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Fasting glycemia: A good predictor of weight loss after RYGB
Surgery for Obesity and Related Diseases ] (2014) 00–00
Original article
Fasting glycemia: a good predictor of weight loss after RYGB Gil Faria, M.D., M.Sc.a,*, John Preto, M.D., M.Sc.a,b, Ana Beatriz Almeida, M.D.a,b, João Tiago Guimarães, M.D., Ph.D.c,d, Conceição Calhau, Ph.D.c, António Taveira-Gomes, M.D., Ph.D.a a
Department of Surgery, Faculty of Medicine, University of Porto, Portugal b Department of Surgery, São João Medical Center, Portugal c Department of Biochemistry, Faculty of Medicine, University of Porto, Portugal d Department of Clinical Pathology, São João Medical Center, Porto, Portugal Received June 26, 2012; accepted November 7, 2013
Abstract
Background: Preoperative prediction of weight loss after Roux-en-Y gastric bypass (RYGB) could help surgeons in managing surgical lists and patients’ expectations. The objective of this study was to understand if preoperative metabolic control might improve surgical results. Methods: Prospective cohort of 163 consecutive patients who underwent RYGB with at least 1 year of follow-up. Results: Most patients were female (90.2%), with a mean age of 38 (19–60) and a BMI of 46.0 (34.3–59.9) kg/m2. After 12 months, the mean body mass index (BMI) was 29.7 kg/m2 (21.5–39.9) with a corresponding percentage of excess weight lost (%EWL) of 78.8% and a percentage of weight loss (%WL) of 35.1%. Patients with the highest preoperative fasting blood glucose (FBG) were older (42 versus 36; P o .001); were more likely to have type 2 diabetes (T2 DM, 40% versus 6.8%; P o .001) and metabolic syndrome (89% versus 25%; P o .001), had a slightly higher BMI (30.8 versus 29.3 kg/ m2; P ¼ .03), and had achieved a significantly lower %EWL and %WL at 12 months (72.5% versus 81.2%; P ¼ .004; 33.2 versus 35.9%; P ¼ .03, respectively). We observed a dose-response effect with increasing FBG (o85 mg/dL, 85–100 mg/dL, and Z100 mg/dL, respectively), with 83.5%, 80.0%, and 72.5% (P ¼ .009) of %EWL at 12 months. By multivariate logistic regression, initial BMI and FBG 4100, were the only variables related (inversely) with the probability of achieving a %EWL 480 or %WL 435. This effect was not detected in patients receiving oral antidiabetic medications. Conclusion: Higher preoperative FBG is independently related to a poorer weight loss 12 months after RYGB; this suggests the need to offer earlier surgical intervention for severely obese patients with impairment of glucose metabolism. The potential for less weight loss in patients with a higher FBG should not discourage RYGB, given the significant metabolic improvement after surgery. (Surg Obes Relat Dis 2014;]:00–00.) r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.
Keywords:
Roux-en-Y gastric bypass; Bariatric surgery; Predictors of weight loss; Fasting glycemia
This work was supported by Fundação Ciência e Tecnologia, through Programa Operacional Potencial Humano da EU (POPH); PEst-OE/SAU/ UI0038/2011, and by a grant from the Harvard Medical School Portugal Program—HMSP-ICJ/SAU-ICT/0007/2009). * Correspondence: Gil Faria, Department of Surgery, Faculty of Medicine, University of Porto, Al Prof. Hernani Monteiro, HSJ Piso 5, Cirurgia Geral, 4200-319 Porto, Portugal. E-mail: [email protected]
Bariatric surgery has been proven to be the most effective and durable treatment [1] for the 21st century epidemic of obesity and the metabolic syndrome. The number of weight loss operations for the treatment of obesity is rapidly increasing all over the world, and most patients achieve a satisfactory weight loss after Roux-en-Y gastric bypass (RYGB). However, up to 18% of patients fail to achieve
1550-7289/14/$ – see front matter r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved. http://dx.doi.org/10.1016/j.soard.2013.11.005
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G. Faria et al. / Surgery for Obesity and Related Diseases ] (2014) 00–00
a body mass index (BMI) o35 kg/m2, and unsuccessful weight loss has been reported in 10%–30% of patients who have undergone bariatric surgery [2]. Several factors, such as gastric pouch size [3], limb length [4], gender [5,6], age [7], socioeconomic status [8,9] and psychological factors [10], have been associated with variations in weight loss, although reasons for individual differences in weight loss are not yet been fully understood. Some studies have concluded that patients with type 2 diabetes mellitus (T2 DM) and metabolic syndrome achieved a lower weight loss, in spite of a significant metabolic improvement [5,7,11–13]. The severity of diabetes [11] and its improvement [14] also are directly related to the percentage of excess weight loss (%EWL). However, some reports have questioned those findings and shown a similar weight loss for patients with and without T2 DM [15], and Perna et al. [16] concluded that uncontrolled T2 DM, before surgery, was related to poor weight loss. Even if weight loss is not the single measure of success after bariatric surgery, the identification of preoperative predictors of weight loss may be important to manage patients’ expectations, to manage surgical lists, and to identify patients who might benefit from tailor-made surgical approaches and closer follow-up [2,13]. As such, the main purpose in designing this study was to identify which preoperative factors might predict weight loss at 12 months. Specifically, the authors wanted to address if a simple measure such as fasting blood glucose (FBG) could be used to predict weight loss outcomes after RYGB. Methods After approval by the institutional ethics review board and written informed consent from all patients participating in the study, a prospective cohort of 163 consecutive patients who had laparoscopic RYGB were recruited at our Medical Center between January 2009 and June 2011. All patients met the inclusion criteria for bariatric surgery (having a BMI 440 kg/m2 or 435 kg/m2 with obesityassociated co-morbidities) and underwent a multidisciplinary preoperative evaluation and the same clinical and nutritional follow-up protocol. All surgeries were performed laparoscopically by a standardized technique. The biliary limb was measured to 70 cm and the alimentary limb to 150 cm. The gastrojejunostomy was constructed semi-mechanically with a linear stapler calibrated over a 36 Fr bougie. Both anastomoses were tested for patency and leakage with methylene blue. As per protocol, patients started oral feeding on the third postoperative day and were discharged after the fifth postoperative day. Antibiotic prophylaxis was performed with a second-generation cephalosporin, and thromboprophylaxis was achieved with low-molecular-weight heparin. Patients were on a proton pump inhibitor for 2 months after
surgery and followed a progressive nutritional regimen. All patients were placed on a multivitamin dietary supplement indefinitely. Follow-up visits at 1, 3, 6, and 12 months were scheduled for every patient. Venous blood samples were collected after an overnight fasting. Preoperative samples were collected between 1 and 3 months before surgery, and postoperative samples were collected 12 months after the surgery. Insulin and C-peptide were measured by an electrochemiluminescent immunoassay using a Cobas e411 automated analyser (Roche, Lisboa, Portugal). Blood glucose was measured using conventional methods with an Olympus AU5400 automated clinical chemistry analyser (Beckman-Coulter, Izasa, Porto, Portugal), and HbA1c was determined by an ion-exchange high-performance liquid chromatography system with a D-10 Bio-Rad analyser (Bio-Rad, Porto, Portugal). The statistical analysis was performed with PASWStatistics v. 18.0 for Macintosh. Two-groups comparisons were performed with the t test, chi-square, or oneway ANOVA tests, as appropriate. Three group comparisons were performed with ANOVA test. Correlations were analyzed with the Pearson correlation, and the multivariate models were analyzed with logistic regression models. All values were considered statistically significant for P o .05.
Results Most patients were female (90.2%) with a mean age of 38 years (19–60 yr) (Table 1). Follow-up was complete for 161 of 163 patients (98.8%), and the mean %EWL and %WL at 12 months was 78.8% and 35.1%, respectively, with 44% of the patients achieving a %EWL Z80 and 46.6% of the patients achieving a %WL Z35. Perioperative complications occurred in 9 patients (5%): 3 anastomotic hemorrhages, 1 intraabdominal bleeding, Table 1 Patients characterization (n ¼ 163)
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Initial BMI (kg/m ) 12 months BMI (kg/m2) %EWL 12 months %WL 12 months Age
T2 DM (%) Metabolic syndrome (%) Hypoglycemic agents (%)
FBG (mg/dL) HbA1c (%)
Mean (⫾SD)
Range
46.0 ⫾ 4.7 29.7 ⫾ 4.0 78.8 ⫾ 17.3 35.15 ⫾ 7.2 38.14 ⫾ 9.4
34.3–59.9 21.5–39.9 34.7–122.5 15.0–54.4 19–60
%
n
16.6 42.9 19.0
27 70 31
Median
Range
92 5.6
65–196 4.8–9.8
BMI ¼ body mass index; %EWL ¼ percentage of excess weight loss; FBG ¼ fasting blood glucose; T2 DM ¼ type 2 diabetes mellitus; %WL ¼ percentage of weight lost.
Fasting Glycemia and Weight Loss After RYGB / Surgery for Obesity and Related Diseases ] (2014) 00–00
2 deep vein thrombosis, 1 intraabdominal abscess, 1 pulmonary infection, and 1 urinary tract infection. Only 1 (.6%) patient required reintervention for control of intraabdominal hemorrhage and 1 patient required percutaneous drainage of an intraabdominal abscess. Long-term complications developed in 7 patients (4.3%): 3 anastomotic strictures, 3 anastomotic ulcers, and 1 symptomatic recurrent hypoglycemia. All patients were managed endoscopically and/or with dietary counseling. The comparison of the characteristics of patients according to %EWL is depicted in Table 2. Patients with % EWL Z80% had a lower baseline BMI and lower values for FBG, insulin, and C-peptide. No other significant differences were found between patients with %EWL Z80% and o80% at 12 months or %WL Z35% or o35%. Patients with T2 DM were older (46 versus 36 years; P o .001) and had a comparable BMI at baseline (46.2 versus 46.0 kg/m2; P ¼ .78) but had a lower %EWL at 12 months (71.1% versus 80.4%; P ¼ .01), %WL (32.2% versus 35.7%; P ¼ .02) and ended the follow-up period with a higher BMI (31.3 versus 29.4 kg/m2; P ¼ .02). There was no relation between HbA1c and %EWL (P ¼ .13) or %WL (P ¼ .36). Metabolic control (as measured by FBG) was directly related to the lowest weight loss, increasing age, and higher prevalence of metabolic syndrome (Table 3). Patients younger than 50 years had higher weight loss (%EWL ¼ 80% versus 70%; P ¼ .01; %WL ¼ 36% versus 32%; P ¼ .04). Patients with preoperative FBG higher than
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100 mg/dL were older by approximately 6 years (Table 3), and patients older than 50 years had higher mean FBG (111 mg/dL versus 93 mg/dL; P o .001). By dividing FBG into 3 categories (o85 mg/dL; [85– 100] mg/dL; Z100 mg/dL), we observed a dose-response effect, respectively, with 83.5% ⫾ 19.4, 80.0% ⫾ 15.6, and 72.5% ⫾ 16.5 of %EWL (P ¼ .009; Fig. 1). A multivariable forward conditional logistic regression for a %EWL at 12 months Z80%, showed that after correction for initial BMI (odds ratio (OR) ¼ .85; P ¼ .001), the preoperative FBG 4100 (OR ¼ .32; P ¼ .02) was the only factor independently (and inversely) related to the outcome. A multivariable logistic regression concluded that only the initial BMI and the FBG 4100 were independently related to the weight loss (Table 4). In patients being treated with antidiabetic medications, there was no relation between FBG and weight loss at 12 months. The association between preoperative FBG and %EWL (and %WL) at 12 months was only significant for patients without these medications. (Fig. 2). Patients with the worst FBG had a significant improvement in metabolic control, such that 89% of patients had metabolic syndrome before RYGB and only 22% (P o .001) fulfilled the criteria 12 months after surgery (Table 5). Discussion Weight control (as low perioperative morbidity and comorbid condition resolution) are the key factors to define a
Table 2 Univariate analysis of patients’ characteristics according to %EWL class
Initial BMI Age Evolution of obesity (years) Physical activity (1–4) Glucose (mg/dL) HbA1c (%) C-peptide (ng/mL) Insulin (μUI/L) T2 DM Metabolic syndrome
Initial BMI Age Evolution of obesity (years) Physical activity (1–4) Glucose (mg/dL) HbA1c (%) C-peptide (ng/mL) Insulin (μUI/L) T2 DM Metabolic syndrome
EWL12 o 80% (n ¼ 90)
EWL12 4 80% (n ¼ 71)
P value
47.3 ⫾ 4.6 39.1 ⫾ 9.7 19.3 ⫾ 8.9 2.3 ⫾ 0.74 97 ⫾ 20 5.72 ⫾ 0.67 4.13 ⫾ 1.32 21.8 ⫾12.6 20% 48.9%
44.3 ⫾ 4.2 37.1 ⫾ 8.9 18.0 ⫾ 8.0 2.3 ⫾ 0.75 93 ⫾ 10 5.56 ⫾ 0.56 3.70 ⫾ 1.01 17.5 ⫾ 9.18 12.7% 36.6%
o.001 .17 .40 .86 .08 .13 .05 .02 .22 .12
WL12 o35% (n ¼ 86)
WL12 435% (n ¼ 75)
P value
45.1 ⫾ 4.4 39.2 ⫾ 9.7 19.3 ⫾ 8.8 2.3 ⫾ 0.72 96 ⫾ 18 5.63 ⫾ 0.54 4.01 ⫾ 1.32 20.8 ⫾12.2 22.1% 45.3%
46.9 ⫾ 4.8 37.2 ⫾ 8.9 18.1 ⫾ 8.2 2.3 ⫾ 0.77 94 ⫾ 18 5.69 ⫾ 0.72 3.86 ⫾ 1.07 18.8 ⫾ 10.4 10.7% 41.3%
.01 .16 .39 .91 .18 .74 .51 .29 .10 .60
BMI ¼ body mass index; %EWL ¼ percentage of excess weight loss; EWL12 ¼ excess weight loss at 12 months; T2 DM ¼ type 2 diabetes mellitus; WL12 ¼ weight loss at 12 months.
G. Faria et al. / Surgery for Obesity and Related Diseases ] (2014) 00–00
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Table 3 Patients’ characteristics according to FBG class
Table 4 Multivariable logistic regression for measures of weight loss at 12 months
FBG o100 mg/dL FBG Z100 mg /dL P value Mean ⫾ SD (n ¼ 116) Mean ⫾ SD (n ¼ 45) Initial BMI Age Obesity duration (years) Physical activity (1–4) Glucose (mg/ dL) HbA1c (%) C-peptide (ng/ mL) Insulin (μUI/L) T2 DM Metabolic syndrome Hypoglycemic treatment
45.8 ⫾ 5.0 36.4 ⫾ 8.8 18.7 ⫾ 8.8
46.5 ⫾ 3 .8 42.5 ⫾ 9.8 18.4 ⫾ 8.4
.48 o.001 .88
2.3 ⫾ 0.76
2.3 ⫾ 0.72
.76
87 ⫾ 7
117 ⫾ 20
o.001
5.44 ⫾ 0.38 3.7 ⫾ 1.1
6.20 ⫾ 0.81 4.8 ⫾ 1–3
o.001 o.001
18.7 ⫾ 11.4 6.8% (8) 24.8% (29)
24.0 ⫾ 10.3 40% (18) 88.9% (40)
.01 o.001 o.001
7.7% (9)
46.7% (21)
o.001
78 ⫾ 8
85 ⫾ 10
o.001
5.2 ⫾ 0.34 7.3 ⫾ 3.6 29.3 ⫾ 4.1 81.2 ⫾ 17.1 35.9 ⫾ 6.8
5.5 ⫾ 0.38 7.7 ⫾ 3.8 30.8 ⫾ 5.7 72.5 ⫾ 16.5 33.2 ⫾ 7.9
o.001 .48 .03 .004 .03
12 months postop Glucose (mg/ dL) HbA1c (%) Insulin (μUI/L) BMI %EWL %WL
BMI ¼ body mass index; %EWL ¼ percentage of excess weight loss; T2 DM ¼ type 2 diabetes mellitus.
successful bariatric operation. Although there is a significant metabolic improvement after a modest weight loss, greater and long-term weight control are required to achieve all of the long-term benefits related with RYGB [17].
Figure 1. Percentage of excess weight lost at 12 months (EWL12), according to group of glycemic control.
Initial BMI FBG 4100 T2 DM Metabolic syndrome Hypoglycemic treatment Age Physical activity
%EWL Z80%
%WL Z35%
OR
P value
OR
P value
0.856 0.275 0.503 0.861 2.73 0.983 0.981
.001 .038 .60 .41 .41 .46 .94
1.092 0.386 0.121 1.584 4.724 0.988 1.144
.038 .048 .111 .061 .205 .603 .605
BMI ¼ body mass index; %EWL ¼ percentage of excess weight loss; T2 DM ¼ type 2 diabetes mellitus; %WL; percentage of weight loss.
For this study, we selected a 1-year follow-up, because it usually represents the time at which the optimal weight loss is observed after bariatric surgery [18]. There is not a consensus of what constitutes a successful weight loss after RYGB, and some authors have reported that a loss of 40%– 50% of the excess weight might be considered acceptable [5,7,19,20]. Our main objective was to identify which patients achieved a greater weight loss, and as such, we decided to use 80% of EWL (and 35% of WL) as our cut-off value, because it was our retrospective median sample in the patients who underwent surgery before the start of this study. Similar to what has been previously reported [2,7,21], patients presented a high interindividual %EWL variability, with a roughly normal distribution whose mean was centered at 78.8% (⫾17%). Thus, it is paramount to understand which factors might be responsible for these variations. Several studies have previously reported that the presence of T2 DM was related to suboptimal weight loss after this surgery [2,5,7,11–13,20,21] . However, this finding has not
Figure 2. Percentage of Excess Weight Lost (%EWL) according to glycemic control and hypoglycemic treatment status.
Fasting Glycemia and Weight Loss After RYGB / Surgery for Obesity and Related Diseases ] (2014) 00–00 Table 5 Metabolic improvement for patients with FBG Z100 mg/dL (n ¼ 45)
Initial BMI Glucose (mg/dL) Insulin (μUI/L) Cholesterol (mg/dL) HDL-c (mg/dL) Triglycerides (mg/dL) T2 DM Metabolic syndrome
Preoperative
12 months
P value
46.5 ⫾ 3.8 117 ⫾ 20 24.0 ⫾ 10 204 ⫾ 39 50 ⫾ 13 145 ⫾ 75 40.0% (18) 88.9% (40)
30.8 ⫾ 3.7 85 ⫾ 10 8.3 ⫾ 4 183 ⫾ 29 60 ⫾ 16 106 ⫾ 35 22.2% (10) 22.2% (10)
o.001 o.001 o.001 .005 .001 .002 o.001 o.001
BMI ¼ body mass index; FBG ¼ fasting blood glucose; T2 DM ¼ type 2 diabetes mellitus
been consistently reported in all the surgical series, and some authors defend that when controlled for other preoperative factors (initial BMI, age, gender, and race), patients with T2 DM have similar results to patients without T2 DM [6,15]. Some authors have postulated that T2 DM was related to a higher degree of insulin resistance and, thus, to higher circulating insulin levels. Insulin, being an anabolic hormone that promotes lipogenesis, might be responsible for a lower degree of weight loss after RYGB [20,22]. Also, intensive treatment for T2 DM (with higher circulating levels of insulin), although related to lower microvascular complications, has been shown to cause a small but significant weight gain [23]. Some reports [2,8,16] have stated that poor long-term glycemic control, as measured by HbA1c, is related to less weight loss after RYGB and even that it is the metabolic control (rather than the presence of T2 DM) that is related to weight loss. Other authors [11,24] proposed that the degree of beta-cell function and the severity of diabetes are linked to the amount of weight loss. In the present sample, after correction for initial BMI, the preoperative glucose control (FBG) was the only factor independently related to weight loss. This suggests that it was not the simple presence of diabetes or resistance to insulin that were related to poorer weight loss. Even for patients with “normal” FBG, it seems that the lowest glucose levels render the best possible outcome. However, it is important to remember that patients with T2 DM may be those with a greater health gain after RYGB, because they experience a significant metabolic improvement [2,15,17] that is not directly related to the amount of weight loss. In spite of this, lower glucose values might just be a surrogate marker for patient compliance with nutritional regimen and, thus, explain the association of lower glucose values with better weight loss at 12 months. One of the strongest predictors for the %EWL has been the initial BMI [2,5–7,21,25] or weight [26]. Several studies have reported this, and it is reasonable to assume that heavier patients have more weight to lose and, as such, have more difficulty in achieving a higher %EWL [6,9,21,27]. Acknowledging this, we considered it important to control
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for this effect in the multivariable analysis. In our sample, there was an inverse correlation between preoperative BMI and weight loss at 12 months. Increasing age has also been related to a lower weight loss after RYGB (and gastric band [27,28]), and several explanations (energy expenditure, physical exercise, lipolysis deficiencies, and psycho-social factors) have been proposed to explain this finding [2,6,7]. In our sample, patients 450 years lost less weight and had higher BMIs at 12 months, which is in accordance with previous reports [6]. Older patients have a higher prevalence and increased severity of T2 DM [11], and in our sample, older patients had higher preoperative FBG levels. In the multivariable analysis, the effect of age was decreased by the effect of FBG. As such, this can be an alternative explanation for the finding of an inverse relation between age and weight loss: it is the increasing metabolic impairment (associated with increasing age) that is related to the poorest outcomes after surgery. Patients with higher FBG are expected to produce more insulin to maintain homeostasis. This environment of hyperinsulinism might be related to a resistance to weight loss, as insulin promotes lipogenesis and inhibits lipolysis [29]. This might explain why several clinical manifestations of glucose homeostasis (T2 DM, insulin resistance, HbA1c, and FBG) have been associated with variations in postoperative weight loss. One appealing hypothesis would be that if FBG is related to weight loss, we could improve the surgical results by lowering glucose levels with antidiabetic medications. From the analysis of our patients, it seems that this effect is only seen in patients who are not being treated with hypoglycemic agents. This finding would need further directed research, ideally with a randomized trial between preoperative glucose optimization or immediate surgery in patients with poor metabolic control. From the present results, it seems that metabolic control is a surrogate marker of the metabolic disease burden and that patients with lower FBG have lower disease burden and, hence, better weight loss after surgery. In spite of less weight loss after RYGB, patients with poor metabolic control have achieved a significant improvement in their metabolic disease, such that, as previously reported, the metabolic improvement is not directly related to weight loss [30]. Some of the strongest aspects of this study are that it is based on a prospective cohort with a thorough clinical characterization of the diabetic status and metabolic control of these patients and that it included a high percentage (99%) of complete follow-up at 12 months. Also, although performed by 5 different surgeons, the surgical technique was standardized, and there were no significant variations of results among surgeons. Some of its limitations are the relatively limited sample size and the short follow-up period. One of the important aspects to
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G. Faria et al. / Surgery for Obesity and Related Diseases ] (2014) 00–00
analyze in future studies is the effect of the preoperative metabolic control on long-term weight control and weight regain. Conclusion Higher preoperative FBG was independently related to a poorer weight loss after RYGB. This association might explain why older patients and patients with T2 DM or insulin resistance have been reported to have a poorer weight loss. Lowering FBG with antidiabetic medications was unrelated to an improvement in surgical outcomes. Our results suggest the need to offer surgical treatment to obese patients with insulin resistance earlier, before severe metabolic illness progresses. The potential for less weight loss in patients with poorest glucose control should not discourage RYGB, given the significant metabolic improvement after surgery. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. References [1] Sjöström L, Lindroos A-K, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004;351:2683–93. [2] Ortega E, Morínigo R, Flores L, et al. Predictive factors of excess body weight loss 1 year after laparoscopic bariatric surgery. Surg Endosc 2012;26:1744–50. [3] Roberts K, Duffy A, Kaufman J, Burrell M, Dziura J, Bell R. Size matters: gastric pouch size correlates with weight loss after laparoscopic Roux-en-Y gastric bypass. Surg Endosc 2007;21:1397–402. [4] Ciovica R, Takata M, Vittinghoff E, et al. The impact of roux limb length on weight loss after gastric bypass. Obes Surg 2008;18:5–10. [5] Melton GB, Steele KE, Schweitzer MA, Lidor AO, Magnuson TH. Suboptimal weight loss after gastric bypass surgery: Correlation of demographics, comorbidities, and insurance status with outcomes. J Gastrointest Surg 2007;12:250–5. [6] Scozzari G, Passera R, Benvenga R, Toppino M, Morino M. Age as a long-term prognostic factor in bariatric surgery. Ann Surg 2012;256: 724–9. [7] Ma Y, Pagoto S, Olendzki B, et al. predictors of weight status following laparoscopic gastric bypass. Obes Surg 2006;16:1227–31. [8] Lee Y-C, Lee W-J, Lee T-S, et al. Prediction of successful weight reduction after bariatric surgery by data mining technologies. Obes Surg 2007;17:1235–41. [9] Júnior WS, Nonino-Borges CB. Clinical predictors of different grades of nonalcoholic fatty liver disease. Obes Surg 2012;22:248–52. [10] Ray EC, Nickels MW, Sayeed S, Sax HC. Predicting success after gastric bypass: the role of psychosocial and behavioral factors. Surgery 2003;134:555–63; discussion 563–4.
[11] Carbonell AM, Wolfe LG, Meador JG, Sugerman HJ, Kellum JM, Maher JW. Does diabetes affect weight loss after gastric bypass? Surg Obes Relat Dis 2008;4:441–4 [12] Perugini RA, Mason R, Czerniach DR, et al. Predictors of complication and suboptimal weight loss after laparoscopic Roux-en-Y gastric bypass: a series of 188 patients. Arch Surg 2003;138:541–5, discussion 545–6. [13] Júnior WS, do Amaral JL, Nonino-Borges CB. Factors related to weight loss up to 4 years after bariatric surgery. Obes Surg 2011;21: 1724–30. [14] Kadera BE, Lum K, Grant J, Pryor AD, Portenier DD, DeMaria EJ. Remission of type 2 diabetes after Roux-en-Y gastric bypass is associated with greater weight loss. Surg Obes Relat Dis 2009;5: 305–9. [15] Yip K, Heinberg L, Giegerich V, Schauer PR, Kashyap SR. Equivalent weight loss with marked metabolic benefit observed in a matched cohort with and without type 2 diabetes 12 months following gastric bypass surgery. Obes Surg 2012;22:1723–9. [16] Perna M, Romagnuolo J, Morgan K, Byrne TK, Baker M. Preoperative hemoglobin A1c and postoperative glucose control in outcomes after gastric bypass for obesity. Surg Obes Relat Dis 2012;8:685–90. [17] Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004;292:1724–37. [18] Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357: 741–52. [19] Prachand VN, Ward M, Alverdy JC. Duodenal switch provides superior resolution of metabolic comorbidities independent of weight loss in the super-obese (BMI Z50 kg/m2) compared with gastric bypass. J Gastrointest Surg 2010;14:211–20. [20] Campos GM, Rabl C, Mulligan K, et al. Factors associated with weight loss after gastric bypass. Arch Surg 2008;143:877–83; discussion 884. [21] Hatoum IJ, Stein HK, Merrifield BF, Kaplan LM. Capacity for physical activity predicts weight loss after Roux-en-Y gastric bypass. Obesity (Silver Spring) 2009;17:92–9. [22] Flier J, Maratos-Flier E. Energy homeostasis and body weight. Curr Biol 2000;10:R215–7. [23] Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837–53. [24] Nannipieri M, Mari A, Anselmino M, et al. The role of beta-cell function and insulin sensitivity in the remission of type 2 diabetes after gastric bypass surgery. J Clin Endocrinol Metab 2011;96: E1372–9. [25] Lutfi R, Torquati A, Sekhar N, Richards WO. Predictors of success after laparoscopic gastric bypass: a multivariate analysis of socioeconomic factors. Surg Endosc 2006;20:864–7. [26] Sczepaniak JP, Owens ML, Garner W, Dako F, Masukawa K, Wilson SE. A simpler method for predicting weight loss in the first year after Roux-en-Y gastric bypass. J Obes. Epub 2012 Jan 19. [27] Dixon JB, Dixon ME, O'Brien PE. Pre-operative predictors of weight loss at 1-year after Lap-Band surgery. Obes Surg 2001;11:200–7. [28] Chevallier J-M, Paita M, Rodde-Dunet M-H, et al. Predictive factors of outcome after gastric banding: a nationwide survey on the role of center activity and patients' behavior. Ann Surg 2007;246:1034–9. [29] Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest 2000;106:473–81. [30] Ikramuddin S, Buchwald H. How bariatric and metabolic operations control metabolic syndrome. Br J Surg 2011;98:1339–41.
Original article
Fasting glycemia: a good predictor of weight loss after RYGB Gil Faria, M.D., M.Sc.a,*, John Preto, M.D., M.Sc.a,b, Ana Beatriz Almeida, M.D.a,b, João Tiago Guimarães, M.D., Ph.D.c,d, Conceição Calhau, Ph.D.c, António Taveira-Gomes, M.D., Ph.D.a a
Department of Surgery, Faculty of Medicine, University of Porto, Portugal b Department of Surgery, São João Medical Center, Portugal c Department of Biochemistry, Faculty of Medicine, University of Porto, Portugal d Department of Clinical Pathology, São João Medical Center, Porto, Portugal Received June 26, 2012; accepted November 7, 2013
Abstract
Background: Preoperative prediction of weight loss after Roux-en-Y gastric bypass (RYGB) could help surgeons in managing surgical lists and patients’ expectations. The objective of this study was to understand if preoperative metabolic control might improve surgical results. Methods: Prospective cohort of 163 consecutive patients who underwent RYGB with at least 1 year of follow-up. Results: Most patients were female (90.2%), with a mean age of 38 (19–60) and a BMI of 46.0 (34.3–59.9) kg/m2. After 12 months, the mean body mass index (BMI) was 29.7 kg/m2 (21.5–39.9) with a corresponding percentage of excess weight lost (%EWL) of 78.8% and a percentage of weight loss (%WL) of 35.1%. Patients with the highest preoperative fasting blood glucose (FBG) were older (42 versus 36; P o .001); were more likely to have type 2 diabetes (T2 DM, 40% versus 6.8%; P o .001) and metabolic syndrome (89% versus 25%; P o .001), had a slightly higher BMI (30.8 versus 29.3 kg/ m2; P ¼ .03), and had achieved a significantly lower %EWL and %WL at 12 months (72.5% versus 81.2%; P ¼ .004; 33.2 versus 35.9%; P ¼ .03, respectively). We observed a dose-response effect with increasing FBG (o85 mg/dL, 85–100 mg/dL, and Z100 mg/dL, respectively), with 83.5%, 80.0%, and 72.5% (P ¼ .009) of %EWL at 12 months. By multivariate logistic regression, initial BMI and FBG 4100, were the only variables related (inversely) with the probability of achieving a %EWL 480 or %WL 435. This effect was not detected in patients receiving oral antidiabetic medications. Conclusion: Higher preoperative FBG is independently related to a poorer weight loss 12 months after RYGB; this suggests the need to offer earlier surgical intervention for severely obese patients with impairment of glucose metabolism. The potential for less weight loss in patients with a higher FBG should not discourage RYGB, given the significant metabolic improvement after surgery. (Surg Obes Relat Dis 2014;]:00–00.) r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved.
Keywords:
Roux-en-Y gastric bypass; Bariatric surgery; Predictors of weight loss; Fasting glycemia
This work was supported by Fundação Ciência e Tecnologia, through Programa Operacional Potencial Humano da EU (POPH); PEst-OE/SAU/ UI0038/2011, and by a grant from the Harvard Medical School Portugal Program—HMSP-ICJ/SAU-ICT/0007/2009). * Correspondence: Gil Faria, Department of Surgery, Faculty of Medicine, University of Porto, Al Prof. Hernani Monteiro, HSJ Piso 5, Cirurgia Geral, 4200-319 Porto, Portugal. E-mail: [email protected]
Bariatric surgery has been proven to be the most effective and durable treatment [1] for the 21st century epidemic of obesity and the metabolic syndrome. The number of weight loss operations for the treatment of obesity is rapidly increasing all over the world, and most patients achieve a satisfactory weight loss after Roux-en-Y gastric bypass (RYGB). However, up to 18% of patients fail to achieve
1550-7289/14/$ – see front matter r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved. http://dx.doi.org/10.1016/j.soard.2013.11.005
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G. Faria et al. / Surgery for Obesity and Related Diseases ] (2014) 00–00
a body mass index (BMI) o35 kg/m2, and unsuccessful weight loss has been reported in 10%–30% of patients who have undergone bariatric surgery [2]. Several factors, such as gastric pouch size [3], limb length [4], gender [5,6], age [7], socioeconomic status [8,9] and psychological factors [10], have been associated with variations in weight loss, although reasons for individual differences in weight loss are not yet been fully understood. Some studies have concluded that patients with type 2 diabetes mellitus (T2 DM) and metabolic syndrome achieved a lower weight loss, in spite of a significant metabolic improvement [5,7,11–13]. The severity of diabetes [11] and its improvement [14] also are directly related to the percentage of excess weight loss (%EWL). However, some reports have questioned those findings and shown a similar weight loss for patients with and without T2 DM [15], and Perna et al. [16] concluded that uncontrolled T2 DM, before surgery, was related to poor weight loss. Even if weight loss is not the single measure of success after bariatric surgery, the identification of preoperative predictors of weight loss may be important to manage patients’ expectations, to manage surgical lists, and to identify patients who might benefit from tailor-made surgical approaches and closer follow-up [2,13]. As such, the main purpose in designing this study was to identify which preoperative factors might predict weight loss at 12 months. Specifically, the authors wanted to address if a simple measure such as fasting blood glucose (FBG) could be used to predict weight loss outcomes after RYGB. Methods After approval by the institutional ethics review board and written informed consent from all patients participating in the study, a prospective cohort of 163 consecutive patients who had laparoscopic RYGB were recruited at our Medical Center between January 2009 and June 2011. All patients met the inclusion criteria for bariatric surgery (having a BMI 440 kg/m2 or 435 kg/m2 with obesityassociated co-morbidities) and underwent a multidisciplinary preoperative evaluation and the same clinical and nutritional follow-up protocol. All surgeries were performed laparoscopically by a standardized technique. The biliary limb was measured to 70 cm and the alimentary limb to 150 cm. The gastrojejunostomy was constructed semi-mechanically with a linear stapler calibrated over a 36 Fr bougie. Both anastomoses were tested for patency and leakage with methylene blue. As per protocol, patients started oral feeding on the third postoperative day and were discharged after the fifth postoperative day. Antibiotic prophylaxis was performed with a second-generation cephalosporin, and thromboprophylaxis was achieved with low-molecular-weight heparin. Patients were on a proton pump inhibitor for 2 months after
surgery and followed a progressive nutritional regimen. All patients were placed on a multivitamin dietary supplement indefinitely. Follow-up visits at 1, 3, 6, and 12 months were scheduled for every patient. Venous blood samples were collected after an overnight fasting. Preoperative samples were collected between 1 and 3 months before surgery, and postoperative samples were collected 12 months after the surgery. Insulin and C-peptide were measured by an electrochemiluminescent immunoassay using a Cobas e411 automated analyser (Roche, Lisboa, Portugal). Blood glucose was measured using conventional methods with an Olympus AU5400 automated clinical chemistry analyser (Beckman-Coulter, Izasa, Porto, Portugal), and HbA1c was determined by an ion-exchange high-performance liquid chromatography system with a D-10 Bio-Rad analyser (Bio-Rad, Porto, Portugal). The statistical analysis was performed with PASWStatistics v. 18.0 for Macintosh. Two-groups comparisons were performed with the t test, chi-square, or oneway ANOVA tests, as appropriate. Three group comparisons were performed with ANOVA test. Correlations were analyzed with the Pearson correlation, and the multivariate models were analyzed with logistic regression models. All values were considered statistically significant for P o .05.
Results Most patients were female (90.2%) with a mean age of 38 years (19–60 yr) (Table 1). Follow-up was complete for 161 of 163 patients (98.8%), and the mean %EWL and %WL at 12 months was 78.8% and 35.1%, respectively, with 44% of the patients achieving a %EWL Z80 and 46.6% of the patients achieving a %WL Z35. Perioperative complications occurred in 9 patients (5%): 3 anastomotic hemorrhages, 1 intraabdominal bleeding, Table 1 Patients characterization (n ¼ 163)
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Initial BMI (kg/m ) 12 months BMI (kg/m2) %EWL 12 months %WL 12 months Age
T2 DM (%) Metabolic syndrome (%) Hypoglycemic agents (%)
FBG (mg/dL) HbA1c (%)
Mean (⫾SD)
Range
46.0 ⫾ 4.7 29.7 ⫾ 4.0 78.8 ⫾ 17.3 35.15 ⫾ 7.2 38.14 ⫾ 9.4
34.3–59.9 21.5–39.9 34.7–122.5 15.0–54.4 19–60
%
n
16.6 42.9 19.0
27 70 31
Median
Range
92 5.6
65–196 4.8–9.8
BMI ¼ body mass index; %EWL ¼ percentage of excess weight loss; FBG ¼ fasting blood glucose; T2 DM ¼ type 2 diabetes mellitus; %WL ¼ percentage of weight lost.
Fasting Glycemia and Weight Loss After RYGB / Surgery for Obesity and Related Diseases ] (2014) 00–00
2 deep vein thrombosis, 1 intraabdominal abscess, 1 pulmonary infection, and 1 urinary tract infection. Only 1 (.6%) patient required reintervention for control of intraabdominal hemorrhage and 1 patient required percutaneous drainage of an intraabdominal abscess. Long-term complications developed in 7 patients (4.3%): 3 anastomotic strictures, 3 anastomotic ulcers, and 1 symptomatic recurrent hypoglycemia. All patients were managed endoscopically and/or with dietary counseling. The comparison of the characteristics of patients according to %EWL is depicted in Table 2. Patients with % EWL Z80% had a lower baseline BMI and lower values for FBG, insulin, and C-peptide. No other significant differences were found between patients with %EWL Z80% and o80% at 12 months or %WL Z35% or o35%. Patients with T2 DM were older (46 versus 36 years; P o .001) and had a comparable BMI at baseline (46.2 versus 46.0 kg/m2; P ¼ .78) but had a lower %EWL at 12 months (71.1% versus 80.4%; P ¼ .01), %WL (32.2% versus 35.7%; P ¼ .02) and ended the follow-up period with a higher BMI (31.3 versus 29.4 kg/m2; P ¼ .02). There was no relation between HbA1c and %EWL (P ¼ .13) or %WL (P ¼ .36). Metabolic control (as measured by FBG) was directly related to the lowest weight loss, increasing age, and higher prevalence of metabolic syndrome (Table 3). Patients younger than 50 years had higher weight loss (%EWL ¼ 80% versus 70%; P ¼ .01; %WL ¼ 36% versus 32%; P ¼ .04). Patients with preoperative FBG higher than
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100 mg/dL were older by approximately 6 years (Table 3), and patients older than 50 years had higher mean FBG (111 mg/dL versus 93 mg/dL; P o .001). By dividing FBG into 3 categories (o85 mg/dL; [85– 100] mg/dL; Z100 mg/dL), we observed a dose-response effect, respectively, with 83.5% ⫾ 19.4, 80.0% ⫾ 15.6, and 72.5% ⫾ 16.5 of %EWL (P ¼ .009; Fig. 1). A multivariable forward conditional logistic regression for a %EWL at 12 months Z80%, showed that after correction for initial BMI (odds ratio (OR) ¼ .85; P ¼ .001), the preoperative FBG 4100 (OR ¼ .32; P ¼ .02) was the only factor independently (and inversely) related to the outcome. A multivariable logistic regression concluded that only the initial BMI and the FBG 4100 were independently related to the weight loss (Table 4). In patients being treated with antidiabetic medications, there was no relation between FBG and weight loss at 12 months. The association between preoperative FBG and %EWL (and %WL) at 12 months was only significant for patients without these medications. (Fig. 2). Patients with the worst FBG had a significant improvement in metabolic control, such that 89% of patients had metabolic syndrome before RYGB and only 22% (P o .001) fulfilled the criteria 12 months after surgery (Table 5). Discussion Weight control (as low perioperative morbidity and comorbid condition resolution) are the key factors to define a
Table 2 Univariate analysis of patients’ characteristics according to %EWL class
Initial BMI Age Evolution of obesity (years) Physical activity (1–4) Glucose (mg/dL) HbA1c (%) C-peptide (ng/mL) Insulin (μUI/L) T2 DM Metabolic syndrome
Initial BMI Age Evolution of obesity (years) Physical activity (1–4) Glucose (mg/dL) HbA1c (%) C-peptide (ng/mL) Insulin (μUI/L) T2 DM Metabolic syndrome
EWL12 o 80% (n ¼ 90)
EWL12 4 80% (n ¼ 71)
P value
47.3 ⫾ 4.6 39.1 ⫾ 9.7 19.3 ⫾ 8.9 2.3 ⫾ 0.74 97 ⫾ 20 5.72 ⫾ 0.67 4.13 ⫾ 1.32 21.8 ⫾12.6 20% 48.9%
44.3 ⫾ 4.2 37.1 ⫾ 8.9 18.0 ⫾ 8.0 2.3 ⫾ 0.75 93 ⫾ 10 5.56 ⫾ 0.56 3.70 ⫾ 1.01 17.5 ⫾ 9.18 12.7% 36.6%
o.001 .17 .40 .86 .08 .13 .05 .02 .22 .12
WL12 o35% (n ¼ 86)
WL12 435% (n ¼ 75)
P value
45.1 ⫾ 4.4 39.2 ⫾ 9.7 19.3 ⫾ 8.8 2.3 ⫾ 0.72 96 ⫾ 18 5.63 ⫾ 0.54 4.01 ⫾ 1.32 20.8 ⫾12.2 22.1% 45.3%
46.9 ⫾ 4.8 37.2 ⫾ 8.9 18.1 ⫾ 8.2 2.3 ⫾ 0.77 94 ⫾ 18 5.69 ⫾ 0.72 3.86 ⫾ 1.07 18.8 ⫾ 10.4 10.7% 41.3%
.01 .16 .39 .91 .18 .74 .51 .29 .10 .60
BMI ¼ body mass index; %EWL ¼ percentage of excess weight loss; EWL12 ¼ excess weight loss at 12 months; T2 DM ¼ type 2 diabetes mellitus; WL12 ¼ weight loss at 12 months.
G. Faria et al. / Surgery for Obesity and Related Diseases ] (2014) 00–00
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Table 3 Patients’ characteristics according to FBG class
Table 4 Multivariable logistic regression for measures of weight loss at 12 months
FBG o100 mg/dL FBG Z100 mg /dL P value Mean ⫾ SD (n ¼ 116) Mean ⫾ SD (n ¼ 45) Initial BMI Age Obesity duration (years) Physical activity (1–4) Glucose (mg/ dL) HbA1c (%) C-peptide (ng/ mL) Insulin (μUI/L) T2 DM Metabolic syndrome Hypoglycemic treatment
45.8 ⫾ 5.0 36.4 ⫾ 8.8 18.7 ⫾ 8.8
46.5 ⫾ 3 .8 42.5 ⫾ 9.8 18.4 ⫾ 8.4
.48 o.001 .88
2.3 ⫾ 0.76
2.3 ⫾ 0.72
.76
87 ⫾ 7
117 ⫾ 20
o.001
5.44 ⫾ 0.38 3.7 ⫾ 1.1
6.20 ⫾ 0.81 4.8 ⫾ 1–3
o.001 o.001
18.7 ⫾ 11.4 6.8% (8) 24.8% (29)
24.0 ⫾ 10.3 40% (18) 88.9% (40)
.01 o.001 o.001
7.7% (9)
46.7% (21)
o.001
78 ⫾ 8
85 ⫾ 10
o.001
5.2 ⫾ 0.34 7.3 ⫾ 3.6 29.3 ⫾ 4.1 81.2 ⫾ 17.1 35.9 ⫾ 6.8
5.5 ⫾ 0.38 7.7 ⫾ 3.8 30.8 ⫾ 5.7 72.5 ⫾ 16.5 33.2 ⫾ 7.9
o.001 .48 .03 .004 .03
12 months postop Glucose (mg/ dL) HbA1c (%) Insulin (μUI/L) BMI %EWL %WL
BMI ¼ body mass index; %EWL ¼ percentage of excess weight loss; T2 DM ¼ type 2 diabetes mellitus.
successful bariatric operation. Although there is a significant metabolic improvement after a modest weight loss, greater and long-term weight control are required to achieve all of the long-term benefits related with RYGB [17].
Figure 1. Percentage of excess weight lost at 12 months (EWL12), according to group of glycemic control.
Initial BMI FBG 4100 T2 DM Metabolic syndrome Hypoglycemic treatment Age Physical activity
%EWL Z80%
%WL Z35%
OR
P value
OR
P value
0.856 0.275 0.503 0.861 2.73 0.983 0.981
.001 .038 .60 .41 .41 .46 .94
1.092 0.386 0.121 1.584 4.724 0.988 1.144
.038 .048 .111 .061 .205 .603 .605
BMI ¼ body mass index; %EWL ¼ percentage of excess weight loss; T2 DM ¼ type 2 diabetes mellitus; %WL; percentage of weight loss.
For this study, we selected a 1-year follow-up, because it usually represents the time at which the optimal weight loss is observed after bariatric surgery [18]. There is not a consensus of what constitutes a successful weight loss after RYGB, and some authors have reported that a loss of 40%– 50% of the excess weight might be considered acceptable [5,7,19,20]. Our main objective was to identify which patients achieved a greater weight loss, and as such, we decided to use 80% of EWL (and 35% of WL) as our cut-off value, because it was our retrospective median sample in the patients who underwent surgery before the start of this study. Similar to what has been previously reported [2,7,21], patients presented a high interindividual %EWL variability, with a roughly normal distribution whose mean was centered at 78.8% (⫾17%). Thus, it is paramount to understand which factors might be responsible for these variations. Several studies have previously reported that the presence of T2 DM was related to suboptimal weight loss after this surgery [2,5,7,11–13,20,21] . However, this finding has not
Figure 2. Percentage of Excess Weight Lost (%EWL) according to glycemic control and hypoglycemic treatment status.
Fasting Glycemia and Weight Loss After RYGB / Surgery for Obesity and Related Diseases ] (2014) 00–00 Table 5 Metabolic improvement for patients with FBG Z100 mg/dL (n ¼ 45)
Initial BMI Glucose (mg/dL) Insulin (μUI/L) Cholesterol (mg/dL) HDL-c (mg/dL) Triglycerides (mg/dL) T2 DM Metabolic syndrome
Preoperative
12 months
P value
46.5 ⫾ 3.8 117 ⫾ 20 24.0 ⫾ 10 204 ⫾ 39 50 ⫾ 13 145 ⫾ 75 40.0% (18) 88.9% (40)
30.8 ⫾ 3.7 85 ⫾ 10 8.3 ⫾ 4 183 ⫾ 29 60 ⫾ 16 106 ⫾ 35 22.2% (10) 22.2% (10)
o.001 o.001 o.001 .005 .001 .002 o.001 o.001
BMI ¼ body mass index; FBG ¼ fasting blood glucose; T2 DM ¼ type 2 diabetes mellitus
been consistently reported in all the surgical series, and some authors defend that when controlled for other preoperative factors (initial BMI, age, gender, and race), patients with T2 DM have similar results to patients without T2 DM [6,15]. Some authors have postulated that T2 DM was related to a higher degree of insulin resistance and, thus, to higher circulating insulin levels. Insulin, being an anabolic hormone that promotes lipogenesis, might be responsible for a lower degree of weight loss after RYGB [20,22]. Also, intensive treatment for T2 DM (with higher circulating levels of insulin), although related to lower microvascular complications, has been shown to cause a small but significant weight gain [23]. Some reports [2,8,16] have stated that poor long-term glycemic control, as measured by HbA1c, is related to less weight loss after RYGB and even that it is the metabolic control (rather than the presence of T2 DM) that is related to weight loss. Other authors [11,24] proposed that the degree of beta-cell function and the severity of diabetes are linked to the amount of weight loss. In the present sample, after correction for initial BMI, the preoperative glucose control (FBG) was the only factor independently related to weight loss. This suggests that it was not the simple presence of diabetes or resistance to insulin that were related to poorer weight loss. Even for patients with “normal” FBG, it seems that the lowest glucose levels render the best possible outcome. However, it is important to remember that patients with T2 DM may be those with a greater health gain after RYGB, because they experience a significant metabolic improvement [2,15,17] that is not directly related to the amount of weight loss. In spite of this, lower glucose values might just be a surrogate marker for patient compliance with nutritional regimen and, thus, explain the association of lower glucose values with better weight loss at 12 months. One of the strongest predictors for the %EWL has been the initial BMI [2,5–7,21,25] or weight [26]. Several studies have reported this, and it is reasonable to assume that heavier patients have more weight to lose and, as such, have more difficulty in achieving a higher %EWL [6,9,21,27]. Acknowledging this, we considered it important to control
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for this effect in the multivariable analysis. In our sample, there was an inverse correlation between preoperative BMI and weight loss at 12 months. Increasing age has also been related to a lower weight loss after RYGB (and gastric band [27,28]), and several explanations (energy expenditure, physical exercise, lipolysis deficiencies, and psycho-social factors) have been proposed to explain this finding [2,6,7]. In our sample, patients 450 years lost less weight and had higher BMIs at 12 months, which is in accordance with previous reports [6]. Older patients have a higher prevalence and increased severity of T2 DM [11], and in our sample, older patients had higher preoperative FBG levels. In the multivariable analysis, the effect of age was decreased by the effect of FBG. As such, this can be an alternative explanation for the finding of an inverse relation between age and weight loss: it is the increasing metabolic impairment (associated with increasing age) that is related to the poorest outcomes after surgery. Patients with higher FBG are expected to produce more insulin to maintain homeostasis. This environment of hyperinsulinism might be related to a resistance to weight loss, as insulin promotes lipogenesis and inhibits lipolysis [29]. This might explain why several clinical manifestations of glucose homeostasis (T2 DM, insulin resistance, HbA1c, and FBG) have been associated with variations in postoperative weight loss. One appealing hypothesis would be that if FBG is related to weight loss, we could improve the surgical results by lowering glucose levels with antidiabetic medications. From the analysis of our patients, it seems that this effect is only seen in patients who are not being treated with hypoglycemic agents. This finding would need further directed research, ideally with a randomized trial between preoperative glucose optimization or immediate surgery in patients with poor metabolic control. From the present results, it seems that metabolic control is a surrogate marker of the metabolic disease burden and that patients with lower FBG have lower disease burden and, hence, better weight loss after surgery. In spite of less weight loss after RYGB, patients with poor metabolic control have achieved a significant improvement in their metabolic disease, such that, as previously reported, the metabolic improvement is not directly related to weight loss [30]. Some of the strongest aspects of this study are that it is based on a prospective cohort with a thorough clinical characterization of the diabetic status and metabolic control of these patients and that it included a high percentage (99%) of complete follow-up at 12 months. Also, although performed by 5 different surgeons, the surgical technique was standardized, and there were no significant variations of results among surgeons. Some of its limitations are the relatively limited sample size and the short follow-up period. One of the important aspects to
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analyze in future studies is the effect of the preoperative metabolic control on long-term weight control and weight regain. Conclusion Higher preoperative FBG was independently related to a poorer weight loss after RYGB. This association might explain why older patients and patients with T2 DM or insulin resistance have been reported to have a poorer weight loss. Lowering FBG with antidiabetic medications was unrelated to an improvement in surgical outcomes. Our results suggest the need to offer surgical treatment to obese patients with insulin resistance earlier, before severe metabolic illness progresses. The potential for less weight loss in patients with poorest glucose control should not discourage RYGB, given the significant metabolic improvement after surgery. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. References [1] Sjöström L, Lindroos A-K, Peltonen M, et al. Lifestyle, diabetes, and cardiovascular risk factors 10 years after bariatric surgery. N Engl J Med 2004;351:2683–93. [2] Ortega E, Morínigo R, Flores L, et al. Predictive factors of excess body weight loss 1 year after laparoscopic bariatric surgery. Surg Endosc 2012;26:1744–50. [3] Roberts K, Duffy A, Kaufman J, Burrell M, Dziura J, Bell R. Size matters: gastric pouch size correlates with weight loss after laparoscopic Roux-en-Y gastric bypass. Surg Endosc 2007;21:1397–402. [4] Ciovica R, Takata M, Vittinghoff E, et al. The impact of roux limb length on weight loss after gastric bypass. Obes Surg 2008;18:5–10. [5] Melton GB, Steele KE, Schweitzer MA, Lidor AO, Magnuson TH. Suboptimal weight loss after gastric bypass surgery: Correlation of demographics, comorbidities, and insurance status with outcomes. J Gastrointest Surg 2007;12:250–5. [6] Scozzari G, Passera R, Benvenga R, Toppino M, Morino M. Age as a long-term prognostic factor in bariatric surgery. Ann Surg 2012;256: 724–9. [7] Ma Y, Pagoto S, Olendzki B, et al. predictors of weight status following laparoscopic gastric bypass. Obes Surg 2006;16:1227–31. [8] Lee Y-C, Lee W-J, Lee T-S, et al. Prediction of successful weight reduction after bariatric surgery by data mining technologies. Obes Surg 2007;17:1235–41. [9] Júnior WS, Nonino-Borges CB. Clinical predictors of different grades of nonalcoholic fatty liver disease. Obes Surg 2012;22:248–52. [10] Ray EC, Nickels MW, Sayeed S, Sax HC. Predicting success after gastric bypass: the role of psychosocial and behavioral factors. Surgery 2003;134:555–63; discussion 563–4.
[11] Carbonell AM, Wolfe LG, Meador JG, Sugerman HJ, Kellum JM, Maher JW. Does diabetes affect weight loss after gastric bypass? Surg Obes Relat Dis 2008;4:441–4 [12] Perugini RA, Mason R, Czerniach DR, et al. Predictors of complication and suboptimal weight loss after laparoscopic Roux-en-Y gastric bypass: a series of 188 patients. Arch Surg 2003;138:541–5, discussion 545–6. [13] Júnior WS, do Amaral JL, Nonino-Borges CB. Factors related to weight loss up to 4 years after bariatric surgery. Obes Surg 2011;21: 1724–30. [14] Kadera BE, Lum K, Grant J, Pryor AD, Portenier DD, DeMaria EJ. Remission of type 2 diabetes after Roux-en-Y gastric bypass is associated with greater weight loss. Surg Obes Relat Dis 2009;5: 305–9. [15] Yip K, Heinberg L, Giegerich V, Schauer PR, Kashyap SR. Equivalent weight loss with marked metabolic benefit observed in a matched cohort with and without type 2 diabetes 12 months following gastric bypass surgery. Obes Surg 2012;22:1723–9. [16] Perna M, Romagnuolo J, Morgan K, Byrne TK, Baker M. Preoperative hemoglobin A1c and postoperative glucose control in outcomes after gastric bypass for obesity. Surg Obes Relat Dis 2012;8:685–90. [17] Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA 2004;292:1724–37. [18] Sjöström L, Narbro K, Sjöström CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med 2007;357: 741–52. [19] Prachand VN, Ward M, Alverdy JC. Duodenal switch provides superior resolution of metabolic comorbidities independent of weight loss in the super-obese (BMI Z50 kg/m2) compared with gastric bypass. J Gastrointest Surg 2010;14:211–20. [20] Campos GM, Rabl C, Mulligan K, et al. Factors associated with weight loss after gastric bypass. Arch Surg 2008;143:877–83; discussion 884. [21] Hatoum IJ, Stein HK, Merrifield BF, Kaplan LM. Capacity for physical activity predicts weight loss after Roux-en-Y gastric bypass. Obesity (Silver Spring) 2009;17:92–9. [22] Flier J, Maratos-Flier E. Energy homeostasis and body weight. Curr Biol 2000;10:R215–7. [23] Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet 1998;352:837–53. [24] Nannipieri M, Mari A, Anselmino M, et al. The role of beta-cell function and insulin sensitivity in the remission of type 2 diabetes after gastric bypass surgery. J Clin Endocrinol Metab 2011;96: E1372–9. [25] Lutfi R, Torquati A, Sekhar N, Richards WO. Predictors of success after laparoscopic gastric bypass: a multivariate analysis of socioeconomic factors. Surg Endosc 2006;20:864–7. [26] Sczepaniak JP, Owens ML, Garner W, Dako F, Masukawa K, Wilson SE. A simpler method for predicting weight loss in the first year after Roux-en-Y gastric bypass. J Obes. Epub 2012 Jan 19. [27] Dixon JB, Dixon ME, O'Brien PE. Pre-operative predictors of weight loss at 1-year after Lap-Band surgery. Obes Surg 2001;11:200–7. [28] Chevallier J-M, Paita M, Rodde-Dunet M-H, et al. Predictive factors of outcome after gastric banding: a nationwide survey on the role of center activity and patients' behavior. Ann Surg 2007;246:1034–9. [29] Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest 2000;106:473–81. [30] Ikramuddin S, Buchwald H. How bariatric and metabolic operations control metabolic syndrome. Br J Surg 2011;98:1339–41.