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<front>
<journal-meta>
<journal-id journal-id-type="publisher-id">Front. Public Health</journal-id>
<journal-title>Frontiers in Public Health</journal-title>
<abbrev-journal-title abbrev-type="pubmed">Front. Public Health</abbrev-journal-title>
<issn pub-type="epub">2296-2565</issn>
<publisher>
<publisher-name>Frontiers Media S.A.</publisher-name>
</publisher>
</journal-meta>
<article-meta>
<article-id pub-id-type="doi">10.3389/fpubh.2022.878845</article-id>
<article-categories>
<subj-group subj-group-type="heading">
<subject>Public Health</subject>
<subj-group>
<subject>Original Research</subject>
</subj-group>
</subj-group>
</article-categories>
<title-group>
<article-title>Association Between History of Gestational Diabetes Mellitus and the Risk of Arthritis in Women</article-title>
</title-group>
<contrib-group>
<contrib contrib-type="author">
<name><surname>Mao</surname> <given-names>Yuanyuan</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Hu</surname> <given-names>Wenbin</given-names></name>
<xref ref-type="aff" rid="aff3"><sup>3</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Xia</surname> <given-names>Bin</given-names></name>
<xref ref-type="aff" rid="aff1"><sup>1</sup></xref>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author">
<name><surname>Liu</surname> <given-names>Li</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
</contrib>
<contrib contrib-type="author" corresp="yes">
<name><surname>Liu</surname> <given-names>Qin</given-names></name>
<xref ref-type="aff" rid="aff2"><sup>2</sup></xref>
<xref ref-type="corresp" rid="c001"><sup>&#x0002A;</sup></xref>
<uri xlink:href="http://loop.frontiersin.org/people/1612437/overview"/>
</contrib>
</contrib-group>
<aff id="aff1"><sup>1</sup><institution>Suzhou Medical College of Soochow University</institution>, <addr-line>Suzhou</addr-line>, <country>China</country></aff>
<aff id="aff2"><sup>2</sup><institution>Department of Obstetrics and Gynecology, The First People&#x00027;s Hospital of Kunshan Affiliated With Jiangsu University</institution>, <addr-line>Suzhou</addr-line>, <country>China</country></aff>
<aff id="aff3"><sup>3</sup><institution>Department of Chronic and Noncommunicable Disease Control and Preventions, The Kunshan Center for Disease Control and Prevention</institution>, <addr-line>Suzhou</addr-line>, <country>China</country></aff>
<author-notes>
<fn fn-type="edited-by"><p>Edited by: Luis Sobrevia, Pontificia Universidad Cat&#x000F3;lica de Chile, Chile</p></fn>
<fn fn-type="edited-by"><p>Reviewed by: Paola Valero, University of Talca, Chile; Gonzalo Andr&#x000E9;s Fuentes Rodr&#x000ED;guez, University Medical Center Groningen, Netherlands</p></fn>
<corresp id="c001">&#x0002A;Correspondence: Qin Liu <email>liuqin1434&#x00040;163.com</email></corresp>
<fn fn-type="other" id="fn001"><p>This article was submitted to Clinical Diabetes, a section of the journal Frontiers in Public Health</p></fn></author-notes>
<pub-date pub-type="epub">
<day>27</day>
<month>05</month>
<year>2022</year>
</pub-date>
<pub-date pub-type="collection">
<year>2022</year>
</pub-date>
<volume>10</volume>
<elocation-id>878845</elocation-id>
<history>
<date date-type="received">
<day>18</day>
<month>02</month>
<year>2022</year>
</date>
<date date-type="accepted">
<day>28</day>
<month>04</month>
<year>2022</year>
</date>
</history>
<permissions>
<copyright-statement>Copyright &#x000A9; 2022 Mao, Hu, Xia, Liu and Liu.</copyright-statement>
<copyright-year>2022</copyright-year>
<copyright-holder>Mao, Hu, Xia, Liu and Liu</copyright-holder>
<license xlink:href="http://creativecommons.org/licenses/by/4.0/"><p>This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.</p></license> </permissions>
<abstract>
<sec>
<title>Objective</title>
<p>The association between gestational diabetes mellitus (GDM) and the risk of arthritis has not been reported. GDM increases the risk of long-term complications including diabetes and metabolic syndrome that are positively associated with the risk of arthritis. This study aimed to explore the association between GDM and the risk of arthritis.</p></sec>
<sec>
<title>Methods</title>
<p>Women (age &#x02265; 20 years) who had delivered at least one live birth were included from the 2007 to 2018 National Health and Nutrition Examination Survey cohort (<italic>N</italic> = 11,997). Patients who had a history of GDM and arthritis were identified by in-home interview. Subgroup analyses were conducted by arthritis types and status of obesity, current diabetes, metabolic syndrome, smoking, alcohol drinking, and physical activity.</p></sec>
<sec>
<title>Results</title>
<p>GDM was associated with increased odds of arthritis [multivariable-adjusted odds ratio (95% confidence interval): 1.31 (1.06&#x02013;1.62)], and the result was similar in sensitivity analysis with further adjustment for metabolic syndrome [1.30 (1.05&#x02013;1.60)]. In subgroup analyses, GDM was associated with increased odds of osteoarthritis [1.47 (1.05&#x02013;2.06)], while no association was observed with rheumatoid arthritis [1.04 (0.69&#x02013;1.57)] and other types [1.26 (0.94&#x02013;1.68)]. GDM was associated with increased odds of arthritis in women without metabolic syndrome [1.34 (1.00&#x02013;1.78)] and diabetes [1.35 (1.03&#x02013;1.76)], in obese individuals [1.64 (1.24&#x02013;2.16)], current/former smokers [1.43 (1.05&#x02013;1.95)], and current drinkers [1.76 (1.00&#x02013;3.14)], and in individuals engaging in higher levels of physical activity [1.53 (1.06&#x02013;2.20)].</p></sec>
<sec>
<title>Conclusions</title>
<p>GDM was associated with increased odds of arthritis, and the association was independent of type 2 diabetes and metabolic syndrome.</p></sec></abstract>
<kwd-group>
<kwd>arthritis</kwd>
<kwd>National Health and Nutrition Examination Survey</kwd>
<kwd>type 2 diabetes</kwd>
<kwd>metabolic syndrome</kwd>
<kwd>gestational diabetes mellitus</kwd>
</kwd-group>
<counts>
<fig-count count="1"/>
<table-count count="4"/>
<equation-count count="0"/>
<ref-count count="41"/>
<page-count count="8"/>
<word-count count="5278"/>
</counts>
</article-meta>
</front>
<body>
<sec sec-type="intro" id="s1">
<title>Introduction</title>
<p>Gestational diabetes mellitus (GDM) is diabetes that develops during pregnancy, and is currently the most common medical complication of pregnancy (<xref ref-type="bibr" rid="B1">1</xref>). The prevalence of GDM was estimated to be 7.6% in the US (<xref ref-type="bibr" rid="B2">2</xref>), and the overall weighted GDM prevalence in European countries was estimated at 10.9% (<xref ref-type="bibr" rid="B3">3</xref>). GDM increases the risk of long-term complications, including obesity, type 2 diabetes, metabolic syndrome, cancer, and cardiovascular disease (<xref ref-type="bibr" rid="B1">1</xref>, <xref ref-type="bibr" rid="B4">4</xref>&#x02013;<xref ref-type="bibr" rid="B7">7</xref>), and GDM provides unique opportunities for improving maternal health (<xref ref-type="bibr" rid="B8">8</xref>). Musculoskeletal conditions account for a significant proportion of non-communicable diseases contributing to disability adjusted life years, with osteoarthritis contributing most to this burden (<xref ref-type="bibr" rid="B9">9</xref>). The major arthritis-related disorders such as osteoarthritis and rheumatoid arthritis collectively make arthritis rank among the most common disabling health conditions (<xref ref-type="bibr" rid="B10">10</xref>). The global prevalence of rheumatoid arthritis was 460 per 100,000 population (<xref ref-type="bibr" rid="B11">11</xref>). The global age-standardized years lived with disability rate for osteoarthritis in 2017 was 118.8, an increase of 9.6% from 1990 (<xref ref-type="bibr" rid="B12">12</xref>).</p>
<p>Chronic inflammation may play a significant role in the development of arthritis-related disorders such as osteoarthritis and rheumatoid arthritis (<xref ref-type="bibr" rid="B13">13</xref>, <xref ref-type="bibr" rid="B14">14</xref>). Inflammation and oxidative stress participate in the development of GDM and exert potentially harmful effects on the short and long-term maternal health (<xref ref-type="bibr" rid="B15">15</xref>). In addition, the long-term complications of GDM including obesity, type 2 diabetes, and metabolic syndrome are also positively associated with arthritis (<xref ref-type="bibr" rid="B16">16</xref>&#x02013;<xref ref-type="bibr" rid="B20">20</xref>). However, the association between GDM and the risk of arthritis has not been reported in epidemiological studies. Based on the above-mentioned findings, we hypothesize that GDM is associated with increased odds of arthritis. In this study, we first explored the association between a history of GDM and the odds of arthritis in women, and then conducted stratified analyses to determine whether the association could still be observed in the absence of type 2 diabetes and metabolic syndrome. In addition, stratified analyses were also conducted by the modifiable risk factors for arthritis development, including smoking (<xref ref-type="bibr" rid="B21">21</xref>&#x02013;<xref ref-type="bibr" rid="B23">23</xref>), alcohol drinking (<xref ref-type="bibr" rid="B24">24</xref>, <xref ref-type="bibr" rid="B25">25</xref>), and low levels of physical activity (<xref ref-type="bibr" rid="B26">26</xref>, <xref ref-type="bibr" rid="B27">27</xref>).</p></sec>
<sec sec-type="materials and methods" id="s2">
<title>Materials and Methods</title>
<sec>
<title>Study Populations</title>
<p>The National Health and Nutrition Examination Survey (NHANES) is a program of studies designed to assess the health and nutritional status of US adults and children. The survey examines a nationally representative sample of about 5,000 persons each year. We used data from six cycles of the NHANES cohort (2007/2008 to 2017/2018), as these cycles specifically provided information for a history of GDM.</p>
<p>The inclusion criteria are as follows: (<xref ref-type="bibr" rid="B1">1</xref>) women aged 20 years or older; (<xref ref-type="bibr" rid="B2">2</xref>) women with at least one live birth; (<xref ref-type="bibr" rid="B3">3</xref>) women responding to the questions regarding a history of GDM; and (<xref ref-type="bibr" rid="B4">4</xref>) women responding to the questions regarding arthritis. In addition, women who were diagnosed with diabetes or arthritis prior to a diagnosis of GDM were excluded. Finally, we included 11,997 women in this study.</p></sec>
<sec>
<title>A History of GDM and Arthritis</title>
<p>The exposure for the analysis was the response to the question, &#x0201C;During your pregnancy, were you ever told by a doctor or other health professional that you had diabetes, sugar diabetes, or gestational diabetes?&#x0201D; and we considered women who answered yes to the above question as having a history of GDM (<xref ref-type="bibr" rid="B28">28</xref>, <xref ref-type="bibr" rid="B29">29</xref>). The outcome for the analysis was arthritis, and patients with arthritis were identified with the questions of &#x0201C;doctor ever said you had arthritis?&#x0201D; and &#x0201C;which type of arthritis was it?&#x0201D;.</p></sec>
<sec>
<title>Other Variables</title>
<p>According to the previous studies (<xref ref-type="bibr" rid="B23">23</xref>, <xref ref-type="bibr" rid="B30">30</xref>, <xref ref-type="bibr" rid="B31">31</xref>), the following covariates were included: age, race/ethnicity (Mexican&#x02013;American, Other Hispanic, Non-Hispanic White, Non-Hispanic Black, Other Races), body mass index (BMI, under/normal weight: &#x0003C;25 kg/m<sup>2</sup>, overweight: 25 to &#x0003C;30 kg/m<sup>2</sup>, obesity: &#x02265;30 kg/m<sup>2</sup>), education ( &#x02264; high school, some college or AA degree, &#x02265;college graduate), annual family income (&#x0003C; $20,000, $20,000&#x02013;$44,999, $45,000&#x02013;$74,999, &#x02265;$75,000), smoking (current smoker, former smoker, never smoker), alcohol drinking (g/day), and physical activity (vigorous/moderate recreational activities for at least 10 min continuously in a typical week). In addition, current diabetes and metabolic syndrome were also considered in stratified analyses. Current diabetes was defined using a self-reported diagnosis of diabetes outside pregnancy or, if diabetes was not previously diagnosed, by a hemoglobin A1c level &#x02265; 6.5%, a fasting plasma glucose level &#x02265; 126 mg/dL, or 2-h plasma glucose &#x02265; 200 mg/dL (<xref ref-type="bibr" rid="B32">32</xref>). Type 1 diabetes was defined as an onset age of self-reported diagnosis of diabetes &#x0003C;30 years and currently taking insulin (<xref ref-type="bibr" rid="B29">29</xref>). Any 3 of the 5 following metabolic-related disorders constitute diagnosis of metabolic syndrome (<xref ref-type="bibr" rid="B33">33</xref>): elevated blood pressure (&#x02265;130 mm Hg systolic blood pressure, &#x02265;85 mm Hg diastolic blood pressure), elevated waist circumference (&#x02265;102 cm in men, &#x02265;88 cm in women), reduced HDL-C (&#x0003C;40 mg/dL in men, &#x0003C;50 mg/dL in women), elevated triglycerides (&#x02265;150 mg/dL), and elevated fasting glucose (&#x02265;100 mg/dL).</p></sec>
<sec>
<title>Statistical Analysis</title>
<p>The logistic regression was used to calculate the odds ratios (95% confidence interval) [OR (95% CI)] of arthritis for women with a GDM history compared with those without a history of GDM. We calculated three different logistic regression models. Model 1 was adjusted for demographic variables (age and race/ethnicity). Model 2 included the covariates of model 1 with additional adjustment for BMI and socioeconomic status (education and family income). Model 3 included the covariates of model 2 with additional adjustment for health behaviors (alcohol drinking, smoking, and physical activity). Stratified analyses were conducted by arthritis types (osteoarthritis, rheumatoid arthritis, and other types), current status of metabolic syndrome (yes, no), obesity (yes, no), and current diabetes (yes, no), smoking (never, current/former), alcohol drinking (yes, no), and physical activity (vigorous/ moderate recreational activities for at least 10 min continuously in a typical week: yes, no). Tests for interactions were performed by using cross-product terms of GDM with these stratified factors. In addition, because GDM was associated with lower HDL-C, and increased BMI, blood pressure, total cholesterol, triglycerides, and glucose (<xref ref-type="bibr" rid="B34">34</xref>), we also conducted a sensitivity analysis in which we further adjusted for metabolic syndrome to determine whether these metabolic-related disorders could account for the association between GDM and the risk of arthritis. New multi-year sample weight was computed by dividing the 2-year sample weights by 6 (six cycles of NHANES were included in this study). All analyses used sample weights, strata, and primary sampling units to account for the complex, multistage, stratified, and cluster-sampling design of NHANES. All analyses were conducted with Stata 12.0, and <italic>P</italic> &#x02264; 0.05 was considered statistically significant.</p></sec></sec>
<sec sec-type="results" id="s3">
<title>Results</title>
<p>Among the 11,997 women included in this study, the weighted prevalence of GDM and arthritis was 8.00 and 34.72%, respectively. Women with a GDM history were more likely to be younger, engage in physical activity, and show higher prevalence of obesity, current diabetes (type 1 diabetes accounts for 2%), and metabolic syndrome. Annual family income and education levels differed significantly between women with a history of GDM and women without a history of GDM, while smoking status and alcohol drinking did not differ significantly between the two groups. Detailed characteristics of the participants are shown in <xref ref-type="table" rid="T1">Tables 1</xref>, <xref ref-type="table" rid="T2">2</xref>. The associations between the characteristics of the participants and arthritis are shown in <xref ref-type="table" rid="T3">Table 3</xref>, and all these characteristics were associated with arthritis.</p>
<table-wrap position="float" id="T1">
<label>Table 1</label>
<caption><p>Characteristics of the 2007&#x02013;2018 NHANES adults according to the presence or absence of a history of gestational diabetes mellitus (GDM).</p></caption>
<table frame="hsides" rules="groups">
<thead><tr>
<th valign="top" align="left"><bold>Variables</bold></th>
<th valign="top" align="center"><bold>Women with GDM</bold></th>
<th valign="top" align="center"><bold>Women without GDM</bold></th>
<th valign="top" align="center"><bold><italic>P<sup><bold><italic>a</italic></bold></sup></italic></bold></th>
</tr>
<tr>
<th/>
<th valign="top" align="center"><bold>(928)</bold></th>
<th valign="top" align="center"><bold>(11,069)</bold></th>
<th/>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Age [years, mean (SD)]</td>
<td valign="top" align="center">45.45 (12.31)</td>
<td valign="top" align="center">53.47 (16.76)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">Race/ethnicity (%)</td>
<td/>
<td/>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Mexican American</td>
<td valign="top" align="center">21.77</td>
<td valign="top" align="center">15.78</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Other Hispanic</td>
<td valign="top" align="center">11.42</td>
<td valign="top" align="center">11.66</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Non-Hispanic White</td>
<td valign="top" align="center">35.78</td>
<td valign="top" align="center">40.77</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Non-Hispanic Black</td>
<td valign="top" align="center">17.78</td>
<td valign="top" align="center">22.12</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Other Race</td>
<td valign="top" align="center">13.25</td>
<td valign="top" align="center">9.66</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Annual family income (%)</td>
<td/>
<td/>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x0003C; $20,000</td>
<td valign="top" align="center">20.74</td>
<td valign="top" align="center">26.64</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">$20,000&#x02013;$34,999</td>
<td valign="top" align="center">33.37</td>
<td valign="top" align="center">33.71</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">$35,000&#x02013;$74,999</td>
<td valign="top" align="center">18.83</td>
<td valign="top" align="center">17.58</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x02265;$75,000</td>
<td valign="top" align="center">27.06</td>
<td valign="top" align="center">22.07</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Education (%)</td>
<td/>
<td/>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;&#x02264; high school</td>
<td valign="top" align="center">43.64</td>
<td valign="top" align="center">50.14</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Some college or AA degree</td>
<td valign="top" align="center">35.99</td>
<td valign="top" align="center">30.63</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;&#x02265;College graduate</td>
<td valign="top" align="center">20.37</td>
<td valign="top" align="center">19.23</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Vigorous/moderate recreational activities for at least 10 min continuously in a typical week (%)</td>
<td valign="top" align="center">44.29</td>
<td valign="top" align="center">40.85</td>
<td valign="top" align="center">0.04</td>
</tr>
<tr>
<td valign="top" align="left">Smoking (%)</td>
<td/>
<td/>
<td valign="top" align="center">0.34</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Current smoker</td>
<td valign="top" align="center">18.86</td>
<td valign="top" align="center">17.45</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Former smoker</td>
<td valign="top" align="center">18.00</td>
<td valign="top" align="center">19.64</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Never smoker</td>
<td valign="top" align="center">63.15</td>
<td valign="top" align="center">62.91</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Alcohol (g/day)</td>
<td valign="top" align="center">4.21</td>
<td valign="top" align="center">4.04</td>
<td valign="top" align="center">0.70</td>
</tr>
<tr>
<td valign="top" align="left">Obesity (%)</td>
<td valign="top" align="center">56.06</td>
<td valign="top" align="center">43.05</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">Current diabetes (%)</td>
<td valign="top" align="center">35.56</td>
<td valign="top" align="center">18.21</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">Metabolic syndrome (%)</td>
<td valign="top" align="center">49.78</td>
<td valign="top" align="center">40.18</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p><italic>M, Mean values; SD, standard deviation</italic>.</p>
<p><italic><sup>a</sup> t-test was performed for continuous variables, and Chi-square test was performed for categorical variables</italic>.</p>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="T2">
<label>Table 2</label>
<caption><p>Characteristics of the 2007&#x02013;2018 NHANES adults according to the presence or absence of arthritis.</p></caption>
<table frame="hsides" rules="groups">
<thead><tr>
<th valign="top" align="left"><bold>Variables</bold></th>
<th valign="top" align="center"><bold>Women with arthritis</bold></th>
<th valign="top" align="center"><bold>Women without arthritis</bold></th>
<th valign="top" align="center"><bold><italic>P<sup><bold><italic>a</italic></bold></sup></italic></bold></th>
</tr>
<tr>
<th/>
<th valign="top" align="center"><bold>(4,293)</bold></th>
<th valign="top" align="center"><bold>(7,704)</bold></th>
<th/>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Age [years, mean (SD)]</td>
<td valign="top" align="center">62.53 (12.22)</td>
<td valign="top" align="center">47.46 (15.82)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">Race/ethnicity (%)</td>
<td/>
<td/>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Mexican American</td>
<td valign="top" align="center">11.95</td>
<td valign="top" align="center">18.64</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Other Hispanic</td>
<td valign="top" align="center">10.65</td>
<td valign="top" align="center">12.20</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Non-Hispanic White</td>
<td valign="top" align="center">48.26</td>
<td valign="top" align="center">35.99</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Non-Hispanic Black</td>
<td valign="top" align="center">22.36</td>
<td valign="top" align="center">21.47</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Other Race</td>
<td valign="top" align="center">6.78</td>
<td valign="top" align="center">11.70</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Annual family income (%)</td>
<td/>
<td/>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;&#x0003C; $20,000</td>
<td valign="top" align="center">33.10</td>
<td valign="top" align="center">22.32</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;$20,000&#x02013;$34,999</td>
<td valign="top" align="center">33.47</td>
<td valign="top" align="center">33.80</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;$35,000&#x02013;$74,999</td>
<td valign="top" align="center">15.97</td>
<td valign="top" align="center">18.63</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;&#x02265;$75,000</td>
<td valign="top" align="center">17.45</td>
<td valign="top" align="center">25.25</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Education (%)</td>
<td/>
<td/>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;&#x02264; High school</td>
<td valign="top" align="center">54.27</td>
<td valign="top" align="center">47.06</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Some college or AA degree</td>
<td valign="top" align="center">31.06</td>
<td valign="top" align="center">31.03</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;&#x02265;College graduate</td>
<td valign="top" align="center">14.67</td>
<td valign="top" align="center">21.92</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Vigorous/ moderate recreational activities for at least 10 min continuously in a typical week (%)</td>
<td valign="top" align="center">31.10</td>
<td valign="top" align="center">40.49</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Smoking (%)</td>
<td/>
<td/>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Current smoker</td>
<td valign="top" align="center">18.57</td>
<td valign="top" align="center">17.00</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Former smoker</td>
<td valign="top" align="center">26.42</td>
<td valign="top" align="center">15.67</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Never smoker</td>
<td valign="top" align="center">55.02</td>
<td valign="top" align="center">67.33</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Alcohol (g/day)</td>
<td valign="top" align="center">3.67 (12.83)</td>
<td valign="top" align="center">4.27 (13.26)</td>
<td valign="top" align="center">0.02</td>
</tr>
<tr>
<td valign="top" align="left">Obesity (%)</td>
<td valign="top" align="center">53.02</td>
<td valign="top" align="center">39.10</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">Current diabetes (%)</td>
<td valign="top" align="center">29.54</td>
<td valign="top" align="center">13.99</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">Metabolic syndrome (%)</td>
<td valign="top" align="center">51.46</td>
<td valign="top" align="center">35.05</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p><italic>M, Mean values; SD, standard deviation</italic>.</p>
<p><italic><sup>a</sup>t-test was performed for continuous variables, and Chi-square test was performed for categorical variables</italic>.</p>
</table-wrap-foot>
</table-wrap>
<table-wrap position="float" id="T3">
<label>Table 3</label>
<caption><p>Association between population characteristics and arthritis.</p></caption>
<table frame="hsides" rules="groups">
<thead><tr>
<th valign="top" align="left"><bold>Characteristics</bold></th>
<th valign="top" align="center"><bold>Odds ratio (95% confidence</bold></th>
<th valign="top" align="center"><bold><italic>P<sup><bold><italic>a</italic></bold></sup></italic></bold></th>
</tr>
<tr>
<th/>
<th valign="top" align="center"><bold>interval) of arthritis</bold></th>
<th/>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Age</td>
<td valign="top" align="center">1.07 (1.06&#x02013;1.08)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left" colspan="3">Race/ethnicity</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Mexican American</td>
<td valign="top" align="center">1.00</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Other Hispanic</td>
<td valign="top" align="center">1.41 (1.20&#x02013;1.65)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Non-Hispanic White</td>
<td valign="top" align="center">2.54 (2.21&#x02013;2.91)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Non-Hispanic Black</td>
<td valign="top" align="center">1.91 (1.67&#x02013;2.19)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Other Race</td>
<td valign="top" align="center">1.45 (1.14&#x02013;1.84)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left" colspan="3">Annual family income</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;&#x0003C; $20,000</td>
<td valign="top" align="center">1.00</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;$20,000&#x02013;$34,999</td>
<td valign="top" align="center">0.76 (0.67&#x02013;0.85)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;$35,000&#x02013;$74,999</td>
<td valign="top" align="center">0.65 (0.55&#x02013;0.75)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;&#x02265;$75,000</td>
<td valign="top" align="center">0.52 (0.44&#x02013;0.61)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left" colspan="3">Education</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;&#x02264; High school</td>
<td valign="top" align="center">1.00</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Some college or AA degree</td>
<td valign="top" align="center">0.90 (0.79&#x02013;1.02)</td>
<td valign="top" align="center">0.11</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;&#x02265;College graduate</td>
<td valign="top" align="center">0.58 (0.50&#x02013;0.67)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">Vigorous/ moderate recreational activities for at least 10 min continuously in a typical week</td>
<td valign="top" align="center">1.41 (1.27&#x02013;1.58)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">Smoking</td>
<td/>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Never smoker</td>
<td valign="top" align="center">1.00</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Former smoker</td>
<td valign="top" align="center">1.95 (1.68&#x02013;2.27)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Current smoker</td>
<td valign="top" align="center">1.37 (1.22&#x02013;1.54)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">Alcohol (g/day)</td>
<td valign="top" align="center">0.99 (0.98&#x02013;1.00)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">Obesity</td>
<td valign="top" align="center">2.09 (1.84&#x02013;2.36)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">Current diabetes</td>
<td valign="top" align="center">2.91 (2.61&#x02013;3.25)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">Metabolic syndrome</td>
<td valign="top" align="center">2.08 (1.88&#x02013;2.31)</td>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p><sup>a</sup><italic>The P values for significance tests</italic>.</p>
</table-wrap-foot>
</table-wrap>
<p>Overall, the findings on the association between a history of GDM and the odds of arthritis were similar across the three statistical models, while the observed association was attenuated slightly in model 2 and model 3. In model 3, a history of GDM was associated with increased odds of arthritis [OR (95% CI): 1.31 (1.06&#x02013;1.62), <italic>P</italic> &#x0003C; 0.05], and the result was similar in sensitivity analysis with further adjustment for metabolic syndrome [1.30 (1.05&#x02013;1.60)]. In subgroup analyses by arthritis types, a history of GDM was associated with increased odds of osteoarthritis [1.47 (1.05&#x02013;2.06)], while no association was observed with rheumatoid arthritis [1.04 (0.69&#x02013;1.57)] and other types [1.26 (0.94&#x02013;1.68)] (<xref ref-type="table" rid="T4">Table 4</xref>, <xref ref-type="fig" rid="F1">Figure 1</xref>).</p>
<table-wrap position="float" id="T4">
<label>Table 4</label>
<caption><p>Odds ratios of arthritis for women with a history of gestational diabetes mellitus compared with those without a history of gestational diabetes mellitus.</p></caption>
<table frame="hsides" rules="groups">
<thead><tr>
<th valign="top" align="left"><bold>Groups</bold></th>
<th valign="top" align="center" colspan="5" style="border-bottom: thin solid #000000;"><bold>Odds ratios (95% confidence intervals)</bold></th>
</tr>
<tr>
<th/>
<th valign="top" align="center"><bold>Cases of arthritis/N</bold></th>
<th valign="top" align="center"><bold>Model 1</bold></th>
<th valign="top" align="center"><bold>Model 2</bold></th>
<th valign="top" align="center"><bold>Model 3</bold></th>
<th valign="top" align="center"><bold><italic>P</italic><sub>for interaction</sub></bold></th>
</tr>
</thead>
<tbody>
<tr>
<td valign="top" align="left">Overall</td>
<td valign="top" align="center">4,293/11,997</td>
<td valign="top" align="center">1.46 (1.18&#x02013;1.80)&#x0002A;&#x0002A;</td>
<td valign="top" align="center">1.32 (1.06&#x02013;1.64)&#x0002A;</td>
<td valign="top" align="center">1.31 (1.06&#x02013;1.62)&#x0002A;</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Arthritis types</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Osteoarthritis</td>
<td valign="top" align="center">1,798/11,997</td>
<td valign="top" align="center">1.66 (1.22&#x02013;2.29)&#x0002A;&#x0002A;</td>
<td valign="top" align="center">1.46 (1.05&#x02013;2.03)&#x0002A;</td>
<td valign="top" align="center">1.47 (1.05&#x02013;2.06)&#x0002A;</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Rheumatoid arthritis</td>
<td valign="top" align="center">834/11,997</td>
<td valign="top" align="center">1.17 (0.77&#x02013;1.77)</td>
<td valign="top" align="center">1.11 (0.75&#x02013;1.63)</td>
<td valign="top" align="center">1.04 (0.69&#x02013;1.57)</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Others</td>
<td valign="top" align="center">1,661/11,997</td>
<td valign="top" align="center">1.32 (0.99&#x02013;1.76)</td>
<td valign="top" align="center">1.25 (0.93&#x02013;1.67)</td>
<td valign="top" align="center">1.26 (0.94&#x02013;1.68)</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Metabolic syndrome</td>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">0.12</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Yes</td>
<td valign="top" align="center">2,209/4,909</td>
<td valign="top" align="center">1.29 (0.99&#x02013;1.69)</td>
<td valign="top" align="center">1.18 (0.89&#x02013;1.57)</td>
<td valign="top" align="center">1.24 (0.94&#x02013;1.63)</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;No</td>
<td valign="top" align="center">2,084/7,088</td>
<td valign="top" align="center">1.42 (1.07&#x02013;1.88)&#x0002A;</td>
<td valign="top" align="center">1.39 (1.05&#x02013;1.85)&#x0002A;</td>
<td valign="top" align="center">1.34 (1.00&#x02013;1.78)&#x0002A;</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Obesity</td>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">0.05</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Yes</td>
<td valign="top" align="center">2,244/5,233</td>
<td valign="top" align="center">1.61 (1.24&#x02013;2.10)&#x0002A;&#x0002A;</td>
<td valign="top" align="center">1.65 (1.24&#x02013;2.19)&#x0002A;&#x0002A;</td>
<td valign="top" align="center">1.64 (1.24&#x02013;2.16)&#x0002A;&#x0002A;</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;No</td>
<td valign="top" align="center">1,988/6,643</td>
<td valign="top" align="center">0.95 (0.63&#x02013;1.43)</td>
<td valign="top" align="center">0.93 (0.61&#x02013;1.41)</td>
<td valign="top" align="center">0.95 (0.62&#x02013;1.45)</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Current diabetes</td>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">&#x0003C;0.01</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Yes</td>
<td valign="top" align="center">1,268/2,346</td>
<td valign="top" align="center">0.86 (0.62&#x02013;1.20)</td>
<td valign="top" align="center">0.83 (0.60&#x02013;1.15)</td>
<td valign="top" align="center">0.82 (0.58&#x02013;1.16)</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;No</td>
<td valign="top" align="center">3,025/9,651</td>
<td valign="top" align="center">1.39 (1.06&#x02013;1.83)&#x0002A;</td>
<td valign="top" align="center">1.34 (1.01&#x02013;1.76)&#x0002A;</td>
<td valign="top" align="center">1.35 (1.03&#x02013;1.76)&#x0002A;</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Smoking</td>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">0.59</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Never</td>
<td valign="top" align="center">2,362/7,549</td>
<td valign="top" align="center">1.40 (1.04&#x02013;1.89)&#x0002A;</td>
<td valign="top" align="center">1.25 (0.91&#x02013;1.73)</td>
<td valign="top" align="center">1.23 (0.89&#x02013;1.71)</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Current/former</td>
<td valign="top" align="center">1,931/4,448</td>
<td valign="top" align="center">1.59 (1.18&#x02013;2.14)&#x0002A;&#x0002A;</td>
<td valign="top" align="center">1.42 (1.05&#x02013;1.94)&#x0002A;</td>
<td valign="top" align="center">1.43 (1.05&#x02013;1.95)&#x0002A;</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Current drinker</td>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">0.42</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Yes</td>
<td valign="top" align="center">3,355/9,152</td>
<td valign="top" align="center">1.81 (1.05&#x02013;3.13)&#x0002A;</td>
<td valign="top" align="center">1.68 (0.98&#x02013;2.87)</td>
<td valign="top" align="center">1.76 (1.00&#x02013;3.14)&#x0002A;</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;No</td>
<td valign="top" align="center">938/2,845</td>
<td valign="top" align="center">1.35 (1.09&#x02013;1.67)&#x0002A;&#x0002A;</td>
<td valign="top" align="center">1.22 (0.97&#x02013;1.53)</td>
<td valign="top" align="center">1.20 (0.95&#x02013;1.52)</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">Physical activity<sup>a</sup></td>
<td/>
<td/>
<td/>
<td/>
<td valign="top" align="center">0.63</td>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;Yes</td>
<td valign="top" align="center">2,862/7,064</td>
<td valign="top" align="center">1.63 (1.15&#x02013;2.32)&#x0002A;&#x0002A;</td>
<td valign="top" align="center">1.51 (1.07&#x02013;2.13)&#x0002A;</td>
<td valign="top" align="center">1.53 (1.06&#x02013;2.20)&#x0002A;</td>
<td/>
</tr>
<tr>
<td valign="top" align="left">&#x000A0;&#x000A0;&#x000A0;No</td>
<td valign="top" align="center">1,431/4,933</td>
<td valign="top" align="center">1.32 (1.00&#x02013;1.74)&#x0002A;</td>
<td valign="top" align="center">1.16 (0.87&#x02013;1.53)</td>
<td valign="top" align="center">1.13 (0.86&#x02013;1.49)</td>
<td/>
</tr>
</tbody>
</table>
<table-wrap-foot>
<p><italic>&#x0002A;P &#x0003C;0.05, &#x0002A;&#x0002A;P &#x0003C;0.01</italic>.</p>
<p><italic>Model 1: adjusted for age and race/ethnicity.</italic></p>
<p><italic>Model 2: adjusted for covariates in model 1 and body mass index, education, and annual family income.</italic></p>
<p><italic>Model 3: adjusted for covariates in model 2 and alcohol drinking, smoking, and recreational physical activity.</italic></p>
<p><italic><sup>a</sup>Vigorous/moderate recreational activities for at least 10 min continuously in a typical week</italic>.</p>
</table-wrap-foot>
</table-wrap>
<fig id="F1" position="float">
<label>Figure 1</label>
<caption><p>Odds ratios of arthritis for women with a history of gestational diabetes mellitus compared with those without a history of gestational diabetes mellitus. MetS, metabolic syndrome; OR (95% CI), Odds ratio (95% confidence interval).</p></caption>
<graphic mimetype="image" mime-subtype="tiff" xlink:href="fpubh-10-878845-g0001.tif"/>
</fig>
<p>In stratified analyses by current status of metabolic syndrome, diabetes, obesity and physical activity, a history of GDM was associated with increased odds of arthritis in obese women [1.64 (1.24&#x02013;2.16)] and in women without metabolic syndrome [1.34 (1.00&#x02013;1.78)] and current diabetes [1.35 (1.03&#x02013;1.76)]. In stratified analyses by status of smoking, alcohol drinking and physical activity, a history of GDM was associated with increased odds of arthritis in current/former smokers [1.43 (1.05&#x02013;1.95)], current drinkers [1.76 (1.00&#x02013;3.14)], and individuals engaging in higher levels of physical activity [1.53 (1.06&#x02013;2.20)]. The interactions between a history of GDM and obesity (<italic>P</italic> = 0.05) and current diabetes (<italic>P</italic> &#x0003C; 0.01) were significant. However, the interactions with metabolic syndrome (<italic>P</italic> = 0.12), smoking (<italic>P</italic> = 0.59), alcohol drinking (<italic>P</italic> = 0.42), and physical activity (<italic>P</italic> = 0.63) were not significant (<xref ref-type="table" rid="T4">Table 4</xref>), respectively, which may arise from the relatively wide range of 95% CIs or the possibility that these variables are independent of the history of GDM.</p></sec>
<sec sec-type="discussion" id="s4">
<title>Discussion</title>
<p>To our knowledge, this is the first epidemiological study to explore the association between GDM and the risk of arthritis. In this national survey cohort of 11,997 women, women with a history of GDM tended to have increased odds of arthritis, and the finding was robust even after accounting for metabolic syndrome that is potentially related to subsequent arthritis. Importantly, women with a history of GDM in whom metabolic syndrome and diabetes does not develop still have increased odds of arthritis. In stratified analyses, the association between a history of GDM and arthritis was observed in smokers, alcohol drinkers, and women engaging in higher levels of physical activity. In addition, GDM was significantly associated with increased odds of osteoarthritis, while no significant association was found with rheumatoid arthritis and other types.</p>
<p>Several potential reasons may explain the association between GDM and the risk of arthritis. First, women with a history of GDM were found to have a nearly 10-fold higher risk of developing type 2 diabetes than healthy controls [relative risk (95% CI): 9.51 (7.14&#x02013;12.67)] (<xref ref-type="bibr" rid="B4">4</xref>), and a previous meta-analysis showed that type 2 diabetes was associated with increased odds of arthritis [OR (95%): 1.45 (1.18&#x02013;1.78)] (<xref ref-type="bibr" rid="B20">20</xref>). Furthermore, patients with diabetes mellitus had 2.18 [95% (1.12&#x02013;4.24)] times the odds of having osteoarthritis (<xref ref-type="bibr" rid="B35">35</xref>), which is the most common type of arthritis (<xref ref-type="bibr" rid="B13">13</xref>). Second, a recent meta-analysis found that the OR (95% CI) for metabolic syndrome was 3.45 (2.80&#x02013;4.25) in women with a history of GDM compared to women without a history of GDM (<xref ref-type="bibr" rid="B5">5</xref>), and metabolic syndrome [OR (95% CI): 1.42 (1.16&#x02013;1.73)], hypertension [1.70 (1.41&#x02013;2.05), and hyperglycemia [1.23 (1.05&#x02013;1.42)] were all positively associated with odds of osteoarthritis (<xref ref-type="bibr" rid="B19">19</xref>). Third, women with a history of GDM have significantly higher BMI (1.54 kg/m<sup>2</sup>, 95% CI: 1.32 to 2.46) (<xref ref-type="bibr" rid="B34">34</xref>). Compared to normal weight subjects, overweight and obese subjects had 15% (95%CI: 1.03&#x02013;1.29) and 31% (1.12&#x02013;1.53) higher odds of rheumatoid arthritis (<xref ref-type="bibr" rid="B36">36</xref>), respectively, and the associations were stronger with osteoarthritis [overweight: 2.45 (1.88&#x02013;3.20), obesity: 4.55 (2.90&#x02013;7.13)] (<xref ref-type="bibr" rid="B18">18</xref>). These findings are consistent with those from our study in which a history of GDM was associated with odds of osteoarthritis but not rheumatoid arthritis. In addition, the association between a history of GDM and odds of arthritis was only observed in subjects with obesity [1.64 (1.24&#x02013;2.16)], and the association was attenuated in model 2 also adjusting for BMI [1.32 (1.06&#x02013;1.64)]. These findings suggested that BMI may partially account for the observed association between GDM and the odds of arthritis. However, the association between a history of GDM and the odds of arthritis remained significant in women without metabolic syndrome [1.34 (1.00&#x02013;1.78)] and current diabetes [1.35 (1.03&#x02013;1.76)], and a similar result was found in sensitivity analysis with further adjustment for metabolic syndrome [1.30 (1.05&#x02013;1.60)]. These findings suggested the observed association between a history of GDM and the odds of arthritis was independent of type 2 diabetes and metabolic syndrome. These findings are comparable with those from previous studies in which the long-term risk for cardiovascular disease associated with GDM was not dependent upon intercurrent type 2 diabetes (<xref ref-type="bibr" rid="B7">7</xref>), but maybe explained partly by BMI (<xref ref-type="bibr" rid="B28">28</xref>).</p>
<p>Results from this study showed that a history of GDM was significantly associated with increased odds of arthritis among smokers, alcohol drinkers, and women engaging in higher levels of physical activity. While smoking was inversely associated with the risk of osteoarthritis in both observational studies (<xref ref-type="bibr" rid="B22">22</xref>) and Mendelian randomization studies (<xref ref-type="bibr" rid="B21">21</xref>, <xref ref-type="bibr" rid="B37">37</xref>), a positive association was found between smoking and the risk of rheumatoid arthritis in both observational studies (<xref ref-type="bibr" rid="B38">38</xref>) and a Mendelian randomization study (<xref ref-type="bibr" rid="B39">39</xref>). These results indicate that the effects of smoking on arthritis may differ by different clinical subtypes of arthritis. Low to moderate alcohol consumption was found inversely associated with the development of both osteoarthritis (<xref ref-type="bibr" rid="B24">24</xref>) and rheumatoid arthritis (<xref ref-type="bibr" rid="B25">25</xref>), while a positive association was also found between alcohol consumption and osteoarthritis prevalence in the Korean NHANES assessed by the alcohol use disorders identification test (<xref ref-type="bibr" rid="B40">40</xref>). Findings on the association between physical activity and arthritis are conflicting. While physical activity was found to be inversely associated with arthritis in observational studies (<xref ref-type="bibr" rid="B26">26</xref>, <xref ref-type="bibr" rid="B27">27</xref>), physical activity may constitute an important risk factor for arthritis progression prediction with a machine learning approach (<xref ref-type="bibr" rid="B41">41</xref>). In this study, physical activity was also found positively associated with prevalence of arthritis [1.41 (1.27&#x02013;1.58)] (<xref ref-type="table" rid="T3">Table 3</xref>). These findings indicate that the association between physical activity and arthritis may differ by clinical subtypes of arthritis, and intensity and measurement methods of physical activity (<xref ref-type="bibr" rid="B26">26</xref>, <xref ref-type="bibr" rid="B27">27</xref>, <xref ref-type="bibr" rid="B41">41</xref>), which need to be confirmed further. In summary, the findings available on the associations between smoking, alcohol drinking, and physical activity and arthritis remain contradictory, and the potential interactions between a history of GDM and these life-style factors on the risk of arthritis deserve to the confirmed further.</p>
<p>There are several limitations in this study. First, the causality cannot be determined because this is a cross-sectional study, and the causality should be confirmed further in prospective cohort studies. Second, a GDM history and arthritis diagnosis were based on self-report and misclassification could be of concern. However, data from the NHANES are considered to be valid to assess the prevalence of GDM and arthritis in the general population (<xref ref-type="bibr" rid="B10">10</xref>, <xref ref-type="bibr" rid="B28">28</xref>, <xref ref-type="bibr" rid="B29">29</xref>), and misclassification of patients with undiagnosed arthritis and GDM as healthy controls could have weakened the association.</p>
<p>In summary, a history of GDM was associated with increased odds of arthritis in this nationally representative cohort, and the association was independent of metabolic syndrome and type 2 diabetes. The association between a history of GDM and arthritis was observed in smokers, alcohol drinkers, and women engaging in higher levels of physical activity. The causality should be confirmed further in prospective cohort studies.</p></sec>
<sec id="s5">
<title>Code Availability</title>
<p>Analytic code will be made available from the corresponding author.</p></sec>
<sec sec-type="data-availability" id="s6">
<title>Data Availability Statement</title>
<p>The original contributions presented in the study are included in the article/supplementary files, further inquiries can be directed to the corresponding author/s.</p></sec>
<sec id="s7">
<title>Ethics Statement</title>
<p>The studies involving human participants were reviewed and approved by National Center for Health Statistics Research Ethics Review Board. The patients/participants provided their written informed consent to participate in this study.</p></sec>
<sec id="s8">
<title>Author Contributions</title>
<p>YM and QL designed the study. WH conducted the statistical analysis. YM, BX, LL, and QL drafted the manuscript. QL made critical revisions. All authors contributed to the article and approved the submitted version.</p></sec>
<sec sec-type="funding-information" id="s9">
<title>Funding</title>
<p>The authors received support from the Maternal and Child Health Research Project of Jiangsu Province (No. F201720) and the Development Science and Technology Project of Kunshan (No. KS1646).</p></sec>
<sec sec-type="COI-statement" id="conf1">
<title>Conflict of Interest</title>
<p>The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.</p></sec>
<sec sec-type="disclaimer" id="s10">
<title>Publisher&#x00027;s Note</title>
<p>All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.</p></sec> </body>
<back>
<ack><p>The authors are grateful to the National Center for Health Statistics of the Centers for Disease Control and Prevention for sharing the data.</p>
</ack>
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