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Outcomes of ACL Reconstruction in Patients with Diabetes

BROPHY, ROBERT H.; HUSTON, LAURA J.; WRIGHT, RICK W.; NWOSU, SAMUEL K.; KAEDING, CHRISTOPHER C.; PARKER, RICHARD D.; ANDRISH, JACK T.; MARX, ROBERT G.; MCCARTY, ERIC C.; AMENDOLA, ANNUNZIATO; WOLF, BRIAN R.; DUNN, WARREN R.; WOLCOTT, MICHELLE L.; SPINDLER, KURT P.

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Medicine & Science in Sports & Exercise: June 2016 - Volume 48 - Issue 6 - p 969-973
doi: 10.1249/MSS.0000000000000876
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Abstract

Diabetes mellitus is a significant and growing concern in the United States and around the world. A prevalence of 7.3% among adults in the United States noted in the early 2000s (20) had increased to 11.3% by 2011 (2). In adults, over 90% have type 2 diabetes (6), characterized by resistance to insulin and defects in insulin secretion, caused by a combination of genetic and environmental factors. However, most pediatric and adolescent patients have type 1 diabetes (9), which is caused by loss of insulin production, usually due to an autoimmune process, which can occur at any age but usually occurs before the age of 30 yr. Between 2001 and 2009, the prevalence of type 1 diabetes in children and adolescents increased 21.1%, whereas the prevalence of type 2 diabetes in the same population increased 30.5% (9).

Physical activity is important for disease management in patients with type 1 diabetes (23), and a recent study demonstrated that physical activity modifies the risk of first acute myocardial infarction in these patients (19). Furthermore, physical activity is protective against the development of type 2 diabetes (15). Active individuals are at risk for injury of the anterior cruciate ligament (ACL) in the knee, which is often treated with surgical reconstruction to facilitate maintenance of physical activity. However, studies have demonstrated that the activity level decreases significantly at 2 yr after ACL reconstruction (ACLR) (11), with even further decline at the 6-yr follow-up (28).

Although diabetes and hyperglycemia are estimated to occur in 5%–30% of all types of patients admitted to the hospital (29), there are limited data on the prevalence of diabetes in outpatient orthopedic surgery (24). On the basis of two recent studies, the prevalence of diabetes in patients undergoing ACLR appears to be approximately 1% (4,21). Patients with diabetes undergoing ACLR are likely to have type 1 diabetes, particularly among adolescent and young adult patients, although some young, and more likely mature, patients may have type 2 diabetes. Although a recent study demonstrated that diabetes is associated with a higher risk of infection after ACLR (4), there are no data on whether diabetes influences other outcomes in patients undergoing ACLR. In addition to influencing the risk of infection, diabetes could also affect the risk of additional surgery in a number of other ways, such as risk for manipulation due to stiffness or revision due to compromised healing rates, as well as clinical outcomes. The purpose of this study was to test the hypotheses that diabetes is associated with (a) the patient-reported outcome, specifically the activity level, at 2 yr after ACLR, and (b) the risk of subsequent surgery 2 yr after ACLR.

METHODS

With Institutional Review Board approval, we reviewed patients who had been initially enrolled in our prospective longitudinal cohort between 2002 and 2005. After obtaining written informed consent, patients completed a questionnaire including but not limited to a series of validated patient-reported outcome measures (Knee Injury and Osteoarthritis Outcome Score (KOOS) [26], International Knee Documentation Committee (IKDC) subjective knee form [13], and the Marx activity rating scale [17]) and general health information before their surgery. Patients who self-reported diabetes on the basis of comorbidity questions within the questionnaire before surgery were identified from the database.

Twenty-three of 2198 ACLR patients (1.0%) self-reported diabetes at the time of their ACLR. In order to confirm the accuracy of the diagnosis, the medical records from these patients with accessible information were reviewed. Twenty-two of our 23 patients identified in the database as having a diagnosis of diabetes were confirmed to have the disease at the time of ACLR, whereas one patient had no information available within their medical record that could either confirm or deny this self-reported diagnosis.

The main outcome measures of interest were 2-yr IKDC, KOOS subscales (symptoms, pain, activity of daily living, sports/recreation, knee-related quality of life), Marx activity level outcome scores, subsequent surgery on the ipsilateral knee, and subsequent surgery on the contralateral knee. In this study, we defined “subsequent surgery” to include any revision ACLR (on the ipsilateral knee); primary ACLR (on the contralateral knee); arthroscopic procedure involving meniscal cartilage, articular cartilage, hardware removal, arthrofibrosis, or infection; or total knee arthroplasty procedure. Given a previous study demonstrating a higher risk of infection after ACLR in patients with diabetes (4), we also reported the rate of subsequent surgery excluding infection on the ipsilateral knee.

Patient-specific covariates that were evaluated in our model included age, sex, body mass index (BMI), smoking status, diagnosis of diabetes, reconstruction type (primary or revision ACLR), graft type (bone–tendon–bone autograft, hamstring autograft, or “other,” which included all allografts, as well as any autograft + allograft combination), and baseline IKDC, KOOS, and Marx activity scores.

To describe our patient sample, we summarized categorical variables with frequencies and percentages and continuous variables with their median and interquartile range. To examine evidence for unadjusted associations with diabetes status, we used the Pearson chi-square test for categorical variables and the Wilcoxon test for continuous variables.

We used multivariable regression analyses to characterize the independent (adjusted) associations between the baseline risk factors and the dependent outcome variables of subsequent surgery (both ipsilateral and contralateral) and the clinical outcome scores after ACLR (IKDC, KOOS, and Marx scores). For the binary outcome measures (subsequent surgery of ipsilateral and contralateral knees, yes/no) multivariable logistic regression models were fit, and for the ordinal continuous outcome measures (IKDC, KOOS, and Marx scores), proportional odds regression models were fit. When fitting the multivariable models, the estimates for the continuous variable effects were reported on a linear scale; we thus interpret the odds of the outcome per one unit change in each of the patients’ continuous characteristics. For each model, the associated regression parameter estimates were exponentiated to obtain OR along with their 95% CI. To avoid casewise deletion of records with missing covariates, we used multiple imputation via predictive mean matching. Statistical analysis was performed using open-source R statistical software (www.cran.r-project.org).

RESULTS

The only significant difference in baseline demographics between patients with diabetes and those without was the KOOS pain subscale (Table 1). There were trends toward more males, higher BMI, and lower baseline activity among patients with diabetes. The overall follow-up rate for the entire cohort was 1905/2198 (87%) for patient-reported outcomes and 2096/2198 (95%) for subsequent surgery information. Among patients with diabetes (n = 23), there was 100% follow-up for patient-reported outcomes and subsequent surgeries. Among the patients without diabetes, there was 87% (1882/2175) follow-up for patient-reported outcomes and 96% (2073/2175) follow-up for subsequent surgeries.

TABLE 1
TABLE 1:
Baseline patient characteristics between groups.

Patient-reported outcome measures.

At 2 yr after ACLR, univariate results indicate that patients with diabetes have a higher Marx activity level but lower (poorer) IKDC and KOOS pain, activities of daily living (ADL), and sports/recreation outcomes scores (Table 2). Using our multivariable modeling to control for our independent variables of interest, we found that diabetes was a significant positive influence on 2-yr Marx activity scores but was a negative influence on 2-yr IKDC, KOOS pain, ADL, and sports/recreation subscores (Table 3).

TABLE 2
TABLE 2:
Median (25%, 75% quartile) outcome scores between groups at 2 yr.
TABLE 3
TABLE 3:
Modeling estimates at 2 yr (diabetic cohort only).

For example, on the basis of our adjusted regression analysis, patients with diabetes in our study were approximately three times more likely (OR = 2.96; 95% CI, 1.30–6.77) to have a higher Marx activity level score than a nondiabetic patient at 2 yr post-ACL surgery. Patients with diabetes were more likely to have significantly worse IKDC and KOOS pain, ADL, and sports/recreation subscale scores compared with nondiabetic patients. For instance, at 2 yr post-ACL surgery, patients with diabetes were associated with a 53% decrease (OR = 0.47; 95% CI, 0.23–0.98) in the odds of a higher IKDC score; a 56% decrease (OR = 0.44; 95% CI, 0.21–0.90) in the odds of a higher KOOS pain score; a 58% decrease (OR = 0.42; 95% CI, 0.19–0.93) in the odds of a higher KOOS ADL score; and a 56% decrease (OR = 0.44; 95% CI, 0.22–0.88) in the odds of a higher KOOS sports/recreation score.

Incidence of subsequent surgery.

Among the patients with diabetes, 21.7% (5/23) underwent additional surgery on the ipsilateral knee (13% excluding surgical treatment of infection) and 8.7% (2/23) underwent surgery on the contralateral knee (Table 4). The rate of additional surgery in patients without diabetes was 15.4% (319/2073) on the ipsilateral knee (14.7% excluding surgical treatment of infection) and 6.2% (129/2069) on the contralateral knee. The multivariable model indicated no significant differences between the two groups in terms of additional surgery on the ipsilateral or contralateral knee.

TABLE 4
TABLE 4:
Number (%) of subsequent ipsilateral and contralateral surgeries between groups.

DISCUSSION

Patients with diabetes maintain a higher level of activity after ACLR than patients without diabetes, despite having slightly worse patient-reported outcomes. A history of diabetes does not increase the risk of overall additional surgery on the ipsilateral or contralateral limb after ACLR, despite an increased risk of surgical treatment for postoperative infection (4).

It is clinically relevant that these patients maintain a higher activity level after ACLR, considering the importance of physical activity for glycemic control and overall health in patients with diabetes. Although it is not clear what would happen to the activity level in patients with diabetes if they did not undergo ACLR, the conventional wisdom is that the activity level decreases in patients with ACL tears who do not undergo ACLR. This suggests that ACLR has a tangible health benefit for patients with diabetes, i.e., keeping them active. Why patients with diabetes have a higher activity level after ACLR than patients without diabetes is not clear. Most likely, it reflects the motivation of patients with diabetes to stay active as part of their disease management. In studies investigating return to play after ACLR in football (18) and soccer (3) players, athletes were more likely to cite life changes, such as graduation, employment, or starting a family, as the main reason for not returning to sport rather than the injury itself. Patients with diabetes may be more motivated to maintain their activity in the face of these life changes.

Another notable finding is that patients with diabetes do not have an overall higher risk of subsequent surgery after ACLR compared with patients without diabetes, even though patients with diabetes do have a higher risk for infection after ACLR (4). In a previous study, the likelihood of infection after ACLR increased 18.8-fold in patients with diabetes compared with patients without diabetes (4). Although patients with diabetes undergoing ACLR should be made aware of their increased risk for infection, they can also be reassured that they do not face an elevated risk of overall subsequent surgery, such as revision ACLR or debridement/manipulation for loss of motion.

Short-term patient-reported outcomes after ACLR are slightly worse in patients with diabetes. It is important to note that the decrement in KOOS pain (−3) and ADL (−6) scores for patients with diabetes does not exceed the minimal clinically important difference for the KOOS instrument of 8–10 points (12,17,25,26). In contrast to the decreased KOOS and IKDC scores, patients with diabetes have a higher level of activity after ACLR. However, the minimal clinically important difference for the Marx activity scale has not been established to date (27).

Other studies have shown worse outcomes after other types of orthopedic surgery in patients with diabetes. Diabetes has been associated with a higher rate of complications after lumbar fusion (5,12), total knee arthroplasty (14,30), and total shoulder replacement (22). Uncontrolled diabetes has been shown to be particularly devastating after total joint arthroplasty (16), although a recent study did not find an association between diabetes, both controlled and uncontrolled, and complications after total knee replacement (1). Diabetes has been shown to be associated with less range of motion and worse clinical outcomes after arthroscopic rotator cuff repair (8,10), as well as a lower health-related quality of life (7), similar to our findings in ACLR patients.

Although this cohort is prospective, relatively large, and collected at several centers, which improves generalizability, our study is limited by the self-reporting of diabetes within the comorbidity section of the questionnaire. Although we confirmed that those who reported diabetes do in fact have the disease, it is possible that we are underreporting if some patients did not know they have diabetes. Screening for diabetes is not currently the standard of care before ACLR. Furthermore, we do not have data on glycemic control, which has been shown to be an important variable affecting infection risk after other knee surgeries (16). The study also lacks direct physical examination measures of outcome such as stability and knee range of motion. Range of motion could be particularly important because diabetes is associated with tendon stiffness. However, the lack of physical examination should not influence the incidence of subsequent surgery, nor the 2-yr clinical outcome measurements. Finally, the relatively small sample of patients with diabetes may be underpowered to pick up relevant differences in baseline demographics or patient-reported outcomes. The wide CI values in the reported OR reflect the limitations of the small sample size. There is the risk of Type II error, particularly for events such as subsequent surgery. Nevertheless, this study did find statistically significant differences between patients with and without diabetes that are likely to be clinically relevant. Other differences may exist as well, and further study of this area with larger datasets is likely warranted.

Despite these limitations, this is the first study to look at the effect of diabetes on outcomes after ACLR. These patients maintain a higher activity level after ACLR than patients without diabetes despite lower patient-reported outcomes, although the decrement in outcomes may not be clinically significant. Diabetes is not associated with a higher risk for subsequent surgery overall even with an increased risk of surgical washout for infection (4). Although patients with diabetes should be counseled about their increased risk of infection and slightly worse clinical outcomes, ACLR can be an appropriate treatment for symptomatic ACL tears in this population, particularly given the potential to maintain a higher level of physical activity, which is an integral component of disease management and health optimization for these patients.

The authors thank the research coordinators, analysts, and support staff from the Multicenter Orthopaedic Outcomes Network (MOON) knee sites (Cleveland Clinic, Cleveland, OH; Vanderbilt University Medical Center, Nashville, TN; The Ohio State University, Columbus, OH; University of Iowa, Iowa City, IA; Washington University in St. Louis, St. Louis, MO; Hospital for Special Surgery, New York, NY; and University of Colorado, Denver, CO), whose efforts related to regulatory, data collection, subject follow-up, data quality control, analyses, and manuscript preparation make this consortium possible. We also thank all the subjects who generously enrolled and participated in this study.

Research reported in this publication was partially supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health under Award Number R01AR053684 (K. P. Spindler). The content is solely the responsibility of the authors and do not necessarily represent official views of the National Institutes of Health. The project was also partially supported by the Orthopaedic Research and Education Foundation and the Vanderbilt Sports Medicine Research Fund, which received unrestricted educational gifts from Smith and Nephew Endoscopy and DonJoy Orthopaedics.

R. H. B. developed the study concept and design. R. H. B., R. W. W., C. C. K., R. D. P., J. T. A., R. G. M., E. C. M., A. A., B. R. W., W. R. D., M. L. W., and K. P. S. acquired the data. R. H. B., L. J. H., and S. K. N. analyzed and interpreted the data. R. H. B. and L. J. H. drafted the manuscript. R. H. B., L. J. H., R. W. W., S. K. N., C. C. K., R. D. P., J. T. A., R. G. M., E. C. M., A. A., B. R. W., W. R. D., M. L. W., and K. P. S. critically revised the manuscript for important intellectual content. S. K. N. performed the statistical analysis. K. P. S. obtained funding. R. H. B. and L. J. H. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

No potential conflicts of interest relevant to this article were reported. The results of this study do not constitute endorsement by the American College of Sports Medicine.

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Keywords:

ANTERIOR CRUCIATE LIGAMENT; PATIENT-REPORTED OUTCOMES; ACTIVITY LEVEL; KNEE INSTABILITY

© 2016 American College of Sports Medicine