Q J Med 2014; 107:721–726
doi:10.1093/qjmed/hcu060 Advance Access Publication 19 March 2014
Metabolic outcomes 2 years following gastric bypass surgery
in people with type 2 diabetes: an observational cohort study
F. BEHBEHANI1,2, B.J. AMMORI1,3, J.P. NEW1,2, L.K.M. SUMMERS1,2, H. SORAN1,4 and
A.A. SYED1,2
From the 1Faculty of Medical and Human Sciences, The University of Manchester, Manchester,
2
Department of Diabetes, Endocrinology and Obesity Medicine, Salford Royal NHS Foundation Trust
and University Teaching Hospital, Salford, 3Department of Bariatric and Upper Gastrointestinal
Surgery, Salford Royal NHS Foundation Trust and University Teaching Hospital, Salford and
4
Cardiovascular Trials Unit, Central Manchester University Hospital NHS Foundation Trust,
Manchester, UK
Address correspondence to Dr A.A. Syed, Department of Diabetes, Endocrinology and Obesity Medicine, NW1
Ladywell Building, Salford Royal NHS Foundation Trust, Salford M6 8HD, UK. email: [email protected]
Received 16 February 2014 and in revised form 5 March 2014
Summary
Background: Gastric bypass surgery induces early
remission or significant improvement in type 2
diabetes (T2D).
Aim: To assess effectiveness of stopping glucoselowering treatment at the time of surgery.
Design: Observational cohort analysis.
Methods: We identified 101 patients (62 women)
with T2D who had undergone gastric bypass surgery
at a mean (SD, standard deviation) age of 51.4 (9.0)
years. We recorded weight, body mass index (BMI),
glycosylated haemoglobin (HbA1c), blood pressure
(BP), total and high-density lipoprotein (HDL)
cholesterol preoperatively and at a median 4, 12
and 24 months postoperatively, and changes to glucose-lowering therapy.
Results: Mean (SD) baseline BMI was 50.3 (6.3)
kg/m2, HbA1c 65.3 (18.5) mmol/mol, systolic BP
146.0 (18.0) mmHg, diastolic BP 87.0 (10.8)
Introduction
The global obesity epidemic, by increasing the risk
of acquiring type 2 diabetes (T2D) several fold,1,2 is
fuelling the worldwide prevalence of diabetes in
adults, with a projected increase of 69% in developing countries and 20% in developed countries
mmHg and total cholesterol-to-HDL cholesterol
ratio 4.0 (1.2). Mean (95% confidence interval) reduction in BMI was 16.4 (14.1–18.7) kg/m2, HbA1c
23.6 (17.6–29.6) mmol/mol, systolic BP 12.9 (5.9–
19.8) mmHg, diastolic BP 6.1 (1.8–10.5) mmHg and
total cholesterol-to-HDL cholesterol ratio 1.1 (0.6–
1.5) at 24 months (P < 0.001 for all measures).
Although 91% of patients were receiving glucoselowering therapies preoperatively, complete
(HbA1c < 42 mmol/mol) and partial (HbA1c
42–48 mmol/mol) remissions of T2D were seen in
62.1% and 5.2% at 2 years postoperatively.
Conclusions: Cessation of glucose-lowering therapies in people with T2D at the time of gastric
bypass surgery was clinically effective. The majority
of patients remained in complete or partial remission
of diabetes up to 2 years postoperatively.
between 2010 and 2030.3 Although lifestyle and
dietary measures and anti-obesity pharmacotherapy
are widely recommended as the primary treatment
approach for obesity, bariatric surgery remains the
most clinically effective and cost-effective intervention for people with morbid obesity compared with
non-surgical interventions.4,5 Thus, the global
! The Author 2014. Published by Oxford University Press on behalf of the Association of Physicians.
All rights reserved. For Permissions, please email: [email protected]
722
F. Behbehani et al.
Table 1 Baseline mean (SD) measurements in people with T2D who had undergone gastric bypass surgery
Age (years)
Weight (kg)
BMI (kg/m2)
Duration of diabetes (months)
HbA1c (mmol/mol)
Systolic BP (mm Hg)
Diastolic BP (mm Hg)
Total cholesterol (mM)
HDL cholesterol (mM)
Total cholesterol:HDL cholesterol
All (n = 101)
Men (n = 39)
Women (n = 62)
Pa
51.4
139.3
50.3
76.6
65.3
146.0
87.0
4.6
1.2
4.0
52.2
153.4
49.9
78.6
70.2
145.5
87.6
4.5
1.1
4.2
50.8
130.4
50.6
75.4
62.3
146.3
86.7
4.6
1.3
3.8
ns
<0.001
ns
ns
0.04
ns
ns
ns
<0.01
ns
(9.0)
(23.2)
(6.3)
(64.0)
(18.5)
(18.0)
(10.8)
(1.1)
(0.3)
(1.2)
(7.8)
(20.8)
(6.5)
(56.3)
(19.0)
(17.6)
(12.9)
(1.0)
(0.2)
(1.2)
(9.7)
(20.1)
(6.2)
(68.9)
(17.8)
(18.4)
(9.3)
(1.1)
(0.3)
(1.2)
ns, non-significant. aMen vs. women, Student’s t-test.
uptake of bariatric surgery has increased exponentially in the past decade.6,7 Bariatric surgery reduces
mortality in people with a body mass index
(BMI) 5 35 kg/m2 and results in resolution or
improvement in the severity of several co-morbid
conditions including T2D, hyperlipidaemia and
hypertension.8,9 Following an earlier audit at our
centre which confirmed early remission or improvement in T2D following gastric bypass surgery, we
introduced a protocol of cessation of glucose-lowering treatment in the immediate post-operative
period with subsequent monitoring of glycaemic
control.10 We now report a cohort analysis of
weight loss and metabolic outcomes of gastric
bypass surgery in people with T2D to assess the
clinical effectiveness of this strategy.
Methods
We carried out an observational cohort analysis
of bariatric surgical patients in the setting of a
National Health Service university teaching hospital
that serves the population of Greater Manchester
in northwest England.10,11 Data were gathered prospectively in an automated database. We identified
people with T2D who had undergone gastric bypass surgery since the time of the previous audit.10
Data extracted for this analysis included preoperative and postoperative body weight, glycosylated
haemoglobin (HbA1c), blood pressure (BP), total
and high-density lipoprotein (HDL) cholesterol,
and changes to glucose-lowering therapies.
Weight loss outcomes were reported as reduction
in BMI and/or percent excess weight loss
(%EWL).12 Remission of diabetes was defined as
complete (HbA1c < 42 mmol/mol)
or partial
(HbA1c 42–48 mmol/mol) in the absence of active
pharmacologic therapy.13 Comparisons of means
were performed by Student’s t-test, and contingency
tables of categorical variables were analysed by
Fisher’s exact test. Comparisons among groups
were done by one-way analysis of variance followed by Tukey’s multiple comparison test.
P < 0.05 was considered statistically significant and
95% confidence interval (95% CI) was reported as a
measure of precision. Data were analysed with SPSS
20.0 (IBM Corp., New York, NY) and Prism 4.03
(GraphPad Software Inc., La Jolla, CA). Permission
was obtained from the Caldicott Guardian of our
institution.
Results
We identified 62 women (61.4%) and 39 men with
T2D with an overall mean (SD, standard deviation)
baseline age of 51.4 (9.0) years and BMI 50.3 (6.3)
kg/m2 who had undergone gastric bypass surgery.
There were no significant differences between men
and women in age, BMI, duration of diabetes, systolic and diastolic BPs, total cholesterol and total
cholesterol-to-HDL cholesterol ratio at baseline
(Table 1). Following gastric bypass surgery there
was significant weight loss with a mean (95% CI)
reduction in BMI of 16.4 (14.1–18.7) kg/m2
(P < 0.0001 for trend) at 24 months (Figure 1a). The
mean (standard error) %EWL was 65.2 (2.2) %
(P < 0.0001 for trend) at 24 months (Figure 1b).
The mean (95% CI) reduction in HbA1c was 23.6
(17.6–29.6) mmol/mol (P < 0.0001 for trend) at 24
months (Figure 1c). HbA1c was 5 48.0 mmol/mol
in 83.8% patients preoperatively and 20.7% patients
by 4 months (P < 0.001) and maintained up to 24
months postoperatively (Figure 1d). HbA1c in a
two-group analysis by age, using the median age
Metabolic outcomes
723
Figure 1. Outcome measures over time following gastric bypass surgery in obese people with T2D: BMI (a); percent excess
weight loss (b); glycosylated haemoglobin (c); proportion (%) of patients in three bands of glycosylated haemoglobin levels
(d); systolic and diastolic BPs (e); HDL and non-HDL cholesterol (f).
of 51 years as the cutoff, was similar at baseline
but there were greater reductions in younger
compared with older individuals by 4 months after
gastric bypass surgery and maintained up to 24
months (Table 2). Likewise, there were significantly
greater reductions in HbA1c in patients with shorter
duration of diabetes in a two-group analysis using
the median duration of 59 months as the cutoff
(Table 2). There were no significant differences in
HbA1c reduction based on greater or lesser degree
of weight loss in a two-group analysis using the median BMI at 24 months of 33.35 kg/m2 as the cutoff.
Ninety-one percent of patients were receiving glucose-lowering therapies preoperatively, including
724
F. Behbehani et al.
Table 2 Mean (SD) glycosylated haemoglobin (mmol/mol) before and after gastric bypass surgery by age and diabetes
duration
Age
Baseline
4 months
12 months
24 months
Duration of diabetes
<51 years
551 years
Pa
<59 months
559 months
Pa
62.3
37.8
36.3
37.2
68.1
44.5
43.1
45.5
ns
<0.01
<0.01
<0.01
61.5
36.8
35.5
36.4
69.1
45.7
44.9
45.9
0.040
<0.001
<0.001
<0.001
(18.3)
(8.7)
(7.5)
(8.1)
(18.5)
(9.5)
(11.8)
(13.4)
(16.8)
(5.0)
(6.1)
(7.4)
(19.5)
(10.9)
(12.2)
(13.2)
a
Student’s t-test, equal variances not assumed.
67% on oral hypoglycaemic agents (OHAs) and
24% on insulin OHAs. Glucose-lowering therapies were stopped completely in 80 patients at the
time of surgery. Of those patients who continued
treatment, 12 were on metformin, two on sulphonylureas and four on insulin OHA (unknown in three
patients). Complete and partial remissions of T2D
were seen in 66.2% and 4.4% of patients at 1 year
and 62.1% and 5.2% at 2 years postoperatively. Of
24 patients who were on insulin OHAs preoperatively, 20 (83%) came off insulin treatment, of whom
eight (40%) achieved complete withdrawal of glucose-lowering treatment; the remaining four (17%)
of patients had reduced insulin requirements.
The mean (95% CI) reduction in systolic BP was
12.9 (5.9–19.8) mm Hg (P < 0.0001) and diastolic
BP 6.1 (1.8–10.5) mm Hg (P < 0.0001) (Figure 1e)
and non-HDL cholesterol 0.54 (0.10–0.98) mmol/l
(P = 0.001) (Figure 1f). Systolic BP was >140 mm Hg
in 60.4% of patients preoperatively compared with
30.0% at 2 years postoperatively (P = 0.001). Totalto-HDL cholesterol ratio was >4.0 in 44.7% of patients preoperatively compared with 10.5% at 2
years postoperatively (P < 0.0001).
Discussion
We assessed the clinical effectiveness of stopping
glucose-lowering therapies on the day of gastric
bypass surgery in obese people with T2D and
report that two-thirds of patients remained in complete or partial remission of T2D up to 2 years postoperatively. This is consistent with previous studies
that have reported resolution or improvement of diabetes in 80% of gastric bypass patients at two or
more years of follow-up.8
It has been well recognized that remission of glucose intolerance following gastric bypass surgery
occurs in the immediate postoperative period long
before clinically significant weight loss has
occurred. It has been demonstrated that the twin
defects of beta cell failure and insulin resistance
that underlie T2D can be reversed by acute negative
energy balance alone;14 these changes occurred in
association with decreases in pancreatic and liver
triacylglycerol concentrations. Although this may
hold true of gastric bypass surgery as well, changes
in the enteroinsular axis have also been implicated.10 Although plasma concentrations of ghrelin,
an orexigenic hormone expressed mainly in the gastric fundus, increase with diet-induced weight loss,
gastric bypass surgery is associated with markedly
suppressed levels, possibly contributing to the
weight-reducing effect of the procedure.15 On the
other hand, gastric bypass has been associated
with a marked increase in plasma concentrations
of the anorectic gut hormones, glucagon like peptide-1 (GLP-1) and peptide YY in response to nutrient ingestion,16 and they probably play a key role in
sustaining postoperative weight loss.17 Emerging
evidence from preclinical studies suggests that potentiation of GLP-1 activity can increase beta-cell
mass, stimulate beta-cell proliferation, increase
beta-cell neogenesis and inhibit beta-cell apoptosis.18 Although this remains to be seen in clinical
studies in humans, augmentation of GLP-1 by gastric
bypass surgery raises the exciting possibility of reversal of diabetes disease progression.10
Factors that predict remission of diabetes following bariatric surgery include younger age, shorter
duration of diabetes and greater weight loss.19 We
also confirmed that there were greater reductions in
glycosylated haemoglobin in individuals who were
younger or had shorter diabetes duration. These
findings support the argument for considering bariatric surgery sooner rather than later in the management of T2D associated with morbid obesity. The
degree of weight loss, however, did not influence
the amount of reduction in HbA1c in our study.
This lends further credence to the weight-independent mechanisms of improvement in glycaemic control by gastric bypass surgery. Studies have also
Metabolic outcomes
shown benefits in terms of reduction in cardiovascular events and mortality on long term follow-up
of bariatric patients. The Swedish Obese Subjects
study, which compared 2010 post-bariatric surgery
patients with 2037 non-surgical patients matched
for age, sex, BMI and co-morbidities, demonstrated
a reduction in myocardial infarction rate of 43% and
all cause mortality rate of 31% up to 15 years
postoperatively.20
Despite prospectively filled automated, electronic
database for data collection, our study was restricted
by the retrospective nature of the cohort analysis.
We were unable to examine the influence of specific preoperative anti-diabetic therapies such as
GLP-1 receptor agonists on postoperative clinical
outcomes due to small numbers in sub-group analyses. Although glycosylated haemoglobin reflects
sub-acute glycaemic control, we were unable to collect capillary blood glucose data or undertake continuous glucose monitoring due to the constraints of
routine clinical care and logistical challenges.
Similarly, in the absence of clinical utility, measurement of hormones involved in the regulation of the
entero-insular axis was beyond the scope and
means of this work.
Despite these limitations, our pragmatic, observational study confirms significant weight loss and
early remission or improvement in T2D following
gastric bypass surgery as reported previously. In
addition, we report that our protocol for stopping
glucose-lowering treatments in the immediate postoperative period in people with T2D prior to discharge from hospital was safe and effective. To our
knowledge, this is the first report of such an
approach of immediate discontinuation of glucoselowering therapies at the time of gastric bypass surgery. As patients have markedly reduced food intake
following gastric bypass surgery, our protocol
minimizes the risk of post-operative hypoglycaemia.
Patients were advised intensive monitoring of
capillary blood glucose concentrations and review
by specialist nurses and/or their primary diabetes
care providers. In patients who continue to manifest
hyperglycaemia, glucose-lowering therapies may be
re-introduced in a phased manner as clinically
indicated.
Conclusion
We conclude that cessation of glucose-lowering
therapies in people with T2D at the time of gastric
bypass surgery was clinically effective. The majority
of patients remained in complete or partial remission
of diabetes up to 2 years postoperatively.
725
Acknowledgements
This work was presented as an Oral Communication
at the Diabetes UK annual professional conference
(2013).21
Conflict of interest: None declared.
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