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    Topic review

    Diabetes on Cervical Spine Surgery

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    Submitted by: Atsushi Kimura

    Definition

    Ossification of the posterior longitudinal ligament (OPLL) is a multifactorial disease that develops under complex genetic and environmental conditions. The ectopic ossification causes chronic compression of the spinal cord, which leads to neurological dysfunction below the level of compression. Although the prevalence of OPLL in the general population is relatively low, ranging from 0.1 to 2.5% in the United States and 1.9 to 4.3% in Japan , OPLL accounts for 18 to 35% as an etiology of degenerative cervical myelopathy (DCM), which requires surgical treatment. Thus, OPLL is a major etiology of DCM, irrespective of race or region.
    OPLL is associated with an increased prevalence of diabetes mellitus (DM). The prevalence of DM in patients with OPLL is 27% in the United States . DM increases the prevalence of comorbidities, such as obesity, hypertension, common infections, and systemic vascular diseases, thereby exerting a negative impact on spinal surgeries. Several studies have investigated the impact of DM on surgical outcomes in patients undergoing surgical treatment for cervical spondylotic myelopathy (CSM) or DCM (CSM and OPLL). Despite the high prevalence of DM in patients with OPLL, only a few retrospective case series have analyzed DM as a prognostic factor for the surgical management of cervical OPLL.

    1. Introduction

    Ossification of the posterior longitudinal ligament (OPLL) is commonly associated with diabetes mellitus (DM); however, the impact of DM on cervical spine surgery for OPLL remains unclear. This study was performed to evaluate the influence of diabetes DM on the outcomes following cervical spine surgery for OPLL. In total, 478 patients with cervical OPLL who underwent surgical treatment were prospectively recruited from April 2015 to July 2017. Functional measurements were conducted at baseline and at 6 months, 1 year, and 2 years after surgery using JOA and JOACMEQ scores. The incidence of postoperative complications was categorized into early (≤30 days) and late (>30 days), depending on the time from surgery. From the initial group of 478 patients, 402 completed the 2-year follow-up and were included in the analysis. Of the 402 patients, 127 (32%) had DM as a comorbid disease. The overall incidence of postoperative complications was significantly higher in patients with DM than in patients without DM in both the early and late postoperative periods. The patients with DM had a significantly lower JOA score and JOACMEQ scores in the domains of lower extremity function and quality of life than those without DM at the 2-year follow-up.

    2. Analysis on Results

    2.1. Patients’ Characteristics and Baseline Functions

    From the initial group of 478 participants, 402 completed the 2-year follow-up (follow-up rate: 84%) and were included in the analysis. Of the 402 patients, 127 (32%) had DM as a comorbid disease. The 127 patients with DM comprised 123 patients with non-insulin-dependent DM and 4 patients with insulin-dependent DM. The comparisons of patients’ demographics and baseline functions between patients with and without DM are summarized in Table 1. The patients with DM had a significantly higher body mass index (BMI) and rates of hypertension, myocardial infarction, and anticoagulant/antiplatelet medication than those without DM. Additionally, the patients with DM had significantly inferior lower extremity function measured using the JOACMEQ and significantly higher visual analog scale scores for neck pain than those without DM. Regarding surgical methods, the patients with DM had a significantly higher rate of PDF and a significantly higher number of surgical levels than those without DM.
    Table 1. Patients’ characteristics and baseline functions.
    Characteristics With DM (N = 127) Without DM (N = 275) p Value *
    Age 64.2 ± 11.0 64.0 ± 11.9 0.743
    Gender (Male/Female) 90/37 208/67 0.328
    BMI 26.5 ± 4.5 25.3 ± 4.3 0.006
    Medical comorbidities      
    Hypertension 59 (46) 94 (34) 0.021
    Cerebral infarction 11 (9) 10 (4) 0.051
    Myocardial infarction 8 (6) 6 (2) 0.044
    Musculoskeletal disease 18(14) 31 (11) 0.416
    Connective tissue disease 1 (0.8) 3 (1.1) 1.000
    Anticoagulant/antiplatelet medication 26 (20) 34 (12) 0.049
    Duration of symptoms (month) 46.7 ± 62.3 41.4 ± 66.0 0.189
    JOA score 10.5 ± 2.6 10.7 ± 3.0 0.341
    JOACMEQ      
    Cervical spine 60.8 ± 31.2 61.5 ± 28.7 0.944
    Upper extremity 68.8 ± 25.2 72.6± 24.3 0.126
    Lower extremity 52.4 ± 29.4 59.4 ± 29.4 0.019
    Bladder 71.5 ± 23.6 72.9 ± 22.2 0.430
    QOL 42.5 ± 19.8 44.4 ± 18.3 0.179
    Neck pain VAS 47.6 ± 32.3 39.8 ± 30.7 0.035
    Imaging finding      
    C2-C7 Cobb angle (degree) 8.6 ± 12.9 10.1 ± 10.5 0.258
    Range of motion (degree) 24.7 ± 12.4 28.1 ± 14.4 0.051
    Occupancy ratio of OPLL (%) 45.7 ± 15.6 43.3 ± 15.3 0.173
    K-line (−) 42 (33) 93 (34) 0.883
    Surgical method      
    ADF 21 (17) 68 (25) 0.071
    PDF 39 (31) 52 (19) 0.010
    LP 63 (50) 148 (54) 0.453
    APF 4 (3) 7 (3) 0.748
    No. of surgical levels 4 (3–5) 4 (3–4) 0.029
    Data are shown as mean ± standard deviation, number (%), or median (25–75th percentile). * p values were calculated using the unpaired t-test for means, Fisher’s exact test for proportions, or the Wilcoxon signed rank test for medians. DM, diabetes mellitus; BMI, body mass index; JOA, Japanese Orthopedic Association; JOACMEQ, Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire; QOL, quality of life; VAS, visual analog scale; OPLL, ossification of the posterior longitudinal ligament; ADF, anterior decompression and fusion; PDF, posterior decompression and fusion; LP, laminoplasty; APF, combined anterior and posterior fusion.
     

     

    2.2. Postoperative Complications

    The incidence of postoperative complications is shown in Table 2. Each early complication showed no significant difference between the groups, except urinary tract infection; however, the overall incidence of early complications was significantly higher in the patients with DM than in the patients without DM. Similarly, the overall incidence of late complications was significantly higher in the patients with DM than in the patients without DM.
    Table 2. Incidence of early and late postoperative complications.
    Complication With DM (N = 127) Without DM (N = 275) p Value *
    Early (≤30 days from surgery)      
    Neurological deterioration 12 (9) 30 (11) 0.727
    CSF leakage 6 (5) 14 (5) 1.000
    Dysphasia 3 (2) 8 (3) 1.000
    Graft bone failure 3 (2) 5 (2) 0.712
    Instrument failure 2 (1.6) 5 (2) 1.000
    Wound infection 2 (1.6) 4 (1.5) 1.000
    Wound dehiscence 2 (1.6) 2 (0.7) 0.594
    Epidural hematoma 1 (0.8) 1 (0.4) 0.533
    Upper air way obstruction 1 (0.8) 1 (0.4) 0.533
    Urinary tract infection 6 (5) 3 (1) 0.031
    Delirium 4 (3) 5 (2) 0.472
    Deep vein thrombosis 1 (0.8) 2 (0.7) 1.000
    Gastrointestinal bleeding 0 (0) 3 (1) 0.555
    Heart failure 1 (0.8) 1 (0.4) 0.533
    Liver dysfunction 1 (0.8) 1 (0.4) 0.533
    Brain infarction 0 (0) 1 (0.4) 1.000
    Pneumonia 0 (0) 1 (0.4) 1.000
    Cholecystitis 1 (0.8) 0 (0) 0.316
    Any early complications 43 (34) 66 (24) 0.041
    Late (>30 days from surgery)      
    Instrument failure 6 (5) 5 (2) 0.109
    Lumbar spinal stenosis 3 (2) 8 (3) 1.000
    Adjacent segment disease 2 (1.6) 1 (0.4) 0.236
    Thoracic OPLL 1 (0.8) 1 (0.4) 0.533
    C5 palsy 1 (0.8) 1 (0.4) 0.528
    Non-union 0 (0) 2 (0.7) 1.000
    Wound infection 0 (0) 2 (0.7) 1.000
    Dysphasia 2 (1.6) 0 (0) 0.099
    Stroke 2 (1.6) 0 (0) 0.099
    Urinary tract infection 2 (1.6) 1 (0.4) 0.236
    Pneumonia 2 (1.6) 0 (0) 0.099
    Parkinson’s disease 0 (0) 2 (0.7) 1.000
    Multiple sclerosis 0 (0) 1 (0.4) 1.000
    Any late complications 19 (15) 21 (8) 0.031
    Data are shown as number (%). * p values were calculated using Fisher’s exact test. DM, diabetes mellitus; CSF, cerebrospinal fluid; OPLL, ossification of the posterior longitudinal ligament; C5 palsy, 5th cervical spinal nerve palsy.

     

    2.3. Functional Outcomes

    The functional outcomes at the 2-year follow-up are presented in Table 3. The patients with DM had a significantly lower JOA score than those without DM. Furthermore, the patients with DM had significantly lower JOACMEQ scores in the domains of lower extremity function and QOL than the patients with DM. The comparisons of postoperative functional gain between the patients with and without DM are summarized in Table 4. The average postoperative gains of functional scores were consistently lower in the patients with DM than in those without DM; however, the difference did not reach statistical significance in any functional measures.
    Table 3. Comparisons of functional outcomes between patients with and without diabetes mellitus at the 2-year follow-up.
    Outcome With DM (N = 127) Without DM (N = 275) p Value *
    JOA score 13.1 ± 2.8 13.8 ± 2.5 0.024
    JOACMEQ      
    Cervical spine 60.7 ± 20.1 62.8 ± 32.1 0.389
    Upper extremity 77.9 ± 20.0 81.1 ± 19.5 0.105
    Lower extremity 61.0 ± 28.1 67.7 ± 28.1 0.026
    Bladder 75.1 ± 22.4 77.1 ± 21.3 0.369
    QOL 49.6 ± 18.7 54.1 ± 19.2 0.036
    Neck pain VAS 40.6 ± 31.1 36.0 ± 30.0 0.197
    Data are shown as mean ± standard deviation. * p values were calculated using the Mann–Whitney U test. DM, diabetes mellitus; JOA, Japanese Orthopedic Association; JOACMEQ, Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire; QOL, quality of life; VAS, visual analog scale.
     
    Table 4. Comparisons of postoperative functional gain between patients with and without diabetes mellitus.
    Outcome With DM (N = 127) Without DM (N = 275) p Value *
    Recovery rate of JOA score 40.8 ± 33.6 48.7 ± 32.5 0.051
    Postoperative gain in JOA score 2.6 ± 2.4 3.1 ± 2.5 0.151
    Postoperative gain in JOACMEQ      
    Cervical spine −3.1 ± 29.2 1.6 ± 34.1 0.230
    Upper extremity 6.4 ± 23.1 8.4 ± 22.1 0.251
    Lower extremity 6.2 ± 24.5 7.6 ± 24.2 0.826
    Bladder 0.9 ± 20.7 3.0 ± 19.8 0.639
    QOL 4.9 ± 16.7 9.3 ± 18.9 0.094
    Postoperative change in neck pain VAS −5.8 ± 32.6 −3.2 ± 33.7 0.625
    Data are shown as mean ± standard deviation. * p values were calculated using the Mann–Whitney U test. DM, diabetes mellitus; JOA, Japanese Orthopedic Association; JOACMEQ, Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire; QOL, quality of life; VAS, visual analog scale.

     

    2.4. Time-Dependent Change of Functional Outcomes

    The time-dependent change in the JOA score is shown in Figure 1. The average JOA score was consistently lower in the patients with DM than in the patients without DM during the observation period. The difference between the groups increased over time and reached statistical significance at the 2-year follow-up. Similarly, the average scores of the five JOACMEQ domains were lower in the patients with DM than in the patients without DM (Figure 2). The difference in lower extremity function was significant during the observation period, except for the 1-year follow-up (p = 0.056). The difference in upper extremity function showed statistical significance at the 6-month follow-up and returned to a comparable level at the 1-year follow-up or later. Similar to the change in the JOA score, the difference in the QOL domain of the JOACMEQ between the groups increased over time and reached statistical significance at the 2-year follow-up.
    Figure 1. Time-dependent change in the JOA score. The average JOA score was consistently lower in patients with than without DM during the observation period. The difference between the groups increased over time and reached statistical significance at the 2-year follow-up. * p < 0.05, unpaired t-test. JOA, Japanese Orthopedic Association; DM, diabetes mellitus.
    Figure 2. Time-dependent change in JOACMEQ scores. The difference in lower extremity function was significant during the observation period, except for the 1-year follow-up. The difference in upper extremity function showed statistical significance at the 6-month follow-up. The difference in the QOL domain between the groups increased over time and reached statistical significance at the 2-year follow-up. * p < 0.05, unpaired t-test. JOACMEQ, Japanese Orthopedic Association Cervical Myelopathy Evaluation Questionnaire; DM, diabetes mellitus; QOL, quality of life.

    2.5. Surgical Outcomes Stratified by Surgical Procedures

    Surgical outcomes were compared among the four surgical procedures (Table 5). The PDF group had a significantly lower preoperative JOA score than the LP group (p = 0.007, one-way ANOVA followed by Tukey’s post hoc test). The ADF group showed a significantly higher postoperative JOA score than the PDF group (p = 0.011, one-way ANOVA followed by Tukey’s post hoc test). However, the recovery rate of the JOA score showed no significant difference among the groups. The incidence of early postoperative complications was significantly higher in the ADF and PDF groups than in the LP group.
    Table 5. Comparisons of surgical outcomes stratified by surgical procedures.
      Surgical Procedure p Value
    ADF (N = 89) LP (N = 211) PDF (N = 91) APF (N = 11)
    No. of levels decompressed 3 4 5 4 <0.001 *
    No. of levels fused 3 N/A 5 4 <0.001 *
    Preoperative JOA score 10.9 ± 2.6 10.9 ± 2.7 9.7 ± 3.3 9.5 ± 3.2 0.002 *
    Postoperative JOA score 14.1 ± 2.4 13.7 ± 2.4 12.9 ± 3.1 12.7 ± 2.7 0.010 *
    Recovery rate of JOA score 53.1 ± 31.1 44.3 ± 33.7 44.9 ± 33.1 38.7 ± 30.4 0.157 *
    Early complication 34 (38) 38 (18) 34 (37) 3 (27) <0.001
    Late complication 12 (13) 15 (7) 13 (14) 0 (0) 0.067
    Data are shown as median, mean ± standard deviation, or number (%). * One-way analysis of variance. Chi-square test. ADF, anterior decompression and fusion; LP, laminoplasty; PDF, posterior decom-pression and fusion; APF, combined anterior and posterior fusion; JOA, Japanese Orthopedic Association.

     

    2.6. Surgical Outcomes Stratified by Treatment Modalities for DM

    Surgical outcomes were stratified into three groups based on the treatment modalities (Table 6). The preoperative HbA1c level differed significantly among the groups. The patients in the insulin therapy group had a significantly higher preoperative HbA1c level than the patients in the other groups (p < 0.001, one-way ANOVA followed by Tukey’s post hoc test). However, neither functional outcomes nor the incidence of postoperative complications showed significant differences among the groups.
    Table 6. Comparisons of surgical outcomes stratified by treatment modalities for diabetes mellitus.
      Treatment Modality p Value
    Dietary Control (N = 32) Oral Antidiabetics (N = 78) Insulin Therapy (N = 17)
    Preoperative HbA1c 6.7 ± 1.3 6.7 ± 0.8 7.7 ± 1.1 <0.001 *
    Preoperative JOA score 10.7 ± 3.3 10.5 ± 2.2 10.2 ± 3.1 0.788 *
    Postoperative JOA score 13.3 ± 3.5 13.1 ± 2.6 13.2 ± 2.7 0.917 *
    Recovery rate of JOA score 42.6 ± 29.0 38.6 ± 36.9 47.6 ± 25.3 0.576 *
    Early (≤30 days from surgery) complications 10 (31) 29 (38) 5 (24) 0.518
    Late (>30 days from surgery) complication 2 (6) 16 (21) 1 (6) 0.086
    Data are shown as mean ± standard deviation or number (%). * One-way analysis of variance. Chi-square test. HbA1c, glycated hemoglobin; JOA, Japanese Orthopedic Association.

     

    3. Discussion

    DM substantially increases the risk of developing systemic complications after surgical interventions through several pathological mechanisms. First, DM impairs the function of endothelial and vascular smooth muscle cells, which leads to systemic atherosclerosis and its complications, such as cardiac infarction, cerebral infarction, peripheral vascular diseases, nephropathy, and retinopathy [1]. Second, type 2 DM is associated with increased comorbid rates of obesity and hypertension, and the coexistence of these conditions further increases the risk of macrovascular and microvascular complications [2]. Finally, DM increases patients’ susceptibility to infections, such as lower respiratory tract infection, urinary tract infection, and skin and mucous membrane infection, because of the impaired innate and adaptive immune responses against invading pathogens [3]. Indeed, in this study, the patients with DM showed a significantly higher BMI and rate of hypertension, myocardial infarction, and anticoagulant/antiplatelet medication than those without DM at baseline. Furthermore, the patients with DM had a significantly higher incidence of urinary tract infection in the early postoperative period. These results indicate that patients with OPLL have an increased risk of systemic complications after surgery. Although we could not find statistical significance, except for urinary tract infection, the significantly higher overall incidence of complications may be attributed to various systemic comorbidities associated with DM.
    The impact of DM on surgical outcomes after spine surgery remains controversial. Armaghani et al. [4] demonstrated that DM is associated with worse patient-reported outcomes, such as the Neck Disability Index and EuroQOL-5 Dimensions, when patients with DM were compared with those without DM following elective cervical spine surgery. However, Arnold et al. [5] concluded that the outcomes of surgical decompression for CSM are similar in patients with and without DM, except for the 36-Item Short Form Health Survey Physical Functioning scores. More recently, Nori et al. [6] showed that patients with CSM who had DM experienced improvements in neurological function following posterior decompression to the same extent observed in those without DM. This study focused exclusively on patients with OPLL and showed comparable neurological improvements measured using both the JOA score and JOACMEQ scores between patients with and without DM, although the functional outcomes at the 2-year follow-up were significantly worse in patients with DM than in those without DM. The significantly worse functional outcomes at the endpoint were partly attributable to the significantly worse lower extremity function at baseline in patients with DM than in patients without DM. The significantly lower baseline physical function is consistent with that in past studies that demonstrate that older individuals with DM are associated with weaker muscle strength and a higher risk of impaired physical function than their age-matched counterparts without DM [7][8]. Furthermore, the significantly higher rate of medical comorbidities and the significantly higher incidence of postoperative complications in patients with DM may interfere with functional outcomes. Although most of the medical comorbidities and postoperative complications are not directly associated with neurological functions, poorer general health conditions might impair not only physical functions but also QOL. Indeed, patients with DM had a significantly lower score in the QOL domain of the JOACMEQ than patients without DM.
    A recent systematic review demonstrated that HbA1c is predictive for postoperative infection and functional outcomes in patients undergoing spine surgery and that an HbA1c level of >6.5 to 6.9% is associated with an increased risk of postoperative complications. However, in the present study, the preoperative HbA1c level showed no significant association with either functional outcomes or the incidence of postoperative complications. One possible explanation for this inconsistency may be the small number of patients with DM in the present study. Our sample size may be insufficient to detect the predictive value of HbA1c on surgical outcomes. Consistent with our results, Nagoshi et al. [9] recently showed no significant correlation between the preoperative HbA1c level and postoperative JOA score in 47 patients with concurrent OPLL and DM. Furthermore, some patients with a high preoperative HbA1c level received perioperative insulin therapy. Rigorous glycemic control during the perioperative period might reduce the risk of postoperative complications associated with poorly controlled DM, resulting in a reduced predictive accuracy of the preoperative HbA1c level. A further large-scale prospective study is required to clarify the predictive value of HbA1c and its optimal cut-off point to identify patients with an increased risk of postoperative complications.

    The entry is from 10.3390/jcm10153375

    References

    1. Creager, M.A.; Luscher, T.F.; Cosentino, F.; Beckman, J.A. Diabetes and vascular disease: Pathophysiology, clinical consequences, and medical therapy: Part I. Circulation 2003, 108, 1527–1532.
    2. Zanella, M.T.; Kohlmann, O., Jr.; Ribeiro, A.B. Treatment of obesity hypertension and diabetes syndrome. Hypertension 2001, 38 Pt 2, 705–708.
    3. Berbudi, A.; Rahmadika, N.; Tjahjadi, A.I.; Ruslami, R. Type 2 Diabetes and its Impact on the Immune System. Curr. Diabetes Rev. 2020, 16, 442–449.
    4. Armaghani, S.J.; Archer, K.R.; Rolfe, R.; Demaio, D.N.; Devin, C.J. Diabetes Is Related to Worse Patient-Reported Outcomes at Two Years Following Spine Surgery. J. Bone Jt. Surg. Am. 2016, 98, 15–22.
    5. Arnold, P.M.; Fehlings, M.G.; Kopjar, B.; Yoon, S.T.; Massicotte, E.M.; Vaccaro, A.R.; Brodke, D.S.; Shaffrey, C.I.; Smith, J.S.; Woodard, E.J.; et al. Mild diabetes is not a contraindication for surgical decompression in cervical spondylotic myelopathy: Results of the AOSpine North America multicenter prospective study (CSM). Spine J. 2014, 14, 65–72.
    6. Nori, S.; Nagoshi, N.; Yoshioka, K.; Nojiri, K.; Takahashi, Y.; Fukuda, K.; Ikegami, T.; Yoshida, H.; Iga, T.; Tsuji, O.; et al. Diabetes Does Not Adversely Affect Neurological Recovery and Reduction of Neck Pain After Posterior Decompression Surgery for Cervical Spondylotic Myelopathy: Results from a Retrospective Multicenter Study of 675 Patients. Spine 2020, 46, 433–439.
    7. Sayer, A.A.; Dennison, E.M.; Syddall, H.E.; Gilbody, H.J.; Phillips, D.I.; Cooper, C. Type 2 diabetes, muscle strength, and impaired physical function: The tip of the iceberg? Diabetes Care 2005, 28, 2541–2542.
    8. Wong, E.; Backholer, K.; Gearon, E.; Harding, J.; Freak-Poli, R.; Stevenson, C.; Peeters, A. Diabetes and risk of physical disability in adults: A systematic review and meta-analysis. Lancet Diabetes Endocrinol. 2013, 1, 106–114.
    9. Nagoshi, N.; Watanabe, K.; Nakamura, M.; Matsumoto, M.; Li, N.; Ma, S.; He, D.; Tian, W.; Jeon, H.; Lee, J.J.; et al. Does Diabetes Affect the Surgical Outcomes in Cases With Cervical Ossification of the Posterior Longitudinal Ligament? A Multicenter Study from Asia Pacific Spine Study Group. Glob. Spine J. 2021.
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