- Email: [email protected]
Glycated albumin increases with disease activity in rheumatoid factor positive rheumatoid arthritis patients with normal fasting glucose and HbA1c
G Model BONSOI-4371; No. of Pages 4
ARTICLE IN PRESS Joint Bone Spine xxx (2016) xxx–xxx
Available online at
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Letter to the Editor Glycated albumin increases with disease activity 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 inflammatory 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 affecting GA level.
We consecutively screened 250 RA patients in this study, and finally analyzed data of 205 RA patients (Fig. S1; See the supplementary material associated with this article online). This study was approved by the Institutional Review Board of Severance Hospital. 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.
http://dx.doi.org/10.1016/j.jbspin.2016.01.011 1297-319X/© 2016 Société franc¸aise 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 rheumatoid arthritis patients with normal fasting glucose and HbA1c . Joint Bone Spine (2016), http://dx.doi.org/10.1016/j.jbspin.2016.01.011
Demographics Age, years Female gender, number (%) Disease duration (days) Body mass index, kg/m2 Hypertension, number (%) Systolic blood pressure, mmHg
ESR, mm/hr CRP, mg/L Fasting glucose, mg/dL Hemoglobin A1c, % Glycated albumin, % Total protein, mg/dL Serum albumin, mg/dL Blood urea nitrogen, mg/dL Creatinine, mg/dL eGFR (CKD-EPI), mL/min/1.73 m2 Uric acid, mg/dL Alkaline phosphatase, IU/L Aspartate aminotransferase, IU/L Alanine aminotransferase, IU/L Total bilirubin, mg/dL Gamma-glutamyltranspeptidase, IU/L Prothrombin time, INR Creatine phosphokinase, IU/L Total cholesterol, mg/dL High density cholesterol, mg/dL Low density cholesterol, mg/dL
Inactive RA (DAS28-ESR) (n = 70)
P-value
Active RA (DAS28-CRP) (n = 70)
Inactive RA (DAS28-CRP) (n = 135)
P-value
56.0 (46.0–65.5) 165 (80.5) 1,050 (584.5–1,953.0) 22.7 (20.4–24.5) 65 (31.7) 124.0 (113.0–133.0) 72.0 (67.0–80.0) 40 (19.5)
56.4 ± 11.7 109 (80.7) 1,450.4 ± 1,106.1
54.4 ± 13.7 56 (80.0) 1,396.6 ± 1,133.0
0.305 0.899 0.746
56.1 ± 12.6 54 (77.1) 1,528.0 ± 1,145.7
55.5 ± 12.4 111 (82.2) 1,382.2 ± 1,096.4
0.729 0.384 0.382
22.9 ± 3.2 44 (32.6) 123.2 ± 13.0
22.4 ± 2.6 21 (30.0) 122.4 ± 14.0
0.266 0.705 0.694
23.0 ± 3.1 20 (28.6) 122.9 ± 13.6
22.6 ± 3.0 45 (33.3) 123.0 ± 13.3
0.362 0.487 0.951
73.6 ± 10.1 27 (20.0)
73.5 ± 9.9 13 (18.6)
0.942 0.807 0.802
73.1 ± 10.1 18 (25.7)
73.8 ± 10.0 22 (16.3)
0.662 0.107 0.698
169 (82.4) 17 (8.3) 19 (9.3)
112 (83.0) 10 (7.4) 13 (9.6)
57 (81.4) 7 (10.0) 6 (8.6)
57 (76.0) 5 (6.7) 8 (10.7)
112 (83.0) 12 (8.9) 11 (8.2)
79/129 (61.2) 6,820.0 (5,650.0–8,110.0) 13.0 (12.5–13.8) 262,000.0 (226,000.0–307,000.0) 30.0 (17.0–44.5) 1.8 (0.8–4.7) 91.0 (87.0–97.0) 5.5 (5.3–5.8) 13.1 (12.2–14.7) 7.0 (6.7–7.3) 4.2 (4.0–4.3) 14.7 (12.0–17.6) 0.7 (0.6–0.8) 102.0 (92.0–109.5) 4.0 (3.2–4.9) 63.0 (52.5–76.5) 19.0 (16.0–23.0) 16.0 (12.0–21.0) 0.5 (0.5–0.6) 200 (12.0–39.0) 0.9 (0.9–1.0) 62.0 (43.5–88.0) 183.0 (161.0209.0) 56.0 (47.5–66.0) 105.3 (84.9–126.7)
54/90 (60.0) 7,382.4 ± 1,852.0
25/39 (64.1) 7,133.6 ± 1,854.9
0.660 0.364
28/43 (65.1) 7,537.6 ± 1,692.2
51/86 (59.3) 7,173.0 ± 1,924.2
0.523 0.165
13.0 ± 1.3 271,950.0 ± 71,582.0
13.2 ± 1.3 265,730.0 ± 58,199.0
0.236 0.504
13.1 ± 1.2 276,840.0 ± 71,862.0
13.0 ± 1.3 266,190.0 ± 64,678.0
0.645 0.300
42.3 ± 23.2 7.0 ± 11.0 93.0 ± 9.8 5.6 ± 0.3 13.8 ± 1.8 7.0 ± 0.5 4.2 ± 0.3 15.6 ± 4.9 0.7 ± 0.2 99.5 ± 14.2 4.2 ± 1.2 68.6 ± 17.6 20.4 ± 6.2 17.7 ± 8.4 0.6 ± 0.2 25.2 ± 14.4 0.9 ± 0.1 74.6 ± 61.4 187.1 ± 36.2
18.7 ± 12.3 1.2 ± 1.0 91.7 ± 9.7 5.5 ± 0.4 12.8 ± 1.4 6.9 ± 0.4 4.2 ± 0.3 14.5 ± 3.8 0.7 ± 0.1 102.9 ± 12.9 4.0 ± 1.1 60.8 ± 17.7 21.0 ± 6.6 19.2 ± 8.4 0.6 ± 0.2 23.8 ± 14.1 0.9 ± 0.1 80.7 ± 49.0 182.9 ± 32.8
< 0.001 < 0.001 0.367 0.602 < 0.001 0.232 0.739 0.063 0.573 0.159 0.168 0.003 0.562 0.222 0.674 0.493 0.638 0.437 0.407
46.5 ± 26.2 11.6 ± 13.7 93.3 ± 10.9 5.6 ± 0.3 14.4 ± 1.7 7.0 ± 0.5 4.1 ± 0.3 16.1 ± 5.7 0.7 ± 0.2 98.9 ± 15.9 4.3 ± 1.3 69.6 ± 17.3 19.8 ± 5.8 17.2 ± 7.3 0.6 ± 0.2 25.5 ± 14.4 0.9 ± 0.1 68.6 ± 51.8 181.1 ± 35.5
28.0 ± 18.4 1.6 ± 1.3 92.2 ± 9.1 5.5 ± 0.4 13.0 ± 1.5 7.0 ± 0.4 4.2 ± 0.3 14.8 ± 3.9 0.7 ± 0.1 101.3 ± 12.5 4.0 ± 1.1 64.0 ± 18.1 21.1 ± 6.6 18.7 ± 8.9 0.6 ± 0.2 24.3 ± 14.3 0.9 ± 0.1 80.9 ± 59.9 188.1 ± 34.7
< 0.001 < 0.001 0.491 0.460 < 0.001 0.635 0.239 0.060 0.115 0.233 0.056 0.033 0.138 0.213 0.105 0.560 0.616 0.130 0.179
56.4 ± 13.9 106.6 ± 29.2
59.1 ± 13.7 107.6 ± 28.3
0.176 0.813
55.3 ± 14.7 102.5 ± 29.8
58.4 ± 13.3 109.2 ± 28.2
0.153 0.128
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Hemoglobin, g/dL Platelet, count/mm3
Active RA (DAS28-ESR) (n = 135)
Letter to the Editor / Joint Bone Spine xxx (2016) xxx–xxx
Diastolic blood pressure, mmHg Dyslipidemia, number (%) Smoking, number (%) Non-smoker Ex-smoker Current smoker Laboratory results Anti-CCP, number (%)a (n = 129) White blood cell, count/mm3
Total (n = 205)
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Please cite this article in press as: Park J-S, et al. Glycated albumin increases with disease activity in rheumatoid factor positive rheumatoid arthritis patients with normal fasting glucose and HbA1c . Joint Bone Spine (2016), http://dx.doi.org/10.1016/j.jbspin.2016.01.011
Table 1 Comparison variables between patients with active and inactive RA based on DAS28-ESR > 3.2 and DAS28-CRP > 3.2.
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Variables
Apo lipoprotein B, mg/dL Lipoprotein(a), mg/dL Clinical features related to disease activity Tender joint count, number Swollen joint count, number Patient global health VAS, mm DAS28-ESR DAS28-CRP Medications Methotrexate (n = 181) Weekly dose, mg Cumulative dose, mg Prednisolone (n = 159) Daily dose, mg Cumulative dose, mg
Active RA (DAS28-ESR) (n = 135)
Inactive RA (DAS28-ESR) (n = 70)
P-value
Active RA (DAS28-CRP) (n = 70)
Inactive RA (DAS28-CRP) (n = 135)
P-value
98.0 (71.0–133.5) 160.3 (141.1–182.9) 90.1 (74.1–105.5) 14.6 (7.1–26.1)
117.9 ± 72.3 160.6 ± 31.1
112.7 ± 76.5 166.1 ± 29.4
0.639 0.214
110.2 ± 57.7 156.9 ± 35.0
119.1 ± 80.7 165.4 ± 27.7
0.364 0.081
91.6 ± 21.4 23.3 ± 26.1
91.0 ± 20.7 19.0 ± 19.2
0.858 0.186
88.7 ± 22.7 25.5 ± 23.5
92.8 ± 20.2 19.9 ± 24.2
0.205 0.115
2.0 (1.0–4.0) 1.0 (0.0–3.0) 20.0 (10.0–40.0) 3.7 (2.9–4.6) 2.7 (2.0–3.5)
3.9 ± 2.7 2.8 ± 2.7 34.9 ± 19.8 4.5 ± 1.0 3.5 ± 1.1
0.8 ± 0.8 0.4 ± 0.6 11.9 ± 8.2 2.5 ± 0.5 1.9 ± 0.5
< 0.001 < 0.001 < 0.001 < 0.001 < 0.001
5.7 ± 2.7 4.4 ± 2.8 47.3 ± 17.8 5.1 ± 0.9 4.3 ± 0.9
1.4 ± 1.1 0.7 ± 0.8 16.5 ± 10.9 3.1 ± 0.8 2.2 ± 0.6
< 0.001 < 0.001 < 0.001 < 0.001 < 0.001
11.2 (8.8–11.4) 1,495.0 (902.5–3,379.0)
9.8 ± 4.4 2,265.8 ± 1,650.5
9.9 ± 4.2 2,147.5 ± 1,620.1
0.958 0.644
9.1 ± 3.8 2,323.4 ± 1,660.9
10.2 ± 4.5 2,174.2 ± 1,628.5
0.107 0.565
2.0 (0.5–3.9) 1,500.0 (1,019.8–2,780.0)
2.8 ± 2.9 3,371.4 ± 2,981.2
2.5 ± 2.7 2,880.6 ± 1,850.1
0.364 0.274
2.5 ± 2.3 3,125.5 ± 2,906.4
2.8 ± 3.1 3,252.5 ± 2,533.1
0.514 0.784
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%).
ARTICLE IN PRESS
Triglyceride, mg/dL Apo lipoprotein A1, mg/dL
Total (n = 205)
Letter to the Editor / Joint Bone Spine xxx (2016) xxx–xxx
Please cite this article in press as: Park J-S, et al. Glycated albumin increases with disease activity in rheumatoid factor positive rheumatoid arthritis patients with normal fasting glucose and HbA1c . Joint Bone Spine (2016), http://dx.doi.org/10.1016/j.jbspin.2016.01.011
Table 1 (Continued)
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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
DAS28-ESR > 3.2 (active RA) Glycated albumin ≥ 12.95% CRP ≥ 1.65 mg/L Alkaline phosphatase ≥ 60.5 IU/L DAS28-CRP > 3.2 (active RA) Glycated albumin ≥ 13.95% ESR ≥ 43.5 mm/hr Alkaline phosphatase ≥ 60.5 IU/L
Univariate analysis
Multivariate analysis
Exp (B)
95% Confidential interval
P-value
Odds ratio
95% Confidential interval
P-value
3.439 11.081 3.407
1.882, 6.283 5.384, 22.806 1.866, 6.223
< 0.001 < 0.001 < 0.001
4.881 12.972 3.573
2.263, 10.529 5.782, 29.101 1.705, 7.488
< 0.001 < 0.001 0.001
5.677 4.870 2.167
3.026, 10.652 2.545, 9.316 1.174, 3.998
< 0.001 < 0.001 0.013
6.399 4.509 1.908
3.197, 12.809 2.165, 9.392 0.928, 3.926
< 0.001 < 0.001 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 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. References [1] Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001;344:907–16. [2] Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 1996;14:397–440. [3] Zwerina J, Redlich K, Schett G, et al. Pathogenesis of rheumatoid arthritis: targeting cytokines. Ann N Y Acad Sci 2005;1051:716–29. [4] Koga M, Kasayama S. Clinical impact of glycated albumin as another glycemic control marker. Endocr J 2010;57:751–62. [5] Kim KJ, Lee BW. The roles of glycated albumin as intermediate glycation index and pathogenic protein. Diabetes Metab J 2012;36:98–107. [6] Pu LJ, Lu L, Xu XW, et al. Value of serum glycated albumin and highsensitivity C-reactive protein levels in the prediction of presence of coronary artery disease in patients with type 2 diabetes. Cardiovasc Diabetol 2006; 5:27. [7] Lu L, Pu LJ, Xu XW, et al. Association of serum levels of glycated albumin, Creactive protein and tumor necrosis factor-alpha with the severity of coronary artery disease and renal impairment in patients with type 2 diabetes mellitus. Clin Biochem 2007;40:810–6.
[8] Jung CH, Hwang YC, Kim KJ, et al. Development of an HbA1c -based conversion equation for estimating glycated albumin in a Korean population with a wide range of glucose intolerance. PLoS One 2014;9:e95729. [9] Lee SW, Park HJ, Kim BK, et al. Leflunomide increases the risk of silent liver fibrosis in patients with rheumatoid arthritis receiving methotrexate. Arthritis Res Ther 2012;14:R232. [10] van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis 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: [email protected] (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 rheumatoid arthritis patients with normal fasting glucose and HbA1c . Joint Bone Spine (2016), http://dx.doi.org/10.1016/j.jbspin.2016.01.011
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 activity 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 inflammatory 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 affecting GA level.
We consecutively screened 250 RA patients in this study, and finally analyzed data of 205 RA patients (Fig. S1; See the supplementary material associated with this article online). This study was approved by the Institutional Review Board of Severance Hospital. 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.
http://dx.doi.org/10.1016/j.jbspin.2016.01.011 1297-319X/© 2016 Société franc¸aise 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 rheumatoid arthritis patients with normal fasting glucose and HbA1c . Joint Bone Spine (2016), http://dx.doi.org/10.1016/j.jbspin.2016.01.011
Demographics Age, years Female gender, number (%) Disease duration (days) Body mass index, kg/m2 Hypertension, number (%) Systolic blood pressure, mmHg
ESR, mm/hr CRP, mg/L Fasting glucose, mg/dL Hemoglobin A1c, % Glycated albumin, % Total protein, mg/dL Serum albumin, mg/dL Blood urea nitrogen, mg/dL Creatinine, mg/dL eGFR (CKD-EPI), mL/min/1.73 m2 Uric acid, mg/dL Alkaline phosphatase, IU/L Aspartate aminotransferase, IU/L Alanine aminotransferase, IU/L Total bilirubin, mg/dL Gamma-glutamyltranspeptidase, IU/L Prothrombin time, INR Creatine phosphokinase, IU/L Total cholesterol, mg/dL High density cholesterol, mg/dL Low density cholesterol, mg/dL
Inactive RA (DAS28-ESR) (n = 70)
P-value
Active RA (DAS28-CRP) (n = 70)
Inactive RA (DAS28-CRP) (n = 135)
P-value
56.0 (46.0–65.5) 165 (80.5) 1,050 (584.5–1,953.0) 22.7 (20.4–24.5) 65 (31.7) 124.0 (113.0–133.0) 72.0 (67.0–80.0) 40 (19.5)
56.4 ± 11.7 109 (80.7) 1,450.4 ± 1,106.1
54.4 ± 13.7 56 (80.0) 1,396.6 ± 1,133.0
0.305 0.899 0.746
56.1 ± 12.6 54 (77.1) 1,528.0 ± 1,145.7
55.5 ± 12.4 111 (82.2) 1,382.2 ± 1,096.4
0.729 0.384 0.382
22.9 ± 3.2 44 (32.6) 123.2 ± 13.0
22.4 ± 2.6 21 (30.0) 122.4 ± 14.0
0.266 0.705 0.694
23.0 ± 3.1 20 (28.6) 122.9 ± 13.6
22.6 ± 3.0 45 (33.3) 123.0 ± 13.3
0.362 0.487 0.951
73.6 ± 10.1 27 (20.0)
73.5 ± 9.9 13 (18.6)
0.942 0.807 0.802
73.1 ± 10.1 18 (25.7)
73.8 ± 10.0 22 (16.3)
0.662 0.107 0.698
169 (82.4) 17 (8.3) 19 (9.3)
112 (83.0) 10 (7.4) 13 (9.6)
57 (81.4) 7 (10.0) 6 (8.6)
57 (76.0) 5 (6.7) 8 (10.7)
112 (83.0) 12 (8.9) 11 (8.2)
79/129 (61.2) 6,820.0 (5,650.0–8,110.0) 13.0 (12.5–13.8) 262,000.0 (226,000.0–307,000.0) 30.0 (17.0–44.5) 1.8 (0.8–4.7) 91.0 (87.0–97.0) 5.5 (5.3–5.8) 13.1 (12.2–14.7) 7.0 (6.7–7.3) 4.2 (4.0–4.3) 14.7 (12.0–17.6) 0.7 (0.6–0.8) 102.0 (92.0–109.5) 4.0 (3.2–4.9) 63.0 (52.5–76.5) 19.0 (16.0–23.0) 16.0 (12.0–21.0) 0.5 (0.5–0.6) 200 (12.0–39.0) 0.9 (0.9–1.0) 62.0 (43.5–88.0) 183.0 (161.0209.0) 56.0 (47.5–66.0) 105.3 (84.9–126.7)
54/90 (60.0) 7,382.4 ± 1,852.0
25/39 (64.1) 7,133.6 ± 1,854.9
0.660 0.364
28/43 (65.1) 7,537.6 ± 1,692.2
51/86 (59.3) 7,173.0 ± 1,924.2
0.523 0.165
13.0 ± 1.3 271,950.0 ± 71,582.0
13.2 ± 1.3 265,730.0 ± 58,199.0
0.236 0.504
13.1 ± 1.2 276,840.0 ± 71,862.0
13.0 ± 1.3 266,190.0 ± 64,678.0
0.645 0.300
42.3 ± 23.2 7.0 ± 11.0 93.0 ± 9.8 5.6 ± 0.3 13.8 ± 1.8 7.0 ± 0.5 4.2 ± 0.3 15.6 ± 4.9 0.7 ± 0.2 99.5 ± 14.2 4.2 ± 1.2 68.6 ± 17.6 20.4 ± 6.2 17.7 ± 8.4 0.6 ± 0.2 25.2 ± 14.4 0.9 ± 0.1 74.6 ± 61.4 187.1 ± 36.2
18.7 ± 12.3 1.2 ± 1.0 91.7 ± 9.7 5.5 ± 0.4 12.8 ± 1.4 6.9 ± 0.4 4.2 ± 0.3 14.5 ± 3.8 0.7 ± 0.1 102.9 ± 12.9 4.0 ± 1.1 60.8 ± 17.7 21.0 ± 6.6 19.2 ± 8.4 0.6 ± 0.2 23.8 ± 14.1 0.9 ± 0.1 80.7 ± 49.0 182.9 ± 32.8
< 0.001 < 0.001 0.367 0.602 < 0.001 0.232 0.739 0.063 0.573 0.159 0.168 0.003 0.562 0.222 0.674 0.493 0.638 0.437 0.407
46.5 ± 26.2 11.6 ± 13.7 93.3 ± 10.9 5.6 ± 0.3 14.4 ± 1.7 7.0 ± 0.5 4.1 ± 0.3 16.1 ± 5.7 0.7 ± 0.2 98.9 ± 15.9 4.3 ± 1.3 69.6 ± 17.3 19.8 ± 5.8 17.2 ± 7.3 0.6 ± 0.2 25.5 ± 14.4 0.9 ± 0.1 68.6 ± 51.8 181.1 ± 35.5
28.0 ± 18.4 1.6 ± 1.3 92.2 ± 9.1 5.5 ± 0.4 13.0 ± 1.5 7.0 ± 0.4 4.2 ± 0.3 14.8 ± 3.9 0.7 ± 0.1 101.3 ± 12.5 4.0 ± 1.1 64.0 ± 18.1 21.1 ± 6.6 18.7 ± 8.9 0.6 ± 0.2 24.3 ± 14.3 0.9 ± 0.1 80.9 ± 59.9 188.1 ± 34.7
< 0.001 < 0.001 0.491 0.460 < 0.001 0.635 0.239 0.060 0.115 0.233 0.056 0.033 0.138 0.213 0.105 0.560 0.616 0.130 0.179
56.4 ± 13.9 106.6 ± 29.2
59.1 ± 13.7 107.6 ± 28.3
0.176 0.813
55.3 ± 14.7 102.5 ± 29.8
58.4 ± 13.3 109.2 ± 28.2
0.153 0.128
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Hemoglobin, g/dL Platelet, count/mm3
Active RA (DAS28-ESR) (n = 135)
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Diastolic blood pressure, mmHg Dyslipidemia, number (%) Smoking, number (%) Non-smoker Ex-smoker Current smoker Laboratory results Anti-CCP, number (%)a (n = 129) White blood cell, count/mm3
Total (n = 205)
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Table 1 Comparison variables between patients with active and inactive RA based on DAS28-ESR > 3.2 and DAS28-CRP > 3.2.
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Variables
Apo lipoprotein B, mg/dL Lipoprotein(a), mg/dL Clinical features related to disease activity Tender joint count, number Swollen joint count, number Patient global health VAS, mm DAS28-ESR DAS28-CRP Medications Methotrexate (n = 181) Weekly dose, mg Cumulative dose, mg Prednisolone (n = 159) Daily dose, mg Cumulative dose, mg
Active RA (DAS28-ESR) (n = 135)
Inactive RA (DAS28-ESR) (n = 70)
P-value
Active RA (DAS28-CRP) (n = 70)
Inactive RA (DAS28-CRP) (n = 135)
P-value
98.0 (71.0–133.5) 160.3 (141.1–182.9) 90.1 (74.1–105.5) 14.6 (7.1–26.1)
117.9 ± 72.3 160.6 ± 31.1
112.7 ± 76.5 166.1 ± 29.4
0.639 0.214
110.2 ± 57.7 156.9 ± 35.0
119.1 ± 80.7 165.4 ± 27.7
0.364 0.081
91.6 ± 21.4 23.3 ± 26.1
91.0 ± 20.7 19.0 ± 19.2
0.858 0.186
88.7 ± 22.7 25.5 ± 23.5
92.8 ± 20.2 19.9 ± 24.2
0.205 0.115
2.0 (1.0–4.0) 1.0 (0.0–3.0) 20.0 (10.0–40.0) 3.7 (2.9–4.6) 2.7 (2.0–3.5)
3.9 ± 2.7 2.8 ± 2.7 34.9 ± 19.8 4.5 ± 1.0 3.5 ± 1.1
0.8 ± 0.8 0.4 ± 0.6 11.9 ± 8.2 2.5 ± 0.5 1.9 ± 0.5
< 0.001 < 0.001 < 0.001 < 0.001 < 0.001
5.7 ± 2.7 4.4 ± 2.8 47.3 ± 17.8 5.1 ± 0.9 4.3 ± 0.9
1.4 ± 1.1 0.7 ± 0.8 16.5 ± 10.9 3.1 ± 0.8 2.2 ± 0.6
< 0.001 < 0.001 < 0.001 < 0.001 < 0.001
11.2 (8.8–11.4) 1,495.0 (902.5–3,379.0)
9.8 ± 4.4 2,265.8 ± 1,650.5
9.9 ± 4.2 2,147.5 ± 1,620.1
0.958 0.644
9.1 ± 3.8 2,323.4 ± 1,660.9
10.2 ± 4.5 2,174.2 ± 1,628.5
0.107 0.565
2.0 (0.5–3.9) 1,500.0 (1,019.8–2,780.0)
2.8 ± 2.9 3,371.4 ± 2,981.2
2.5 ± 2.7 2,880.6 ± 1,850.1
0.364 0.274
2.5 ± 2.3 3,125.5 ± 2,906.4
2.8 ± 3.1 3,252.5 ± 2,533.1
0.514 0.784
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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Triglyceride, mg/dL Apo lipoprotein A1, mg/dL
Total (n = 205)
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Table 1 (Continued)
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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
DAS28-ESR > 3.2 (active RA) Glycated albumin ≥ 12.95% CRP ≥ 1.65 mg/L Alkaline phosphatase ≥ 60.5 IU/L DAS28-CRP > 3.2 (active RA) Glycated albumin ≥ 13.95% ESR ≥ 43.5 mm/hr Alkaline phosphatase ≥ 60.5 IU/L
Univariate analysis
Multivariate analysis
Exp (B)
95% Confidential interval
P-value
Odds ratio
95% Confidential interval
P-value
3.439 11.081 3.407
1.882, 6.283 5.384, 22.806 1.866, 6.223
< 0.001 < 0.001 < 0.001
4.881 12.972 3.573
2.263, 10.529 5.782, 29.101 1.705, 7.488
< 0.001 < 0.001 0.001
5.677 4.870 2.167
3.026, 10.652 2.545, 9.316 1.174, 3.998
< 0.001 < 0.001 0.013
6.399 4.509 1.908
3.197, 12.809 2.165, 9.392 0.928, 3.926
< 0.001 < 0.001 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 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. References [1] Choy EH, Panayi GS. Cytokine pathways and joint inflammation in rheumatoid arthritis. N Engl J Med 2001;344:907–16. [2] Feldmann M, Brennan FM, Maini RN. Role of cytokines in rheumatoid arthritis. Annu Rev Immunol 1996;14:397–440. [3] Zwerina J, Redlich K, Schett G, et al. Pathogenesis of rheumatoid arthritis: targeting cytokines. Ann N Y Acad Sci 2005;1051:716–29. [4] Koga M, Kasayama S. Clinical impact of glycated albumin as another glycemic control marker. Endocr J 2010;57:751–62. [5] Kim KJ, Lee BW. The roles of glycated albumin as intermediate glycation index and pathogenic protein. Diabetes Metab J 2012;36:98–107. [6] Pu LJ, Lu L, Xu XW, et al. Value of serum glycated albumin and highsensitivity C-reactive protein levels in the prediction of presence of coronary artery disease in patients with type 2 diabetes. Cardiovasc Diabetol 2006; 5:27. [7] Lu L, Pu LJ, Xu XW, et al. Association of serum levels of glycated albumin, Creactive protein and tumor necrosis factor-alpha with the severity of coronary artery disease and renal impairment in patients with type 2 diabetes mellitus. Clin Biochem 2007;40:810–6.
[8] Jung CH, Hwang YC, Kim KJ, et al. Development of an HbA1c -based conversion equation for estimating glycated albumin in a Korean population with a wide range of glucose intolerance. PLoS One 2014;9:e95729. [9] Lee SW, Park HJ, Kim BK, et al. Leflunomide increases the risk of silent liver fibrosis in patients with rheumatoid arthritis receiving methotrexate. Arthritis Res Ther 2012;14:R232. [10] van Gestel AM, Haagsma CJ, van Riel PL. Validation of rheumatoid arthritis 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: [email protected] (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 rheumatoid arthritis patients with normal fasting glucose and HbA1c . Joint Bone Spine (2016), http://dx.doi.org/10.1016/j.jbspin.2016.01.011