Accepted Manuscript Spinal Cord Injury Increases the Risk of Type 2 Diabetes: A Population-Based Cohort Study Yun-Ju Lai, MD Cheng-Li Lin, MSc Yen-Jung Chang, PhD Ming-Chia Lin, MSc ShihTan Lee, MD Fung-Chang Sung, PhD Wen-Yuan Lee, MD Chia-Hung Kao, MD PII:
S1529-9430(13)01988-8
DOI:
10.1016/j.spinee.2013.12.011
Reference:
SPINEE 55704
To appear in:
The Spine Journal
Received Date: 21 December 2012 Revised Date:
22 November 2013
Accepted Date: 13 December 2013
Please cite this article as: Lai Y-J, Lin C-L, Chang Y-J, Lin M-C, Lee S-T, Sung F-C, Lee W-Y, Kao C-H, Spinal Cord Injury Increases the Risk of Type 2 Diabetes: A Population-Based Cohort Study, The Spine Journal (2014), doi: 10.1016/j.spinee.2013.12.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Spinal Cord Injury Increases the Risk of Type 2 Diabetes: A Population-Based
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Cohort Study
Short title: SCI and risk of diabetes
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Yun-Ju Lai, MD1
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Cheng-Li Lin, MSc2 Yen-Jung Chang, PhD2 Ming-Chia Lin, MSc3 Shih-Tan Lee, MD4
Wen-Yuan Lee, MD6,7,
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Chia-Hung Kao, MD6,8
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Fung-Chang Sung, PhD2,5
Division of Endocrinology and Metabolism, Department of Internal Medicine, Puli
Branch of Taichung Veterans General Hospital, Taichung, Taiwan; 2Management Office for Health Data, 8Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan; 3Department of Nuclear Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan; 4Department of Family
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Medicine, Puli Branch of Taichung Veterans General Hospital, Taichung, Taiwan; 5
Department of Public Health, 6Graduate Institute of Clinical Medicine Science and
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School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; 7China Medical University Hospital Taipei Branch, Taipei, Taiwan
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Ming-Chia Lin and Yun-Ju Lai contributed equally to this work.
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Corresponding author: Dr. Chia-Hung Kao, Graduate Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 404, Taiwan. Tel.: +886 4 22052121x7412; Fax.: +886 4
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22336174. E-mail: [email protected]
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Contributors:
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Conception/Design: Yun-Ju Lai, Ming-Chia Lin, Chia-Hung Kao Provision of study material or patients: Shih-Tan Lee, Cheng-Li Lin, Fung-Chang Sung, Wen-Yuan Lee Collection and/or assembly of data: Cheng-Li Lin, Yen-Jung Chang, Fung-Chang Sung Data analysis and interpretation: Yun-Ju Lai, Ming-Chia Lin, Chia-Hung Kao
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Manuscript writing: Yun-Ju Lai, Cheng-Li Lin, Yen-Jung Chang, Ming-Chia Lin, Chia-Hung Kao
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Final approval of manuscript: All authors
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ACKNOWLEDGMENTS
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The study was supported in part by the study projects (DMR-101-061 and DMR-100-076) in our hospital and Taiwan Department of Health Clinical Trial and Research Center and for Excellence (DOH102-TD-B-111-004), and Taiwan Department of Health Cancer Research Center for Excellence
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(DOH102-TD-C-111-005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional
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external funding received for this study.
Conflict of interest All authors state that they have no conflicts of interest.
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Revised Manuscript: Ms. No. SPINEE-D-13-00020R3
2 Spinal Cord Injury Increases the Risk of Type 2 Diabetes: A Population-Based
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Cohort Study
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5 Short title: SCI and the Risk of Diabetes
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Abstract
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Background: Previous studies on the risk and prevalence of diabetes among spinal
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cord injury (SCI) patients are limited and controversial.
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Purpose: The primary aim of this study is to compare the risk and incidence rate (IR)
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of type 2 diabetes in SCI and non-SCI patients.
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Study Design/Setting: This is a population-based retrospective cohort study.
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Patient Sample: Data from Taiwan’s National Health Insurance Research Database
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for the period 1997 to 2010 were analyzed. Patients aged 20 years and older newly
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identified with SCIs during this period were included in the SCI cohort. A non-SCI
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comparison cohort was randomly selected from National Health Insurance
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beneficiaries and matched with the SCI cohort based on age, sex, and index date.
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Outcome Measures: Both cohorts were followed until the first of the following
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occurred: the diagnosis of type 2 diabetes (ICD-9-CM codes 250), withdrawal from
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the insurance system, the end of 2010, or death.
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Methods: A Cox proportional hazards regression analysis was used to estimate the
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risk of developing diabetes. The funders had no role in study design, data collection
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and analysis, decision to publish, or preparation of the manuscript.
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Results: Taiwan possesses an older SCI population, with a mean age of 51.6 years.
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The IR for diabetes in patients with and without SCIs was 22.1 per 10 000
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person-years and 17.2 per 10 000 person-years, respectively. The adjusted hazard
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ratio (HR) for diabetes was 1.33 times higher in patients with SCIs than in those
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without SCIs. In patients with SCIs, men (adjusted HR = 1.23, 95% confidence
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interval (CI) = 1.04–1.44), older people (adjusted HR = 4.26 in patients > 65 y, 95%
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CI = 3.16–5.74), patients with comorbidity (adjusted HR = 1.36, 95 % CI =
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1.14–1.62), and patients with a complete thoracic SCI (T-spine injury) (adjusted HR =
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2.13, 95% CI = 0.95–4.79) were more likely to be diagnosed with diabetes than were
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other patient subgroups.
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Conclusion: Our findings may facilitate the prioritizing of preventive health
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strategies and the planning of long-term care for SCI patients.
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Keywords: spinal cord injury (SCI); type 2 diabetes; cohort study.
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Introduction
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Spinal cord injury (SCI) is a common and devastating event that can result in severe
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disability, increased mortality, and use of medical resources. In Taiwan, the reported
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incidence of SCIs is approximately 2.46 per 10 000 person-years, 61.2% of which
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are traumatic cases (1). Cervical SCIs are predominant. Elderly men, people with a
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low socioeconomic status, those in rural areas, and those with preexisting
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comorbidities such as hypertension, diabetes, dyslipidemia, chronic obstructive
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pulmonary disease, chronic renal failure, and Parkinson’s disease are more likely to
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suffer from SCIs than are other patient groups (1).
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An SCI induces various changes in systemic physiology that can lead to many
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complications that considerably affect the function and quality of life. The life
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expectancy of survivors of SCIs is approximately 90% of that of the general
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population (2, 3). The most common causes of death after a traumatic SCI are
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diseases of the respiratory system, followed by cardiovascular events. These 2 causes
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of death include more than 50% of all deaths of SCI patients (2). Patients with SCIs
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typically live sedentary lifestyles and experience weight gain and metabolic changes,
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which may cause premature coronary heart disease (4, 5). In addition, patients with
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SCIs are reportedly at higher risk of insulin resistance, atherogenic lipid profile, and
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the metabolic syndrome, which are precursors of diabetes and coronary artery disease,
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compared with age-matched people from the general population (4, 6). They tend to
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possess less lean body mass and greater adiposity than do the non-SCI populations (7).
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A recent study of veterans with SCIs identified approximately 20% as obese and 33%
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as overweight (5). Increased prevalence of cardiovascular risk factors in SCI patients
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leads to higher incidence of hypertension and ischemic heart disease than in non-SCI
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populations (6, 8).
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Previous reports on the risk and prevalence of diabetes among SCI patients are limited
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and conflicting. In 2006, Lavela et al suggested that the prevalence of diabetes is
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higher in veterans with SCIs than in the civilian population (9). Wahman et al further
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reported that patients with paraplegia exhibited higher prevalence of diabetes mellitus,
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hypertension, and dyslipidemia, compared with the general population (10). However,
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a study by Banerjea et al identified that the prevalence of diabetes in SCI patients was
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similar to that in the general older population (11). The results of a recent study by
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LaVela et al further indicated that the prevalence of diabetes was similar in men with
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and without SCIs (12).
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Therefore, the primary aim of this study was to compare the risk and incidence rate
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(IR) of diabetes in SCI and non-SCI groups based on data from Taiwan’s National
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Health Research Insurance Database (NHRID).
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1 2 Material and Methods
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Data sources
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A retrospective study was conducted using claims data obtained from Taiwan’s
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National Health Research Institutes (NHRI). Taiwan initiated its single-payer National
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Health Insurance (NHI) program in March 1995, which covered approximately 99%
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of Taiwan’s 23.74 million residents in 2009 (13). The NHRI maintains and updates
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the NHIRD. We analyzed data from the NHIRD for the period 1997 to 2010; the data
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are released by the NHRI for public use. The scrambled identifications of insured
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individuals are available through link files that include the registry of medical
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facilities, details of inpatient orders, ambulatory care data, and sociodemographic
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information for each patient. Diagnoses are coded according to the International
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Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM). We
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confirm that all data was de-identified and analyzed anonymously. In addition, this
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study was approved by the Ethics Review Board of China Medical University
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(CMU-REC-101-012).
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Study patients
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In this study, patients with newly identified SCIs (ICD-9-CM codes 806 and 952) 6
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from 1997 to 2010 were selected for data analysis. Patients aged 20 years or younger
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and those with a previous diagnosis of diabetes were excluded from the study. The
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remaining patients were included in the SCI cohort. The date on which SCI patients
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received a diagnosis according to the inpatient claims data was defined as the index
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date. We classified SCI patients into subgroups: C-spine SCI (ICD-9-CM codes 8060,
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8061, 9520, 95200, 95201, 95202, 95203, 95204, 95205, 95206, 95207, 95208,
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95209), complete T-spine SCI (ICD-9-CM 806.21, 806.26, 952.11, 952.16),
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incomplete T-spine SCI (ICD-9-CM codes 8062, 8063, 9521), and lumbar, sacral, and
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coccygeal (L-S-Co-spine) SCI ( ICD-9-CM codes 8064, 8065, 8066, 8067, 8068,
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8069, 9522, 9523, 9524, 9528, 9529). A non-SCI comparison cohort was randomly
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selected from the NHI beneficiaries aged 20 years and older and matched with the
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SCI cohort in a 4:1 ratio based on age (every 5 y), sex, and index date.
13 Outcome measures
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For each patient, the duration of a follow-up evaluation was measured from the index
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date until the first of the following occurred: diagnosis of type 2 diabetes (ICD-9-CM
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codes 250), withdrawal from the insurance system, the end of 2010, or death. Baseline
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comorbidity histories of hypertension (ICD-9-CM codes 401–405), hyperlipidemia
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(ICD-9-CM code 272), chronic kidney disease (ICD-9-CM code 585), stroke
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(ICD-9-CM codes 430–438), coronary heart disease (ICD-9-CM codes 411.1, 411.81,
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411.89, 413, 414.0, 414.8, and 414.9), and congestive heart failure (ICD-9-CM code
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428) were identified according to their diagnoses in the inpatient claims data prior to
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the index date.
2 Statistical analysis
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Demographic factors, including age, sex, and comorbidities, were compared between
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the SCI and non-SCI cohorts. A chi-square test was used to evaluate the differences
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between the groups. The IRs of type 2 diabetes from the follow-up evaluation until
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the end of 2010 were calculated for the 2 groups. In addition, the IR ratio (IRR) of the
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SCI cohort compared with the non-SCI cohort was calculated. Multiple Cox
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proportional hazard regression analyses were conducted to calculate the related hazard
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ratios (HRs) and 95% confidence intervals (CIs) for risk of type 2 diabetes associated
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with SCI. The diabetes-free survival rates were estimated using the Kaplan-Meier
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method and the log-rank test was used to compare the survival curves of the SCI and
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non-SCI cohorts. All analyses were performed using the SAS System for Windows,
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Version 9.1, and results were considered statistically significant if 2-tailed P values
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were less than .05.
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Results
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During the evaluation period, we identified 52 420 patients for inclusion in the SCI 8
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cohort and 209 680 patients for inclusion in the non-SCI comparison cohort (Table
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1). Patients were predominantly men (63.6%), possessing a mean age of 51.6 years in
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the non-SCI cohort and 51.7 years in the SCI cohort. Comparison of the SCI and the
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non-SCI cohorts revealed that patients in the SCI cohort were more likely to have
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hypertension (16.20% vs 7.19%), hyperlipidemia (3.68% vs 1.72%), chronic kidney
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disease (1.01% vs 0.49%), stroke (6.23% vs 3.20%), coronary heart disease (6.84% vs
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3.33%), and congestive heart failure (2.56% vs 1.10%) than were patients in the
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non-SCI cohort. The mean duration of follow-up evaluations was 5.98 years in the
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SCI cohort and 6.50 years in the non-SCI comparison cohort. The incidence of type 2
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diabetes was slightly higher in the SCI cohort than in the non-SCI cohort (22.1 per
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10 000 person-y vs 17.2 per 10 000 person-y), with an IRR of 1.28 (95% CI =
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1.24–1.32) (Table 2). A Cox proportional hazard regression model analysis further
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revealed that patients with SCIs were 1.33 times more likely to develop type 2
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diabetes than were non-SCI patients (95% CI = 1.22–1.45), after controlling for age,
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sex, and comorbidity. The IRR of type 2 diabetes was higher in men than in women
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(IRR = 1.40, 95% CI = 1.35–1.46 vs IRR = 1.13, 95% CI = 1.07–1.19). Generally, the
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incidence of type 2 diabetes increased with age in both cohorts. The IRR of type 2
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diabetes was highest in the youngest evaluated age group (20–34 y; IRR = 7.27, 95%
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CI = 6.82–7.75), and the adjusted HR for elderly patients compared with those aged
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20 to 34 years was 17.4 (95% CI = 14.1–21.6). The IR of type 2 diabetes was higher
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in patients with comorbidity than in patients without comorbidity. Table 3 shows the
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incidence rates, crude and adjusted HRs, and 95% CIs of type 2 diabetes according to
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different levels of lesion of SCI. Compared with the non-SCI cohort, patients with
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C-spine injuries exhibited a 20% higher risk of type 2 diabetes (adjusted HR = 1.20,
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95% CI = 1.06–1.36), whereas those with complete T-spine injuries exhibited a 135%
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higher risk, and those with incomplete T-spine injuries exhibited a 60% higher risk
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(adjusted HR = 1.60, 95% CI = 1.34–1.92). Patients with lumbar, sacral, and
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coccygeal spine injuries (L-S-Co-spine injury) exhibited a 38% higher risk of type 2
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diabetes than the non-SCI comparison cohort did (adjusted HR = 1.38, 95% CI =
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1.21–1.57). Table 4 shows the adjusted HRs for development of diabetes based on age,
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sex, comorbidity, and level of lesion of SCI. Male SCI patients were more likely to
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suffer from diabetes than were female SCI patients (adjusted HR = 1.23, 95% CI =
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1.04–1.44). Older SCI patients were more likely to suffer from diabetes than were
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younger SCI patients (adjusted HR = 4.26 in patients aged > 65 y; 95% CI =
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3.16–5.74). Patients with complete T-spine injuries were more likely to suffer from
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diabetes than were patients with C-spine injuries (adjusted HR = 2.13, 95% CI =
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0.95–4.79). The Kaplan-Meier method revealed that the cumulative incidence of type
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2 diabetes during the follow-up period was 0.42% higher in the SCI patients than in
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the non-SCI patients (log-rank test P < .0001) (Fig. 1).
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Our results revealed that SCI patients were predominantly men, were older than
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65 years, and possessed comorbidities such as hypertension, hyperlipidemia, chronic
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kidney disease, stroke, coronary heart disease, and congestive heart failure (Table 1).
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In addition, the majority of these patients suffered from C-spine injuries (Table 3).
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This is consistent with the epidemiological report from a Taiwanese nationwide study
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conducted by Wu et al in 2011 (1). The IR of type 2 diabetes was considerably higher
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in the SCI cohort than in the non-SCI cohort. The IR of type 2 diabetes increased with
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age and comorbidities in both cohorts (Table 3). Among patients with SCIs, those
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with complete T-spine injuries exhibited the highest risk of developing diabetes
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(Tables 3 and 4).
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Some of our findings require further investigation. In our study, the case number of
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patients with complete T-spine injuries was 274, which was considerably fewer than
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patients with C-spine injuries, incomplete T-spine injuries, and L-S-Co-spine injuries
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(Table 3). The expected functional recovery following a complete T-spine injury is
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more satisfactory than that following a complete C-spine injury. However, our study
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revealed that patients with complete T-spine injury possessed the highest risk of
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diabetes. Some detailed patient information was not available in our data set, such as
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data on associated injuries, physical activity, body weight, lipid profile, blood
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pressure, use of medication, and rehabilitation resources. In addition, we did not
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possess data regarding mortality. Early death rates after admission for traumatic SCI
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range from 4% to 20% (14). Other reasons that patients with C-spine SCIs are less
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likely to develop diabetes may exist. DeVivo discovered that patients with C1 to C3
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injuries possess a 6.6-fold increased risk of death, C4 to C5 injuries a 2.5 increased
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risk, and C6 to C8 a 1.5 increased risk, when compared with those patients with SCIs
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that occurred in the thoracic or lower cord (15). A reduced life expectancy might
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explain why patients with C-spine SCIs are less likely to develop diabetes. In our
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study, patients with C-spine injuries might possess an increased risk of mortality and
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reduced life expectancy, which might explain why patients with T-spine injuries
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demonstrated higher risk of developing diabetes than those with C-spine injuries.
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Previous studies have reported rates of diabetes in patients with SCIs as ranging
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from 13% to 22% (1, 16, 17). In 2006, Lavela et al reported that the overall
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prevalence of diabetes in patients with SCIs was 20%, which was 3 times higher than
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in the general population (9). In our study, the identified diabetes IR in the SCI group
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was 22.1 per 10 000 person-years. The diabetes IR in the non-SCI group was 17.2 12
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per 10 000 person-years, which was higher than the rate in Taiwan’s general
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population, namely, 7.6 per 1000 person-years in men and 6.9 per 1000 person-years
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in women (18). According to our results, the IR of diabetes in SCI patients was 1.28
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times that seen in the non-SCI population and approximately 3 times the reported IR
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of the general population. Because the non-SCI comparison cohort was matched with
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the SCI cohort on age, both cohorts were predominantly elderly men and exhibited
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higher diabetes risks than did the general population.
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Table 4 displays the risk factors for diabetes in the SCI and non-SCI patients.
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According to the American Diabetes Association’s position statement in 2012, risk factors for diabetes include the following: age > 45 years, body mass index (BMI) >
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25 kg/m2, physical inactivity, having a first-degree relative with diabetes, being a
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member of a high-risk ethnic population (eg, African American, Latino, Native
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American, Asian American, or Pacific Islander), being a woman who delivered a baby
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weighing > 9 lb or has been diagnosed with gestational diabetes mellitus,
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hypertension (≥ 140/90 mm Hg, or undergoing therapy for hypertension), a
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high-density lipoprotein cholesterol (HDL-C) level ≥ 35 mg/dL (0.90 mmol/L) or a
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triglyceride level ≥ 250 mg/dL (2.82 mmol/L), polycystic ovary syndrome,
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hemoglobin A1C > 5.7%, impaired glucose tolerance, impaired fasting glucose, other
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clinical conditions associated with insulin resistance (eg, severe obesity, acanthosis
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nigricans), and a history of cardiovascular disease (19). Although follow-up studies on
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SCI patients did not establish risk estimates commonly used for the general
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population, nearly all risk factors tended to be more prevalent in SCI patients that in
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ambulatory patients (20). In our study, in the SCI group, elderly men (mean age 51.7
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y ± 18.3 y) with comorbidity, including hypertension, hyperlipidemia, chronic kidney
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disease, stroke, coronary heart disease, and congestive heart failure, were predominant.
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They possessed a greater number of risk factors for diabetes than did the non-SCI
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subgroups and the general population. In SCI patients, associated injuries, such as
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injuries to the head, chest, abdomen, pelvis, and extremities are common (21). Daily
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energy expenditure is considerably lower in SCI patients than in non-SCI patients
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because of lack of motor function, lack of accessibility, and fewer opportunities to
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engage in physical activity. These patients tend to engage in limited activity, live
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sedentary lifestyles, and experience weight gain, nervous system dysfunction, and
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increased inflammatory response. SCI patients also suffer from abdominal obesity,
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increased body fat, and decreased lean body mass (22). In a previous study, BMI ≥ 25
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kg/m2 was associated with a considerably high prevalence of diabetes in male
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veterans with SCIs and disorders. This risk was particularly pronounced if their BMI
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was ≥ 27.5 kg/m2 (23).
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in SCI patients. Other studies that have used laboratory data similarly have revealed
2
increased cardiovascular risk in SCI patients. Inflammatory markers that correlate
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with an increased risk of cardiovascular disease are reportedly more prevalent in
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patients with SCIs than in non-SCI patients (24). A previous study identified that
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patients with C-spine injuries experience an enhanced lipid peroxidation process and
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decreased plasma antioxidant potential (25). Other studies have reported a high
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prevalence of dyslipidemia and decreased levels of HDL-C in SCI patients compared
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with non-SCI groups (24, 26). We presumed that inflammatory markers and
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autonomic dysfunction might be underlying mechanisms that cause the increased
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diabetes risk in SCI patients.
The spinal cord is essential for autonomic nervous system regulation of the
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cardiovascular system because the preganglionic neurons controlling the heart and
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blood vessels originate in the thoracolumbar spinal segments. The site and extent of
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an SCI determine the degree of autonomic involvement in a cardiovascular
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dysfunction postinjury (27). Autonomic dysfunction caused by an SCI is associated
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with several conditions that increase cardiovascular risk, including blood pressure
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abnormalities, heart-rate variability, arrhythmias, and a blunted cardiovascular
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response to exercise that can limit physical activity (20). Following the induction of
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SCIs in experimental animals, Bravo et al observed immediate hypotension, which
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they attributed to an autonomic imbalance involving the predominance of
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parasympathetic activity. The authors proposed that episodic hypertension might then
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develop as part of a condition called autonomic dysreflexia (28). Hypertension
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reportedly increases in patients with paraplegia, but not in those with tetraplegia (8).
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Our study was subject to limitations. First, the NHIRD provides ICD-9-CM
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diagnosis codes, but not detailed patient information such as data on BMI, physical
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activity, blood pressure, blood glucose levels, serum HDL-C and triglyceride levels,
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and family history of type 2 diabetes, all of which are risk factors for diabetes. Second,
9
evidence from a retrospective cohort study is generally of lower methodological
10
quality than that from randomized trials because of bias related to adjustment for
11
confounders. Despite adequate control of confounding factors, a major limitation of
12
our study was potential bias because of possible unmeasured or unknown confounders.
13
Third, the diagnoses in the NHI claims primarily serve the purpose of administrative
14
billing and do not undergo verification for scientific purposes. We were unable to
15
contact the patients directly to obtain further information because of the anonymity
16
assured by their identification numbers. However, the data that we obtained on SCIs
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and diabetes diagnoses were highly reliable because of the considerable sample size.
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Finally, mortality data were not available in our dataset; therefore, we were unable to
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conduct an analysis to determine if greater mortality occurs in the C-spine cohort.
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Some of our findings require further investigation. Further research should be conducted to investigate the reason that patients with complete T-spine injuries
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possess high risk and IR of diabetes. Some detailed patient information was not
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available, such as data on BMI, physical activity, blood pressure, blood glucose levels,
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serum HDL-C and triglyceride levels, family history of type 2 diabetes, and mortality. In conclusion, our findings suggest that patients with SCIs possess higher risk
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and IR of diabetes than non-SCI patients do, particularly patients who are men, aged
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65 and older, exhibit comorbidity, and have experienced complete T-spine injuries.
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Reference:
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1.
Wu JC, Chen YC, Liu L, Chen TJ, Huang WC, Cheng H, et al. Effects of age, gender, and socio-economic status on the incidence of spinal cord injury: an
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assessment using the eleven-year comprehensive nationwide database of
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Taiwan. J Neurotrauma. 2012;29(5):889-97. 2.
Frankel HL, Coll JR, Charlifue SW, Whiteneck GG, Gardner BP, Jamous MA,
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Weaver FM, Collins EG, Kurichi J, Miskevics S, Smith B, Rajan S, et al.
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Lavela SL, Weaver FM, Goldstein B, Chen K, Miskevics S, Rajan S, et al. Diabetes mellitus in individuals with spinal cord injury or disorder. J Spinal
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Banerjea R, Sambamoorthi U, Weaver F, Maney M, Pogach LM, Findley T.
Risk of stroke, heart attack, and diabetes complications among veterans with spinal cord injury. Arch Phys Med Rehabil. 2008;89(8):1448-53.
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LaVela SL, Evans CT, Prohaska TR, Miskevics S, Ganesh SP, Weaver FM. Males aging with a spinal cord injury: prevalence of cardiovascular and 19
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metabolic conditions. Arch Phys Med Rehabil. 2012;93(1):90-5.
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Cheng TM. Taiwan’s National Health Insurance system: high value for the dollar. In Okma, K.G.H. and Crivelli, L. ed. Six Countries, Six Reform Models:
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The Health Reform Experience of Israel, the Netherlands, New Zealand,
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Singapore, Switzerland and Taiwan. New Jersey: World Scientific.
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Daverat P, Gagnon M, Dartigues JF, Mazaux JM, Barat M. Initial factors
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predicting survival in patients with a spinal cord injury. J Neurol Neurosurg
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Psychiatry. 1989;52(3):403-6. 15.
patients with spinal cord injuries. Arch Intern Med. 1989;149(8):1761-6.
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DeVivo MJ, Kartus PL, Stover SL, Rutt RD, Fine PR. Cause of death for
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Bauman WA, Spungen AM. Disorders of carbohydrate and lipid metabolism in veterans with paraplegia or quadriplegia: a model of premature aging.
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Metabolism. 1994;43(6):749-56.
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Bauman WA, Adkins RH, Spungen AM, Herbert R, Schechter C, Smith D, et
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Chang CH, Shau WY, Jiang YD, Li HY, Chang TJ, Sheu WH, et al. Type 2 diabetes prevalence and incidence among adults in Taiwan during 1999-2004: 20
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a national health insurance data set study. Diabet Med. 2010;27(6):636-43.
1 19.
1:S11-63.
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Standards of medical care in diabetes--2012. Diabetes Care. 2012;35 Suppl
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overview of prevalence, risk, evaluation, and management. Am J Phys Med
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Chu D, Lee YH, Lin CH, Chou P, Yang NP. Prevalence of associated injuries
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Liang H, Chen D, Wang Y, Rimmer JH, Braunschweig CL. Different risk
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factor patterns for metabolic syndrome in men with spinal cord injury
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Med Rehabil. 2007;88(9):1198-204.
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Nash MS, Mendez AJ. A guideline-driven assessment of need for cardiovascular disease risk intervention in persons with chronic paraplegia. 21
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Wozniak A, Kasprzak HA, Wozniak B, Drewa G, Beuth W, Sniegocki M, et al. [Lipid peroxidation and antioxidant potential in patients with cervical spinal
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cord injury]. Neurol Neurochir Pol. 2003;37(5):1025-35; discussion 36. 26.
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Mathias CJ. Orthostatic hypotension and paroxysmal hypertension in humans with high spinal cord injury. Prog Brain Res. 2006;152:231-43.
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6 7
Bauman WA, Spungen AM. Coronary heart disease in individuals with spinal
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Bravo G, Guizar-Sahagun G, Ibarra A, Centurion D, Villalon CM. Cardiovascular alterations after spinal cord injury: an overview. Curr Med
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Chem Cardiovasc Hematol Agents. 2004;2(2):133-48.
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Legends:
2
Table 1─Demographic characteristics and comorbidities in cohorts with and without
3
spinal cord injury
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4
Table 2─Incidence of diabetes by sex, age and comorbidity and Cox model measured
6
hazards ratio for patients with spinal cord injury compared those without spinal cord
7
injury
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8 9 10
Table 3─Incidence, crude and adjusted hazard ratio of diabetes among different spine level SCI
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Table 4─Risks factor of diabetes in SCI patients and Non-SCI patients
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Figure 1─Probability free of diabetes for patients with (dashed line) or without (solid
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line) spinal cord injury.
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Table 1. Demographic characteristics and comorbidities in cohorts with and without spinal cord injury
Spinal cord injury Yes
n = 209680
n =52420
76432(36.5) 19108(36.5) 133248(63.6) 33312(63.6)
46272(22.1) 36544(17.4) 38440(18.3) 30476(14.5)
11568(22.1) 9136(17.4) 9610(18.3) 7619(14.5)
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0.60 0.99
57948(27.6) 14487(27.6) 15068(7.19) 3603(1.72) 1027(0.49) 6700(3.20) 6988(3.33) 2301(1.10)
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&:Chi-Square Test
51.7±18.3
0.99
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65+ Comorbidity Hypertension Hyperlipidemia Chronic kidney disease Stroke Coronary heart disease Congestive heart failure
51.6±18.3
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Age, mean±SD Stratify age 20-34 35-44 45-54 55-64
p-value
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Sex Female Male
No
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Variable
8473(16.2) 1927(3.68) 531(1.01) 3266(6.23) 3588(6.84) 1341(2.56)
S1529-9430(13)01988-8
DOI:
10.1016/j.spinee.2013.12.011
Reference:
SPINEE 55704
To appear in:
The Spine Journal
Received Date: 21 December 2012 Revised Date:
22 November 2013
Accepted Date: 13 December 2013
Please cite this article as: Lai Y-J, Lin C-L, Chang Y-J, Lin M-C, Lee S-T, Sung F-C, Lee W-Y, Kao C-H, Spinal Cord Injury Increases the Risk of Type 2 Diabetes: A Population-Based Cohort Study, The Spine Journal (2014), doi: 10.1016/j.spinee.2013.12.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Spinal Cord Injury Increases the Risk of Type 2 Diabetes: A Population-Based
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Cohort Study
Short title: SCI and risk of diabetes
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Yun-Ju Lai, MD1
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Cheng-Li Lin, MSc2 Yen-Jung Chang, PhD2 Ming-Chia Lin, MSc3 Shih-Tan Lee, MD4
Wen-Yuan Lee, MD6,7,
1
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Chia-Hung Kao, MD6,8
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Fung-Chang Sung, PhD2,5
Division of Endocrinology and Metabolism, Department of Internal Medicine, Puli
Branch of Taichung Veterans General Hospital, Taichung, Taiwan; 2Management Office for Health Data, 8Department of Nuclear Medicine and PET Center, China Medical University Hospital, Taichung, Taiwan; 3Department of Nuclear Medicine, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan; 4Department of Family
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Medicine, Puli Branch of Taichung Veterans General Hospital, Taichung, Taiwan; 5
Department of Public Health, 6Graduate Institute of Clinical Medicine Science and
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School of Medicine, College of Medicine, China Medical University, Taichung, Taiwan; 7China Medical University Hospital Taipei Branch, Taipei, Taiwan
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Ming-Chia Lin and Yun-Ju Lai contributed equally to this work.
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Corresponding author: Dr. Chia-Hung Kao, Graduate Institute of Clinical Medicine Science and School of Medicine, College of Medicine, China Medical University, No. 2, Yuh-Der Road, Taichung 404, Taiwan. Tel.: +886 4 22052121x7412; Fax.: +886 4
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22336174. E-mail: [email protected]
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Contributors:
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Conception/Design: Yun-Ju Lai, Ming-Chia Lin, Chia-Hung Kao Provision of study material or patients: Shih-Tan Lee, Cheng-Li Lin, Fung-Chang Sung, Wen-Yuan Lee Collection and/or assembly of data: Cheng-Li Lin, Yen-Jung Chang, Fung-Chang Sung Data analysis and interpretation: Yun-Ju Lai, Ming-Chia Lin, Chia-Hung Kao
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Manuscript writing: Yun-Ju Lai, Cheng-Li Lin, Yen-Jung Chang, Ming-Chia Lin, Chia-Hung Kao
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Final approval of manuscript: All authors
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ACKNOWLEDGMENTS
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The study was supported in part by the study projects (DMR-101-061 and DMR-100-076) in our hospital and Taiwan Department of Health Clinical Trial and Research Center and for Excellence (DOH102-TD-B-111-004), and Taiwan Department of Health Cancer Research Center for Excellence
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(DOH102-TD-C-111-005). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. No additional
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external funding received for this study.
Conflict of interest All authors state that they have no conflicts of interest.
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Revised Manuscript: Ms. No. SPINEE-D-13-00020R3
2 Spinal Cord Injury Increases the Risk of Type 2 Diabetes: A Population-Based
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Cohort Study
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5 Short title: SCI and the Risk of Diabetes
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Abstract
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Background: Previous studies on the risk and prevalence of diabetes among spinal
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cord injury (SCI) patients are limited and controversial.
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Purpose: The primary aim of this study is to compare the risk and incidence rate (IR)
5
of type 2 diabetes in SCI and non-SCI patients.
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Study Design/Setting: This is a population-based retrospective cohort study.
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Patient Sample: Data from Taiwan’s National Health Insurance Research Database
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for the period 1997 to 2010 were analyzed. Patients aged 20 years and older newly
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identified with SCIs during this period were included in the SCI cohort. A non-SCI
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comparison cohort was randomly selected from National Health Insurance
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beneficiaries and matched with the SCI cohort based on age, sex, and index date.
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Outcome Measures: Both cohorts were followed until the first of the following
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occurred: the diagnosis of type 2 diabetes (ICD-9-CM codes 250), withdrawal from
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the insurance system, the end of 2010, or death.
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Methods: A Cox proportional hazards regression analysis was used to estimate the
16
risk of developing diabetes. The funders had no role in study design, data collection
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and analysis, decision to publish, or preparation of the manuscript.
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Results: Taiwan possesses an older SCI population, with a mean age of 51.6 years.
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The IR for diabetes in patients with and without SCIs was 22.1 per 10 000
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person-years and 17.2 per 10 000 person-years, respectively. The adjusted hazard
2
ratio (HR) for diabetes was 1.33 times higher in patients with SCIs than in those
3
without SCIs. In patients with SCIs, men (adjusted HR = 1.23, 95% confidence
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interval (CI) = 1.04–1.44), older people (adjusted HR = 4.26 in patients > 65 y, 95%
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CI = 3.16–5.74), patients with comorbidity (adjusted HR = 1.36, 95 % CI =
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1.14–1.62), and patients with a complete thoracic SCI (T-spine injury) (adjusted HR =
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2.13, 95% CI = 0.95–4.79) were more likely to be diagnosed with diabetes than were
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other patient subgroups.
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Conclusion: Our findings may facilitate the prioritizing of preventive health
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strategies and the planning of long-term care for SCI patients.
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Keywords: spinal cord injury (SCI); type 2 diabetes; cohort study.
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Introduction
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Spinal cord injury (SCI) is a common and devastating event that can result in severe
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disability, increased mortality, and use of medical resources. In Taiwan, the reported
4
incidence of SCIs is approximately 2.46 per 10 000 person-years, 61.2% of which
5
are traumatic cases (1). Cervical SCIs are predominant. Elderly men, people with a
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low socioeconomic status, those in rural areas, and those with preexisting
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comorbidities such as hypertension, diabetes, dyslipidemia, chronic obstructive
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pulmonary disease, chronic renal failure, and Parkinson’s disease are more likely to
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suffer from SCIs than are other patient groups (1).
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An SCI induces various changes in systemic physiology that can lead to many
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complications that considerably affect the function and quality of life. The life
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expectancy of survivors of SCIs is approximately 90% of that of the general
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population (2, 3). The most common causes of death after a traumatic SCI are
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diseases of the respiratory system, followed by cardiovascular events. These 2 causes
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of death include more than 50% of all deaths of SCI patients (2). Patients with SCIs
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typically live sedentary lifestyles and experience weight gain and metabolic changes,
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which may cause premature coronary heart disease (4, 5). In addition, patients with
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SCIs are reportedly at higher risk of insulin resistance, atherogenic lipid profile, and
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the metabolic syndrome, which are precursors of diabetes and coronary artery disease,
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compared with age-matched people from the general population (4, 6). They tend to
2
possess less lean body mass and greater adiposity than do the non-SCI populations (7).
3
A recent study of veterans with SCIs identified approximately 20% as obese and 33%
4
as overweight (5). Increased prevalence of cardiovascular risk factors in SCI patients
5
leads to higher incidence of hypertension and ischemic heart disease than in non-SCI
6
populations (6, 8).
7
Previous reports on the risk and prevalence of diabetes among SCI patients are limited
8
and conflicting. In 2006, Lavela et al suggested that the prevalence of diabetes is
9
higher in veterans with SCIs than in the civilian population (9). Wahman et al further
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reported that patients with paraplegia exhibited higher prevalence of diabetes mellitus,
11
hypertension, and dyslipidemia, compared with the general population (10). However,
12
a study by Banerjea et al identified that the prevalence of diabetes in SCI patients was
13
similar to that in the general older population (11). The results of a recent study by
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LaVela et al further indicated that the prevalence of diabetes was similar in men with
15
and without SCIs (12).
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Therefore, the primary aim of this study was to compare the risk and incidence rate
17
(IR) of diabetes in SCI and non-SCI groups based on data from Taiwan’s National
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Health Research Insurance Database (NHRID).
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1 2 Material and Methods
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Data sources
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A retrospective study was conducted using claims data obtained from Taiwan’s
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National Health Research Institutes (NHRI). Taiwan initiated its single-payer National
7
Health Insurance (NHI) program in March 1995, which covered approximately 99%
8
of Taiwan’s 23.74 million residents in 2009 (13). The NHRI maintains and updates
9
the NHIRD. We analyzed data from the NHIRD for the period 1997 to 2010; the data
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are released by the NHRI for public use. The scrambled identifications of insured
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individuals are available through link files that include the registry of medical
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facilities, details of inpatient orders, ambulatory care data, and sociodemographic
13
information for each patient. Diagnoses are coded according to the International
14
Classification of Disease, 9th Revision, Clinical Modification (ICD-9-CM). We
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confirm that all data was de-identified and analyzed anonymously. In addition, this
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study was approved by the Ethics Review Board of China Medical University
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(CMU-REC-101-012).
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Study patients
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In this study, patients with newly identified SCIs (ICD-9-CM codes 806 and 952) 6
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from 1997 to 2010 were selected for data analysis. Patients aged 20 years or younger
2
and those with a previous diagnosis of diabetes were excluded from the study. The
3
remaining patients were included in the SCI cohort. The date on which SCI patients
4
received a diagnosis according to the inpatient claims data was defined as the index
5
date. We classified SCI patients into subgroups: C-spine SCI (ICD-9-CM codes 8060,
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8061, 9520, 95200, 95201, 95202, 95203, 95204, 95205, 95206, 95207, 95208,
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95209), complete T-spine SCI (ICD-9-CM 806.21, 806.26, 952.11, 952.16),
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incomplete T-spine SCI (ICD-9-CM codes 8062, 8063, 9521), and lumbar, sacral, and
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coccygeal (L-S-Co-spine) SCI ( ICD-9-CM codes 8064, 8065, 8066, 8067, 8068,
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8069, 9522, 9523, 9524, 9528, 9529). A non-SCI comparison cohort was randomly
11
selected from the NHI beneficiaries aged 20 years and older and matched with the
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SCI cohort in a 4:1 ratio based on age (every 5 y), sex, and index date.
13 Outcome measures
15
For each patient, the duration of a follow-up evaluation was measured from the index
16
date until the first of the following occurred: diagnosis of type 2 diabetes (ICD-9-CM
17
codes 250), withdrawal from the insurance system, the end of 2010, or death. Baseline
18
comorbidity histories of hypertension (ICD-9-CM codes 401–405), hyperlipidemia
19
(ICD-9-CM code 272), chronic kidney disease (ICD-9-CM code 585), stroke
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(ICD-9-CM codes 430–438), coronary heart disease (ICD-9-CM codes 411.1, 411.81,
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411.89, 413, 414.0, 414.8, and 414.9), and congestive heart failure (ICD-9-CM code
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428) were identified according to their diagnoses in the inpatient claims data prior to
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the index date.
2 Statistical analysis
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Demographic factors, including age, sex, and comorbidities, were compared between
5
the SCI and non-SCI cohorts. A chi-square test was used to evaluate the differences
6
between the groups. The IRs of type 2 diabetes from the follow-up evaluation until
7
the end of 2010 were calculated for the 2 groups. In addition, the IR ratio (IRR) of the
8
SCI cohort compared with the non-SCI cohort was calculated. Multiple Cox
9
proportional hazard regression analyses were conducted to calculate the related hazard
10
ratios (HRs) and 95% confidence intervals (CIs) for risk of type 2 diabetes associated
11
with SCI. The diabetes-free survival rates were estimated using the Kaplan-Meier
12
method and the log-rank test was used to compare the survival curves of the SCI and
13
non-SCI cohorts. All analyses were performed using the SAS System for Windows,
14
Version 9.1, and results were considered statistically significant if 2-tailed P values
15
were less than .05.
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Results
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During the evaluation period, we identified 52 420 patients for inclusion in the SCI 8
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cohort and 209 680 patients for inclusion in the non-SCI comparison cohort (Table
2
1). Patients were predominantly men (63.6%), possessing a mean age of 51.6 years in
3
the non-SCI cohort and 51.7 years in the SCI cohort. Comparison of the SCI and the
4
non-SCI cohorts revealed that patients in the SCI cohort were more likely to have
5
hypertension (16.20% vs 7.19%), hyperlipidemia (3.68% vs 1.72%), chronic kidney
6
disease (1.01% vs 0.49%), stroke (6.23% vs 3.20%), coronary heart disease (6.84% vs
7
3.33%), and congestive heart failure (2.56% vs 1.10%) than were patients in the
8
non-SCI cohort. The mean duration of follow-up evaluations was 5.98 years in the
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SCI cohort and 6.50 years in the non-SCI comparison cohort. The incidence of type 2
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diabetes was slightly higher in the SCI cohort than in the non-SCI cohort (22.1 per
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10 000 person-y vs 17.2 per 10 000 person-y), with an IRR of 1.28 (95% CI =
12
1.24–1.32) (Table 2). A Cox proportional hazard regression model analysis further
13
revealed that patients with SCIs were 1.33 times more likely to develop type 2
14
diabetes than were non-SCI patients (95% CI = 1.22–1.45), after controlling for age,
15
sex, and comorbidity. The IRR of type 2 diabetes was higher in men than in women
16
(IRR = 1.40, 95% CI = 1.35–1.46 vs IRR = 1.13, 95% CI = 1.07–1.19). Generally, the
17
incidence of type 2 diabetes increased with age in both cohorts. The IRR of type 2
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diabetes was highest in the youngest evaluated age group (20–34 y; IRR = 7.27, 95%
19
CI = 6.82–7.75), and the adjusted HR for elderly patients compared with those aged
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20 to 34 years was 17.4 (95% CI = 14.1–21.6). The IR of type 2 diabetes was higher
2
in patients with comorbidity than in patients without comorbidity. Table 3 shows the
3
incidence rates, crude and adjusted HRs, and 95% CIs of type 2 diabetes according to
4
different levels of lesion of SCI. Compared with the non-SCI cohort, patients with
5
C-spine injuries exhibited a 20% higher risk of type 2 diabetes (adjusted HR = 1.20,
6
95% CI = 1.06–1.36), whereas those with complete T-spine injuries exhibited a 135%
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higher risk, and those with incomplete T-spine injuries exhibited a 60% higher risk
8
(adjusted HR = 1.60, 95% CI = 1.34–1.92). Patients with lumbar, sacral, and
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coccygeal spine injuries (L-S-Co-spine injury) exhibited a 38% higher risk of type 2
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diabetes than the non-SCI comparison cohort did (adjusted HR = 1.38, 95% CI =
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1.21–1.57). Table 4 shows the adjusted HRs for development of diabetes based on age,
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sex, comorbidity, and level of lesion of SCI. Male SCI patients were more likely to
13
suffer from diabetes than were female SCI patients (adjusted HR = 1.23, 95% CI =
14
1.04–1.44). Older SCI patients were more likely to suffer from diabetes than were
15
younger SCI patients (adjusted HR = 4.26 in patients aged > 65 y; 95% CI =
16
3.16–5.74). Patients with complete T-spine injuries were more likely to suffer from
17
diabetes than were patients with C-spine injuries (adjusted HR = 2.13, 95% CI =
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0.95–4.79). The Kaplan-Meier method revealed that the cumulative incidence of type
19
2 diabetes during the follow-up period was 0.42% higher in the SCI patients than in
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the non-SCI patients (log-rank test P < .0001) (Fig. 1).
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Our results revealed that SCI patients were predominantly men, were older than
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65 years, and possessed comorbidities such as hypertension, hyperlipidemia, chronic
7
kidney disease, stroke, coronary heart disease, and congestive heart failure (Table 1).
8
In addition, the majority of these patients suffered from C-spine injuries (Table 3).
9
This is consistent with the epidemiological report from a Taiwanese nationwide study
10
conducted by Wu et al in 2011 (1). The IR of type 2 diabetes was considerably higher
11
in the SCI cohort than in the non-SCI cohort. The IR of type 2 diabetes increased with
12
age and comorbidities in both cohorts (Table 3). Among patients with SCIs, those
13
with complete T-spine injuries exhibited the highest risk of developing diabetes
14
(Tables 3 and 4).
15
Some of our findings require further investigation. In our study, the case number of
16
patients with complete T-spine injuries was 274, which was considerably fewer than
17
patients with C-spine injuries, incomplete T-spine injuries, and L-S-Co-spine injuries
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(Table 3). The expected functional recovery following a complete T-spine injury is
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more satisfactory than that following a complete C-spine injury. However, our study
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revealed that patients with complete T-spine injury possessed the highest risk of
2
diabetes. Some detailed patient information was not available in our data set, such as
3
data on associated injuries, physical activity, body weight, lipid profile, blood
4
pressure, use of medication, and rehabilitation resources. In addition, we did not
5
possess data regarding mortality. Early death rates after admission for traumatic SCI
6
range from 4% to 20% (14). Other reasons that patients with C-spine SCIs are less
7
likely to develop diabetes may exist. DeVivo discovered that patients with C1 to C3
8
injuries possess a 6.6-fold increased risk of death, C4 to C5 injuries a 2.5 increased
9
risk, and C6 to C8 a 1.5 increased risk, when compared with those patients with SCIs
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that occurred in the thoracic or lower cord (15). A reduced life expectancy might
11
explain why patients with C-spine SCIs are less likely to develop diabetes. In our
12
study, patients with C-spine injuries might possess an increased risk of mortality and
13
reduced life expectancy, which might explain why patients with T-spine injuries
14
demonstrated higher risk of developing diabetes than those with C-spine injuries.
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Previous studies have reported rates of diabetes in patients with SCIs as ranging
16
from 13% to 22% (1, 16, 17). In 2006, Lavela et al reported that the overall
17
prevalence of diabetes in patients with SCIs was 20%, which was 3 times higher than
18
in the general population (9). In our study, the identified diabetes IR in the SCI group
19
was 22.1 per 10 000 person-years. The diabetes IR in the non-SCI group was 17.2 12
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per 10 000 person-years, which was higher than the rate in Taiwan’s general
2
population, namely, 7.6 per 1000 person-years in men and 6.9 per 1000 person-years
3
in women (18). According to our results, the IR of diabetes in SCI patients was 1.28
4
times that seen in the non-SCI population and approximately 3 times the reported IR
5
of the general population. Because the non-SCI comparison cohort was matched with
6
the SCI cohort on age, both cohorts were predominantly elderly men and exhibited
7
higher diabetes risks than did the general population.
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8
Table 4 displays the risk factors for diabetes in the SCI and non-SCI patients.
9
According to the American Diabetes Association’s position statement in 2012, risk factors for diabetes include the following: age > 45 years, body mass index (BMI) >
11
25 kg/m2, physical inactivity, having a first-degree relative with diabetes, being a
12
member of a high-risk ethnic population (eg, African American, Latino, Native
13
American, Asian American, or Pacific Islander), being a woman who delivered a baby
14
weighing > 9 lb or has been diagnosed with gestational diabetes mellitus,
15
hypertension (≥ 140/90 mm Hg, or undergoing therapy for hypertension), a
16
high-density lipoprotein cholesterol (HDL-C) level ≥ 35 mg/dL (0.90 mmol/L) or a
17
triglyceride level ≥ 250 mg/dL (2.82 mmol/L), polycystic ovary syndrome,
18
hemoglobin A1C > 5.7%, impaired glucose tolerance, impaired fasting glucose, other
19
clinical conditions associated with insulin resistance (eg, severe obesity, acanthosis
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nigricans), and a history of cardiovascular disease (19). Although follow-up studies on
2
SCI patients did not establish risk estimates commonly used for the general
3
population, nearly all risk factors tended to be more prevalent in SCI patients that in
4
ambulatory patients (20). In our study, in the SCI group, elderly men (mean age 51.7
5
y ± 18.3 y) with comorbidity, including hypertension, hyperlipidemia, chronic kidney
6
disease, stroke, coronary heart disease, and congestive heart failure, were predominant.
7
They possessed a greater number of risk factors for diabetes than did the non-SCI
8
subgroups and the general population. In SCI patients, associated injuries, such as
9
injuries to the head, chest, abdomen, pelvis, and extremities are common (21). Daily
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energy expenditure is considerably lower in SCI patients than in non-SCI patients
11
because of lack of motor function, lack of accessibility, and fewer opportunities to
12
engage in physical activity. These patients tend to engage in limited activity, live
13
sedentary lifestyles, and experience weight gain, nervous system dysfunction, and
14
increased inflammatory response. SCI patients also suffer from abdominal obesity,
15
increased body fat, and decreased lean body mass (22). In a previous study, BMI ≥ 25
16
kg/m2 was associated with a considerably high prevalence of diabetes in male
17
veterans with SCIs and disorders. This risk was particularly pronounced if their BMI
18
was ≥ 27.5 kg/m2 (23).
19
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This study, which used data from the Taiwan’s NHIRD, reported the diabetic risk 14
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in SCI patients. Other studies that have used laboratory data similarly have revealed
2
increased cardiovascular risk in SCI patients. Inflammatory markers that correlate
3
with an increased risk of cardiovascular disease are reportedly more prevalent in
4
patients with SCIs than in non-SCI patients (24). A previous study identified that
5
patients with C-spine injuries experience an enhanced lipid peroxidation process and
6
decreased plasma antioxidant potential (25). Other studies have reported a high
7
prevalence of dyslipidemia and decreased levels of HDL-C in SCI patients compared
8
with non-SCI groups (24, 26). We presumed that inflammatory markers and
9
autonomic dysfunction might be underlying mechanisms that cause the increased
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diabetes risk in SCI patients.
The spinal cord is essential for autonomic nervous system regulation of the
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cardiovascular system because the preganglionic neurons controlling the heart and
13
blood vessels originate in the thoracolumbar spinal segments. The site and extent of
14
an SCI determine the degree of autonomic involvement in a cardiovascular
15
dysfunction postinjury (27). Autonomic dysfunction caused by an SCI is associated
16
with several conditions that increase cardiovascular risk, including blood pressure
17
abnormalities, heart-rate variability, arrhythmias, and a blunted cardiovascular
18
response to exercise that can limit physical activity (20). Following the induction of
19
SCIs in experimental animals, Bravo et al observed immediate hypotension, which
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they attributed to an autonomic imbalance involving the predominance of
2
parasympathetic activity. The authors proposed that episodic hypertension might then
3
develop as part of a condition called autonomic dysreflexia (28). Hypertension
4
reportedly increases in patients with paraplegia, but not in those with tetraplegia (8).
5
Our study was subject to limitations. First, the NHIRD provides ICD-9-CM
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diagnosis codes, but not detailed patient information such as data on BMI, physical
7
activity, blood pressure, blood glucose levels, serum HDL-C and triglyceride levels,
8
and family history of type 2 diabetes, all of which are risk factors for diabetes. Second,
9
evidence from a retrospective cohort study is generally of lower methodological
10
quality than that from randomized trials because of bias related to adjustment for
11
confounders. Despite adequate control of confounding factors, a major limitation of
12
our study was potential bias because of possible unmeasured or unknown confounders.
13
Third, the diagnoses in the NHI claims primarily serve the purpose of administrative
14
billing and do not undergo verification for scientific purposes. We were unable to
15
contact the patients directly to obtain further information because of the anonymity
16
assured by their identification numbers. However, the data that we obtained on SCIs
17
and diabetes diagnoses were highly reliable because of the considerable sample size.
18
Finally, mortality data were not available in our dataset; therefore, we were unable to
19
conduct an analysis to determine if greater mortality occurs in the C-spine cohort.
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1
Some of our findings require further investigation. Further research should be conducted to investigate the reason that patients with complete T-spine injuries
3
possess high risk and IR of diabetes. Some detailed patient information was not
4
available, such as data on BMI, physical activity, blood pressure, blood glucose levels,
5
serum HDL-C and triglyceride levels, family history of type 2 diabetes, and mortality. In conclusion, our findings suggest that patients with SCIs possess higher risk
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and IR of diabetes than non-SCI patients do, particularly patients who are men, aged
8
65 and older, exhibit comorbidity, and have experienced complete T-spine injuries.
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Legends:
2
Table 1─Demographic characteristics and comorbidities in cohorts with and without
3
spinal cord injury
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4
Table 2─Incidence of diabetes by sex, age and comorbidity and Cox model measured
6
hazards ratio for patients with spinal cord injury compared those without spinal cord
7
injury
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8 9 10
Table 3─Incidence, crude and adjusted hazard ratio of diabetes among different spine level SCI
12
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Table 4─Risks factor of diabetes in SCI patients and Non-SCI patients
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Figure 1─Probability free of diabetes for patients with (dashed line) or without (solid
15
line) spinal cord injury.
16 17
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Table 1. Demographic characteristics and comorbidities in cohorts with and without spinal cord injury
Spinal cord injury Yes
n = 209680
n =52420
76432(36.5) 19108(36.5) 133248(63.6) 33312(63.6)
46272(22.1) 36544(17.4) 38440(18.3) 30476(14.5)
11568(22.1) 9136(17.4) 9610(18.3) 7619(14.5)
AC C
0.60 0.99
57948(27.6) 14487(27.6) 15068(7.19) 3603(1.72) 1027(0.49) 6700(3.20) 6988(3.33) 2301(1.10)
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&:Chi-Square Test
51.7±18.3
0.99
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65+ Comorbidity Hypertension Hyperlipidemia Chronic kidney disease Stroke Coronary heart disease Congestive heart failure
51.6±18.3
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Age, mean±SD Stratify age 20-34 35-44 45-54 55-64
p-value
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Sex Female Male
No
SC
Variable
8473(16.2) 1927(3.68) 531(1.01) 3266(6.23) 3588(6.84) 1341(2.56)
