Effect of Laparoscopic Sleeve Gastrectomy on Type 2 Diabetes Mellitus Obese Patients

Effect of Laparoscopic Sleeve Gastrectomy on Type 2 Diabetes

Mellitus Obese Patients

Youhanna Shohdy Shafik, MD; MRCS (Eng);1  John Adel Sedkey,1 Sherif AbdelHalim, MD;1 Hany Aly Hussein, MD2

1Department of General Surgery, Faculty of Medicine. 2Department of Internal Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Background: Type 2 diabetes mellitus represents high proportion of diabetics which is mainly due to obesity and insulin resistance. Obesity is asscoiated with many co-morbidities like type 2 DM, cardiovascular (CV) complications, hypertension and dyslipidymia. Laparoscopic sleeve gastrectomy (LSG) was used as the first stage in a multistage procedure in obese patients with at least two severe co-morbidities. Two years after sleeve gastrectomy, more than 50% of those patients showed resolution of their co morbidities. Bariatric surgery has emerged as a highly effective management for morbid obesity and many related co-morbidities, including type 2 diabetes mellitus (T2DM). However, it has recently been approved that LSG is more than a gastric restrictive operation. It has been suggested that the changes in ghrelin and peptide YY after LSG may help to explain the weight loss results. So the aim of this study was to evaluate the effect of laparoscopic sleeve gastrectomy (LSG) on obese patients with type 2 DM.

Methods: This study was conducted on 30 obese patients suffering from T2DM (9 males and 21 females) who underwent laparoscopic sleeve gastrectomy at the Ain Shams University Hospital (El-Demerdash) and Ain Shams Specialized Hospital. Follow up of the patients was done for a period of 6 months to investigate their HbA1c changes and diabetic status.

Results: Our results showed significant reduction in the mean level of HbA1c (p<0.001) at 6 months follow-up post-surgery, with 16.7% (5 patients) completely cured from T2DM while 40% (12 patients) became pre-diabetic and 43.3% (13 patients) remained diabetic.

Conclusion: Most patients with type 2 DM experience resolution or improvement in diabetic status after LSG. LSG might play an important role as a metabolic therapy for patients with type 2 DM.

Key words: Obesity- type 2 diabetes mellitus- Laparoscopic sleeve gastrectomy.

Introduction

Type 2 diabetes mellitus and obesity are assumed to be two major public health problems worldwide nowadays.  Vascular  complications  are  thought to be the leading cause of disability in diabetics. The high cardiovascular (CV) risk that diabetes induces is better explained by approaching not only hyperglycemia but also the usual coexisting risk factors.1

Better glucose control with lowering hemoglobin A1c  (HbA1c)  value  to  6.5%  yielded  a  10% relative  reduction  in  major  macrovascular  and microvascular events. However, in another study, an  intensive  glucose  control  in  patients  with poorly controlled T2DM had no significant effect on the number of major CV events, deaths, or microvascular complications.1

Remission  of  type  2  DM  can  be  achieved  by surgical procedures in the majority of morbidly obese patients.1

Bariatric surgery is starting to be effective and long-lasting  treatment  for  morbid  obesity  and many related conditions, including type 2 diabetes mellitus (T2DM) and the metabolic syndrome (MS).2

LSG is a surgical procedure, by which a laparoscopic vertical  gastrectomy  is  done,  that  excises  the fundus and the lateral 80% of the gastric body leaving  a  tubular-like  stomach  with  an  intact pylorus.1

Since its introduction, the procedure has gained acceptance due to its simplicity, good results in weight lost, and less complication.1

The aim of this operation is to remove a part of the stomach in order to provide long-lasting control of obesity, to decrease caloric intake, to accelerate gastric emptying, and to decrease the circulating levels of ghrelin Hormone.1

This surgery is associated with increase in insulin sensitivity and ß cell function which could be related to decrease ghrelin levels postoperatively and these results have been compared to non- resection restrictive procedures like adjustable gastric  banding. Therefore,  it  is  assumed  that the  final  effect  of  procedures  involving  gastric transection decreases the serum ghrelin levels and improves insulin sensitivity.3

The other characteristic of the operation is to correct the defective amplification of the late- phase plasma insulin response to glucose by (glucose-dependent insulinotropic polypeptide) (GIP). Both characteristics were addressed in a recent publication of the hormonal changes before and after LSG.1

Also, data collected have shown that Sleeve Gastrectomy (GS) is associated with a high rate of resolution of T2DM and other obesity related co-morbidities such as hypertension, hyperlipidemia, and sleep apnea.4

Aim of the work

To determine the effect of LSG on blood glucose level in type 2 diabetic obese Egyptian patients.

Patients and methods

•   Patients:

This prospective study was conducted on thirty obese Egyptian patients with type 2 diabetes mellitus that underwent LSG at the Ain Shams University   Hospital   (El-Demerdash)   and   Ain Shams Specialized Hospital. All the patients met the  inclusion/exclusion  criteria  followed  the  by the National Institute of Health (NIH) Bariatric guidelines.5

Inclusion criteria: were type 2 diabetic obese patients aged more than 18 years old, BMI ≥35 kg/m2 with duration of  diabetes > 1 year, glycated hemoglobin (HbA1c) ≥ 6.5%,  receiving either oral hypoglycemic drugs (0HG) or insulin or OHG +insulin.

Exclusion criteria: were type 1 diabetic patients, glycated hemoglobin (HbA1c) < 6.5%, age <18 years, BMI < 35 kg/m2, endocrine obesity, a history of medical problems such as mental impairment, drug or alcohol addiction and patients who had previous bariatric surgeries.

Fig 1: Diagram show Sleeve gastrectomy procedure.7

•    Methods:

1.  Preoperative evaluation: The preoperative evaluation included discussing in detail the risks, benefits and long-term consequences of the procedures during the initial encounter with the surgeon, internist and dietician. All patients were examined by a medical team consisting of an internist, a bariatric surgeon, a psychiatrist, and a dietician. All patients were subjected to the following: Full history taking, clinical examination, calculation of body mass index (BMI),6  and laboratory investigations including:       complete   blood   picture,   liver function tests, renal functions tests, hepatitis markers (HBsAg and HCVAb),   glycated hemoglobin (HbA1c) and fasting blood sugar on day of operation. Written informed consent was obtained from all patients before being assigned to surgery.

2.  Operative  technique:  Surgical  technique LSG was performed according to the technique described by Gagner7 - Division of the gastric greater  curvature  vascular  supply,  starting at 6-8 cm from the pylorus and proceeding upwards until the angle of His, was carried out with Harmonic Scalpel, (Ethicon). The LSG was created using a linear stapler Endo GIA, with two sequential 60-mm green load firings for the antrum, followed by two or three sequential 60- mm blue loads for the remaining gastric corpus and fundus. The stapler was applied alongside a 36 Fr calibrating bougie strictly positioned against the lesser curve, to obtain a 120-150 ml gastric pouch. The resected stomach was extracted by enlargement of the 15-mm port-site. Abdominal drainage was left in place.

ِA1

A2

Figs: 2A1,A2 The division of the gastric greater curvature vascular supply,

starting at 6-8 cm from the pylorus.

B1

B2

Figs: 3B1,B2 The LSG is created using a linear stapler (Endo GIA).

3. Postoperative care: All patients were monitored in the recovery room and were transferred to the wards or to the intensive care unit. Early postoperative ambulation was strongly encouraged with patients getting out of bed the evening of the surgery and walking by the first postoperative day. A clear liquid diet was started on first postoperative day, and was advanced to pureed food 2 weeks later, and to solid food by the fourth postoperative week. Patients were advised to take daily multivitamins and supplemental minerals, as well as proton pomp inhibitor (PPI) prophylaxis for 6 months. Follow-up appointments with the internist, surgeon and the dietitian were scheduled at second week, 3, and 6 months postoperatively, with six months follow up of (HbA1c) after laparoscopic sleeve gastrectomy with assessment at 0, 3, 6 months interval. Patients were grouped to non-diabetic (HbA1c<5.7%), pre- diabetic (HbA1c 5.7%- 6.4%),  and  diabetics  (HbA1c≥6.5%)  at  6 month of follow up.

Statistical analysis:

The collected data was revised, coded, tabulated and introduced to a PC using Statistical package for  Social  Science  (SPSS  19.0.1  for  windows; SPSS Inc, Chicago, IL, 2001). Quantitative data was presented as Mean and Standard deviation (±SD) while number and percentage was used to  present  qualitative  data.  Fisher  exact  test was used to analyze qualitative data. Repeated measure ANOVA was used to analyze quantitative data  measured  more  than  two  times  for  one group, with Bonferroni post hoc test for pair wise comparisons. Friedman test was used to analyze quantitative data measured more than two times for one group. ANOVA was used to analyze quantitative data measured between more than two groups.  P Value<0.05 will be considered statistically significant.

Results

1-Descriptive data:

Patients’   descriptive   data   are   described   in Table 1. This study was conducted on 21 Females (70%) and 9 males (30%), their mean age was 33.6±10.51years, range (18-58). The mean pre- operative  weight was 137.87±21.28 Kg (range 101- 166 Kg). The mean pre-operative body mass index was 44.91±5.49 Kg/m² (range 36-55 Kg/ m²) as shown in Table 2. Regarding pre-operative hypoglycemic medications, 20 patients (66.7%) were on OHG, 6 patients (20%) on insulin and 4 patients (13.3%) on both OHG + insulin as shown in Table 2 and Figure 4.

The  mean  pre-operative  fasting  blood  sugar (FBS) on the day of surgery was 197.53±35.2 mg/dl, range (120-283 mg/dl), with mean HbA1c 7.95±0.88 %, range (6.55-10.2%). At 3 months follow-up, there was decline in the mean of HbA1c; it reached 7.27±0.77%, range (5.8-9.14%). At 6 months follow-up, much more decline occurred in the mean of HbA1c; it reached 6.47 ± 0.75 %, range (5.16-8.6%) as shown in Table 3.

30  T2DM  patients  who  underwent  LSG  were enrolled in this study; on follow up at 3 months, 4 patients (13.3%) became pre-diabetic and 26 patients (86.7%) remained diabetic. At 6 months follow up, more improvement occurred, 5 patients (16.7%) became non- diabetic, 12 patients (40%) became pre-diabetic and 13 patients       (43.3%) remained diabetic as shown in Table 4.

2-Comparitive data:

Comparison between the mean values of HbA1c at 0, 3, 6 months follow-up among patients who underwent LSG; revealed a highly significant reduction (p=0.0001) in the mean value of HbA1c at 3 months and at 6 months as shown in Table 5 and Fig. 5.

Follow up of diabetic status of patients for 6 months after LSG revealed a highly significant reduction in the number of diabetic patients (HbA1c≥6.5%) reaching 43.3 % (p=0.001) as shown in Table 6.

In terms of treatment based outcomes, patients who   were   on   OHG   (pre-operative)   showed better reduction in the mean of value of HbA1c (6.39±0.77%) than those on insulin (6.59±0.82%) and OHG+insulin (6.74±0.63%) at the 6 months follow up as shown in Table 7 and Figure 6.

Moreover,  better  reduction  in  the  number  of diabetic patients who were on OHG (35 %)  than 

Table 1: Studied Patients` descriptive data

those on insulin (66.7 %) and OHG+insulin (50%) at the 6 months follow up was noted. However, these differences lacked statistical significance with p=0.643, 0.695 respectively as shown in Table 7.

No   Age      Gender        Weight

.in kgs

BMI

Type of anti diabetic treatment

1     55y      Female       130kgs         42               OHG

2     35y      Female       140kgs         46            INSULIN

3     58y      Female       120kgs       41.5             OHG

4     40y      Female       101kgs         37               OHG

5     37y      Female       109kgs       36.8             OHG

6     37y      Female       124kgs       41.75            OHG

7     44y      Female       162kgs         52         OHG+insulin

8     21y      Female       164kgs         51               OHG

9     38y      Female       107kgs       37.5             OHG

10    43y      Female       128kgs         43               OHG

11    23y      Female       128kgs       44.2             OHG

12    30y        Male         160kgs         49            INSULIN

13    26y        Male         150kgs       48.2           INSULIN

14    18y      Female       133kg          43               OHG

15    30y        Male         154kgs       47.8           INSULIN

16    27y      Female       160kgs       49.5             OHG

17    22y      Female       131kgs         41            INSULIN

18    36y        Male         140kgs         45               OHG

19    28y        Male         165kgs       52.3             OHG

20    43y      Female       108kgs         38               OHG

21    39y      Female       166kgs         55               OHG

22    23y      Female       105kgs         36         OHG+insulin

23    46y       Male         148kgs         47               OHG

24    32y      Female       155kgs         49               OHG

25    28y       Male         157kgs       49.5             OHG

26    45y      Female       122kgs         41               OHG

27    24y      Female       166kgs         54            INSULIN

28    40y       Male         145kgs       44.75       OHG+insulin

29    21y       Male         151kgs        47.5        OHG+insulin

30    19y      Female       107kgs         37               OHG

Table 2: Personal and medical data of the studied patients underwent Laparoscopic Sleeve

Gastrectomy (LSG)

Age

Weight

BMI

Gender

Pre-operative hypogly- cemic medications

Fig 4:  Description of the pre-operative hypoglycemic treatment of the studied patients underwent LSG.

Fig 5: Comparison between mean values of HbA1c at 0, 3, and 6 months follow up postoperative.

Table 3: Description of FBS (preoperative) and HbA1c changes at 0, 3, and 6 months follow up among

patients underwent LSG

Table 4: Description of diabetic status at 0, 3, and 6 months follow up among patients underwent LSG

Table 5: Comparison between mean values of HbA1c at 0, 3, and 6 months follow up among patients

underwent LSG

HbA1c 0 month

Mean        SD±         P         Sig                      post hoc test

HbA1c 0M Vs HbA1c 3M

(pre-operative)                          7.94%       0.88%

HbA1c 3 months                        7.26%       0.71%

0.0001

HS

(HS)

HbA1c 0M Vs HbA1c 6M (HS)

HbA1c 6 months                        6.47%      0.74%                                      HbA1c 3M Vs HbA1c 6M (HS)

HS=highly significant

Table 6: Comparison between preoperative, 3 months and 6 months post-operative diabetic status

among patients underwent LSG

month 0 (pre-operative)

3 month

month 6

P     .Sig

HbA1c

N           %            N          %         N      %

(HbA1c < 5.7%)                  0         0.0%          0       0.0%       5       16.7% Pre Diabetic   0          0.0%     4          13.3%                                     12        40.0%

(HbA1c 5.7  6.4%)

Diabetic

(HbA1c ≥ 6.5%)                 30       100.0%       26      86.7%     13      43.3%

0.001     HS

HS = highly significant

Table 7: Comparison between patients with different treatment regimen as regard mean level of HBA1c and diabetic status at 6 months follow up after LSG

Treatment

OHG                               Insulin        OHG+Insulin

P         .Sig

HbA1c 6M

Non Diabetics

N          %         N         %         N         %

HbA1c 6M

(% HbA1c < 5.7)                      4       20.0%      1       16.7%      0        0%.

Pre Diabetic

(% HbA1c 5.7-6.4)                    9       45.0%      1       16.7%      2      50.0%

Diabetic

(% HbA1c ≥ 6.5)                      7       35.0%      4       66.7%      2      50.0%

**0.695     NS

NS = none significant

Fig 6: Comparison between patients with different treatment regimen as regard mean level of HBA1c at 6 months follow up after surgery.

Discussion

T2DM is considered to be a highly prevalent chronic disease with limited major treatments. Bariatric surgery is suggested as an alternative treatment for T2DM that has possibilities to induce remission of the disease. In 2011, the International Diabetes Federation (IDF) stated that bariatric surgery could be used in obese patients with a BMI >40 kg/m2 and that it might bring benefit to obese T2DM patients with a relatively low BMI (BMI 30~35 kg/m2), who do not respond to the usual medical therapies.8 

However, the effects of bariatric surgery for non- obese T2DM patients have not been established. Although  past  studies  predominantly  focused on the role of bariatric surgery in patients with BMI<35kg/m2, patients with BMI<30kg/m2 were occasionally included in many studies.9 

The results of this study points to the fact that LSG  can  play  a  remarkable  role  in  managing T2DM obese patients. Our study revealed a highly significant reduction in the mean value of HbA1c at 3 and 6 months after surgery (P<0.001). These findings are comparable to those of Wei-Jee Lei et al. who showed that out of 20 diabetic patients type 2 who underwent LSG; median reduction in HbA1c was from 10.1 % to 7.1%.10 

The fact that 56.7 % (n=17) of our patients showed either complete remission (5/30 patients completely cured from T2DM) or improvement (12/30patients  became   pre-diabetic)   of   the disease 6 months after LSG; is keeping with the concept that LSG could be a potential option for the management of T2DM in obese patients.  

Our results were in agreement with those of Guo et al. who conducted a study that included 34 obese patients with T2DM and BMI less than 40 kg/m2  who underwent LSG. The clinical data and 3-year  follow-up outcomes  regarding  remission of diabetes was retrospectively analyzed. It showed the complete remission rate of diabetes at 6, 9, 12, 24 and 36 months was 33.3% (8/24), 50.0% (12/24), 54.2% (13/24), 45.8% (11/24) and 50.0% (12/24), respectively. That study confirms the efficacy of LSG in the treatment of T2DM patients with a BMI less than 40 kg/m2.11  In addition, Abbatini et al. showed 80.9% resolution of T2DM after LSG over a 3-year follow up.12 

With regard to the effect of LSG on T2DM obese patients, in another review that analyzed 27 studies and 673 patients, it was stated that diabetes resolved in 66.2% of the patients, improved in 26.9% of the patients, and was unchanged in 13.1% of patients. The mean decrease in HbA1c levels after an LSG was −1.7%.13 

Although the mechanisms underlying T2DM remission following LSG is not fully determined, some  studies  have reported  favorable changes in insulin sensitivity. Improvement in insulin sensitivity could be attributed to decreased body weight, decreased calorie intake and reduction in inflammatory mediators.12,14  Some believe that hormonal regulation plays a key role. Recent studies have shown that LSG is associated with a marked reduction of ghrelin secretion, which is produced by the gastric fundus and is involved in mealtime hunger regulation. Moreover, ghrelin is known to exert several diabetogenic effects (increase in growth hormone, cortisol, and epinephrine). Therefore its suppression could contribute  to  improved  glucose  homeostasis.15

Interestingly, Peterli et al. measured higher GLP-1 levels following LSG.15

Undoubtedly, bariatric surgery is now becoming a viable treatment option for T2DM in obese patients, with recent large studies showing its superiority over traditional medical therapy.16  However, there is still a lack of large scale studies observing LSG in particular when it comes to diabetes resolution. This is due to the fact that Roux enY gastric bypass (RYGB) remains the gold standard bariatric procedure, with a T2DM remission rate reaching as high as 60%.17  However, recent evidence has been emerging showing no significant difference between LSG and RYGB in treating T2DM, with both procedures showing comparable results in diabetes control.15 Another prospective study conducted by Vidal et al. on the changes in glucose homeostasis in 35 severely obese T2DM subjects undergoing laparoscopic SG (LSG) and 50 subjects undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP); showed at 4-months after surgery, T2DM had resolved respectively in 51.4% and 62.0% of the LSG and LRYGBP operated subjects (P=0.332). That proved that LSG and LRYGBP result in a similar rate of type 2 DM resolution at 4-months after surgery.18 

The current study revealed insignificant difference in HbA1c reduction and T2DM resolution among patients with different treatment regimens. This suggests that LSG might prove to treat the disease regardless of the severity.

Our study has few limitations; first, number of studied  patients  was  relatively  small.  Second, short term follow up for 6 months only. Third, other co-morbidities like hypertension and hypercholesterolemia were not evaluated. 

In conclusion, LSG seems to be a restrictive procedure, but it also appears to induce significant changes in glucose homeostasis regardless of the pre- operative type of hypoglycemic medications.