Preoperative hemoglobin A1c and postoperative glucose control in outcomes after gastric bypass for obesity

Surgery for Obesity and Related Diseases 8 (2012) 685– 690

Original article

Preoperative hemoglobin A1c and postoperative glucose control in outcomes after gastric bypass for obesity Mark Perna, M.D.a,*, Joseph Romagnuolo, M.D., M.Sc.b, Kathyrn Morgan, M.D.a, T. Karl Byrne, M.D.a, Megan Baker, M.D.a b

a Department of Surgery, Medical University of South Carolina, Charleston, South Carolina Department of Medicine (Divisions of Gastroenterology and Hepatology), Medical University of South Carolina, Charleston, South Carolina Received March 18, 2011; accepted August 1, 2011

Abstract

Background: Hemoglobin A1c (HbA1c) is a reliable marker for long-term glycemic control in obese diabetic patients. Roux-en-Y gastric bypass improves HbA1c levels over time. However, it is not clear whether the preoperative HbA1c level is a predictor of the outcome in these patients. Our objectives were to understand the predictive capacity of the preoperative HbA1c level in gastric bypass patients at a single university-based Bariatric Center of Excellence. Methods: We performed a retrospective review of 468 charts from 2006 to 2009 of patients who had undergone Roux-en-Y gastric bypass. Using their preoperative HbA1c status, the patients were categorized and the postoperative outcomes compared. Results: Of the 468 patients reviewed, 310 (66.2%) had a HbA1c of ⬍6.5% (group 1), 92 (19.4%) had a HbA1c of 6.5–7.9% (group 2), and 66 (14.1%) had a HbA1c level of ⬎8.0% (group 3). No difference was found among the 3 groups in baseline body mass index, race, procedure type, length of stay, hospital cost, and smoking status. Groups 2 and 3 were associated with older age, male gender, and higher baseline creatinine. Groups 2 and 3 also had a proportionally greater inpatient postoperative blood glucose level. An elevated postoperative glucose level was independently associated with wound infection (P ⫽ .008) and acute renal failure (P ⫽ .04). Also, group 3 experienced worse outcomes, including less weight loss at 18 months and fewer diabetic remissions. Over time, however, the vast majority in all groups achieved excellent chronic glycemic control, with HbA1c ⬍6.5% after Roux-en-Y gastric bypass. Conclusion: Poor preoperative glycemic control is associated with worse glucose level control postoperatively, fewer diabetic remissions, and less weight loss. An elevated mean postoperative glucose level is independently associated with increased morbidity. (Surg Obes Relat Dis 2012;8: 685– 690.) © 2012 American Society for Metabolic and Bariatric Surgery. All rights reserved.

Keywords:

Gastric bypass; Roux-en-Y gastric bypass; Preoperative hemoglobin A1c; HbA1c; Postoperative blood glucose control; Bariatric glycemic control

Obesity and type 2 diabetes mellitus (T2DM) are increasingly problematic chronic illnesses that lead to a constellation of poor health outcomes. It is estimated that ⬎90% of T2DM is related to excess weight or obesity [1– 6]. Obesity surgery can provide dramatic weight loss. *Correspondence: Mark Perna, M.D., Department of Surgery, Medical University of South Carolina, 96th Jonathan Lucas Avenues, Charleston, SC 29425. E-mail: [email protected]

In so doing, it often facilitates euglycemia without diabetic medication and with associated improvement in fasting glucose levels, insulin sensitivity, and hemoglobin A1c (HbA1c) [7–13]. HbA1c is a highly reliable measure of long-term glycemic control often used to follow ongoing adjustments to medications in patients with T2DM [4]. More recently in the surgical data, HbA1c has been demonstrated to be a preoperative predictor of postoperative outcomes. For example, in cardiac surgery, an elevated preoperative

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M. Perna et al / Surgery for Obesity and Related Diseases 8 (2012) 685– 690

HbA1c has been associated with increased acute kidney injury and mortality [14]. Also, in vascular surgery, elevated HbA1c levels are associated with wound infections and overall 30-day morbidity [15]. Finally, elevated preoperative HbA1c levels in colorectal patients are associated with more infectious complications, such as pneumonia and urinary tract infection [16]. In bariatric surgery, HbA1c is a useful tool for monitoring improvements in glycemic control during the duration of weight loss after Roux-en-Y gastric bypass (RYGB). It is less clear whether the preoperative HbA1c level and its relationship to postoperative glycemic control predict the postoperative outcomes in bariatric patients. In the present study, we aimed to understand the preoperative HbA1c level as a potential predictor of outcomes in the gastric bypass population. Methods From a single institution with American Society for Metabolic and Bariatric Surgery and Surgical Review Corporation Center of Excellence accreditation, the charts of

468 patients who had undergone RYGB for morbid obesity from 2006 to 2009 were retrospectively reviewed with institutional review board approval. The patients were excluded for age ⬍18 years or body mass index (BMI) ⬍40 kg/m2. At our institution, 3 surgeons perform laparoscopic retrocolic, retrogastric RYGB. According to the guidelines from the American Association of Clinical Endocrinologists for HbA1c goals, the patients were divided into 3 groups corresponding to the preoperative glycemic control: 1, excellent preoperative glycemic control (HbA1c ⬍6.5%); 2, moderate control (HbA1c 6.5–7.9%); and 3, poor control (HbA1c ⱖ8%). The groups were compared in terms of postoperative complications, weight loss over time, improvement in HbA1c over time, and resolution of other co-morbidities. In addition, a mean postoperative blood glucose level was calculated from all available inpatient postoperative finger stick or blood glucose analyses. We also sought to determine whether the mean postoperative glucose level had any effect on the incidence of postoperative complications, and, if so, whether it was independent of the baseline HbA1c.

Table 1 Baseline characteristics of HbA1c groups Baseline characteristics Demographics Age (y) Women (%) White race (%) Smoking (%) Procedure Roux limb length (cm) Laparoscopic surgery (%) Economic parameters Length of stay (d) Hospital charges ($) Physiologic parameters Baseline BMI (kg/m2) Baseline weight (kg) Baseline height (cm) Ideal weight (kg) Metabolic parameters Baseline creatinine (mg/dL) Baseline HbA1c (%) Co-morbidities (%) HTN T2DM Sleep apnea HLD GERD Osteoarthritis CAD/CHF

Group 1 (HbA1c ⬍6.5%; n ⫽ 310)

Group 2 (HbA1c 6.5–7.9%; n ⫽ 92)

P value*

44.3 ⫾ .04 82.26 ⫾ 4.26 77.10 ⫾ 4.69 11.36 ⫾ 3.55

50.9 ⫾ 2.1 73.91 ⫾ 9.02 70.65 ⫾ 9.36 9.89 ⫾ 6.17

⬍.001 .077 .207 .694

111.2 ⫾ 4.3 89.03 ⫾ 3.48

112.3 ⫾ 7.7 90.11 ⫾ 6.13

3.0 ⫾ .5 40,318.7 ⫾ 5788.9

3.7 ⫾ 1.4 46,235.2 ⫾ 14,272.4

51.3 ⫾ 1.2 143.0 ⫾ 3.9 166.3 ⫾ 1.0 58.8 ⫾ 2.0

52.1 ⫾ 2.4 145.9 ⫾ 7.5 167.4 ⫾ 2.0 59.7 ⫾ 3.1

Group 3 (HbA1c ⬎8%; n ⫽ 66)

P value†

47.6 ⫾ 2.6 69.70 ⫾ 11.17 71.21 ⫾ 11.01 15.15 ⫾ 8.72

.047 .020 .310 .392

.831 .771

115.8 ⫾ 9.3 84.85 ⫾ 8.72

.453 .338

.222 .372

2.9 ⫾ .3 36,722.5 ⫾ 3788.8

.863 .540

.578 .487 .337 .659

49.1 ⫾ 1.9 141.9 ⫾ 5.8 169.9 ⫾ 1.0 62.9 ⫾ 3.9

.108 .821 .006 .073

.8 ⫾ .02 5.6 ⫾ .04

1.0 ⫾ .2 7.1 ⫾ .1

⬍.001 ⬍.001

.9 ⫾ .1 9.7 ⫾ .4

.030 ⬍.001

64.84 ⫾ 5.32 33.55 ⫾ 5.26 51.29 ⫾ 5.57 47.74 ⫾ 5.57 53.55 ⫾ 5.56 80.14 ⫾ 6.61 11.95 ⫾ 3.62

85.87 ⫾ 7.16 85.87 ⫾ 7.16 59.78 ⫾ 10.07 70.65 ⫾ 9.36 53.26 ⫾ 10.25 78.72 ⫾ 11.83 19.72 ⫾ 8.57

⬍.001 ⬍.001 .152 ⬍.001 .961 .835 .098

80.30 ⫾ 9.67 98.48 ⫾ 2.97 56.06 ⫾ 12.07 59.09 ⫾ 11.95 50.00 ⫾ 12.16 86.49 ⫾ 11.17 18.75 ⫾ 11.16

.015 ⬍.001 .482 .095 .601 .380 .207

HbA1c ⫽ hemoglobin A1c; BMI ⫽ body mass index; HTN ⫽ hypertension; T2DM ⫽ type 2 diabetes mellitus; HLD ⫽ hyperlipidemia; GERD ⫽ gastroesophageal reflux disease; CAD ⫽ coronary artery disease; CHF ⫽ congestive heart failure. Data presented as mean ⫾ 95% confidence interval. * Group 1 versus group 2. † Group 1 versus group 3.

Hemoglobin A1c and Glucose Control in Outcomes / Surgery for Obesity and Related Diseases 8 (2012) 685– 690

Comparisons of the mean values were performed using unpaired 2-tailed Student’s t tests. Categorical data were compared using Fisher’s exact test. Univariate and descriptive statistical calculations were completed using Microsoft Excel (Microsoft, Redmond, WA) and GraphPad QuickCalc software (La Jolla, CA), and multivariate logistic regression analysis was done using Stata, version 7.0 (StataCorp, College Station, TX). Statistical significance was defined as P ⬍ .05. Stepwise multivariate model building was performed using likelihood ratio tests for nested models, with age and gender forced into the model to control for potential confounding related to these demographics. Covariates with P ⬍ .05 were retained in the final model. Other nonsignificant variables demonstrating confounding (a significant change in the point estimates when entered or withdrawn from the model) would have been considered for inclusion, but this situation did not arise. Two adverse outcomes of clinical interest were chosen for the models: (1) wound infection as defined by the Centers for Disease Control guidelines [17]; and (2) ARF, defined as a threefold increase in the serum creatinine level, urine output of ⬍.5 mL/kg/h for 24 hours, or anuria for 12 hours [18]. The predictors of these 2 outcomes, potential confounders, the influence of HbA1c, and postoperative glycemic control were assessed using these models. Results Of the 468 patients reviewed, 310 (66.2%) were included in group 1, 92 (19.7%) in group 2, and 66 (14.1%) in group 3. In groups 1, 2, and 3, the average HbA1c was 5.6%, 7.1%

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(P ⬍ .001), and 9.8% (P ⬍ .001), respectively. No difference was found among the groups in terms of the baseline BMI. The groups were otherwise comparable with respect to ethnicity, procedure type, Roux limb length, length of stay, hospital cost, and smoking status. However, groups 2 and 3 were older, more likely to be male, and had a higher preoperative creatinine (Table 1). Predicting complications No difference was found in overall complications or mortality among the 3 groups. Between groups 1 and 2, no difference was found in the rates of individual complication types. However, group 3 had a greater incidence of wound infections and ARF compared with the most tightly controlled preoperative patient group, group 1 (P ⬍ .05; Table 2). However, group 3 also had a greater mean glucose level, a potential confounder (Table 3). Multivariate logistic regression analyses were performed attempting to quantify the independent effect of HbA1c and mean postoperative glucose level on the outcomes, correcting for other important confounders. For wound infection, the mean glucose level was the only independently associated variable, with an odds ratio of 1.27 for each 20-mg/dL increase (95% confidence interval 1.06 –1.51; P ⫽ .008), although the laparoscopic approach showed a trend toward significance for lower complications (odds ratio .42; P ⫽ .056). The baseline HbA1c, age, and baseline BMI were not significant in this model (P ⫽ NS). For ARF, the 2 independent variables were age (odds ratio 2.70 for each decade increase; 95% confidence interval 1.34 –5.45; P ⫽ .005) and mean glucose level (odds ratio 1.34 for each 20-mg/dL increase; 95% confidence interval

Table 2 Postoperative complications among HbA1c groups Complications

Wound Incisional hernia Wound infection Anastomotic Stomal stenosis Stomal ulcer Anastomotic leak Bariatric related Bowel obstruction Postoperative hemorrhage Acute renal failure Pulmonary embolus Death Total HbA1c ⫽ hemoglobin A1c. Data in parentheses are percentages. * Group 1 versus group 2. † Group 1 versus group 3.

Group 1 (HbA1c ⬍6.5%; n ⫽ 310)

Group 2 (HbA1c 6.5–7.9%; n ⫽ 92)

Group 3 (HbA1c ⬎8%; n ⫽ 66)

Patients (n)

Patients (n)

Patients (n)

P value*

P value†

5 (1.61) 18 (5.81)

0 (0) 5 (5.43)

.22 .89

1 (1.52) 9 (13.64)

.95 .03

5 (1.61) 14 (4.52) 6 (1.94)

3 (3.26) 7 (7.61) 3 (3.26)

.32 .24 .45

2 (3.03) 3 (4.55) 3 (4.55)

.44 .99 .21

15 (4.84) 8 (2.58) 5 (1.61) 5 (1.61) 1 (.32) 82 (26.45)

3 (3.26) 4 (4.35) 3 (3.26) 0 (0) 1 (1.09) 29 (31.52)

.52 .38 .32 .22 .36 .35

0 (0) 1 (1.52) 4 (6.06) 1 (1.52) 0 (0) 24 (36.36)

.07 .61 .03 .95 .65 .13

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Table 3 Postoperative inpatient glucose control and eventual self-reported diabetic outcomes Variable

Group 1 (HbA1c ⬍6.5%)

Group 2 (HbA1c 6.5–7.9%)

P value*

Group 3 (HbA1c8.0%)

P value†

P value‡

Average postoperative glucose level (mg/dL) Mean inpatient glucose level ⬎200 mg/dL postoperatively (n) Average postoperative HbA1c (%) Diabetes Improved Resolved Total

133.6 ⫾ 2.7 5/276 (1.81)

168.3 ⫾ 6.6 14/90 (15.6)

⬍.001 ⬍.001

190.9 ⫾ 9.2 27/66 (41.0)

⬍.001 ⬍.001

⬍.001 .002

5.3 ⫾ .1

5.9 ⫾ .2

⬍.001

6.1 ⫾ .3

⬍.001

.675

18/104 (17.31) 41/104 (39.42) 59/104 (56.73)

24/79 (30.38) 26/79 (32.91) 50/79 (63.29)

36/65 (55.38) 7/65 (10.77) 43/65 (66.15)

⬍.001 ⬍.001 .226

.004 ⬍.001 .824

.037 .368 .373

HbA1c ⫽ hemoglobin A1c. Data presented as mean ⫾ 95% confidence level or numbers, with percentages in parentheses. * Group 1 versus group 2. † Group 1 versus group 3. ‡ Group 2 versus group 3.

1.01–1.77; P ⫽ .04). In this model, the baseline creatinine, presence of hypertension, angiotensin-converting enzyme inhibitor/␤-blocker use, HbA1c level, and BMI were not significant (P ⫽ NS). For both models, the mean glucose level as a continuous variable was more significant than a high versus not high glucose level (dichotomized at 200 mg/dL). Although the baseline creatinine and mean postoperative glucose level had a significant association with each other, the baseline creatinine was not associated with ARF outcome in either univariate or multivariate modeling, and thus was not considered a true confounder. The mean glucose level was also more helpful than the baseline creatinine at explaining the variance in the ARF outcome, as judged by adjusted R-square. Predicting metabolic status All 3 groups had a significant and sustained decrease in HbA1c after RYGB. Groups 2 and 3 had dramatic improvements in glycemic control, although they never equaled the glycemic control in group 1 postoperatively. However, the vast majority of patients reached a HbA1c threshold of ⱕ6.5% and, thus, were considered to have excellent glycemic control even 24 months postoperatively (Fig. 1). Groups 1 and 2 had equivalent weight loss profiles; however, group 3 appeared to have significantly less weight loss statistically over time at 9 and 18 months. Group 3 had approximately a 5–12% smaller reduction from the baseline BMI postoperatively, corresponding to approximately 6 –18 kg of less weight loss (Fig. 2). The preoperative HbA1c level predicted poor glucose control in the hospital postoperatively. An increase in preoperative HbA1c was linearly associated with an increase in the mean postoperative glucose level. A mean glucose level of ⬎200 mg/dL was also predicted by a greater preoperative HbA1c level (15.6% and 41.0% of patients in groups 2 and 3, respectively, versus 1.8% in group 1, P ⬍ .001; Table 3).

All 3 groups of patients with T2DM demonstrated equal rates of either improvement or resolution of T2DM postoperatively. However, as the preoperative HbA1c increased in groups 2 and 3, there was decrease in the likelihood of reporting resolution of T2DM (P ⬍ .001; Table 3). Therefore, the preoperative HbA1c level might predict eventual remission of T2DM postoperatively. Discussion Obesity and T2DM will continue to increase the financial burden on our already strained healthcare system [1– 3,5,6,19]. Our data further confirm that RYGB is an excellent option for improving glycemic control in these patients. These improvements were most profound in patients starting with the poorest glycemic control preoperatively. HbA1c is an established reliable indicator of chronic glycemic control [1] and has previously been useful as a

Fig. 1. Improvements in HbA1c over time in all groups. Group 1 indicated by white bars; group 2, black bars; and group 3, blue bars; solid gray bars, patients without T2DM with preoperative HbA1c ⬍6.5%. Groups were compared using unpaired Student’s t test; error bars indicate 95% confidence intervals. P ⬍ .05 was significant compared with group 1.

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Fig. 2. Weight loss (change in BMI [kg/m2]) during follow-up. Group 1 indicated by dashed line; group 2, solid line; and group 3, dashed, dotted line. Groups were compared using unpaired Student t test; error bars indicate 95% confidence intervals. P ⬍ .05 was significant compared with group 1.

preoperative predictor of surgical outcomes in cardiac, vascular, and colorectal patients [1,15,16,20]. Likewise in the bariatric population, we have demonstrated the preoperative HbA1c to be a valuable predictor of postoperative glucose control, weight loss, and T2DM remission. However, postoperative glucose level was more closely associated with surgical morbidity, such as wound infection and ARF than was HbA1c. Nonetheless, we advocate the use of preoperative HbA1c as a tool for clinicians and surgeons to guide therapy and counsel patients interested in weight loss surgery. Furthermore, given the current data and in the absence of definitive research, we recommend stricter optimization of preoperative HbA1c and the postoperative glucose level, because these were associated with improved postoperative outcomes. Additional studies are needed, focusing on the timing and degree of preoperative optimization as it affects the peri- and postoperative outcomes. The present study had several limitations. First, it was a retrospective study, prone to the usual bias and potential confounders. Relative to the Bariatric Outcome Longitudinal Database study, our patient numbers were small, ultimately limiting the statistical power of the present study. Finally, patient compliance with therapy, which is difficult to control for in a retrospective study, might have influenced the results of our study. References [1] International Expert Committee. International Expert Committee report on the role of the A1C assay in the diagnosis of diabetes. Diabetes Care 2009;32:1327–34. [2] Cowie CC, Rust KF, Byrd-Holt DD, et al. Prevalence of diabetes and impaired fasting glucose in adults in the U.S. population: National Health and Nutrition Examination survey 19992002. Diabetes Care 2006;29:1263– 8. [3] Engelgau MM, Geiss LS, Saaddine JB, et al. The evolving diabetes burden in the United States. Ann Intern Med 2004;140:945–50.

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