Hemoglobin A1c, Not Glycated Albumin, Can Independently Reflect the Ankylosing Spondylitis Disease Activity Score

Sejin Byun; Seung Min Jung; Jason Jungsik Song; Yong-Beom Park; Sang-Won Lee

doi:10.4078/jrd.2018.25.2.131

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Byun, Jung, Song, Park, and Lee: Hemoglobin A1c, Not Glycated Albumin, Can Independently Reflect the Ankylosing Spondylitis Disease Activity Score

Original Article

J Rheum Dis 2018;25(2):131-139.

Published online: 30 April 2018

DOI: https://doi.org/10.4078/jrd.2018.25.2.131

Hemoglobin A1c, Not Glycated Albumin, Can Independently Reflect the Ankylosing Spondylitis Disease Activity Score

Sejin Byun, Seung Min Jung, Jason Jungsik Song, Yong-Beom Park, Sang-Won Lee

Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

Corresponding to: Sang-Won Lee http://orcid.org/orcid.org/0000-0002-8038-3341 Division of Rheumatology, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul 03722, Korea. E-mail: sangwonlee@yuhs.ac

Received 14 June 201019 January 2011 Accepted 20 January 2011

This is a Open Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objective

This study examined whether glycated hemoglobin (HbA1c) and glycated albumin (GA) are well correlated with the Ankylosing Spondylitis Disease Activity Score (ASDAS)-erythrocyte sedimentation rate (ESR), and ASDAS-C-reactive protein (CRP) in AS patients without medical conditions affecting the glycated protein levels.

Methods

The data of 76 patients with AS were analyzed. Univariate and multivariate analyses of the variables associated with ASDAS-ESR and ASDAS-CRP were performed using a linear regression test. The patients were divided into active and inactive AS groups based on an ASDAS-CRP of 2.1, and the variables between the two groups were compared.

Results

ASDAS-ESR did not correlated with either HbA1c or GA. ASDAS-CRP was positively correlated with HbA1c (r=0.315, p=0.006) and the white blood cell (r=0.288, p=0.012), and inversely correlated with hemoglobin (r=−0.241, p=0.036) and serum albumin (r=−0.262, p=0.022), but not GA. Multivariate analysis revealed HbA1c and white blood cell to be significantly correlated with ASDAS-CRP (β=0.234, p=0.033 and β=0.265, p=0.017). The mean HbA1c, not GA, of the active group was significantly higher than that of the inactive group (p=0.020). In addition, the optimal cutoff value of HbA1c was set to 5.6, and the patients with HbA1c ≥5.6 were found to have a 3.3 times higher risk of active AS than those without.

Conclusion

HbA1c was significantly correlated with ASDAS-CRP, and could be a useful marker to reflect ASDAS-CRP in AS patients without medical conditions affecting the glycated protein levels.

Keywords: Ankylosing spondylitis, Glycated hemoglobin A, Glycosylated serum albumin

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Figure 1.

Optimal cutoff values of HbA1c to reflect active ankylosing spondylitis. Active ankylosing spondylitis in patients having HbA1c ≥5.6 was identified more often than in those having HbA1c ＜5.6 (62.9% vs. 34.1%, p=0.012). Patients having HbA1c more than 5.6 showed significantly enhanced risk of active AS than those having not (RR=3.264). ASDAS: ankylosing spondylitis disease activity score, CRP: C-reactive protein, RR: relative risk, HbA1c: hemoglobin A1c, AS: ankylosing spondylitis.

Supplementary Table 1.

Correlation among variables related to glucose metabolism and disease activity of ankylosing spondylitis (n=76)

	BMI	HbA1c	GA	Fasting glucose	ASDAS-ESR	ASDAS-CRP	BASDAI	BAS-G
BMI	1
HbA1c	0.227*	1
GA	−0.268*	0.400*	1
Fasting glucose	0.331*	0.405*	0.186	1
ASDAS-ESR	0.013	0.220	0.105	0.011	1
ASDAS-CRP	0.032	0.315*	0.135	0.037	0.792*	1
BASDAI	0.019	0.226*	0.192	0.010	0.719*	0.774*	1
BAS-G	0.039	0.401*	0.221	0.166	0.568*	0.617*	0.655*	1
BASFI	−0.118	0.124	0.111	0.013	0.376*	0.322*	0.211	0.279*

BMI: body mass index, HbA1c: haemoglobin A1c, GA: glycated albumin, ASDAS: ankylosing spondylitis disease activity score, BASDAI: Bath ankylosing spondylitis disease activity index, BAS-G: Bath ankylosing spondylitis patient global score, BASFI: Bath ankylosing spondylitis disease activity functional index.

^* p＜0.05.

Table 1.

Baseline characteristics of patients with ankylosing spondylitis (n=76)

Variable	Value
Demographic data
Age (yr)	39.0 (18.0)
Male gender	58 (76.3)
Follow-up duration (yr)	5.0 (8.5)
Smoking	29 (38.2)
BMI (kg/m²)	24.0 (5.0)
HLA-B27	60 (78.9)
Syndesmophyte formation	20 (26.3)
Laboratory results
HbA1c (%)	5.5 (0.4)
GA (%)	12.7 (1.5)
Fasting glucose (mg/dL)	95.5 (12.8)
ESR (mm/h)	19.0 (28.0)
CRP (mg/L)	2.3 (5.9)
Ferritin (mg/dL)	75.5 (70.0)
White blood cell (/mm³)	7,325.0 (2,580.0)
Hemoglobin (g/dL)	14.9 (2.4)
Platelet×10³ (/mm³)	261.0 (69.5)
Albumin (mg/dL)	4.4 (0.5)
Blood urea nitrogen (mg/dL)	13.9 (4.4)
Creatinine (mg/dL)	0.8 (0.2)
Alkaline phosphatase (IU/L)	70.0 (26.0)
Aspartate aminotransferase (IU/L)	21.0 (8.0)
Alanine aminotransferase (IU/L)	18.0 (17.0)
Total cholesterol (mg/dL)	188.0 (40.5)
High density cholesterol (mg/dL)	53.0 (17.0)
Low density cholesterol (mg/dL)	107.8 (24.4)
Triglyceride (mg/dL)	96.0 (76.0)
Disease activity indexes
ASDAS-ESR	2.2 (1.5)
ASDAS-CRP	1.8 (1.4)
BASDAI	3.3 (2.4)
BAS-G	3.0 (3.3)
BASFI	1.3 (2.6)
Medications
Glucocorticoid use	7 (9.2)
Methotrexate use	5 (6.6)
Sulfasalazine use	39 (51.3)
Anti-TNF agents use	27 (35.5)

Values are expressed as median (interquartile range, IQR) or number (%). BMI: body mass index, HLA: human leukocyte antigen, HbA1c: hemoglobin A1c, GA: glycated albumin, ESR: erythrocyte sedimentation rate, CRP: C-reactive protein, ASDAS: ankylosing spondylitis disease activity score, BASDAI: bath ankylosing spondylitis disease activity index, BAS-G: bath ankylosing spondylitis patient global score, BASFI: bath ankylosing spondylitis disease activity functional index, TNF: tumour necrosis factor.

Table 2.

Univariate and multivariate analysis of ASDAS-ESR and other variables

Variable	Univariate analysis			Multivariate analysis
Variable	Regression coefficient (crude B)	Correlation coefficient (R=β)	p-value	Standardized β*	95% confidential interval	p-value
Demographic data
Age (yr)	0.013	0.172	0.136
Follow-up duration (yr)	−0.002	−0.011	0.923
BMI (kg/m²)	0.003	0.013	0.910
Laboratory results
HbA1c (%)	0.661	0.220	0.056	0.102	−0.298, 0.911	0.316
GA (%)	0.069	0.105	0.368
Fasting glucose (mg/dL)	0.001	0.011	0.923
ESR (mm/h)	N/A	N/A	N/A
CRP (mg/L)	0.054	0.448	＜0.001
Ferritin (mg/dL)	−0.002	−0.145	0.296
White blood cell (/mm³)	0.120	0.266	0.020	0.266	0.028, 0.211	0.011
Hemoglobin (g/dL)	−0.229	−0.414	＜0.001	−0.355	−0.316, −0.075	0.002
Platelet×10³ (/mm³)	0.003	0.206	0.074
Serum albumin (mg/dL)	−1.187	−0.394	＜0.001	−0.195	−1.249, 0.075	0.081
Blood urea nitrogen (mg/dL)	0.057	0.223	0.053
Creatinine (mg/dL)	−0.620	−0.104	0.373
Alkaline phosphatase (IU/L)	0.009	0.181	0.121
Aspartate aminotransferase (IU	/L) 0.004	0.029	0.805
Alanine aminotransferase (IU/L)	0.004	0.040	0.734
Total cholesterol (mg/dL)	0.003	0.109	0.350
High density cholesterol (mg/dL)	0.005	0.078	0.569
Low density cholesterol (mg/dL)	−0.001	−0.040	0.765
Triglyceride (mg/dL)	0.002	0.121	0.366
Medications
Glucocorticoid use	0.350	0.106	0.364
Methotrexate use	−0.056	−0.015	0.901
Sulfasalazine use	0.385	0.201	0.082
Anti-TNF agents use	−0.140	−0.070	0.548

ASDAS: ankylosing spondylitis disease activity score, ESR: erythrocyte sedimentation rate, BMI: body mass index, HbA1c: hemoglobin A1c, GA: glycated albumin, CRP: C-reactive protein, TNF: tumour necrosis factor, N/A: not available. *CRP was not included in multivariate analysis, because CRP is a variable closely correlated with ESR (ASDAS-ESR) in inflammation in order not to confound the interpretation of statistical results.

Table 3.

Univariate and multivariate analysis of ASDAS-CRP and other variables

Variable	Univariate analysis			Multivariate analysis
Variable	Regression coefficient (crude B)	Correlation coefficient (R=β)	p-value	Standardized β*	95% confidential interval	p-value
Demographic data
Age (yr)	0.013	0.164	0.158
Follow-up duration (yr)	0.015	0.105	0.367
BMI (kg/m²)	0.008	0.032	0.781
Laboratory results
HbA1c (%)	0.972	0.315	0.006	0.234	0.060, 1.383	0.033
GA (%)	0.091	0.135	0.244
Fasting glucose (mg/dL)	0.004	0.037	0.750
ESR (mm/h)	0.026	0.477	＜0.001
CRP (mg/L)	N/A	N/A	N/A
Ferritin (mg/dL)	−0.003	−0.199	0.150
White blood cell (/mm³)	0.133	0.288	0.012	0.265	0.022, 0.222	0.017
Hemoglobin (g/dL)	−0.137	−0.241	0.036	−0.204	−0.248, 0.016	0.084
Platelet×10³ (/mm³)	0.002	0153	0.186
Serum albumin (mg/dL)	−0.811	−0.262	0.022	−0.099	−1.030, 0.419	0.404
Blood urea nitrogen (mg/dL)	0.027	0.104	0.373
Creatinine (mg/dL)	−0.243	−0.040	0.734
Alkaline phosphatase (IU/L)	0.011	0.212	0.068
Aspartate aminotransferase (IU/L	L) 0.015	0.098	0.402
Alanine aminotransferase (IU/L)	0.014	0.145	0.213
Total cholesterol (mg/dL)	0.004	0.119	0.307
High density cholesterol (mg/dL)	−0.012	−0.159	0.246
Low density cholesterol (mg/dL)	0.002	0.069	0.609
Triglyceride (mg/dL)	0.004	0.184	0.166
Medications
Glucocorticoid use	0.147	0.044	0.707
Methotrexate use	0.236	0.060	0.604
Sulfasalazine use Anti-TNF agents use	0.349−0.325	0.180 −0.161	0.120 0.166

ASDAS: ankylosing spondylitis disease activity score, CRP: C-reactive protein, BMI: body mass index, HbA1c: hemoglobin A1c, GA: glycated albumin, ESR: erythrocyte sedimentation rate, TNF: tumour necrosis factor, N/A: not available.

^* ESR was not included in multivariate analysis, because ESR is a variable closely correlated with CRP (ASDAS-CRP) in inflammation in order not to confound the interpretation of statistical results.

Table 4.

Comparison variables between patients with active and inactive ankylosing spondylitis based on ASDAS-CRP ＞2.1

Variable	Inactive AS (n=40)	Active AS (n=36)	p-value
Demographic data
Age (yr)	37.3±11.2	40.8±12.8	0.201
Male gender	34 (85.0)	24 (66.7)	0.061
Follow-up duration (yr)	7.7±6.4	8.0±7.4	0.824
Smoking	14 (35.0)	15 (41.7)	0.055
BMI (kg/m²)	24.5±4.0	23.9±4.0	0.526
HLA-B27	30 (75.0)	30 (83.3)	0.374
Laboratory results
HbA1c (%)	5.4±0.3	5.6±0.3	0.020
GA (%)	12.7±1.2	13.0±1.7	0.395
Fasting glucose (mg/dL)	97.7±9.8	95.9±9.7	0.414
ESR (mm/h)	14.3±11.7	30.6±18.8	＜0.001
CRP (mg/L)	N/A	N/A	N/A
Ferritin (mg/dL)	107.7±69.4	75.3±73.1	0.100
White blood cell (/mm³)	7,088.5±1,767.6	8,273.6±2,280.8	0.013
Hemoglobin (g/dL)	15.0±1.4	14.0±1.9	0.008
Platelet×10³ (/mm³)	252.1±45.4	275.6±75.3	0.110
Albumin (mg/dL)	4.5±0.3	4.3±0.3	0.016
Blood urea nitrogen (mg/dL)	14.1±3.4	14.9±4.1	0.330
Creatinine (mg/dL)	0.8±0.2	0.8±0.2	0.551
Alkaline phosphatase (IU/L)	69.1±18.1	74.5±20.3	0.230
Aspartate aminotransferase (IU/L)	20.5±7.1	21.6±5.7	0.442
Alanine aminotransferase (IU/L)	19.7±10.1	21.7±9.5	0.398
Total cholesterol (mg/dL)	189.7±28.3	194.0±31.6	0.534
High density cholesterol (mg/dL)	53.4±8.6	50.7±15.8	0.425
Low density cholesterol (mg/dL)	116.8±31.4	116.3±29.3	0.945
Triglyceride (mg/dL)	95.5±39.3	113.4±49.1	0.129
Disease activity
ASDAS-ESR	1.8±0.6	3.1±0.8	＜0.001
ASDAS-CRP	N/A	N/A	N/A
BASDAI	2.5±1.2	4.5±1.7	＜0.001
BAS-G	2.5±1.7	4.7±2.2	＜0.001
BASFI	1.7±4.3	2.9±1.8	0.185
Medications
Glucocorticoid use	2 (5.0)	5 (13.8)	0.181
Methotrexate use	2 (5.0)	3 (8.3)	0.651
Sulfasalazine use	19 (47.5)	20 (55.5)	0.258
Anti-TNF antibody use	16 (40.0)	11 (30.6)	0.390

Values are expressed as mean±standard deviation or number (%). ASDAS: ankylosing spondylitis disease activity score, CRP: C-reactive protein, AS: ankylosing spondylitis, BMI: body mass index, HLA: human leukocyte antigen, HbA1c: hemoglobin A1c, GA: glycated albumin, ESR: erythrocyte sedimentation rate, BASDAI: bath ankylosing spondylitis disease activity index, BAS-G: bath ankylosing spondylitis patient global score, BASFI: bath ankylosing spondylitis disease activity functional index, TNF: tumour necrosis factor, N/A: not available.

Table 5.

Multivariate logistic regression analysis using variables with statistical significance between patients with active and inactive ankylosing spondylitis based on ASDAS-CRP ＞2.1

Variable	Odds ratio	95% confidence interval	p-value
HbA1c (%)	4.132	0.704, 24.240	0.116
White blood cell (/mm³)	1.442	1.067, 1.947	0.017
Hemoglobin (g/dL)	0.656	0.456, 0.940	0.022
Albumin (mg/dL)	0.482	0.075, 3.086	0.441

ASDAS: ankylosing spondylitis disease activity score, CRP: C-reactive protein, HbA1c: hemoglobin A1c.

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