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Association between low 25-hydroxyvitamin D, insulin resistance and arterial stiffness in nondiabetic women with systemic lupus erythematosus JM Sabio, JA Vargas-Hitos, J Martinez-Bordonado, N Navarrete-Navarrete, A Díaz-Chamorro, C Olvera-Porcel, M Zamora and J Jiménez-Alonso Lupus published online 12 September 2014 DOI: 10.1177/0961203314551811 The online version of this article can be found at: http://lup.sagepub.com/content/early/2014/09/12/0961203314551811
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(LUP)
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Lupus (2014) 0,
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Association between low 25-hydroxyvitamin D, insulin resistance and arterial stiffness in nondiabetic women with systemic lupus erythematosus JM Sabio1, JA Vargas-Hitos1, J Martinez-Bordonado1, N Navarrete-Navarrete1, A Dı´ az-Chamorro1, C Olvera-Porcel2, M Zamora1 and J Jime´nez-Alonso1 1
Systemic Autoimmune Diseases Unit, Department of Internal Medicine, University Hospital Virgen de las Nieves, Granada, Spain; and 2 Department of Statistics, Fundacio´n para la Investigacio´n Biosanitaria de Andalucı´ a Oriental (FIBAO), Granada, Spain
Objective: The objective of this paper is to examine if there is an association between low levels of 25-hydroxyvitamin D (25(OH)D) and insulin resistance (IR) in nondiabetic women with systemic lupus erythematosus (SLE) and to evaluate its impact on arterial stiffness. Patients and methods: In this cross-sectional study 25(OH)D, insulin, insulin resistance measured by the homeostatic model assessment (HOMA-IR), homocysteine, fibrinogen, characteristics of SLE, medications and pulse-wave velocity (PWV) were measured in 106 nondiabetic women with SLE and 101 matched controls. Results: Women with SLE tended to have lower 25(OH)D levels (p ¼ 0.078) and a higher frequency of 25(OH)D deficiency (defined as 30 UI/l, and medians (IQR) of C3 and C4 levels were 91 (77–107) mg/ dl and 16 (9–20) mg/dl. Prednisone and hydroxychloroquine (HCQ) were taken by 68% and 90% of patients. The median (IQR) daily prednisone dose was 2.5 (0–5) mg. Immunosuppressants were used concurrently in 41% of patients (azathioprine 6%, methotrexate 12%, and mycophenolate 24%). Differences between SLE and control women The median age and the educational level were similar in both groups. In contrast to what was expected, 25(OH)D levels were only marginally lower in patients than in controls (p ¼ 0.078). In addition, the frequency of 25(OH)D insufficiency was similar in both groups (83% vs. 69%, p ¼ 0.125) and 25(OH)D deficiency trended to be higher in the SLE group but did not reach statistical significance (8.5% vs. 2.1%, p ¼ 0.058) (Table 1). Both MetS and IR were more frequent in patients than in controls (OR 4.0, 95% CI 1.3–12.5, p ¼ 0.015 and OR 2.3, 95% CI 1.01–5.36, p ¼ 0.050). Consistently, median insulin levels and HOMA-IR were significantly higher in women with SLE (Table 1). PWV was significantly higher in patients (7.6 (6.9–8.4) vs. 7.1 (6.4–7.8) m/s, p ¼ 0.001)). Seven women in the SLE group and none of controls had a history of atherosclerotic CVD. Other CVD risk factor differences between both groups are summarized in Table 1.
Seasonal variation of 25(OH)D levels, photoprotection and use of vitamin D supplementation 25(OH)D levels varied notably depending on the season in which the vitamin was measured. When considering all participants, the median (IQR) of 25(OH)D in the summer was significantly higher than in the winter (23.1 (17.9–30.1) ng/ml vs. 20.0 (13.3–36.0) ng/ml; p ¼ 0.001). By groups, seasonal differences in 25(OH)D levels were present in controls (24.2 (18.4–30.8) ng/ml vs. 19.3 (12.8–23.0) ng/ml; p ¼ 0.001) but not in patients (22.0 (16.0– 28.0) ng/ml vs. 21.0 (15.3–27.0) ng/ml; p ¼ 0.106). Forty-four percent of women with SLE in comparison with 80% of controls were included during the winter (p < 0.001). The use of photoprotection was similar in patients with or without photosensitivity (86% vs. 84%). Photoprotection did not significantly modify levels of 25(OH)D (p ¼ 0.643) and sunscreen use was similar in summer (44%) and winter (41%). Furthermore, taking vitamin D supplements did not significantly influence levels of 25(OH)D (p ¼ 0.107). There was no association between 25(OH)D and use of immunosuppressants, HCQ or prednisone (Table 2). Association between 25(OH)D and IR and other cardiovascular factors In nondiabetic women with SLE, an unadjusted linear regression analysis showed that 25(OH)D levels inversely correlated with insulin levels (p ¼ 0.003), HOMA-IR (p ¼ 0.003) and C4 (p ¼ 0.028), and there was a trend toward significance with fibrinogen levels (p ¼ 0.063). No correlations were found with the rest of the cardiometabolic parameters, SLE-related characteristics and activity, prednisone dose and inflammatory markers. After adjustment for BMI (model 1), the correlation remained significant for insulin, HOMA-IR and C4, and there was also a trend toward significance for fibrinogen, but not for PWV. Identical results to those obtained in model 1 were found after adjustment for BMI and age (model 2), and for BMI, age, SLEDAI, C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), fibrinogen, daily prednisone dose, estimated glomerular filtration rate (eGFR) and seasonal variation (model 3) (Table 3). Interestingly, a trend toward correlation was observed between 25(OH)D and fibrinogen in model 3 (p ¼ 0.060). When we compared patients in the first quartile for 25(OH)D (16 ng/ml) with those in the fourth quartile (OH)D (27 ng/ml), the former had higher Lupus
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(LUP)
[1–9] [PREPRINTER stage]
25(OH)D and insulin resistance in SLE JM Sabio et al.
4
Table 1 Characteristics of the study population
Demographic characteristics Age, years Educational level Secondary education, n (%) University education, n (%) 25(OH) vitamin D status 25(OH) vitamin D, ng/ml 25(OH) vitamin D
http://lup.sagepub.com/
Association between low 25-hydroxyvitamin D, insulin resistance and arterial stiffness in nondiabetic women with systemic lupus erythematosus JM Sabio, JA Vargas-Hitos, J Martinez-Bordonado, N Navarrete-Navarrete, A Díaz-Chamorro, C Olvera-Porcel, M Zamora and J Jiménez-Alonso Lupus published online 12 September 2014 DOI: 10.1177/0961203314551811 The online version of this article can be found at: http://lup.sagepub.com/content/early/2014/09/12/0961203314551811
Published by: http://www.sagepublications.com
Additional services and information for Lupus can be found at: Email Alerts: http://lup.sagepub.com/cgi/alerts Subscriptions: http://lup.sagepub.com/subscriptions Reprints: http://www.sagepub.com/journalsReprints.nav Permissions: http://www.sagepub.com/journalsPermissions.nav
>> OnlineFirst Version of Record - Sep 12, 2014 What is This?
Downloaded from lup.sagepub.com at University of British Columbia Library on November 25, 2014
XML Template (2014) [11.9.2014–6:36pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/LUPJ/Vol00000/140191/APPFile/SG-LUPJ140191.3d
(LUP)
[1–9] [PREPRINTER stage]
Lupus (2014) 0,
1–9
http://lup.sagepub.com
PAPER
Association between low 25-hydroxyvitamin D, insulin resistance and arterial stiffness in nondiabetic women with systemic lupus erythematosus JM Sabio1, JA Vargas-Hitos1, J Martinez-Bordonado1, N Navarrete-Navarrete1, A Dı´ az-Chamorro1, C Olvera-Porcel2, M Zamora1 and J Jime´nez-Alonso1 1
Systemic Autoimmune Diseases Unit, Department of Internal Medicine, University Hospital Virgen de las Nieves, Granada, Spain; and 2 Department of Statistics, Fundacio´n para la Investigacio´n Biosanitaria de Andalucı´ a Oriental (FIBAO), Granada, Spain
Objective: The objective of this paper is to examine if there is an association between low levels of 25-hydroxyvitamin D (25(OH)D) and insulin resistance (IR) in nondiabetic women with systemic lupus erythematosus (SLE) and to evaluate its impact on arterial stiffness. Patients and methods: In this cross-sectional study 25(OH)D, insulin, insulin resistance measured by the homeostatic model assessment (HOMA-IR), homocysteine, fibrinogen, characteristics of SLE, medications and pulse-wave velocity (PWV) were measured in 106 nondiabetic women with SLE and 101 matched controls. Results: Women with SLE tended to have lower 25(OH)D levels (p ¼ 0.078) and a higher frequency of 25(OH)D deficiency (defined as 30 UI/l, and medians (IQR) of C3 and C4 levels were 91 (77–107) mg/ dl and 16 (9–20) mg/dl. Prednisone and hydroxychloroquine (HCQ) were taken by 68% and 90% of patients. The median (IQR) daily prednisone dose was 2.5 (0–5) mg. Immunosuppressants were used concurrently in 41% of patients (azathioprine 6%, methotrexate 12%, and mycophenolate 24%). Differences between SLE and control women The median age and the educational level were similar in both groups. In contrast to what was expected, 25(OH)D levels were only marginally lower in patients than in controls (p ¼ 0.078). In addition, the frequency of 25(OH)D insufficiency was similar in both groups (83% vs. 69%, p ¼ 0.125) and 25(OH)D deficiency trended to be higher in the SLE group but did not reach statistical significance (8.5% vs. 2.1%, p ¼ 0.058) (Table 1). Both MetS and IR were more frequent in patients than in controls (OR 4.0, 95% CI 1.3–12.5, p ¼ 0.015 and OR 2.3, 95% CI 1.01–5.36, p ¼ 0.050). Consistently, median insulin levels and HOMA-IR were significantly higher in women with SLE (Table 1). PWV was significantly higher in patients (7.6 (6.9–8.4) vs. 7.1 (6.4–7.8) m/s, p ¼ 0.001)). Seven women in the SLE group and none of controls had a history of atherosclerotic CVD. Other CVD risk factor differences between both groups are summarized in Table 1.
Seasonal variation of 25(OH)D levels, photoprotection and use of vitamin D supplementation 25(OH)D levels varied notably depending on the season in which the vitamin was measured. When considering all participants, the median (IQR) of 25(OH)D in the summer was significantly higher than in the winter (23.1 (17.9–30.1) ng/ml vs. 20.0 (13.3–36.0) ng/ml; p ¼ 0.001). By groups, seasonal differences in 25(OH)D levels were present in controls (24.2 (18.4–30.8) ng/ml vs. 19.3 (12.8–23.0) ng/ml; p ¼ 0.001) but not in patients (22.0 (16.0– 28.0) ng/ml vs. 21.0 (15.3–27.0) ng/ml; p ¼ 0.106). Forty-four percent of women with SLE in comparison with 80% of controls were included during the winter (p < 0.001). The use of photoprotection was similar in patients with or without photosensitivity (86% vs. 84%). Photoprotection did not significantly modify levels of 25(OH)D (p ¼ 0.643) and sunscreen use was similar in summer (44%) and winter (41%). Furthermore, taking vitamin D supplements did not significantly influence levels of 25(OH)D (p ¼ 0.107). There was no association between 25(OH)D and use of immunosuppressants, HCQ or prednisone (Table 2). Association between 25(OH)D and IR and other cardiovascular factors In nondiabetic women with SLE, an unadjusted linear regression analysis showed that 25(OH)D levels inversely correlated with insulin levels (p ¼ 0.003), HOMA-IR (p ¼ 0.003) and C4 (p ¼ 0.028), and there was a trend toward significance with fibrinogen levels (p ¼ 0.063). No correlations were found with the rest of the cardiometabolic parameters, SLE-related characteristics and activity, prednisone dose and inflammatory markers. After adjustment for BMI (model 1), the correlation remained significant for insulin, HOMA-IR and C4, and there was also a trend toward significance for fibrinogen, but not for PWV. Identical results to those obtained in model 1 were found after adjustment for BMI and age (model 2), and for BMI, age, SLEDAI, C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR), fibrinogen, daily prednisone dose, estimated glomerular filtration rate (eGFR) and seasonal variation (model 3) (Table 3). Interestingly, a trend toward correlation was observed between 25(OH)D and fibrinogen in model 3 (p ¼ 0.060). When we compared patients in the first quartile for 25(OH)D (16 ng/ml) with those in the fourth quartile (OH)D (27 ng/ml), the former had higher Lupus
Downloaded from lup.sagepub.com at University of British Columbia Library on November 25, 2014
XML Template (2014) [11.9.2014–6:36pm] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/LUPJ/Vol00000/140191/APPFile/SG-LUPJ140191.3d
(LUP)
[1–9] [PREPRINTER stage]
25(OH)D and insulin resistance in SLE JM Sabio et al.
4
Table 1 Characteristics of the study population
Demographic characteristics Age, years Educational level Secondary education, n (%) University education, n (%) 25(OH) vitamin D status 25(OH) vitamin D, ng/ml 25(OH) vitamin D
