Post-Surgery Outcomes in Patients with Diabetes and Elevated HbA1c

Investigation into the effect of surgery and post-surgery outcomes in patients with diabetes with consistently high blood glucose — from mortality to length of hospital stay.

A diabetes diagnosis is associated with mortality and morbidity concerns, but pair that with surgical procedures, which inherently cause stress, and you’re looking at a troublesome combination. Currently, data regarding the association between HbA1c and surgical outcomes is quite contradictory, some showing higher mortality and major complications while others have found no association. Most studies lack glycemic data, and it is very clear that research is necessary. More often than not, studies are relying on perioperative blood glucose readings, which is concerning given its variability due to stress, trauma, and preoperative fasting. Therefore, HbA1c, a superior indicator, should be used in analyses as it is less likely to be affected by those variables.

A recent prospective, observational study performed in Melbourne, Australia sought to confirm the hypothesis that diabetes and HbA1c have an independent association with adverse outcomes post-surgery. From May 2013 to January 2016, 7,565 patients were enrolled in the study and followed for 6 months. The primary outcome of the study was mortality within 6 months. Several secondary outcomes were assessed, including presence of major complications, admission to the intensive care unit (ICU), use of mechanical ventilation, hospital length of stay (LOS), hospital readmission within 6 months, and hospital cost. Detailed inclusion criteria, exclusion criteria, and pertinent study definitions are located in Table 1: Inclusion/Exclusion Criteria & Definitions.

Table 1: Inclusion/Exclusion Criteria & Definitions
Inclusion Criteria	Age ≥ 54 years, surgery with one or more overnight hospital stay(s), HbA1c measurement (< 3 months prior or 7 days post-surgery), serum creatinine level
Exclusion Criteria	Patients undergoing minor interventional or noninterventional procedures (i.e. gastroscopy, colonoscopy, bronchoscopy, MRI, etc.).
Study Definitions
Diabetes Classification (per American Diabetes Association)	Normoglycemia: HbA1c < 5.7% Pre-diabetes mellitus: HbA1c ≥ 5.7% Diabetes mellitus: HbA1c ≥ 6.5% or existing diabetes diagnosis
LOS	Admission to discharge
Readmission	Readmission to hospital within 6-month follow up period
Major Hospital-Acquired Complications	Used Clavien-Dindo Classification (assigns severity scores to surgical complications). Major Complication: Grade ≥ 4 (including life-threatening complications and death while in hospital)

Statistical analysis focused on diabetes status as a categorical variable (i.e. with or without diabetes) and HbA1c as a continuous marker. Additionally, a classification and regression tree (CART) analysis was performed to assess several interactions, including patient characteristics, HbA1c, LOS, and lastly outcome of 6-month mortality. The goal of a CART analysis is to predict 6-month mortality risk. Analysis of the baseline characteristics revealed that most patients were male, had a higher median eGFR, longer median length of surgery, and had less diabetes. A detailed summary of primary and secondary outcomes can be found at the end of this article in Table 2: Primary Outcome Results and Table 3: Secondary Outcome Results

Table 2: Primary Outcome Results
Primary Outcome: Incidence of 6-month mortality
Diabetes Classification	Without DM: 6% (95% CI 5.5-6.8%) With DM: 9% (95% CI 7.4-9.7%)
Diabetes Presence	Increased mortality 6-month post-surgery aOR (95% CI 1.05-1.58; p = 0.014)
HbA1c	No significance found
aOR – adjusted odds ratio*

Table 3: Secondary Outcome Results
Major Complications (Clavien-Dindo Grade ≥ 4)
Diabetes Classification	Without DM: 14% (95% CI 13-15%) With DM: 21% (95% CI 20-23%)
Diabetes Presence	Associated with increased risk of major complications aOR 1.32 (95% CI 1.14-1.52 ; p < 0.001)
HbA1c	Every 1% increase in HbA1c associated with increased risk of major complications aOR 1.07 (95% CI 1.01-1.14 ; p = 0.030)
ICU Admission
Diabetes Classification	Without DM: 18% (95% CI 17-19) With DM: 27% (95% CI 26-29)
Diabetes Presence	Associated with an increased likelihood of ICU admission aOR 1.50 (95% CI 1.28-1.75 ; p < 0.001)
HbA1c	Every 1% increase in HbA1c associated with increased likelihood of ICU admission aOR 1.14 (95% CI 1.07-1.21 ; p < 0.001)
Mechanical Ventilation (MV)
Diabetes Classification	Without DM: 10% (95% CI 9-11) With DM: 16% (95% CI 15-18)
Diabetes Presence	Associated with an increased likelihood of receiving MV aOR 1.67 (95% CI 1.32-2.10; p < 0.001)
HbA1c	No significance found
Hospital LOS
Diabetes Classification	Without DM: Median LOS 6 (IQR 3-11) With DM: Median LOS 7 (IQR 4-14)
Diabetes Presence	Associated with increased LOS aIRR 1.08 (95% CI 1.04-1.12 ; p < 0.001)
HbA1c	Every 1% increase in HbA1c associated with increased LOS aIRR 1.05 (95% CI 1.03-1.05 ; p < 0.001)
Incidence of 6-month Readmission
Diabetes Classification	Without DM: 16% (95% CI 15-17) With DM: 17% (95% CI 15-19)
Diabetes Presence	No significance found
HbA1c	No significance found
Cost
Median Cost of Episode	Study population: $18,189 Without DM: $17,439 (IQR 11,438-27,564) With DM: $20,440 (12,186-33,261) p < 0.001
aOR – adjusted odds ratio aIRR – adjusted incidence rate ratio

Yong et al found that diabetes and elevated HbA1c are associated with adverse outcomes following surgery. The outcomes analyzed included 6-month mortality, major complications, mechanical ventilation, LOS, and ICU admission and were all found to be increased in those with diabetes. Lastly, habig diabetes is associated with higher median hospital costs and higher 6-month mortality risk.

As with most research, the results are only as strong as the study design and methods used. In this study, several strengths can be found largely in the study design selected. Prospective studies with a large sample size enhances the generalizability of conclusions. Furthermore, previous research has not consistently obtained HbA1c measurements and appropriately diagnosed diabetes with guidelines, thus establishing relationships between surgical outcomes and hyperglycemia was difficult. This study addressed those issues and successfully obtained data for every subject. While the study has some definite strengths, some limitations exist. Firstly, the study design while strong still has some shortcomings, specifically because of the observational quality. But the biggest limitation is the presence of comorbidities, which are possible confounding variables. Investigators attempted to adjust for the comorbidities, but their impact should still be noted.

Overall, this study’s findings were consistent with previous research, but some new evidence was discovered. The realization that higher HbA1c is associated with worsened outcomes post-surgery suggests the need for correcting glycemic levels prior to surgery.

Practice Pearls:

• A diabetes diagnosis and elevated HbA1c is associated with adverse outcomes after surgery; poor outcomes include 6-month mortality, major complications, mechanical ventilation, LOS, and ICU admission.
• Diabetes is associated with higher median hospital costs and a higher 6-month mortality risk.
• Yong et al shed light on the importance of preoperative glycemic control as it can prevent poor outcomes.
• Prediabetes was not considered a risk factor for worsened outcomes post-surgery.

Reference:

Yong, P., Weinberg, L, Torkamani, N., Churilov, L., Robbins, R., Ma, R., Bellomo, R., Lam, Q., Burns, J., Hart, G., et al. The Presence of Diabetes and Higher HbA1c Are Independently Associated With Adverse Outcomes After Surgery. Diabetes Care. 41 (2018): 1172-1179. https://doi.org/10.2337/dc17-2304.

Kaytie A. Weierstahl, Pharm.D. Candidate, LECOM School of Pharmacy