OBES SURG (2018) 28:497–505 DOI 10.1007/s11695-017-2874-4
ORIGINAL CONTRIBUTIONS
Efficacy of Sleeve Gastrectomy with Duodenal-Jejunal Bypass for the Treatment of Obese Severe Diabetes Patients in Japan: a Retrospective Multicenter Study Takeshi Naitoh 1 & Kazunori Kasama 2 & Yosuke Seki 2 & Masayuki Ohta 3 & Takashi Oshiro 4 & Akira Sasaki 5 & Yasuhiro Miyazaki 6 & Tsuyoshi Yamaguchi 7 & Hideki Hayashi 8 & Hirofumi Imoto 1 & Naoki Tanaka 1 & Michiaki Unno 1
Published online: 9 August 2017 # Springer Science+Business Media, LLC 2017
Abstract Background The incidence of obesity with type 2 diabetes (T2DM) is increasing in Japan. The main bariatric surgery procedures in Japan are laparoscopic sleeve gastrectomy (LSG) and LSG with duodenal-jejunal bypass (LSG/DJB) because of the high incidence of gastric cancer and difficulty exploring a remnant stomach after gastric bypass. However, few studies have compared the antidiabetic effect of LSG/DJB with LSG alone. Purpose The purpose of this study is to compare the antidiabetic effect of LSG/DJB with that of LSG alone in Japanese obese diabetic patients.
Methods This was a retrospective multicenter study including 298 cases: 177 and 121 LSG and LSG/DJB cases, respectively. We investigated the antidiabetic effect of these two procedures at 12 months after surgery. Univariate and multivariate analyses were done to evaluate the predictive factors of T2DM remission. Results The diabetes remission rate at 12 months after surgery was 80.8% for LSG and 86.0% for LSG/DJB. Insulin use and HbA1c ≤ 6.7% were significant predictive factors in multivariate analysis for all patients. In patients with ABCD score ≥ 6, the diabetes remission rate was 94.8% and there was no difference between procedures. Only duration of diabetes and
* Takeshi Naitoh
[email protected]
Naoki Tanaka
[email protected] Michiaki Unno
[email protected]
Kazunori Kasama
[email protected] Yosuke Seki
[email protected]
1
Department of Surgery, Tohoku University Graduate School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan
2
Weight loss and Metabolic Surgery Center, Yotsuya Medical Cube, Tokyo, Japan
Takashi Oshiro
[email protected]
3
Department of Gastroenterological and Pediatric Surgery, Oita University Faculty of Medicine, Oita, Japan
Akira Sasaki
[email protected]
4
Department of Surgery, Sakura Hospital, Toho University Medical Center, Sakura, Japan
Yasuhiro Miyazaki
[email protected]
5
Department of Surgery, Iwate Medical University School of Medicine, Morioka, Japan
Tsuyoshi Yamaguchi
[email protected]
6
Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
Hideki Hayashi
[email protected]
7
Department of Surgery, Shiga University of Medical Science, Otsu, Japan
Hirofumi Imoto
[email protected]
8
Research Center for Frontier Medical Engineering, Chiba University, Chiba, Japan
Masayuki Ohta
[email protected]
498
insulin use were significant predictive factors both in univariate and multivariate analyses. However, in cases with ABCD score ≤ 5, the remission rate was 70.3% and procedure type was the most significant predictive factor for diabetes remission (odds ratio [OR] 5.140). Conclusions Although both LSG and LSG/DJB have good antidiabetic effects in Japanese obese patients, LSG/DJB is more effective for patients with lower ABCD scores. Keywords Bariatric surgery . Metabolic surgery . Sleeve gastrectomy with duodenal-jejunal bypass . Diabetes mellitus . Morbid obesity
OBES SURG (2018) 28:497–505
Sleeve gastrectomy with duodenal-jejunal bypass (LSG/ DJB) is a modification of the bilio-pancreatic diversion with duodenal switch (BPD/DS), allowing for the possible avoidance of nutritional deficiency and the exploration of the remnant stomach through a physiological route [19, 20]. We think that LSG/DJB would be a suitable bypass procedure for Japanese patients. There are very few articles comparing body weight loss or T2DM remission between LSG and LSG/DJB, especially for patients with lower ABCD scores. Therefore, the aim of this study was to compare the antidiabetic effect of LSG/DJB with that of LSG alone in Japanese obese T2DM patients and to determine factors predictive of diabetes remission after surgery.
Introduction Patients and Methods Bariatric surgery has historically been uncommon in Japan. According to a national survey, only 3% of the population was considered obese (body mass index [BMI] over 30 kg/m2), until recently [1]. However, due to changes in dietary habits, morbidly obese patients and those with type 2 diabetes (T2DM) are increasing rapidly in Japan, similar to other countries. The pandemic of T2DM is an urgent problem. T2DM and obesity are closely related. Obesity is the greatest risk factor for T2DM progression. However, it is also well known that T2DM in Asian patients tends to become severe at a relatively lower BMI [2–5]. Therefore, the demand for bariatric or metabolic surgery will increase as a treatment for T2DM rather than a treatment for morbid obesity in Japan. Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the most popular procedure in Western countries for bariatric and metabolic surgery [6]. LRYGB or other malabsorptive procedures are considered more effective in terms of body weight loss and antidiabetic effects than restrictive surgery alone [7–11]. In contrast, laparoscopic sleeve gastrectomy (LSG) is the only officially approved procedure in Japan, and no bypass surgery is yet approved for bariatric and metabolic surgery by the National Health Insurance system. Moreover, since the incidence of gastric cancer is high and the exploration of the remnant stomach is difficult, LRYGB is not widely accepted in Japan. However, in our early experience with LSG, we sometimes saw patients in whom LSG was not sufficiently effective, both for body weight loss and for T2DM improvement [12–14]. The ABCD score, proposed by Lee et al. [15, 16], is predictive of T2DM resolution after metabolic surgery. The ABCD score is calculated from patient age, BMI, preoperative serum C-peptide immunoreactivity (CPR) level, and duration of diabetes. Patients with a lower ABCD score are likely to have a lower T2DM remission rate after surgery [17, 18]. We therefore have been insistent on the need for bypass surgery in Japan for the treatment of severe T2DM.
Data Collection This was a multicenter, retrospective, observational study to validate the safety and efficacy of LSG and LSG/DJB for obese T2DM patients. Obese T2DM patients underwent LSG or LSG/DJB in each institution from January 2005 to December 2015. Patients whose BMI was 35 kg/m2 or more at the first visit and who were between 18 and 65 years old were included in this study. The following preoperative data were collected from patient records: age, body weight, height, BMI, fasting serum CPR, duration of diabetes, HbA1c, fasting blood glucose (FBG), and history of insulin administration. Operative information and short-term outcomes were also collected. Evaluation of T2DM resolution was done using patient data at 12 months after surgery. Complete remission (CR) was defined as no medication required and HbA1c < 6.0%, partial remission (PR) as no medication required and HbA1c < 6.5%, improved (Imp) as medication reduced and HbA1c < 7.0%, and no change (NC) as HbA1c ≥ 7.0%, regardless of medication [21]. The remission rate of diabetes was defined as the sum of the CR and PR numbers divided by the total number of cases. The ABCD score was defined as the sum of the scores for age, BMI, CPR, and duration of diabetes (Table 1). Operative Procedure All procedures were performed laparoscopically. LSG was done using a standard method [22, 23]. Briefly, after placement of trocars, a pneumoperitoneum was created with carbon dioxide gas using a pressure of 10–20 mmHg, and the greater curvature of the stomach was devascularized by dissecting the large omentum. The transection of the stomach was then started from 4 to 6 cm proximal to the pylorus until the angle
OBES SURG (2018) 28:497–505 Table 1
499
Variables and score used for calculating ABCD
Score
0
1
2
3
Age (years old)
≥ 40 < 27
< 40 27–34.9
35–41.9
> 42
< 2.0 >8
2–2.9 4–7.9
3–4.9 1–3.9
>5 42 kg/m Complications within 30 days (C-D ≥ 3) Duration of diabetes < 4 years
74 69 99
6 4 5
0.894 0.733
6 110
0 2
0.556 0.002
No insulin use HbA1c ≤ 6.7%a sCPR ≥ 3.0 ng/mLa
131 58 124
4 1 7
0.001 0.120 0.876
LSG/DJB Sex Male
0.186
Female Age < 40 years old 2a
LSG laparoscopic sleeve gastrectomy, LSG/DJB laparoscopic sleeve gastrectomy with duodenal-jejunal bypass, BMI body mass index, sCPR serum Cpeptide immunoreactivity level, C-D Clavien-Dindo classification, 95%CI 95% confidence interval a
At first visit
cases of LSG and 47 cases of LSG/DJB. The overall diabetes remission rate was 60.3%, and the remission rate for each procedure was 41.9% in LSG and 72.3% in LSG/DJB. The difference in remission rates between procedures was more than 30%, and this was statistically significant (p = 0.007). Duration of diabetes 60 kg/m 2 ) are quite rare in Japan. However, T2DM in Asian patients tends to become severe at a relatively low BMI [2–5]; thus, bypass surgeries are more effective for T2DM remission [7–11]. Moreover, the American Diabetes Association recently released a recommendation regarding metabolic surgery to include inadequately controlled T2DM patients with a BMI ≥ 32.5 kg/ m2 for Asians, and the Japan Diabetes Society also endorsed this recommendation [29]. Therefore, we believe that bypass surgeries are beneficial, especially for severe T2DM patients. LSG/DJB is similar to BPD/DS, but the limb length is much shorter at 50–150 cm for the bilio-pancreatic limb and 100–150 cm for the alimentary limb; as a result, a common channel length is more than 300 cm [19]. LSG/DJB would be a suitable bypass procedure for Japanese patients. However, few reports have compared the efficacy of LSG/DJB with LSG alone. This multicenter study was a retrospective, observational study, and the number of cases was almost 300. The excess body weight loss at 12 months after surgery was significantly higher for LSG/DJB (59.4% for LSG, 67.0% for LSG/DJB,
OBES SURG (2018) 28:497–505 Table 5
503
Diabetes status at 12 months after surgery and predictive factors for diabetes remission in cases with ABCD score ≤ 5
Valuables
Surgical procedures LSG
CR/PR
Improve/NC
Univariate analysis
Multivariate logistic regression analysis
n = 102 (70.3%)
n = 43
p value
Odds ratio
95%CI
p value
5.140
2.070–12.762
42 kg/m Complications within 30 days (C-D ≥ 3) Duration of diabetes < 4 years
55 7 39
23 3 17
0.980 0.883
4 13
5 2
0.079 0.144
3.993 2.691
0.880–18.111 0.503–14.409
0.073 0.248
No-insulin use HbA1c ≤ 6.7%a sCPR ≥ 3.0 ng/mLa
69 24 39
16 4 12
0.001 0.047 0.234
4.247 2.927
1.797–10.034 0.832–10.295
0.001 0.094
Female Age < 40 years old 2a
LSG laparoscopic sleeve gastrectomy, LSG/DJB laparoscopic sleeve gastrectomy with duodenal-jejunal bypass, BMI body mass index, sCPR serum Cpeptide immunoreactivity level, C-D Clavien-Dindo classification, 95%CI 95% confidence interval a
At first visit
p = 0.001). The complication rate within 30 days after surgery was not statistically different between LSG and LSG/DJB. Diabetes backgrounds of patients for each surgical procedure were different because severe patients tended to undergo LSG/ DJB. Based on this result, the overall T2DM remission rate was 82.9%: 80.8% for LSG and 86.0% for LSG/DJB. Furthermore, for patients with an ABCD score of ≥ 6, the remission rate increased to 94.8%, with 95.0% for LSG and 94.2% for LSG/DJB groups. These results indicate that both LSG and LSG/DJB induce significant improvement in diabetes, and that LSG would be sufficient for those with a high ABCD score. Table 6
However, for patients who have a lower ABCD score, the remission rate decreased to 70.3% and there was almost an 18% difference between the two surgical procedures favoring LSG/DJB. Based on multivariate analysis, the surgical procedure is a significant predictive factor for achievement of diabetes remission and the odds ratio was 5.140. These results suggest that LSG/DJB should be strongly recommended for patients with an ABCD score ≤ 5 to achieve diabetes remission. Insulin use is another strong predictive factor for diabetes remission after surgery. In all subgroups, insulin use is a significant predictive variable as shown through multivariate
Diabetes status at 12 months after surgery and predictive factors for diabetes remission in insulin users
Valuables
Surgical procedures LSG LSG/DJB Age < 40 years old BMI > 42 kg/m2a sCPR ≥ 3.0 ng/mLa Duration of diabetes < 4 years HbA1c ≤ 6.7%a
CR/PR
Improve/NC
Univariate analysis
Multivariate logistic regression analysis
n = 47 (60.3%)
n = 31
p value
Odds ratio
13 (41.9%) 34 (72.3%) 11 24
18 13 5 15
0.431 0.817
22 11 6
11 2 1
0.320 0.038 0.124
95%CI
p value
5.141
1.749–15.111
0.003
4.860 10.145
0.875–27.011 0.975–105.582
0.071 0.053
0.007
LSG laparoscopic sleeve gastrectomy, LSG/DJB laparoscopic sleeve gastrectomy with duodenal-jejunal bypass, BMI body mass index, sCPR serum Cpeptide immunoreactivity level, C-D Clavien-Dindo classification, 95%CI 95% confidence interval a
At first visit
504
analysis. According to subgroup analysis of insulin use cases, the diabetes remission rate for LSG decreased to 41.9%, while LSG/DJB had a higher rate at 72.3%; the procedure was the strongest predictive factor for T2DM remission in multivariate analysis. Therefore, we recommend that patients who are insulin-dependent undergo LSG/DJB regardless of ABCD score. There are several limitations in this study. First, the design was retrospective and observational. However, conducting a prospective randomized trial is extremely difficult in Japan because of the limitations of the National Health Insurance system. Although a propensity-score matching study may have been effective, patient backgrounds were very different, making it difficult to match cases between the two groups. Second, the number of patients was small. Small sample size is a critical problem but this cannot be solved due to the current situation in Japan. Finally, the number of cases varied greatly among participating institutions. The proportion of number of cases ranged from 3 to 54% among institutions. Despite these limitations, LSG/DJB is still effective for patients with severe diabetes.
OBES SURG (2018) 28:497–505
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Conclusion Therefore, although further evaluation is needed, we conclude that LSG is as effective as LSG/DJB for those whose ABCD score is ≥ 6; however, LSG/DJB is significantly more effective than LSG alone for obese diabetic patients with a lower ABCD score. We recommend that T2DM patients who use insulin or whose ABCD score is ≤ 5 undergo LSG/DJB.
Acknowledgements We gratefully acknowledge the work of past and present members of each institution for collecting patient data and supporting surgery or patient care.
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Compliance with Ethical Standards Conflict of Interest The authors declare that they have no conflicts of interest. Ethical and Consent Statement All procedures and data collection were in accordance with the ethical standards of the institutional and Japanese national research committees or the ethical standards of the Helsinki Declaration of 1975. LSG was done per usual clinical practice. Written informed consent was obtained for LSG/DJB because it is not approved by the national insurance system in Japan, and the procedure was performed with a private or institutional expense for clinical research. A consent form for retrospective data collection was not obtained, but the outline of this study was registered and released at the UMIN Clinical Trials Registry (UMIN-CTR) site (UMIN000020292), and the opportunity for patients to opt-out was guaranteed. All clinical data were anonymized to protect privacy.
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