, a significant fluctuation in blood glucose, or a change in the serum half-life of albumin or the erythrocyte life span.^1,2 In particular, anemia, liver diseases, kidney diseases, and thyroid disease that affect the erythrocyte life span and albumin metabolism are commonly associated with diabetes, which may cause the discrepancy between HbA1c and GA.^3-5 Doctors measuring HbA1c and GA should take such impacts into account. On the other hand, if a doctor was unaware of the presence of such diseases, it might be possible to predict them from discrepancies in the HbA1c and GA values, including the GA/HbA1c ratio. Therefore, offering all-inclusive and relatively evaluated information of diseases, as well as the magnitude of their influence to GA/HbA1c ratio, would be useful for the treatment of diabetes.

We enrolled subjects with more than 6 months of follow-up after diagnosis and included subjects with stable glycemic control status and stable symptoms of anemia (macrocytic: n = 21; normocytic: n = 36; microcytic: n = 56), kidney disease (dialysis patients: n = 40; nephrotic syndrome: n = 15), thyroid dysfunction (hypothyroidism: n = 37; hyperthyroidism: n = 55), and healthy control (n = 80). In addition, we also included subjects with type 2 diabetes mellitus (T2DM) but without diabetes complications (n = 197), and subjects with impaired glucose tolerance (IGT) or T2DM who have liver disease (fatty liver: n = 167; chronic hepatitis: n = 27; hepatic cirrhosis: n = 38). GA ⁶ and HbA1c were measured and the GA/HbA1c ratio was calculated.

As a result, in patients without diabetes, compared to healthy subjects (2.6 ± 0.19), the GA/HbA1c ratio was significantly higher in macrocytic anemia (3.4 ± 0.50, P = .000), normocytic anemia (2.8 ± 0.31, P = .031), dialysis patients (3.3 ± 0.52, P = .000), and hypothyroidism (3.0 ± 0.38, P = .000), and was significantly lower in microcytic anemia (2.5 ± 0.22, P = .000), nephrotic syndrome (1.6 ± 0.28, P = .000), and hyperthyroidism (2.2 ± 0.24, P = .000). In the group of subjects with IGT or T2DM, the GA/HbA1c ratio was significantly lower in fatty liver (2.6 ± 0.26, P = .000), significantly higher in hepatic cirrhosis (3.8 ± 0.62, P = .000), and there was no significant difference in chronic hepatitis (3.0 ± 0.39, P = .143) compared to that of subjects with T2DM but without diabetes complications (3.0 ± 0.24). Table 1 summarizes the results of the present study.

Table 1.

Baseline Characteristics and GA/HbA1c Ratio of Patients with Anemia, Kidney Disease, Thyroid Dysfunction, and Liver Disease.

Subjects	n	Age	GA/HbA1c	HbA1c (%)	GA (%)	FPG (mg/dL)	Hb (g/dL)	ALB (g/dL)
Healthy subjects	80	40.2 ± 11.4	2.6 ± 0.19	5.42 ± 0.25	13.93 ± 0.96	89.6 ± 77.5	14.12 ± 1.25	4.65 ± 0.31
Macrocytic anemia	21	76.3 ± 10.8 †	3.4 ± 0.50	5.10 ± 0.67	16.92 ± 1.28	101.2 ± 18.6	9.32 ± 1.25	3.64 ± 0.53
Normocytic anemia	36	72.0 ± 14.9 †	2.8 ± 0.31	5.55 ± 0.65	15.47 ± 1.93	109.8 ± 13.7	8.43 ± 1.20	3.14 ± 0.78
Microcytic anemia	56	57.5 ± 18.2 ††	2.5 ± 0.22	5.82 ± 0.57	14.53 ± 1.38	101.3 ± 15.2	8.56 ± 1.55	3.93 ± 0.45
Dialysis patients	40	73.6 ± 11.6 †	3.3 ± 0.52	5.22 ± 0.54	16.87 ± 2.47	108.8 ± 19.7	9.89 ± 1.41	3.15 ± 0.68
Nephrotic syndrome	15	40.9 ± 20.3 †	1.6 ± 0.28	5.55 ± 0.37	8.65 ± 1.49	106.1 ± 21.5	14.01 ± 2.15	1.56 ± 0.40
Hyperthyroidism	55	41.3 ± 15.0 †	2.2 ± 0.24	5.45 ± 0.38	12.08 ± 1.46	105.6 ± 14.1	13.44 ± 1.33	4.07 ± 0.37
Hypothyroidism	37	68.5 ± 14.4 †	3.0 ± 0.38	5.60 ± 0.52	16.64 ± 2.09	103.7 ± 15.9	12.20 ± 1.56	4.08 ± 0.45
Type 2 diabetes mellitus	197	68.0 ± 10.8	3.0 ± 0.24	8.03 ± 1.34	24.37 ± 4.82	172.2 ± 63.6	13.60 ± 1.55	4.06 ± 0.36
Fatty liver*	167	63.8 ± 12.0 ‡	2.6 ± 0.26	8.45 ± 1.37	21.66 ± 4.09	179.4 ± 67.2	14.41 ± 1.54	4.16 ± 0.33
Chronic hepatitis*	27	60.9 ± 12.1ns	3.0 ± 0.39	7.71 ± 1.08	23.01 ± 4.33	159.9 ± 42.9	14.24 ± 1.34	4.02 ± 0.31
Hepatic cirrhosis*	38	67.8 ± 7.2 ‡	3.8 ± 0.62	7.46 ± 1.42	27.87 ± 5.92	165.0 ± 85.3	12.52 ± 1.93	3.56 ± 0.52

*

Liver diseases with impaired glucose tolerance or diabetes mellitus. ^†P < .01, ^††P < .05 versus healthy subjects. ^‡P < .01 versus type 2 diabetes mellitus. ns, not significant.

In conclusion, the present study showed the detailed influences of various diseases by subdivision. When measuring HbA1c or GA for the treatment of diabetes, doctors should check for the existence of anemia, renal diseases, thyroid disease, and liver diseases. If there is no information about such diseases, the GA/HbA1c ratio may provide additional useful information for interpretation.