Impact of Hemoglobin Glycation Index on Complications Following Orthopedic Surgery: A Retrospective Comparative Propensity Score-Matched Study

Abstract

Objective: Patients with impaired glucose metabolism have an increased incidence of post-operative complications. The best marker for glycemic control prior to elective orthopedic surgery remains unclear. We aimed to assess the utility of the hemoglobin glycation index (HGI) in predicting early complications following elective orthopedic surgery.

Methods: We retrospectively enrolled 1496 patients who underwent elective orthopedic surgery at Fujian Provincial Hospital in China from Jan 2015 to Jan 2023. Restricted cubic spline (RCS) was used to select the cutoff value of HGI. Propensity score matching (PSM) was performed to reduce confounding bias, and multivariate logistic regression models (with and without adjustment) for complication outcomes were applied to evaluate the odds ratios of HGI.

Results: The U-shaped curve in RCS analysis suggested dividing HGI into three subgroups: the reference interval (−0.76 to −0.10), the lower group (≤ −0.76), and the higher group (> −0.10). The incidence of early complications significantly increased from the lower (12.5%) and higher (12.2%) subgroups to the reference interval (6.9%). Following PSM, total postoperative complications were more common in patients with lower HGI (OR: 3.272, 95% CI: 1.417–7.556), but patients in the higher HGI subgroup had a higher risk of incision complications (OR: 3.735, 95% CI: 1.295–10.769).

Conclusions: After adjusting for HbA1c levels, higher HGI (> −0.1) was a risk factor for incision complications, but not for other complications. The risk of overall postoperative complications in patients with lower HGIs (≤ −0.76) should not be ignored.

Keywords

HbA1c / hemoglobin glycation index / postoperative complication / restricted cubic spline

References

[1] P. Hernigou and M. M. Scarlat, “Growth in Musculoskeletal Pathology Worldwide: The Role of Societe Internationale de Chirurgie Orthopedique et de Traumatologie and Publications,” International Orthopaedics 46, no. 9 (2022): 1913-1920.

[2] E. L. Sink, M. Leunig, I. Zaltz, J. C. Gilbert, J. Clohisy, and Academic Network for Conservational Hip Outcomes Research G, “Reliability of a Complication Classification System for Orthopaedic Surgery,” Clinical Orthopaedics and Related Research 470, no. 8 (2012): 2220-2226, https://doi.org/10.1007/s11999-012-2343-2.

[3] M. Sloan, A. Premkumar, and N. P. Sheth, “Projected Volume of Primary Total Joint Arthroplasty in the U.S., 2014 to 2030,” Journal of Bone and Joint Surgery. American Volume 100, no. 17 (2018): 1455-1460.

[4] M. A. Martinez-Huedo, R. Jimenez-Garcia, I. Jimenez-Trujillo, V. Hernandez-Barrera, B. Del Rio Lopez, and A. Lopez-de-Andres, “Effect of Type 2 Diabetes on in-Hospital Postoperative Complications and Mortality After Primary Total Hip and Knee Arthroplasty,” Journal of Arthroplasty 32, no. 12 (2017): 3729-3734.e2.

[5] A. A. Acott, S. A. Theus, and L. T. Kim, “Long-Term Glucose Control and Risk of Perioperative Complications,” American Journal of Surgery 198, no. 5 (2009): 596-599.

[6] J. M. Blankush, I. M. Leitman, A. Soleiman, and T. Tran, “Association Between Elevated Pre-Operative Glycosylated Hemoglobin and Post-Operative Infections After Non-Emergent Surgery,” Annals of Medicine and Surgery (London) 10 (2016): 77-82, https://doi.org/10.1016/j.amsu.2016.07.025.

[7] S. Lu, M. Y. Bao, S. M. Miao, et al., “Prevalence of Hypertension, Diabetes, and Dyslipidemia, and Their Additive Effects on Myocardial Infarction and Stroke: A Cross-Sectional Study in Nanjing, China,” Annals of Translational Medicine 7, no. 18 (2019): 436.

[8] W. J. Choi, J. S. Lee, M. Lee, J. H. Park, and J. W. Lee, “The Impact of Diabetes on the Short- To Mid-Term Outcome of Total Ankle Replacement,” Bone & Joint Journal 96-B, no. 12 (2014): 1674-1680, https://doi.org/10.1302/0301-620X.96B12.34364.

[9] H. S. Han and S. B. Kang, “Relations Between Long-Term Glycemic Control and Postoperative Wound and Infectious Complications After Total Knee Arthroplasty in Type 2 Diabetics,” Clinical Orthopaedics and Related Research 5, no. 2 (2013): 118-123, https://doi.org/10.4055/cios.2013.5.2.118.

[10] W. van den Boom, R. A. Schroeder, M. W. Manning, T. L. Setji, G. O. Fiestan, and D. B. Dunson, “Effect of A1C and Glucose on Postoperative Mortality in Noncardiac and Cardiac Surgeries,” Diabetes Care 41, no. 4 (2018): 782-788.

[11] A. Frisch, P. Chandra, D. Smiley, et al., “Prevalence and Clinical Outcome of Hyperglycemia in the Perioperative Period in Noncardiac Surgery,” Diabetes Care 33, no. 8 (2010): 1783-1788.

[12] W. F. Bower, L. Jin, M. J. Underwood, et al., “Overt Diabetes Mellitus Adversely Affects Surgical Outcomes of Noncardiovascular Patients,” Surgery 147, no. 5 (2010): 670-675.

[13] U. O. Gustafsson, A. Thorell, M. Soop, O. Ljungqvist, and J. Nygren, “Haemoglobin A1c as a Predictor of Postoperative Hyperglycaemia and Complications After Major Colorectal Surgery,” British Journal of Surgery 96, no. 11 (2009): 1358-1364.

[14] M. Habous, R. Tal, A. Tealab, et al., “Defining a Glycated Haemoglobin (HbA1c) Level That Predicts Increased Risk of Penile Implant Infection,” BJU International 121, no. 2 (2018): 293-300.

[15] K. E. Rollins, K. K. Varadhan, K. Dhatariya, and D. N. Lobo, “Systematic Review of the Impact of HbA1c on Outcomes Following Surgery in Patients With Diabetes Mellitus,” Clinical Nutrition 35, no. 2 (2016): 308-316.

[16] L. F. Lopez, P. D. Reaven, and S. M. Harman, “Review: The Relationship of Hemoglobin A1c to Postoperative Surgical Risk With an Emphasis on Joint Replacement Surgery,” Journal of Diabetes and its Complications 31, no. 12 (2017): 1710-1718.

[17] L. S. Stryker, M. P. Abdel, M. E. Morrey, M. M. Morrow, D. J. Kor, and B. F. Morrey, “Elevated Postoperative Blood Glucose and Preoperative Hemoglobin A1C Are Associated With Increased Wound Complications Following Total Joint Arthroplasty,” Journal of Bone and Joint Surgery 95, no. 9 (2013): 808-814.S1-2.

[18] J. M. Hempe, S. Liu, L. Myers, R. J. McCarter, J. B. Buse, and V. Fonseca, “The Hemoglobin Glycation Index Identifies Subpopulations With Harms or Benefits From Intensive Treatment in the ACCORD Trial,” Diabetes Care 38, no. 6 (2015): 1067-1074, https://doi.org/10.2337/dc14-1844.

[19] L. Rawlins, M. P. Rawlins, C. C. Brown, and D. L. Schumacher, “Effect of Elevated Hemoglobin A1c in Diabetic Patients on Complication Rates After Roux-En-Y Gastric Bypass,” Surgery for Obesity and Related Diseases 9, no. 5 (2013): 749-752.

[20] M. D. McElvany, P. H. Chan, H. A. Prentice, E. W. Paxton, M. T. Dillon, and R. A. Navarro, “Diabetes Disease Severity Was Not Associated With Risk of Deep Infection or Revision After Shoulder Arthroplasty,” Clinical Orthopaedics and Related Research 477, no. 6 (2019): 1358-1369.

[21] R. Iorio, K. M. Williams, A. J. Marcantonio, L. M. Specht, J. F. Tilzey, and W. L. Healy, “Diabetes Mellitus, Hemoglobin A1C, and the Incidence of Total Joint Arthroplasty Infection,” Journal of Arthroplasty 27, no. 5 (2012): 726-729.e1.

[22] J. M. Hempe and D. S. Hsia, “Variation in the Hemoglobin Glycation Index,” Journal of Diabetes and its Complications 36, no. 7 (2022): 108223.

[23] S. Liu, J. M. Hempe, R. J. McCarter, S. Li, and V. A. Fonseca, “Association Between Inflammation and Biological Variation in Hemoglobin A1c in U.S. Nondiabetic Adults,” Journal of Clinical Endocrinology and Metabolism 100, no. 6 (2015): 2364-2371.

[24] C. Carette and S. Czernichow, “Harms and Benefits of the Haemoglobin Glycation Index (HGI),” European Journal of Preventive Cardiology 24, no. 13 (2017): 1402-1404.

[25] J. R. Kang, J. B. Friedrich, D. P. Hanel, D. P. Barei, and J. A. Bishop, “Surgical Wound Closure in Orthopaedic Surgery,” Current Orthopaedic Practice 26, no. 4 (2015): 403-410.

[26] Society CD, “Guideline for the Prevention and Treatment of Type 2 Diabetes Mellitus in China (2020 Edition),” Chinese Journal of Diabetes Mellitus 13, no. 4 (2021): 94.

[27] B. Finger, J. Brase, J. He, W. J. Gibson, K. Wirtz, and B. C. Flynn, “Elevated Hemoglobin A1c Is Associated With Lower Socioeconomic Position and Increased Postoperative Infections and Longer Hospital Stay After Cardiac Surgical Procedures,” Annals of Thoracic Surgery 103, no. 1 (2017): 145-151.

[28] R. J. McCarter, J. M. Hempe, R. Gomez, and S. A. Chalew, “Biological Variation in HbA1c Predicts Risk of Retinopathy and Nephropathy in Type 1 Diabetes,” Diabetes Care 27, no. 6 (2004): 1259-1264.

[29] M. Sandini, O. Strobel, T. Hank, et al., “Pre-Operative Dysglycemia Is Associated With Decreased Survival in Patients With Pancreatic Neuroendocrine Neoplasms,” Surgery 167, no. 3 (2020): 575-580.

[30] H. B. Ostergaard, T. Mandrup-Poulsen, G. F. N. Berkelmans, et al., “Limited Benefit of Haemoglobin Glycation Index as Risk Factor for Cardiovascular Disease in Type 2 Diabetes Patients,” Diabetes & Metabolism 45, no. 3 (2019): 254-260.

[31] S. C. van Steen, M. Woodward, J. Chalmers, et al., “Haemoglobin Glycation Index and Risk for Diabetes-Related Complications in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) Trial,” Diabetologia 61, no. 4 (2018): 780-789, https://doi.org/10.1007/s00125-017-4539-1.

[32] A. L. Christman, E. Selvin, D. J. Margolis, G. S. Lazarus, and L. A. Garza, “Hemoglobin A1c Predicts Healing Rate in Diabetic Wounds,” Journal of Investigative Dermatology 131, no. 10 (2011): 2121-2127.

[33] P. C. Chang, S. C. Tsai, Y. H. Jheng, Y. F. Lin, and C. C. Chen, “Soft-Tissue Wound Healing by Anti-Advanced Glycation End-Products Agents,” Journal of Dental Research 93, no. 4 (2014): 388-393.

[34] L. Lyu, J. Yu, Y. Liu, et al., “High Hemoglobin Glycation Index Is Associated With Telomere Attrition Independent of HbA1c, Mediated by TNFalpha,” Journal of Clinical Endocrinology and Metabolism 107, no. 2 (2022): 462-473.

[35] A. Shaikh-Kader, N. N. Houreld, N. K. Rajendran, and H. Abrahamse, “The Link Between Advanced Glycation End Products and Apoptosis in Delayed Wound Healing,” Cell Biochemistry and Function 37, no. 6 (2019): 432-442.

[36] M. K. Kim, J. S. Jeong, J. S. Yun, et al., “Hemoglobin Glycation Index Predicts Cardiovascular Disease in People With Type 2 Diabetes Mellitus: A 10-Year Longitudinal Cohort Study,” Journal of Diabetes and its Complications 32, no. 10 (2018): 906-910.

[37] M. A. Marini, T. V. Fiorentino, E. Succurro, et al., “Association Between Hemoglobin Glycation Index With Insulin Resistance and Carotid Atherosclerosis in Non-Diabetic Individuals,” PLoS One 12, no. 4 (2017): e0175547.

[38] S. C. van Steen, I. C. Schrieks, J. B. Hoekstra, et al., “The Haemoglobin Glycation Index as Predictor of Diabetes-Related Complications in the AleCardio Trial,” European Journal of Preventive Cardiology 24, no. 8 (2017): 858-866, https://doi.org/10.1177/2047487317692664.

[39] P. Y. Huang, M. Z. Lin, J. P. Wen, et al., “Correlation of Early Postoperative Blood Glucose Levels With Postoperative Complications, Hospital Costs, and Length of Hospital Stay in Patients With Gastrointestinal Malignancies,” Endocrine 48, no. 1 (2015): 187-194.

[40] N. Sakane, Y. Hirota, A. Yamamoto, et al., “Factors Associated With Hemoglobin Glycation Index in Adults With Type 1 Diabetes Mellitus: The FGM-Japan Study,” Journal of Diabetes Investigation 14, no. 4 (2023): 582-590.

[41] C. P. Domingueti, L. M. S. A. Dusse, M. G. Carvalho, L. P. de Sousa, K. B. Gomes, and A. P. Fernandes, “Diabetes Mellitus: The Linkage Between Oxidative Stress, Inflammation, Hypercoagulability and Vascular Complications,” Journal of Diabetes and its Complications 30, no. 4 (2016): 738-745.

[42] M. Turina, D. E. Fry, and H. C. Polk, “Acute Hyperglycemia and the Innate Immune System: Clinical, Cellular, and Molecular Aspects,” Critical Care Medicine 33, no. 7 (2005): 1624-1633.

[43] K. R. Klein, E. Franek, S. Marso, et al., “Hemoglobin Glycation Index, Calculated From a Single Fasting Glucose Value, as a Prediction Tool for Severe Hypoglycemia and Major Adverse Cardiovascular Events in DEVOTE,” BMJ Open Diabetes Research & Care 9, no. 2 (2021): e002339.

[44] J. S. Hwang, S. J. Kim, A. B. Bamne, Y. G. Na, and T. K. Kim, “Do Glycemic Markers Predict Occurrence of Complications After Total Knee Arthroplasty in Patients With Diabetes?,” Clinical Orthopaedics and Related Research 473, no. 5 (2015): 1726-1731.

[45] M. K. Kim, J. S. Jeong, H. S. Kwon, K. H. Baek, and K. H. Song, “Concordance the Hemoglobin Glycation Index With Glycation Gap Using Glycated Albumin in Patients With Type 2 Diabetes,” Journal of Diabetes and its Complications 31, no. 7 (2017): 1127-1131.

RIGHTS & PERMISSIONS

2025 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.