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SA JOURNAL OF DIABETES & VASCULAR DISEASE
REVIEW
VOLUME 8 NUMBER 2 • JUNE 2011
69
patients with mild to moderate obesity (BMI 30–35 kg/m
2
).
30
Of
note, there may be a case for considering bariatric surgery at a lower
BMI in South Asian patients; however, this is an area that requires
further research to clarify the benefits and the risks associated with
the approach.
30,31
Bariatric procedures are mainly categorised into two types:
restrictive and malabsorptive procedures.
32,33
Restrictive procedures
(e.g. laparoscopic adjustable gastric banding, vertical banded
gastroplasty and sleeve gastrectomy) primarily reduce the stomach
size, thus leading to early satiety and reduced food intake. On the
other hand, malabsorptive procedures (e.g. jejunoileal bypass and
biliopancreatic diversion) shorten the length of the small intestine,
limiting the time for digestion and absorptionof nutrients. Combined
malabsorptive and restrictive procedures, such as the Roux-en-Y
gastric bypass, are also commonly performed.
32,33
Of note, incision-
free endoscopic procedures are currently being developed, such as
the TOGA which restricts food intake by creating a small stapled
pouch along the lesser curve of the stomach with the use of flexible
staplers that are introduced and operated through the mouth.
33
Multiple studies have now clearly documented the efficacy of
bariatric surgery in type 2 diabetes patients regarding both weight
loss and glycaemic control.
34,35
Furthermore, several long-term
studies with bariatric interventions have demonstrated sustained
weight reduction in type 2 diabetes patients associated with
remission or even resolution of diabetes and with decreased long-
term mortality.
35,36
A recent meta-analysis has shown that overall,
78.1% of the type 2 diabetes patients experienced complete
resolution of diabetes (i.e. discontinuation of all anti-diabetic
medications and maintenance of glycaemic targets) following
bariatric surgery, which was greater after biliopancreatic diversion/
duodenal switch (95.1%), followed by gastric bypass (80.3%),
gastroplasty (79.7%) and laparoscopic adjustable gastric banding
(56.7%).
35
Of note, certain bariatric procedures which include a
bypass of the duodenum and proximal jejunum, appear to lead to
remission of diabetes independent of weight loss.
37
The underlying
mechanisms are still unclear; however, two main hypotheses
have been proposed: the ‘hindgut’ hypothesis and the ‘foregut’
hypothesis. The ‘hindgut’ hypothesis suggests that re-routing of
nutrients to the distal part of the small intestine may increase
GLP-1 secretion, which in turn can improve glycaemic control. On
the other hand, the ‘foregut’ hypothesis proposes that surgical
bypass of the foregut may benefit type 2 diabetes patients through
inhibition of a yet unknown diabetogenic signal.
37
It is important to note that bariatric surgery, even with minimally
invasive techniques, is inevitably associated with surgical risks
and can lead to acute and long-term complications.
38,39
Acute
complications include haemorrhage, obstruction, anastomotic
leaks, infections and pulmonary emboli, and have been reported
for 5–10% of patients following bariatric procedures. Long-
term complications can also develop in the years after bariatric
surgery, with nutritional deficiencies and gallstones being the
most common.
38
Depending mainly on the procedure, early
mortality rates (i.e. death during the first 30 days) of 0.1–2.0%
have been documented, while mortality after 30 days is reported
to range between 0.1 and 4.6%.
40
Furthermore, bariatric surgery
is associated with a high initial cost, which needs to be taken into
consideration when reviewing the associated benefits. However,
it has been shown that bariatric procedures may be cost-effective
in the long run due to significant reductions in costs related to
comorbidities.
41
The clinical significance of antihyperglycaemic
therapies in weight management: focus on
incretin-based therapies
To date, lifestyle interventions and anti-obesity pharmacotherapy
appear to have a limited long-term weight-loss outcome in type 2
diabetes patients, while bariatric surgery is still generally considered
as a last resort in selected cases. In order to overcome the limitations
of current weight-management strategies in type 2 diabetes, new
treatments that combine a beneficial effect on glycaemic control
with improvements in body weight are actively sought.
Recently, a novel class of antidiabetic agents has been developed
that improves glycaemic control through the incretin effect, which
is mediated largely by two gut hormones (incretins), GLP-1 and
GIP.
42–44
Both incretin hormones are released from neuroendocrine
cells of the small intestine in response to intraluminal carbohydrates
and enhance beta-cell stimulation.
42
GLP-1 also suppresses
glucagon secretion, delays gastric emptying, promotes satiety
and exhibits potential beta-cell preserving properties in animal
and
in-vitro
models.
42
The clinical significance of the latter feature
still needs to be established. Recent data demonstrate that type 2
diabetes is associated with distinct incretin defects.
42,43
Patients with
type 2 diabetes have decreased meal-induced GLP-1 secretion, but
remain sensitive to the peptide. Conversely, GIP secretion remains
almost normal in type 2 diabetes, but the beta-cell sensitivity to GIP
is reduced. Moreover, the half-lives of GLP-1 and GIP are limited to
a few minutes due to rapid degradation by the enzyme DPP-4 and
renal clearance.
42,44
These observations prompted the development
of incretin-based therapies for type 2 diabetes.
Two types of incretin-based therapies are now available in the
UK: GLP-1 receptor agonists (liraglutide and exenatide) and DPP-4
Table 2.
Key features of the licensed anti-obesity drug orlistat
27
Orlistat
27
Mechanism of action Gastric and pancreatic lipase inhibitor
Recommended dose 120 mg three times daily with each main meal –
omit the dose if a meal is missed or contains no fat
Indication
• BMI
≥
30 kg/m
2
• BMI
≥
28 kg/m
2
and obesity-associated
comorbidity
Main contraindications • Chronic malabsorption syndrome
• Cholestasis
• Breast-feeding
Side effects*
Hypoglycaemia, headache, upper respiratory
infection, influenza, steatorrhoea, oily spotting,
liquid stools, increased defecation and faecal
incontinence (associated with intake of high-fat
foods)
Clinical practice points Risk for deficiencies of fat-soluble vitamins
Regular monitoring of patients on oral
anticoagulants
*Side effects rated as very common (
≥
1/10) in Summary of Product
Characteristics.
For full details please refer to Summary of Product Characteristics.
BMI
=
body mass index.
