Bariatric metabolic surgery: An effective treatment of type 2 diabetes.

Background: Bariatric metabolic surgery is evolving as an option for the treatment of type 2 diabetes mellitus (T2DM) in patients with obesity and T2DM, warranting more studies on the efficacy of bariatric metabolic surgery on T2DM. Objective: To determine T2DM remission in patients with obesity and T2DM with up to two years follow-up after bariatric metabolic surgery. Materials and
Methods: A retrospective review of prospectively maintained data was undertaken to identify patients who had T2DM and underwent bariatric surgery at a single centre in 2016. Data collected included age, gender, body mass index (BMI), fasting plasma glucose, haemoglobin A1c, hypertension, (HTN), Obstructive sleep apnea (OSA), initial weight and the weight at intervals of 6, 12, and 24 months. Data on the treatment of T2DM before the surgery was also collected. The criteria of the American Diabetes Association were used for the definition of T2DM remission. Only the data on patients in this study who had more than 12 months' follow-up information was analysed.
Results: Two hundred and eighty patients with T2DM were identified. 191 patients had more than 12 months' follow-up information. Mean age and BMI were 49.58 ± 10.64 years and 44.03 ± 7.86 kg/m2 respectively. There were 29 patients on insulin, 21 (10.9%) on insulin only and 8 (4.2%) on insulin and oral hypoglycaemic agents (OHA). One hundred and forty-six patients (76.4%) were on OHA, 134 on a single OHA and 12 on more than one OHA. Twenty-six patients (13.6%) were newly diagnosed with T2DM when they came in for bariatric metabolic surgery. One hundred and fifty-six patients (81.7%) achieved complete remission. 14 (7.3%) of these patients used to be on insulin with or without OHA and 142 (74.3%) were patients either on OHA or no OHA. There were 12 (6.4%) patients in partial remission. There was improvement in 23 (12.04%). Eight patients were on insulin but at lower doses and 15 were on a single OHA. The average percentage of total weight loss at 6, 12 and 24 months was 29.7%, 33.9% and 35.6% respectively. Patients with shorter duration of T2DM had higher remission rates as compared to patients with longer duration (r = -0.874, P = 0.001). There was also a significant resolution of HTN (81.8%) and OSA (82.3%) after bariatric metabolic surgery.
Conclusion: This study collaborates reports that there is significant remission of T2DM after bariatric metabolic surgery in patients with obesity and T2DM. There is a need for prospective, multi-centre, and long-term studies on bariatric metabolic surgery to treat patients with obesity and T2DM.

INTRODUCTION

Obesity and type 2 diabetes mellitus (T2DM), two major contributors to disability and death, are also growing health problems worldwide.[12] Weight loss surgery or bariatric metabolic surgery that is usually used for the treatment of severe obesity has also been documented as an effective treatment for T2DM in patients with obesity. Almost 80% of patients with obesity who have T2DM and undergo weight loss surgery achieve diabetes remission, compared with only 15% of those who achieve remission with intensive pharmaceutical and lifestyle interventions.[1]

Presently there are various types of bariatric metabolic procedures.[3] These procedures affect their outcomes through many mechanical, physiologic, and neurohormonal mechanisms.[4] Since the cardio-metabolic improvements of these procedures go beyond weight loss, their indications have been broadened to include individuals with varying levels of adiposity and poorly controlled T2DM. The role of bariatric surgery to treat T2DM current challenges and perspectives. In this study, we reviewed and analysed the outcome after bariatric metabolic surgery in a cohort of patients at a single institution. The aim of this study was to assess the effect of bariatric surgery on T2DM remission in patients with obesity and T2DM with up to 2 years’ follow-up after bariatric metabolic surgery.

MATERIALS AND METHODS

Data collection

A retrospective review of data from a prospectively maintained database was undertaken to identify 280 patients with T2DM who underwent bariatric metabolic surgery from January 2016 to December 2016. Out of this 15 sleeve gastrectomy (SG), 5 banded SG, 105 gastric bypass (GBP), 24 banded GBP, 124 mini GBP (MGB) and 7 banded MGB underwent bariatric metabolic surgery respectively. The choice of surgical procedure was based on evaluation of the risk-to-benefit ratio in individual patients, weighing long-term nutritional hazards versus effectiveness on glycaemic control and cardiovascular disease risk. Surgical indications were determined according to the 1991 NIH recommendations.[5] A shared-decision-making approach between patient and surgeon was used to decide what operation the patient received after detailed informed consent explaining the risks and benefits of the operations. Preoperatively, all patients provided written informed consent for their operation and to have de-identified data analysed, presented and published. The institutional review board approved this study.

Data collected

The database included pre-operative demographics and anthropometric data on body mass index (BMI), initial weight, fasting plasma glucose (FPG), haemoglobin A1c (A1c), C-peptide level, type of anti-diabetic treatment and follow-up information.

Outcome measures

The main parameters considered during the study were.

Weight loss

The weight was recorded at every patient visit or through follow-up calls and entered into the computer database. The percentage of total weight loss (%TWL) was calculated by dividing the absolute kgs lost by the patient's as compared to the initial weight.

Diabetes control

The FPG and HbA1c were determined preoperatively and at 6, 12 and 24-month intervals; the data were collected through phone or E-mail via a family physician for patients who were not able to come to the outpatient department.

Definition

A1c is a measure of the degree to which erythrocyte haemoglobin is glycosylated, expressed as per cent of total haemoglobin concentration. Diabetes mellitus was defined as FPG ≥126 mg/dL (7.0 mmol/L) or 2-h plasma glucose ≥200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test or patient with a history of T2DM on anti-diabetic drugs and/or on insulin injections. In June 2009, a definition was presented by the American Diabetes Association multidisciplinary expert panel consensus for T2DM remission which is broadly accepted worldwide.[6] After addressing the challenges concerned in the demarcation of a cure or remission of T2DM, on the basis of three criteria: glycaemia below diabetic range, absence of treatment, and sustainability over time a definition is provided by this panel.[7] Specifically, diabetes remission was defined as.

Complete remission

T2DM with A1c <6.5% and FPG <126 gm/dl for 1 year in the absence of anti-diabetic medications except for metformin.

Partial remission

T2DM with A1c <6.5% and FPG <126 gm/dl for 1 year on medications.

Improvement

T2DM with A1c >6.5% on less medications than before the bariatric metabolic surgery. Only the data on patients in this study who had more than 12 months’ follow-up information was statistically analysed.

Statistical analysis

Statistical package for the social sciences (SPSS) IBM SPSS Statistics for Windows, Version 20.0. Armonk, NY: IBM Corp. was used to perform the statistical analyses. Baseline comparisons were performed using Chi-square test, paired t-test and one-way analysis of variance. Continuous variables were presented as mean ± standard deviation unless otherwise stated. Student's t-test was used to compare the before and after surgery data. We calculated and correlated the remission rates with different variances by Spearman's rho correlation. A P < 0.05 was considered significant.

RESULTS

Two hundred and eighty patients with T2DM were identified. The duration of follow-up ranged from 6 to 24 months. 12 months complete follow-up information was available for 191 (68.2%) patients. The 89 patients with <12 months follow-up were excluded from the study analysis. The 191 patients consisted of 81 (42.4%) females and 110 (57.6%) males. The demographic data and use of oral hypoglycaemic agents (OHA) and/or insulin are shown in Table 1.

Table 1

Demographic profile (n=191)

	T2DM patients, n (%)
Age (years)	49.58±10.64
Gender (female:male)	81 (42.4):110 (57.6)
Height (m)	1.64±0.10
Weight (kg)	118.83±23.77
BMI (kg/m2)	44.03±7.86
A1c (%)	6.02±0.93
FPG (g/dl)	121±0.85
C-peptide	3.38±1.54
OHA 1	134 (70.15)
OHA >1	12 (6.28)
Insulin	21 (10.99)
Insulin + OHA	8 (4.18)
De novo	26 (13.61)

T2DM: Type 2 diabetes mellitus, BMI: Body mass index, A1c: Hemoglobin A1c, FPG: Fasting plasma glucose, OHA: Oral hypoglycemic agents

Weight loss

The mean %TWL at 6, 12 and 24 months was 29.7 ± 7.3, 33.9 ± 8.2 and 35.6 ± 7.9 respectively [Figure 1]. There was a significant association between %TWL and age group (r = 0.621, P = 0.002). %TWL was faster and higher in the younger age group (29–40 years). All patients achieved %TWL >20%. However, there was no relationship between %TWL and duration of T2DM nor with the severity of T2DM [Table 2].

Figure 1

Percentage of weight loss

Table 2

Correlation of percentage of total weight loss and type 2 diabetes remission with age and duration or severity of type 2 diabetes mellitus

	%TWL		T2D remission
	Spearman’s rho	P	Spearman’s rho	P
Duration of T2DM	0.018	0.810	−0.874	0.001**
Age group	0.621	0.002**	0.045	0.643
Severity of T2DM	0.032	0.663	0.077	0.224

**Correlation is significant at the 0.01 level (two-tailed). T2DM: Type 2 diabetes mellitus, %TWL: Percentage of total weight loss, T2D: Type 2 diabetes

Diabetes control

There was a significant reduction in usage of oral anti-diabetic medications after weight loss surgery. There was a significant reduction in the A1c levels. Out of 191 patients, 156 (81.7%) patients achieved complete remission. There were 14 patients in complete remission who used to take insulin. There were 12 (6.3%) patients in partial remission on a single OHA. Two patients in partial remission used to take insulin and 10 used to take multiple OHA. There was improvement in 23 (12.04%) patients. Eight were on insulin but at lower doses and 15 were on a single OHA [Table 3]. An earlier remission was found in patients with shorter duration of T2DM (r = −0.874, P = 0.001).

Table 3

Diabetes remission

	Complete remission	Partial remission	Improvement
n (%)	156 (81.7)	12 (6.3)	23 (12.04)
A1c (%)	5.61±0.24	5.98±0.15	7.69±0.67
FPG (g/dl)	95.03±2.54	96.0±2.32	126.81±1.33
OHA taken	0	12	15
Insulin taken	0	0	8

A1c: Hemoglobin A1c, FPG: Fasting plasma glucose, OHA: Oral hypoglycemic agents

Improvement in co-morbidities

There was a significant resolution of HTN (81.8%) and OSA (82.3%) after bariatric metabolic surgery. All the patients with complete diabetic remission also had complete resolution of HTN (100%) and OSA (100%) [Table 4].

Table 4

Improvement in co-morbidities and correlation with type 2 diabetes mellitus remission

	HTN, n (%)	OSA, n (%)
Improvement in co-morbidities	117/143 (81.8)	116/141 (82.3)
Complete remission (T2DM)	108/108 (100)	106/106 (100)
Partial remission (T2DM)	9/12 (75.0)	10/12 (83.3)
Spearman’s rho	454**	417**
P	0.001	0.001

**Correlation is significant at the 0.01 level (two-tailed). HTN: Hyperseptation, OSA: Obstructive sleep apnea, T2DM: Type 2 diabetes mellitus

DISCUSSION

The main objective of this study was to determine the effects of metabolic surgery on T2DM remission in patients with obesity and T2DM at our institution. We found that there is a significant reduction in the levels of FPG and A1c after surgery. There was a marked reduction in usage of insulin and oral anti-diabetic medications after the metabolic surgery. Of the 29 patients who were on insulin preoperatively, eight still required insulin postoperatively but in much-reduced dosage and two patients were only on OHA. There was a complete T2DM remission rate of 81.7% which is similar to results in other studies.[8910] This high remission rate has also been reported in a meta-analysis of more than 135,000 metabolic surgery patients (mean BMI 47.9) in 621 studies (1990-2006) that found 86.6% of those with T2DM experienced improvement or remission.[11] High remission was also reported by Chang et al. in JAMA surgery meta-analysis of nearly 162,000 patients with obesity (mean BMI 45.6) in 164 studies (2003-2012) where those with T2DM (26.2%) who underwent metabolic surgery had improvement or remission of 95.1% after GBP and 73.8% after gastric banding in randomised controlled trials, and 92.8% after GBP, 67.5% after gastric banding and 85.5% after SG in observational studies.[12] Metabolic surgery is more effective than medical and/or lifestyle interventions including pharmacological therapy in producing T2DM remission, glycaemic control, and weight loss which is confirmed by randomised clinical trials. In these trials, T2DM remained in remission for up to 2 years in 85% of these patients and there was 50% remission rate after metabolic surgery at 5 years and zero for medical therapy.[1314]

The rate and magnitude of %TWL and resolution of T2DM in this study were independent factors of T2DM remission, as diabetes went into remission even before the target %TWL. Faster and higher %TWL was in the younger age group (29–40 years) and patients with shorter duration of T2DM. This is similar to the study by Dixon et al. who found that the percentage of excess weight loss (%EWL) and preoperative duration of T2DM were independent predictors of T2DM remission after gastric banding.[15] It may be due to high basal metabolic rate in the younger age group and easy adaptability to the new milieu. Similarly, Sugerman et al. also found that younger age and %EWL were predictors of T2DM resolution.[16] Better score to predict diabetes remission after bariatric surgery some scoring systems, such as “ABCD” in the diabetes surgery score (age, BMI, C-peptide and duration of T2DM), may help evaluate the effectiveness of T2DM remission after surgery.[17] The DiaRem score increased with T2DM severity determined by individualised metabolic surgery score (P < 0.001).[18] Our study shows the earlier remission was found in patients with shorter duration of T2DM (r = −0.874, P = 0.001).

Our study also shows resolution of HTN and OSA, 81.8% and 82.3% respectively. This is consistent with reports from systematic reviews and meta-analyses based primarily on observational data that have suggested that metabolic surgery may aid in controlling HTN and OSA.[192021] A systematic review by Buchwald et al.[20] (136 studies, 22 094 patients) found an overall 63% resolution of HTN, with procedure-specific percentages of 68%, 43%, and 83% for roux-en-Y GBP (RYGB), adjustable gastric banding, and diversion with a duodenal switch (BPDDS), respectively. Reports show that most patients with obesity experience symptomatic remission of their OSA after metabolic surgery after 1 year. OSA remission rates for SG and RYGB were reportedly 89.2% and 81.2%, respectively.[22]

Study strengths and limitations

The strength of this study is that it collaborates the reported effects of bariatric metabolic surgery on T2DM and other co-morbid conditions. This study has some limitations. Firstly, it is a single institution retrospective study and the patient population of a single ethnic group. Second, this study did not analyse the outcomes by types of metabolic surgeries due to the lack of sufficient number of patients in each type. Third, the follow-up of only 68% beyond 12 months was inadequate. Finally, the issue of recurrence of T2DM could not be addressed because of the relatively, short 2-year follow-up duration of this study. Hence, further studies at multiple sites with different ethnicities and looking at the effects of the different metabolic surgeries with longer follow-up times are needed. We are conducting long term follow-up with the same patients to gather the important information for future prospects such as investigate the long-term effectiveness and safety of metabolic surgery in a different type of surgeries as compared with alternative treatment options, evaluate criteria for surgery that are more appropriate than BMI alone in people with T2DM and also determine which operation is the optimal choice for individual patients.

CONCLUSION

This study corroborates reports that there is significant remission of T2DM after bariatric metabolic surgery in patients with obesity and T2DM. Metabolic surgery is an effective option for the management of patients with obesity and T2DM. There is also a high rate of resolution of OSA and HTN after bariatric metabolic surgery. There is a need for prospective, multi-centre, and long-term studies on bariatric metabolic surgery to treat patients with obesity and T2DM.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.