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BONSOI-4371; No. of Pages 4 ARTICLE IN PRESS
Joint Bone Spine xxx (2016) xxx–xxx
Available online at
ScienceDirect
www.sciencedirect.com
Letter to the Editor
Glycated albumin increases with disease activ-
ity in rheumatoid factor positive rheumatoid
arthritis patients with normal fasting glucose
and HbA1c
a r t i c l e i n f o
Keywords:
Disease Activity Score 28
ESR
CRP
Glycated albumin
Rheumatoid arthritis
HbA1c
Rheumatoid arthritis (RA) is a prototypical autoimmune disease,
characterized by the symmetric inflammation in multiple joints,
leading to progressive destruction of joints [1]. Various immune
cells and cytokines are involved in RA pathogenesis, and they may
also increase the risks of extra-articular complications of RA [2,3].
Glycated albumin (GA) is a newly suggested parameter for
the glycemic status. Compared to glycated hemoglobin (HbA1c ),
GA can more strongly reflect relatively short-term postprandial
plasma glucose rather than mean plasma glucose and predict
the development of cardiovascular disease (CVD) and its severity
[4,5]. Moreover, GA was reported to be correlated with inflamma-
tory burdens such as (C-reactive protein) CRP and inflammatory
cytokines levels [6,7]. Hence, in this study, we investigated whether
GA level might increase with disease activity in rheumatoid factor
positive RA patients who had normal laboratory results including
GA, fasting glucose and HbA1c , and who had no medical history of
abnormal glucose metabolism and other medical conditions affect-
ing GA level.
http://dx.doi.org/10.1016/j.jbspin.2016.01.011
1297-319X/© 2016 Société française de rhumatologie. Published by Elsevier Masson SAS. All rights reserved.
Please cite this article in press as: Park J-S, et al. Glycated albumin increases with disease activity in rheumatoid factor positive rheuma-
toid arthritis patients with normal fasting glucose and HbA1c . Joint Bone Spine (2016), http://dx.doi.org/10.1016/j.jbspin.2016.01.011
We consecutively screened 250 RA patients in this study, and
finally analyzed data of 205 RA patients (Fig. S1; See the supplemen-
tary material associated with this article online). This study was
approved by the Institutional Review Board of Severance Hospi-
tal. Informed consent was obtained from all patients. We collected
12 hour-fasting blood samples and performed laboratory tests
described Table 1 [8]. We calculated the cumulative and weekly
or daily doses of methotrexate and prednisolone [9]. In this study,
we used Disease Activity Score (DAS) 28 using both erythrocyte
sedimentation rate (ESR) (DAS28-ESR) and CRP (DAS28-CRP), and
we defined DAS28 > 3.2 as active RA [10].
In both comparison analyses according to DAS28-ESR and
DAS28-CRP > 3.2, patients with active RA had higher ESR and
CRP levels and DAS28 than those with inactive RA. Patients with
active RA showed significantly higher GA level than those with
inactive RA (13.8 ± 1.8 vs. 12.8 ± 1.4%, P < 0.001 [DAS28-ESR] and
14.4 ± 1.7 vs. 13.0 ± 1.5%, P < 0.001 [DAS28-CRP]). Also, patients
with active RA had significantly higher alkaline phosphatase (ALP)
level than those with inactive RA (P = 0.003 [DAS28-ESR] and
P = 0.033 [DAS28-CRP]). But there were no significant differences
in fasting glucose, HbA1c and the cumulative and daily doses of
medications between the two groups (Table 1). On multivariate
logistic regression analysis of the statistically significant variables,
we found that GA ≥ 12.95%, CRP ≥ 1.65 mg/L and ALP ≥ 60.5 IU/L
were independent predictors of active RA based on DAS28-ESR
(OR 4.881, P < 0.001, OR 12.972, P < 0.001, and OR 3.573, P = 0.001).
Also we found that GA ≥ 13.95% could independently predict active
RA based on DAS28-CRP better than ESR ≥ 43.5 mm/hr (OR 6.399,
P < 0.001 vs. OR 4.509, P < 0.001), but ALP ≥ 60.5 IU/L could not
(Table 2).
We concluded that GA level increased with disease activity in
rheumatoid factor positive RA patients with normal laboratory
results, who had no medical history. Furthermore, GA level showed
the potential to predict active RA, comparable with ESR and CRP.
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BONSOI-4371; No. of Pages 4

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toid arthritis patients with normal fasting glucose and HbA1c . Joint Bone Spine (2016), http://dx.doi.org/10.1016/j.jbspin.2016.01.011
Please cite this article in press as: Park J-S, et al. Glycated albumin increases with disease activity in rheumatoid factor positive rheuma-

Table 1
Comparison variables between patients with active and inactive RA based on DAS28-ESR > 3.2 and DAS28-CRP > 3.2.

Variables Total (n = 205) Active RA Inactive RA P-value Active RA Inactive RA P-value

(DAS28-ESR) (DAS28-ESR) (DAS28-CRP) (DAS28-CRP)
(n = 135) (n = 70) (n = 70) (n = 135)

Demographics
Age, years 56.0 (46.0–65.5) 56.4 ± 11.7 54.4 ± 13.7 0.305 56.1 ± 12.6 55.5 ± 12.4 0.729
Female gender, number (%) 165 (80.5) 109 (80.7) 56 (80.0) 0.899 54 (77.1) 111 (82.2) 0.384
Disease duration (days) 1,050 1,450.4 ± 1,106.1 1,396.6 ± 1,133.0 0.746 1,528.0 ± 1,145.7 1,382.2 ± 1,096.4 0.382
(584.5–1,953.0)
Body mass index, kg/m2 22.7 (20.4–24.5) 22.9 ± 3.2 22.4 ± 2.6 0.266 23.0 ± 3.1 22.6 ± 3.0 0.362
Hypertension, number (%) 65 (31.7) 44 (32.6) 21 (30.0) 0.705 20 (28.6) 45 (33.3) 0.487
Systolic blood pressure, mmHg 124.0 123.2 ± 13.0 122.4 ± 14.0 0.694 122.9 ± 13.6 123.0 ± 13.3 0.951

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(113.0–133.0)
Diastolic blood pressure, mmHg 72.0 (67.0–80.0) 73.6 ± 10.1 73.5 ± 9.9 0.942 73.1 ± 10.1 73.8 ± 10.0 0.662

Letter to the Editor / Joint Bone Spine xxx (2016) xxx–xxx

Dyslipidemia, number (%) 40 (19.5) 27 (20.0) 13 (18.6) 0.807 18 (25.7) 22 (16.3) 0.107
Smoking, number (%) 0.802 0.698
Non-smoker 169 (82.4) 112 (83.0) 57 (81.4) 57 (76.0) 112 (83.0)
Ex-smoker 17 (8.3) 10 (7.4) 7 (10.0) 5 (6.7) 12 (8.9)
Current smoker 19 (9.3) 13 (9.6) 6 (8.6) 8 (10.7) 11 (8.2)
Laboratory results
Anti-CCP, number (%)a (n = 129) 79/129 (61.2) 54/90 (60.0) 25/39 (64.1) 0.660 28/43 (65.1) 51/86 (59.3) 0.523
White blood cell, count/mm3 6,820.0 7,382.4 ± 1,852.0 7,133.6 ± 1,854.9 0.364 7,537.6 ± 1,692.2 7,173.0 ± 1,924.2 0.165
(5,650.0–8,110.0)
Hemoglobin, g/dL 13.0 (12.5–13.8) 13.0 ± 1.3 13.2 ± 1.3 0.236 13.1 ± 1.2 13.0 ± 1.3 0.645
Platelet, count/mm3 262,000.0 271,950.0 ± 71,582.0 265,730.0 ± 58,199.0 0.504 276,840.0 ± 71,862.0 266,190.0 ± 64,678.0 0.300
(226,000.0–307,000.0)
ESR, mm/hr 30.0 (17.0–44.5) 42.3 ± 23.2 18.7 ± 12.3 < 0.001 46.5 ± 26.2 28.0 ± 18.4 < 0.001
CRP, mg/L 1.8 (0.8–4.7) 7.0 ± 11.0 1.2 ± 1.0 < 0.001 11.6 ± 13.7 1.6 ± 1.3 < 0.001
Fasting glucose, mg/dL 91.0 (87.0–97.0) 93.0 ± 9.8 91.7 ± 9.7 0.367 93.3 ± 10.9 92.2 ± 9.1 0.491
Hemoglobin A1c, % 5.5 (5.3–5.8) 5.6 ± 0.3 5.5 ± 0.4 0.602 5.6 ± 0.3 5.5 ± 0.4 0.460
Glycated albumin, % 13.1 (12.2–14.7) 13.8 ± 1.8 12.8 ± 1.4 < 0.001 14.4 ± 1.7 13.0 ± 1.5 < 0.001
Total protein, mg/dL 7.0 (6.7–7.3) 7.0 ± 0.5 6.9 ± 0.4 0.232 7.0 ± 0.5 7.0 ± 0.4 0.635
Serum albumin, mg/dL 4.2 (4.0–4.3) 4.2 ± 0.3 4.2 ± 0.3 0.739 4.1 ± 0.3 4.2 ± 0.3 0.239
Blood urea nitrogen, mg/dL 14.7 (12.0–17.6) 15.6 ± 4.9 14.5 ± 3.8 0.063 16.1 ± 5.7 14.8 ± 3.9 0.060
Creatinine, mg/dL 0.7 (0.6–0.8) 0.7 ± 0.2 0.7 ± 0.1 0.573 0.7 ± 0.2 0.7 ± 0.1 0.115
eGFR (CKD-EPI), mL/min/1.73 m2 102.0 (92.0–109.5) 99.5 ± 14.2 102.9 ± 12.9 0.159 98.9 ± 15.9 101.3 ± 12.5 0.233
Uric acid, mg/dL 4.0 (3.2–4.9) 4.2 ± 1.2 4.0 ± 1.1 0.168 4.3 ± 1.3 4.0 ± 1.1 0.056
Alkaline phosphatase, IU/L 63.0 (52.5–76.5) 68.6 ± 17.6 60.8 ± 17.7 0.003 69.6 ± 17.3 64.0 ± 18.1 0.033
Aspartate aminotransferase, IU/L 19.0 (16.0–23.0) 20.4 ± 6.2 21.0 ± 6.6 0.562 19.8 ± 5.8 21.1 ± 6.6 0.138
Alanine aminotransferase, IU/L 16.0 (12.0–21.0) 17.7 ± 8.4 19.2 ± 8.4 0.222 17.2 ± 7.3 18.7 ± 8.9 0.213
Total bilirubin, mg/dL 0.5 (0.5–0.6) 0.6 ± 0.2 0.6 ± 0.2 0.674 0.6 ± 0.2 0.6 ± 0.2 0.105
Gamma-glutamyltranspeptidase, IU/L 200 (12.0–39.0) 25.2 ± 14.4 23.8 ± 14.1 0.493 25.5 ± 14.4 24.3 ± 14.3 0.560
Prothrombin time, INR 0.9 (0.9–1.0) 0.9 ± 0.1 0.9 ± 0.1 0.638 0.9 ± 0.1 0.9 ± 0.1 0.616
Creatine phosphokinase, IU/L 62.0 (43.5–88.0) 74.6 ± 61.4 80.7 ± 49.0 0.437 68.6 ± 51.8 80.9 ± 59.9 0.130
Total cholesterol, mg/dL 183.0 (161.0- 187.1 ± 36.2 182.9 ± 32.8 0.407 181.1 ± 35.5 188.1 ± 34.7 0.179
209.0)
High density cholesterol, mg/dL 56.0 (47.5–66.0) 56.4 ± 13.9 59.1 ± 13.7 0.176 55.3 ± 14.7 58.4 ± 13.3 0.153
Low density cholesterol, mg/dL 105.3 (84.9–126.7) 106.6 ± 29.2 107.6 ± 28.3 0.813 102.5 ± 29.8 109.2 ± 28.2 0.128
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toid arthritis patients with normal fasting glucose and HbA1c . Joint Bone Spine (2016), http://dx.doi.org/10.1016/j.jbspin.2016.01.011
Please cite this article in press as: Park J-S, et al. Glycated albumin increases with disease activity in rheumatoid factor positive rheuma-

Table 1 (Continued)

Variables Total (n = 205) Active RA Inactive RA P-value Active RA Inactive RA P-value

(DAS28-ESR) (DAS28-ESR) (DAS28-CRP) (DAS28-CRP)

ARTICLE IN PRESS
(n = 135) (n = 70) (n = 70) (n = 135)

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Triglyceride, mg/dL 98.0 (71.0–133.5) 117.9 ± 72.3 112.7 ± 76.5 0.639 110.2 ± 57.7 119.1 ± 80.7 0.364
Apo lipoprotein A1, mg/dL 160.3 160.6 ± 31.1 166.1 ± 29.4 0.214 156.9 ± 35.0 165.4 ± 27.7 0.081
(141.1–182.9)
Apo lipoprotein B, mg/dL 90.1 (74.1–105.5) 91.6 ± 21.4 91.0 ± 20.7 0.858 88.7 ± 22.7 92.8 ± 20.2 0.205
Lipoprotein(a), mg/dL 14.6 (7.1–26.1) 23.3 ± 26.1 19.0 ± 19.2 0.186 25.5 ± 23.5 19.9 ± 24.2 0.115
Clinical features related to disease activity
Tender joint count, number 2.0 (1.0–4.0) 3.9 ± 2.7 0.8 ± 0.8 < 0.001 5.7 ± 2.7 1.4 ± 1.1 < 0.001
Swollen joint count, number 1.0 (0.0–3.0) 2.8 ± 2.7 0.4 ± 0.6 < 0.001 4.4 ± 2.8 0.7 ± 0.8 < 0.001
Patient global health VAS, mm 20.0 (10.0–40.0) 34.9 ± 19.8 11.9 ± 8.2 < 0.001 47.3 ± 17.8 16.5 ± 10.9 < 0.001
DAS28-ESR 3.7 (2.9–4.6) 4.5 ± 1.0 2.5 ± 0.5 < 0.001 5.1 ± 0.9 3.1 ± 0.8 < 0.001
DAS28-CRP 2.7 (2.0–3.5) 3.5 ± 1.1 1.9 ± 0.5 < 0.001 4.3 ± 0.9 2.2 ± 0.6 < 0.001
Medications
Methotrexate (n = 181)
Weekly dose, mg 11.2 (8.8–11.4) 9.8 ± 4.4 9.9 ± 4.2 0.958 9.1 ± 3.8 10.2 ± 4.5 0.107
Cumulative dose, mg 1,495.0 2,265.8 ± 1,650.5 2,147.5 ± 1,620.1 0.644 2,323.4 ± 1,660.9 2,174.2 ± 1,628.5 0.565
(902.5–3,379.0)
Prednisolone (n = 159)
Daily dose, mg 2.0 (0.5–3.9) 2.8 ± 2.9 2.5 ± 2.7 0.364 2.5 ± 2.3 2.8 ± 3.1 0.514
Cumulative dose, mg 1,500.0 3,371.4 ± 2,981.2 2,880.6 ± 1,850.1 0.274 3,125.5 ± 2,906.4 3,252.5 ± 2,533.1 0.784
(1,019.8–2,780.0)

Values are expressed as median (interquartile range, IQR), mean ± standard deviation or number (%). Anti-CCP: anti-cyclic citrullinated peptide; ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; eGFR: estimated
glomerular filtration rate; CKD-EPI: the Chronic Kidney Disease Epidemiology Collaboration; INR: international normalized ratio; VAS: visual analogue scale; DAS28: Disease Activity Score 28.
a
Anti-cyclic citrullinated peptide test had been performed in 129 out of 205 patients (62.9%).

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Table 2
Univariate and multivariate analyses of statistically significant variables according to active RA based on DAS28-ESR and DAS28-CRP.

Variables Univariate analysis Multivariate analysis

Exp (B) 95% Confidential interval P-value Odds ratio 95% Confidential interval P-value

DAS28-ESR > 3.2 (active RA)

Glycated albumin ≥ 12.95% 3.439 1.882, 6.283 < 0.001 4.881 2.263, 10.529 < 0.001
CRP ≥ 1.65 mg/L 11.081 5.384, 22.806 < 0.001 12.972 5.782, 29.101 < 0.001
Alkaline phosphatase ≥ 60.5 IU/L 3.407 1.866, 6.223 < 0.001 3.573 1.705, 7.488 0.001
DAS28-CRP > 3.2 (active RA)
Glycated albumin ≥ 13.95% 5.677 3.026, 10.652 < 0.001 6.399 3.197, 12.809 < 0.001
ESR ≥ 43.5 mm/hr 4.870 2.545, 9.316 < 0.001 4.509 2.165, 9.392 < 0.001
Alkaline phosphatase ≥ 60.5 IU/L 2.167 1.174, 3.998 0.013 1.908 0.928, 3.926 0.079

ESR: erythrocyte sedimentation rate; CRP: C-reactive protein; DAS28: Disease Activity Score 28.

Disclosure of interest
The authors declare that they have no competing interest.
Appendix A. Supplementary data
[10] van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/j.jbspin.
2016.01.011.
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improvement criteria that include simplified joint counts. Arthritis Rheum
1998;41:1845–50.
Jin-Su Park a
Jungsik Song b
Yong-Beom Park b
Soo-Kon Lee b
Sang-Won Lee b,∗
a Division of rheumatology, department of internal
medicine, NHIS Ilsan Hospital, 100, Ilsan-ro,
Ilsandong-gu, Goyang-si, Gyeonggi-do, 10444,
South Korea
b Division of rheumatology, department of internal
medicine, Yonsei University College of Medicine, 50,
Yonsei-ro, Seodaemun–gu, 03722 Seoul, South Korea
∗ Corresponding author.
E-mail address: sangwonlee@yuhs.ac (S.-W. Lee)
Accepted 20 January 2016
Available online xxx

Please cite this article in press as: Park J-S, et al. Glycated albumin increases with disease activity in rheumatoid factor positive rheuma-
toid arthritis patients with normal fasting glucose and HbA1c . Joint Bone Spine (2016), http://dx.doi.org/10.1016/j.jbspin.2016.01.011