1 2 3 Surgery for Obesity and Related Diseases ] (2014) 00–00 4 5 6 Original article 7 8 9 10 Q3 11 Ling L. Chuah, M.B.Ch.B., M.Sc.1,a,*, Alexander D. Miras, MRCP, Ph.D.1,a, 12 13 Dimitris Papamargaritis, M.D., Ph.D.a, Sabina N Jackson, B.Sc.a, Torsten Olbers, M.D., Ph.D.a,b, 14 Q1 Carel W. le Roux, M.B.Ch.B., Ph.D.a,b,c 15 a Metabolic Medicine Research Unit, Imperial College London, United Kingdom b 16 Gastro Surgical Laboratory, University of Gothenburg, Sweden c 17 Diabetes Complications Research Center, Conway Institute, University College Dublin, Ireland 18 19 Abstract Background: Roux-en-Y gastric bypass (RYGB) surgery is associated with rapid postsurgical 20 improvement in glycemic control in patients with type 2 diabetes mellitus (T2 DM). However, there 21 is little outcome-based evidence to guide the glycemic management of this patient group pre22 operatively. Objectives: We conducted 2 pilot studies randomizing patients to assess the impact of 23 intensive glucose management pre- and post-RYGB on clinical outcomes after surgery. Setting: 24 University hospital. 25 Q4 Methods: In the GLUCOSURG-pre randomized controlled trial (RCT), 34 obese T2 DM patients 26 with glycated hemoglobin (HbA1 c) 4 8.5% (69 mmol/mol) undergoing RYGB were randomly 27 assigned to receive either glucose optimization or no optimization 3 months preoperatively. In the 28 GLUCOSURG-post RCT, 35 obese T2 DM patients on insulin were randomly assigned to either 29 intensive or conservative glucose management up to 2 weeks post- RYGB. HbA1c at 1 year post30 RYGB was the primary outcome. Results: In GLUCOSURG-pre, the HbA1 c at 1 year postsurgery was −3.0% (51.9 mmol/mol) in 31 the optimized and −4.0% (45.4 mmol/mol) in the nonoptimized groups (P ¼ .06). In GLUCOSURG32 post, there were no significant differences in HbA1 c at 1 year postsurgery between the intensive and 33 conservative groups [−2.4% (44.3 mmol/mol)] versus [−2.3% (44.3 mmol/mol), P ¼ .73)]. 34 Conclusions: Our pilot studies suggested that neither intensive management of glycemia in the 3 35 months pre- RYGB, nor the first 2 weeks post-RYGB resulted in better glycemic control one year 36 after surgery. RYGB has substantial effects on glucose control, and additional intensive glucose37 lowering interventions do not confer clinical benefits compared to conservative approaches. (Surg 38 Obes Relat Dis 2014;]:00–00.) r 2014 American Society for Metabolic and Bariatric Surgery. All 39 rights reserved. 40 41 Keywords: Gastric bypass; Type 2 diabetes; Preoperative; Postoperative; Glucose management 42 43 44 45 Bariatric surgery is increasingly used as a metabolic diabetes mellitus (T2 DM). However, there is little data to 46 intervention for obese patients with poorly controlled type 2 guide clinicians on how to manage these patients’ glycemia 47 pre- and postoperatively. Elevated glycated hemoglobin 48 (HbA1 c) preoperatively is associated with longer hospital * 49 Correspondence: Dr Ling Ling Chuah, Metabolic Medicine Research length of stay (LOS) and worse postoperative outcomes 50 Unit, Room 8 Level 9 East, Charing Cross Hospital, London W6 8 RF UK. after elective orthopedic and colorectal surgery [1–5]. E-mail: [email protected] 51 1 Unlike other elective surgical procedures, after which Joint first authors. 52 53 http://dx.doi.org/10.1016/j.soard.2014.11.004 54 1550-7289/r 2014 American Society for Metabolic and Bariatric Surgery. All rights reserved. 55

Impact of perioperative management of glycemia in severely obese diabetic patients undergoing gastric bypass surgery

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glucose control normally deteriorates due to surgical stress and inflammation, glucose control improves within days of Roux-en-Y gastric bypass (RYGB) [6]. However, hyperglycemia before RYGB has been associated with more complications postoperatively, less weight loss and fewer patients achieving glycemic “remission” [7]. Information regarding glucose management postbariatric surgery is limited. Scopinaro et al. reported that in patients with BMI o30 kg/m2 and poorly controlled T2 DM, perioperative insulin improved HbA1 c 1 year after biliopancreatic diversion [8]. We found that intensive perioperative glycemic management after RYGB also resulted in better HbA1 c at 1 year [9]. As these were both cohort studies, a randomised controlled trial was required to exclude allocation bias. Moreover, short term insulin therapy has been used in newly diagnosed T2 DM to reverse glucotoxicity and produced evidence of β-cell preservation [10]. Postoperative insulin after islet cell transplant in type 1 diabetes patients also provides “β-cell rest” [11,12]. We designed and performed 2 pilot RCTs to determine the feasibility of a larger RCT which could guide the practical management of glycemia of obese patients with T2 DM undergoing RYGB. The purpose of our study was to test whether the effect size observed in cohort studies would be replicated within a randomized controlled trial when allocation bias was removed. We hypothesised that intensive glycemic management in the months preceding RYGB (GLUCOSURG-pre) and for the 2 weeks after RYGB (GLUCOSURG-post) was superior in terms of glycemic control 1 year postsurgery as compared to conservative glycemic management. Methods These 2 studies were single-center nonblinded RCTs (ClinicalTrials.gov NCT01353118 and NCT01257087) at a certified center of excellence for bariatric surgery in a teaching hospital. A computerised randomization system generated block-randomization with a 1:1 allocation. For the first RCT, “GLUCOSURG-pre,” 41 consecutive patients were recruited between July 2011 and August 2012. The inclusion criteria were a body mass index (BMI) Z 35 kg/m2, known diagnosis of T2 DM, aged between 18 and 70, and an HbA1 c Z8.5% (69 mmol/mol). Exclusion criteria were failure to proceed to surgery, inability to participate in capillary glucose testing, and titration of glucose-lowering pharmacotherapy. For the second RCT, “GLUCOSURG-post,” 42 consecutive patients were recruited between December 2010 and October 2012, and randomly assigned to either intensive or conservative management for 2 weeks after RYGB. The inclusion criteria were BMI Z35 kg/m2, aged 18–70, and a diagnosis of insulin treated T2 DM. The same exclusion criteria for GLUCOSURG-pre applied.

Both protocols were approved by the West London 2 Research Ethics Committee, (reference 11/H0711/1 and 10/ H0711/69). All participants gave written informed consent and the trials were performed according to the principles of the Declaration of Helsinki. Interventions In-hospital perioperative care for both trials. All patients underwent a standard low-calorie diet of 800 kCal for 2 weeks before admission for surgery to decrease their liver size. All glucose-lowering medications were stopped on admission, and short-acting insulin was given as necessary, according to capillary glucose monitoring using an insulin sliding scale. The target capillary glucose (CG) during the admission was 5.0–8.0 mmol/L. RYGB was performed laparoscopically as previously described [13]. Patients were discharged 2 days after surgery, unless they developed a postoperative complication. Metformin 1 g bd was routinely started on the first postoperative day unless patients had a known intolerance or evidence of kidney impairment. In addition, patients were discharged on a once daily longacting insulin analogue at a dose equivalent to their total insulin requirements during the 24 hour before discharge. After discharge, all patients were seen by physician at 2 weeks, 3 months, 6 months, and 12 months. GLUCOSURG-pre After randomization, patients in the intensive management group were assessed in clinic by a metabolic physician. Their glucose-lowering therapy was optimized based on the ADA and EASD guidelines [14]. Intensive management was defined as an absolute reduction in HbA1 cZ1% after 3 months. Patients were asked to check their CG levels premeal every day. Adjustments were made every 2–3 days apart to reduce the incidence of hypoglycemia. Patients randomly assigned to the conservative group did not undergo any glycemic optimization presurgery. After surgery, patients emailed or texted the metabolic physician with their fasting CG readings daily. Insulin doses were titrated using a validated insulin titration protocol [9]. The daily contact was discontinued once glucose readings were within target for at least 3 consecutive days. GLUCOSURG-post Patients were randomly assigned to either intensive or conservative postoperative glucose management before surgery and their glucose-lowering medications were not adjusted before surgery. After discharge, patients in both groups were asked to contact the metabolic physician with their daily fasting CG up to postoperative day 15, in the same way as GLUCOSURG-pre. The dose of the longacting insulin analogue was then adjusted by the physician

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to achieve target fasting CGs of 5.5–6.5 mmol/L in the intensively treated group and 6.5–7.5 mmol/L in the conservative treated group. The metformin dose was not altered. Fasting CG and the “achieved target CG” were used, as it was not possible to see the immediate impact of the adjusted medication on daily changes in HbA1 c. The latter remained the primary outcome of this study. Statistical analysis Power calculations. Based on our data [9], with an absolute reduction in HbA1 c of −3.0% in the group whose glucose control was optimized for 2 weeks after surgery and −1.2% in the group that underwent no optimization, with a standard deviation of 1.7 around the mean, a sample size of 16 patients in each group was needed for a proposed RCT to have 80% power to show significant differences between the groups at α ¼ .05. There are no data on the effects of preoperative glycemic optimization on average glycemia at 1 year after bariatric surgery and as such the GLUCOSURGpre trial was a pilot. Presentation of data Descriptive statistics were expressed as mean ⫾ SEM or median (interquartile range) depending on the normality distribution. Within-group comparisons were made using the paired Student’s t test or the Wilcoxon matched pairs test and between group comparisons using the unpaired Student’s t test or the Mann-Whitney U test depending on the normality distribution. Categorical data were compared using the Fisher’s exact test (Graphpad PRISM software version 5.01, GraphPad Software Incorporation, USA). Statistical significance was accepted as P o .05. Results GLUCOSURG-pre Baseline characteristics. Of 41 patients recruited, 3 did not proceed to surgery and only 38 were randomly assigned. Four were lost to follow-up (Supplementary Fig. 1). After random assignment, the age, gender distribution, BMI, HbA1 c, duration of T2DM, and number of glucose-lowering medication were similar between the groups (Table 1). Effectiveness of the intervention on preoperative glycemic control. In the intensively treated group, HbA1 c was reduced significantly in the 3 months presurgery from 9.9% (85 mmol/mol) to 8.4% (68.3 mmol/mol) (P ¼ .003), whilst the HbA1 c of the conservatively group did not change significantly, from 10.3% (89.1 mmol/mol) to 9.7% (82.5 mmol/mol) (P ¼ .25). HbA1 c of the intensively treated group on the day of surgery was significantly lower than the conservatively treated group (P o .005). Glycemic control at 1 year. Both groups achieved significant reductions in HbA1 c 1 year after surgery. The

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difference in reductions in HbA1 c between both groups missed significance (P ¼ .06). This was in the context of similar reductions in BMI (P ¼ .62) and similar number of glucose-lowering medication used at 1 year (P ¼ .68). Subgroup analysis indicated that 5 (27.8%) conservatively treated patients achieved HbA1 c r6.0%. All patients were on 1 glucose lowering agent. Four (25%) in the intensively treated group achieved HbA1 c r6.0%. All patients were on 1 glucose lowering agent (P ¼ 1.00). Incidence of hypoglycemia. Two patients in the intensively treated group had CG readings o4.0 mmol/L but did not have symptoms of severe hypoglycemia during the 2 weeks monitoring postsurgery. No hypoglycemia was noted in the conservatively treated group. Length of stay. The median length of stay was 3 days for both groups (P ¼ .73, Table 1). Complications. There were no significant differences in the incidence of surgical complications between the 2 groups. One subject from the intensively managed group had a postoperative stroke and 1 developed abdominal pain postsurgery; 1 subject from the conservatively managed group vomited postsurgery, but settled after a prolonged inpatient stay. GLUCOSURG-post Baseline characteristics. Of 42 patients recruited, one was deemed ineligible for bariatric surgery and 6 were lost to follow up (Supplementary Fig. 2). After randomization, the age, gender distribution, BMI, HbA1 c and number of glucose-lowering medication were similar between the groups (Table 2). However, patients in the intensively treated group had T2DM for 5 years longer than the conservatively treated group (P ¼ .02). Effectiveness of the intervention on early postoperative glycemic control. After surgery the mean fasting CG between days 3–15 was significantly lower in the intensively treated group compared to the conservatively treated group (P o .001, Supplementary Fig. 3). Glycemic control at 1 year. Both groups achieved significant reductions in HbA1 c at 1 year postsurgery, but was not significantly different (P ¼ .73). This was in the context of similar reductions in BMI (P ¼ .98) and similar number of glucose-lowering medication used at 1 year (P ¼ .90) Subgroup analysis indicated that 6 (37.5%) conservatively treated patients who achieved HbA1 c r 6.0%, 2 were on one glucose lowering agent. In the intensively treated group, 6 (33.3%) patients achieved HbA1 c r 6.0%, and 6 were on one glucose lowering agent (P ¼ 1.00). Incidence of hypoglycemia. Only one patient in the intensive management group developed an episode of mild hypoglycaemia. Length of stay. The median length of stay was 3 days for both groups (P ¼ .91, Table 2).

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Nonoptimized (n ¼ 18)

Baseline variables Age (yr) Male (%, n) Duration of diabetes (yr) BMI (kg/m²) Outcome variables HbA1 c (%) HbA1 c (mmol/mol) Length of stay (d) 30 days surgical complications (%, n) Hypoglycaemic episodes (n) Number of glucose-lowering medications

Preoperatively

Postoperatively

49.0 (53.0–56.0) 61.1, 11 8.0 (4.0-15.0) 42.1 (39.4–50.8)

N/A N/A N/A 32.1 (29.9–34.4)

10.3 (9.5–11.0) 9.7 ( 8.8–10.9)* 89.1 (80.3–96.7) 82.5 (72.7–95.6)* N/A N/A N/A 2.0 (2.0–2.0)

P (within group)

Optimised (n ¼ 16)

P (within group)

P (between groups at baseline)

P (of change between groups)

Preoperatively

Postoperatively

N/A N/A N/A o.0001

48.5 (41.5–56.75) 56.3, 9 9.5 (5.5–18.3) 46.2 (38.4–55.3)

N/A N/A N/A 36.2 (28.8–38.3)

N/A N/A N/A .008

.93 1.00 .55 .78

N/A N/A N/A .62

6.3 (5.9–6.8)

.0002

6.9 (5.9–7.8)

.0001

.0002

51.9 (41.0–61.7)

.0001

.41 o.005‡ .41 o.005‡

.06

45.4 (41.0-50.8)

9.9 ( 8.9–10.4) 8.4 (7.1–9.3)† 84.7 (73.8–90.2) 68.3 (54.1–78.1)†

3.0 (3.0–4.3) 11.1, 2 1 1.0 (1.0–1.0)

N/A N/A N/A o.0001

3.0 (3.0–4.5) 6.3, 1 1 1.0 (1.0–1.5)

N/A N/A N/A .002

2.0 (2.0–2.0)

.06 .73

1.00 .68

.05

BMI ¼ body mass index; HbA1 c ¼ glycated hemoglobin; N/A ¼ not applicable. Continuous data were analyzed using nonparametric tests and categorical data using the χ2 test. * HbA1 c postrandomisation. † HbA1 c postoptimisation. ‡ P value postoptimisation.

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Table 1 GLUCOSURG-pre. Baseline and 1-year follow-up results for the patients who completed follow up (n ¼ 34)

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.21

.73 .73 .91

.98

Complications. There were no significant differences in the 30-day incidence of surgical complications between the groups (P ¼ 1.00, Table 2).

P (between groups at baseline)

Discussion

.97 .97 N/A 1.00 N/A .01 o.0001 o.0001 N/A N/A N/A .002 BMI ¼ body mass index; HbA1 c ¼ glycated hemoglobin; N/A ¼ not applicable. Continuous data were analysed using nonparametric tests and categorical data using the χ2 test.

8.6 (7.3–10.3) 70.5 (56.3–89.1) N/A N/A N/A 2.0(1.0–2.0) .001 .001 N/A N/A N/A .0002 6.2 (5.8–6.8) 44.3 (39.9–50.8) 3.0 (3.0–4.0) 0 0 1.0 (0.0–1.0) 8.5 (7.6–10.1) 69.4 (59.6–86.9) N/A N/A N/A 3.0(2.0–3.0)

.0003 N/A N/A N/A 32.7 (28.5–40.3) 49.0 (45.5–56.0) 58.8, 10 8.0 (5.0–11.5) 44.6 (41.2–51.1)

Baseline characteristics Age (yr) Male (%, n) Duration of diabetes (yr) BMI (kg/m²) Outcome variables HbA1 c (%) HbA1 c (mmol/mol) Length of stay (d) 30-d surgical complications (%, n) Hypoglycaemic episodes (n) Number of glucose-lowering medications

Postoperatively Preoperatively

6.2 (5.7–7.1) 44.3 (38.8–54.1) 3.0 (3.0–4.0) 5.6 , 1 1 1.0(.0–1.0)

.17 .09 .04 .37 N/A N/A N/A o.0001 N/A N/A N/A 31.8 (27.7–37.7) 55.0 (42.0–59.0) 27.8, 5 15.5 (11.25–19.25) 43.7 (40.0–48.2)

Preoperatively

Intensive (n ¼ 18)

Postoperatively

P (within group)

GLUCOSURG-pre

P (within group) Conservative (n ¼ 17)

Table 2 GLUCOSURG-post. Baseline and 1-year follow-up results for the patients who completed follow-up (n ¼ 35)

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P (of change between groups)

Short Title / Surgery for Obesity and Related Diseases ] (2014) 00–00

Intensive preoperative glycemic management of obese T2DM patients undergoing RYGB was not superior to conservative management in terms of glycemic control at 1 year after surgery, 30-day perioperative complication and LOS. Our pilot data suggest that the reduction of “glycemic burden” in the months preceding bariatric surgery did not translate to better clinical outcomes either in the short or the medium term. This is in contrast to a retrospective study of 468 patients which reported poor glycemic control before bariatric surgery was associated with a higher incidence of wound infections and acute kidney injury perioperatively, less weight loss and fewer cases of remission of T2DM 18 months postoperatively [7]. In another of our prospective cohort studies we found no difference in postoperative complications between patients with or without diabetes [15]. The discrepancies may be due to differences in study design (i.e., retrospective versus prospective randomized trials); and that both groups of patients in GLUCOSURGpre underwent a low-calorie diet for 2 weeks preoperatively. Although the 2 groups were exposed to different glucose levels for the 3 months presurgery, it is likely that glucose readings were similar on the day of surgery. This may explain the lack of difference in the rates of peri-operative complications. At 1 year, there was a nonsignificant trend for the conservatively treated group to have a greater reduction in glycemia; this may be due to the nonsignificantly higher baseline HbA1 c. Nonetheless, glycemic optimization remains crucial in T2DM. We expected to find that intensification of glucoselowering regimes preoperatively would be beneficial for longer term glycemic control, but our pilot RCT did not support this. However, our data do not support withholding or delaying surgery from patients with poorly controlled glycemia when all medical and lifestyle interventions have already been optimized. Anaesthetists who are not familiar with the impact of bariatric surgery may be reluctant to anaesthetise patients with poorly controlled diabetes. Although their approach is understandable, given the wealth of data on poor outcomes in patients with poorly controlled T2DM after nonbariatric surgery, our data questions whether this is the case for bariatric surgery. The only option available currently for this group of patients may be bariatric surgery when all other interventions fail. Even though in our study the intensively treated group managed to improve glycemic control, on the day of surgery their HbA1 c was still elevated at 8.4% (68 mmol/mol). This reflects real-life practice in that the vast

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majority of diabetes patients referred for bariatric surgery have exhausted nonsurgical glucose-lowering treatments and there is less room for additional optimization. Instead, any preoperative interventions could be focused on improving other obesity-associated co-morbidities.

GLUCOSURG-post The GLUCOSURG-post trial indicated that intensive glycemic management for 2 weeks after surgery did not yield better glycemic control at 1 year. Postoperative complications within 30 days were also similar. Unlike other elective surgical procedures after which hyperglycemia is common and is predominantly due to surgical stress, RYGB is different in that it has a substantial effect in improving glucose levels within days after surgery. Consequently, the glucose levels of our conservatively treated group were still in the euglycemic range despite statistically different to the intensive group, the clinical difference was small. This may explain the lack of significant difference in the short and medium term clinical outcomes between the groups. A postoperative glucose management algorithm that maintains fasting glucose o7.5 mmol/L therefore appears to be well tolerated, and any further intensification may not confer clinical benefits nor does it decrease complications. Even though we did not observe an increased rate of hypoglycemic episodes in the intensively treated group in this trial, an overzealous glucose management approach may increase this risk. Limitations include the number of patients in each group being relatively small, but even so, the effect size was small, which suggests that there was only a small chance of our data representing a type II statistical error. A larger trial focussing on glycemic outcome may thus be challenging. Whether better perioperative glycemic control improves postoperative complications requires a very large RCT, because even if the effect size of the intervention is large, the number of postoperative complications is low. The lack of any statistical trends suggests that a larger number of patients may not have altered the final result. In both trials the follow-up was limited to 1 year, and therefore differences in clinical outcomes between the groups in the longer term cannot be excluded. We based the postoperative management of patients on fasting CG readings only, and continuous glucose monitoring may have been superior for assessing glycemic excursions and enabled us to detect hypoglycemia more effectively. Despite randomization in the GLUCOSURG-post trial, the intensively treated group had a longer duration of T2 DM. This may have limited the effect of the intervention on the 1 year glycemic outcome endpoint, although we did not detect any trends that would have suggested this even in the smaller number of patients that had similar duration of diabetes.

Conclusions In conclusion, RYGB had an early and substantial effect on glucose control, and additional intensive glucoselowering interventions did not appear to confer any clinical benefits. Our pilot randomized controlled trial did not confirm the 2 previous cohort studies that concluded intensive management of glycemia for the first 2 weeks after RYGB resulted in better glycemic control one year after surgery. We also did not find evidence that intensive management of glycemia in the 3 months before surgery made a difference. Although our studies were not powered adequately, we did not find any signal of altered LOS or incidence of surgical complications in either group. The small sample size does not make it possible for any conclusions to be extended beyond the study. Our results were inconclusive regarding whether the lack of difference in clinical outcomes is indeed due to the lack of statistical difference in glycemic controls. We did show improving perioperative glycemia was feasible, but a much larger randomized controlled trial would be required to address whether such an approach reduces the already low postoperative complications of RYGB. Disclosures The study was funded by Moulton Foundation and Obesity Research Fund. ADM has received funding from an MRC Clinical Training Fellowship, MRC Centenary Award, and an NIHR Clinical Lectureship. ClR is funded by Science Foundation Ireland /YI/B2480 Acknowledgments The authors thank Jawad Noon for data transcription, and all the staff of Imperial Weight Center for their tireless effort in looking after these patients. Appendix Supplementary data Supplementary data associated with this article can be found in the online version at http://dx.doi.org/10.1016/ j.soard.2014.11.004. References [1] Estrada CA, Young JA, Nifong LW, Chitwood WR Jr. Outcomes and perioperative hyperglycemia in patients with or without diabetes mellitus undergoing coronary artery bypass grafting. Ann Thorac Surg 2003;75:1392–9. [2] Marchant MH Jr, Viens NA, Cook C, Vail TP, Bolognesi MP. The impact of glycemic control and diabetes mellitus on perioperative outcomes after total joint arthroplasty. J Bone Joint Surg Am 2009;91:1621–9. [3] Walid MS, Newman BF, Yelverton JC, Nutter JP, Ajjan M, Robinson JS Jr. Prevalence of previously unknown elevation of glycosylated

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hemoglobin in spine surgery patients and impact on length of stay and total cost. J Hosp Med 2010;5:E10–4. O’Sullivan CJ, Hynes N, Mahendran B, et al. Haemoglobin A1 c (HbA1 C) in non-diabetic and diabetic vascular patients. Is HbA1 C an independent risk factor and predictor of adverse outcomeEur J Vasc Endovasc Surg 2006;32:188–97. Gustafsson UO, Thorell A, Soop M, Ljungqvist O, Nygren J. Haemoglobin A1 c as a predictor of postoperative hyperglycaemia and complications after major colorectal surgery. Br J Surg 2009;96: 1358–64. Neff KJ, Frankel AH, Tam FWK, Sadlier DM, Godson C, le Roux CW. The effect of bariatric surgery on renal function and disease: a focus on outcomes and inflammation. Nephrol Dial Transplant 2013;28:iv73–82. Perna M, Romagnuolo J, Morgan K, Byrne TK, Baker M. Preoperative hemoglobin A1 c and postoperative glucose control in outcomes after gastric bypass for obesity. Surg Obes Relat Dis 2012;8:685–90. Scopinaro N, Adami GF, Papadia FS, et al. Effects of biliopanceratic diversion on type 2 diabetes in patients with BMI 25 to 35. Ann Surg 2011;253:699–703. Fenske W, Pournaras D, Aasheim E, et al. Can a protocol for glycaemic control improve type 2 diabetes outcomes after gastric bypass? Obes Surg 2012;22:90–6

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[10] Raz I, Mosenzon O. Early insulinization to prevent diabetes progression. Diabetes Care 2013;36:S190–7. [11] Bretzel RG, Brandhorst D, Brandhorst H, et al. Improved survival of intraportal pancreatic islet cell allografts in patients with type-1 diabetes mellitus by refined peritransplant management. J Mol Med 1999;77:140–3. [12] Koh A, Senior P, Salam A, et al. Insulin-heparin infusions peritransplant substantially improve single-donor clinical islet transplant success. Transplantation 2010;89:465–71. [13] Thomas RL, Prior SL, Barry JD, et al. Does bariatric surgery adversely impact on diabetic retinopathy in persons with morbid obesity and type 2 diabetes? A pilot study. J Diabetes Complicat 2014;28:191–5. [14] Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32:193–203. [15] Lyons T, Neff KJ, Benn J, Chuah LL, le Roux CW, Gilchrist M. Body mass index and diabetes status do not affect post-operative infection rates after bariatric surgery. Surg Obes Related Dis 2014;10: 291–7.

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Impact of perioperative management of glycemia in severely obese diabetic patients undergoing gastric bypass surgery.

Roux-en-Y gastric bypass (RYGB) surgery is associated with rapid postsurgical improvement in glycemic control in patients with type 2 diabetes mellitu...
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