1900 COPYRIGHT Ó 2017 BY THE JOURNAL OF BONE AND JOINT SURGERY,INCORPORATED A commentary by James G. Wright, CM, MD, MPH, FRCS(C), FRCS(Ed), is linked to the online version of this article at jbjs.org. Serum Fructosamine: A Simple and Inexpensive Test for Assessing Preoperative Glycemic Control Noam Shohat, MD, Majd Tarabichi, MD, Eric H. Tischler, BA, Serge Jabbour, MD, and Javad Parvizi, MD, FRCS Investigation performed at The Rothman Institute at Thomas Jefferson University, Philadelphia, Pennsylvania Background: Although the medical community acknowledges the importance of preoperative glycemic control, the literature is inconclusive and the proper metric for assessment of glycemic control remains unclear. Serum fructosamine reflects the mean glycemic control in a shorter time period compared with glycated hemoglobin (HbA1c). Our aim was to examine its role in predicting adverse outcomes following total joint arthroplasty. Methods: Between 2012 and 2013, we screened all patients undergoing total joint arthroplasty preoperatively using serum HbA1c, fructosamine, and blood glucose levels. On the basis of the recommendations of the American Diabetes Association, 7% was chosen as the cutoff for HbA1c being indicative of poor glycemic control. This threshold correlated with a fructosamine level of 292 mmol/L. All patients were followed and total joint arthroplasty complications were evaluated. We were particularly interested in retrieving details on surgical-site infection (superficial and deep). Patients with fructosamine levels of ‡292 mmol/L were compared with those with fructosamine levels of <292 mmol/L. Compli- cations were evaluated in a univariate analysis followed by a stepwise logistic regression analysis. Results: A total of 829 patients undergoing primary total joint arthroplasty were included in the present study. There were 119 patients (14.4%) with a history of diabetes and 308 patients (37.2%) with HbA1c levels in the prediabetic range. Overall, 51 patients had fructosamine levels of ‡292 mmol/L. Twenty patients (39.2%) had a fructosamine level of ‡292 mmol/L but did not have an HbA1c level of ‡7%. Patients with fructosamine levels of ‡292 mmol/L had a significantly higher risk for deep infection (adjusted odds ratio [OR], 6.2 [95% confidence interval (CI), 1.6 to 24.0]; p = 0.009), readmission (adjusted OR, 3.0 [95% CI, 1.1 to 8.1]; p = 0.03), and reoperation (adjusted OR, 3.4 [95% CI, 1.2 to 9.2]; p = 0.02). In the current study with the given sample size, HbA1c levels of ‡7% failed to show any significant correlation with deep infection (p = 0.14), readmission (p = 1.0), or reoperation (p = 0.7). Conclusions: Serum fructosamine is a simple and inexpensive test that appears to be a good predictor of adverse outcome in patients with known diabetes and those with unrecognized diabetes or hyperglycemia. Our findings suggest that fructosamine can serve as an alternative to HbA1c in the setting of preoperative glycemic assessment. Level of Evidence: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence. atients with diabetes have an increased risk for arthritis1, higher rates of myocardial infarction, stroke, superficial wound P which explains the high proportion of diabetes among complications, and periprosthetic joint infections2,6-8. Periop- patients undergoing total joint arthroplasty, at an esti- erative hyperglycemia has also been shown to be a common mated rate between 8% and 22%2-5. and independent risk factor for periprosthetic joint infection, Patients with diabetes, particularly those with poor gly- even among patients not diagnosed with diabetes9-11. A recent cemic control, have an increased risk for postoperative com- study demonstrated that >30% of patients undergoing total plications following total joint arthroplasty6. This includes joint arthroplasty have undiagnosed hyperglycemia12. Disclosure: There was no external funding source for this study. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work and “yes” to indicate that the author had a patent and/or copyright, planned, pending, or issued, broadly relevant to this work (http://links.lww.com/JBJS/E454). J Bone Joint Surg Am. 2017;99:1900-7 d http://dx.doi.org/10.2106/JBJS.17.00075 1901 T HE J OURNAL OF B ONE &JOINT SURGERY d JBJS. ORG SERUM FRUCTOSAMINE:ASIMPLE AND I NEXPENSIVE T EST FOR VOLUME 99-A d N UMBER 22 d N OVEMBER 15, 2017 ASSESSING P REOPERATIVE GLYCEMIC CONTROL Although diabetes and perioperative hyperglycemia are joints replaced. We modified the Elixhauser comorbidity index by considered by many as independent risk factors for compli- removing the diabetic element of scoring to improve the com- cations following total joint arthroplasty, there is inconsistency parison between groups. Data on dependent variables were with regard to the impact that preoperative glycemic control extracted from our institutional database of prospectively collected has on the outcome of total joint arthroplasty in patients with data. Deep infection was diagnosed on the basis of the Musculo- and without diabetes2,6,7,9,11,13-15. These discrepancies could be skeletal Infection Society (MSIS) criteria29.Superficial infection was attributed to a large extent to the heterogeneity of study designs defined as a local wound complication necessitating further and the variations in the definition of uncontrolled diabetes. treatment. The rate and the reason for readmission or reoperation, Although the American Diabetes Association (ADA) rec- as well as all “medical” complications, including cerebrovascular ommends hemoglobin A1c (HbA1c) as the measure for moni- accident, myocardial infarction, arrhythmia, deep venous throm- toring glycemic control, the role of HbA1c in predicting the bosis, urinary tract infection, mental status change, pneumonia, outcomeofsurgicalproceduresinpatientswithdiabetesiscon- and gastrointestinal complications occurring within 90 days troversial. In the orthopaedic literature, the association between following total joint arthroplasty, were documented. The incidence HbA1c level and adverse outcome is unclear11,13,16-20. Further, the of periprosthetic fractures, stiffness, component loosening, and optimal preoperative HbA1c level in the surgical patients is un- instability (termed “mechanical” complications) was recorded. The known. Another major drawback with using HbA1c as a marker length of hospital stay was also noted. for glycemic control is the delay that is associated with changes in the level of HbA1c with implementation of better glycemic con- Preoperative Glycemic Status trol. HbA1c levels are dependent on the life cycle of red blood cells Patients with HbA1c levels of ‡6.5% at preadmission testing who at 120 days and may take up to 3 months to reflect the changes in had no history of diabetes were considered as patients with newly the glycemic control21. diagnosed diabetes. Patients who had HbA1c levels between 5.7% However, fructosamine measures the level of glycated and 6.4% were categorized as prediabetic. Because patients may serum proteins, mostly albumin22.Itreflects the mean glucose not have complied with our instructions and may not have fasted, levels over a short to intermediate time frame, 14 to 21 days we did not use the serum glucose level for diagnosis of diabetes. (reflecting the turnover of plasma proteins). Fructosamine Fructosamine was measured using quantitative spectro- levels show higher fluctuation than those of HbA1c, better photometry at a $19.77 charge. reflecting the variability and rapid changes of blood glucose The threshold for uncontrolled diabetes based on fruc- among patients with and without diabetes23,24, thus reflecting tosamine is not well established. We therefore examined the quicker response to treatment, and it may be a better marker percentile of uncontrolled diabetics on the basis of an HbA1c for poor glycemic control than HbA1c25-28. cutoff of 7% (as recommended by the ADA) to determine the The primary purpose of this study was to examine the as- fructosamine level being indicative of poor glycemic control. sociation between serum fructosamine levels and the risk for ad- We found 6% of patients (94th percentile) to have poor gly- verse outcomes following total joint arthroplasty among patients cemic control. We then examined what the 94th percentile with and without diabetes. The study also sought to compare value of fructosamine was and found it to be 292 mmol/L. fructosamine level with HbA1c in predicting outcomes. Statistical Analysis Materials and Methods Patients with fructosamine levels of ‡292 mmol/L (high fructos- etween September 2012 and July 2013, we screened all aminegroup)werecomparedwiththose with fructosamine levels Bpatients undergoing elective total hip arthroplasty or total of <292 mmol/L (low fructosamine group). Patients with HbA1c knee arthroplasty for glycemic control using HbA1c levels, levels of ‡7% were compared with those with HbA1c levels of fructosamine levels, and blood glucose levels. Blood samples <7%. To confirm the cutoff chosen for fructosamine (‡292 mmol/ were obtained at the preadmission testing 2 to 4 weeks before L), a receiver operating characteristic (ROC) curve analysis was the surgical procedure. Patients were instructed to fast starting performed and the area under the curve (AUC) was calculated