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Commentary and Perspective   |    
A Spoonful of SugarCommentary on an article by Annette L. Adams, PhD, MPH, et al.: “Surgical Outcomes of Total Knee Replacement According to Diabetes Status and Glycemic Control, 2001 to 2009”
Paul Manner, MD1
1 University of Washington, Seattle, Washington
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This article was chosen to appear electronically on February 27, 2013, in advance of publication in a regularly scheduled issue.



Disclosure: The author received no payments or services, either directly or indirectly (i.e., via his institution), from a third party in support of any aspect of this work. Neither the author nor his institution has had any financial relationship, in the thirty-six months prior to submission of this work, with any entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. Also, the author has not had any other relationships, or engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

Copyright © 2013 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2013 Mar 20;95(6):e37 1-2. doi: 10.2106/JBJS.L.01559
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Nine years of data from Kaiser Permanente’s arthroplasty registry are reviewed in the study by Adams et al. The authors report on the relative risk of complications in patients with diabetes, and they also differentiate between patients with well-controlled and poorly controlled hyperglycemia. In brief, the authors assessed all patients undergoing primary total knee arthroplasty and categorized them according to glycemic status. They then examined postoperative surgical outcomes, including the need for revision, deep infection, and venous thromboembolic disease, as well as incident myocardial infarction and all-cause rehospitalization. With the exception of thromboembolic disease, one year of follow-up was used.
The study cohort included 40,491 patients; 81.3% were identified as not having had diabetes mellitus prior to the index surgery, 12.5% as having had controlled diabetes (hemoglobin [Hb] A1c level of <7.0%), and 6.2% as having had uncontrolled diabetes (HbA1c level of ≥7.0%). Within one year, 10,969 patients or 27.1% were rehospitalized for any reason, 1.1% or 464 required revision, 0.7% developed a deep infection, and 1.0% developed a myocardial infarction. When adjusted for age, sex, body mass index, and comorbidity score, there was no evidence of increased risks due to diabetes. Interestingly, glycemic control made no apparent difference—patients with an HbA1c level of 7.0% (considered the cutoff for adequate control) or more did as well as those with a lower value.
Diabetes is typically considered a predictor for perioperative complications, and there is no shortage of studies associating the presence of diabetes with increased surgical risk. Much work, both in the orthopaedic literature and in the surgical literature as a whole, has been reported on the establishment of appropriate parameters for blood sugar control1-5.
At about the time that Adams et al. began their observations, in 2001, van den Berghe et al. published a study on intensive insulin therapy in a surgical intensive care unit; they demonstrated dramatic improvements in mortality associated with a target blood glucose range of 80 to 110 mg/dL6. That study, cited throughout the surgical literature, resulted in substantial changes in perioperative practice. For example, current guidelines by the Surgical Care Improvement Project for cardiac surgery include aggressive glycemic control. Since 2001, however, failure to duplicate the findings of van den Berghe et al. and increased rates of hypoglycemia have challenged this paradigm7. In a recent review, Lipshutz and Gropper noted that “while avoidance of hyperglycemia is clearly beneficial, the appropriate glucose target and specific subpopulations who might benefit…have yet to be identified.”8
Why did Adams et al. not find that tighter glycemic control was beneficial? A few points can be noted. First, the diabetic patients differed from the nondiabetic patients in that they were more likely to be male, obese, and have additional comorbidity. Second, patients with uncontrolled diabetes were relatively uncommon—perhaps the truly sick patients simply never appeared in the operating room and were thus never counted! Third, the outcomes assessed were also uncommon, and the observation period may not have been long enough to capture all untoward events.
Furthermore, Adams et al. were unable to capture what was done in the hospital for individual patients. For example, despite a lack of evidence of efficacy, the use of an insulin sliding scale is embedded in standard perioperative practice, and this typically results in persistent hyperglycemia9. Coordinating appropriate meals, accurate glucose monitoring, and timely insulin delivery is a daunting task, even in a unified system such as that of Kaiser Permanente, the authors’ home institution.
What conclusion can be drawn from this study? A finding of preoperative hyperglycemia may simply be a marker for worse overall health, in the same way that an elevated ESR (erythrocyte sedimentation rate) represents a marker for nonspecific inflammation. Seen in this light, it makes sense that attacking the hyperglycemia in isolation matters little; we would not consider our work complete if we simply brought the ESR down to acceptable limits in a patient with inflammatory disease! If this is the case, the good results seen with the two diabetic patient groups may reflect the heightened awareness of overall disease burden, including diabetes, with the Kaiser Permanente system devoting more resources to managing these patients.
Finally, Adams et al. are to be commended for avoiding the “file drawer effect,” in which investigators lose interest or fail to write up their findings. A study that supports the null hypothesis is just as valuable as one that demonstrates a positive finding. In this case, Adams et al. show that the diabetic patient is not doomed to a poor result, assuming that prudent care is provided.
Bolognesi  MP;  Marchant  MH  Jr;  Viens  NA;  Cook  C;  Pietrobon  R;  Vail  TP. The impact of diabetes on perioperative patient outcomes after total hip and total knee arthroplasty in the United States. J Arthroplasty.  2008 Sep;23  (6)(Suppl 1):92-8.[CrossRef]
 
Rizvi  AA;  Chillag  SA;  Chillag  KJ. Perioperative management of diabetes and hyperglycemia in patients undergoing orthopaedic surgery. J Am Acad Orthop Surg.  2010 Jul;18(  7):426-35.
 
American Diabetes Association. Executive summary: standards of medical care in diabetes—2012. Diabetes Care.  2012 Jan;35  (35)(Suppl 1):S4-10.[CrossRef]
 
Ata  A;  Lee  J;  Bestle  SL;  Desemone  J;  Stain  SC. Postoperative hyperglycemia and surgical site infection in general surgery patients. Arch Surg.  2010 Sep;145(  9):858-64.[CrossRef]
 
Jämsen  E;  Nevalainen  P;  Kalliovalkama  J;  Moilanen  T. Preoperative hyperglycemia predicts infected total knee replacement. Eur J Intern Med.  2010 Jun;21(  3):196-201.[CrossRef]
 
van den Berghe  G;  Wouters  P;  Weekers  F;  Verwaest  C;  Bruyninckx  F;  Schetz  M;  Vlasselaers  D;  Ferdinande  P;  Lauwers  P;  Bouillon  R. Intensive insulin therapy in critically ill patients. N Engl J Med.  2001 Nov 8;345(  19):1359-67.[CrossRef]
 
McDonnell  ME;  Alexanian  SM;  Junqueira  A;  Cabral  H;  Lazar  HL. Relevance of the Surgical Care Improvement Project on glycemic control in patients undergoing cardiac surgery who receive continuous insulin infusions. J Thorac Cardiovasc Surg.  2012 Oct 9.  [Epub ahead of print].
 
Lipshutz  AK;  Gropper  MA. Perioperative glycemic control: an evidence-based review. Anesthesiology.  2009 Feb;110(  2):408-21.
 
Yalla  NM;  Reynolds  LR. Inpatient glycemic control: an evolving paradigm. Postgrad Med.  2009 May;121(  3):26-32.[CrossRef]
 

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References

Bolognesi  MP;  Marchant  MH  Jr;  Viens  NA;  Cook  C;  Pietrobon  R;  Vail  TP. The impact of diabetes on perioperative patient outcomes after total hip and total knee arthroplasty in the United States. J Arthroplasty.  2008 Sep;23  (6)(Suppl 1):92-8.[CrossRef]
 
Rizvi  AA;  Chillag  SA;  Chillag  KJ. Perioperative management of diabetes and hyperglycemia in patients undergoing orthopaedic surgery. J Am Acad Orthop Surg.  2010 Jul;18(  7):426-35.
 
American Diabetes Association. Executive summary: standards of medical care in diabetes—2012. Diabetes Care.  2012 Jan;35  (35)(Suppl 1):S4-10.[CrossRef]
 
Ata  A;  Lee  J;  Bestle  SL;  Desemone  J;  Stain  SC. Postoperative hyperglycemia and surgical site infection in general surgery patients. Arch Surg.  2010 Sep;145(  9):858-64.[CrossRef]
 
Jämsen  E;  Nevalainen  P;  Kalliovalkama  J;  Moilanen  T. Preoperative hyperglycemia predicts infected total knee replacement. Eur J Intern Med.  2010 Jun;21(  3):196-201.[CrossRef]
 
van den Berghe  G;  Wouters  P;  Weekers  F;  Verwaest  C;  Bruyninckx  F;  Schetz  M;  Vlasselaers  D;  Ferdinande  P;  Lauwers  P;  Bouillon  R. Intensive insulin therapy in critically ill patients. N Engl J Med.  2001 Nov 8;345(  19):1359-67.[CrossRef]
 
McDonnell  ME;  Alexanian  SM;  Junqueira  A;  Cabral  H;  Lazar  HL. Relevance of the Surgical Care Improvement Project on glycemic control in patients undergoing cardiac surgery who receive continuous insulin infusions. J Thorac Cardiovasc Surg.  2012 Oct 9.  [Epub ahead of print].
 
Lipshutz  AK;  Gropper  MA. Perioperative glycemic control: an evidence-based review. Anesthesiology.  2009 Feb;110(  2):408-21.
 
Yalla  NM;  Reynolds  LR. Inpatient glycemic control: an evolving paradigm. Postgrad Med.  2009 May;121(  3):26-32.[CrossRef]
 
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Stefano Bini, Annette Adams, Robert Namba
Posted on March 11, 2013
Clarification
Kaiser Permanente

We thank Dr Manner for his balanced and thoughtful review of our paper. As he points out, there are no shortages of studies looking at surgical risk and diabetes. The majority of these papers, however, focus on acute peri-operative glycemic control. The question we were trying to answer is whether chronically poor glycemic control in the months prior to joint replacement has a measurable impact on outcomes following surgery. As HgA1C measurements reflect a patient's glycemic control over the preceding 3 months, we chose to use this metric as our referent value. In so doing, we were unable to document that glycemic control in the months prior to surgery affects surgical outcomes as defined in our paper. Differently stated, and taking the existing literature on the benefits of peri-operative glycemic control into account, it would appear that euglycemia is most relevant to outcomes when managed in the immediate peri-operative period. Therefore, patients with historically uncontrolled diabetes may not be at higher risk than their historically better controlled counterparts if their blood sugar levels are closely monitored before and after surgery.

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