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CURRENT TOPICS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
76
VOLUME 8 NUMBER 2 • JUNE 2011
Surgical interventions to correct metabolic disorders
RODOLfO LAHseN, MARCOs BeRRY
Abstract
O
besity and related metabolic disorders are increasing,
especially in developing countries. It is widely
accepted that in extremely obese patients bariatric
surgery reduces body weight and improves type 2 diabetes
and the metabolic syndrome. Weight loss partially explains
this effect as do weight loss-independent mechanisms
linked to gut hormones, peptide YY, ghrelin, glucagon-like
peptide-1, and glucose-dependent insulinotropic peptide/
gastric inhibitory polypeptide. Several groups performing
established and novel surgical techniques have shown
encouraging metabolic results. Herein we consider whether
it is theoretically plausible to use surgery as an alternative or
complementary approach to medical treatment of diabetes
in overweight and mildly obese patients.
Keywords:
bariatric surgery, ghrelin, GIP, GLP-1, metabolic surgery,
obesity, type 2 diabetes, PYY
Introduction
Obesity and its related disorders are increasing worldwide, especially
in developing countries.
1,2
As BMI rises, several cardiovascular risk
factors appear, such as type 2 diabetes, hypertension, dyslipidaemia,
and increasing mortality.
3
These factors that tend to cluster are
often linked to insulin resistance and are known as the metabolic
syndrome.
4
Risk factors follow a common and progressive course. Prevalence
of the metabolic syndrome, as observed in clinical practice, is
10–15% in normoglycaemic people, 42–64% in those with glucose
intolerance and 78–84% in those with type 2 diabetes.
5
Diabetic
patients have an increased risk of blindness, chronic kidney disease,
and non-traumatic amputation of lower limbs,
6
while their risk for
acute myocardial infarction is equivalent to that of a person who
has had a previous event.
7
Lifestyle and pharmacological approaches have been
implemented for prevention and treatment of the metabolic
syndrome and type 2 diabetes. Although progress has been made
in recent years, in most cases they are still insufficient to achieve
the proposed targets, especially in patients that need aggressive
and complex therapy regimens due to their high risk.
8-11
Novel
pharmacological therapies that target the incretin system have
been approved for the treatment of type 2 diabetes: GLP-1
agonists and DPP-4 inhibitors. GLP-1 agonists offer extra-glycaemic
benefits, such as a reduction in body weight and possibly blood
pressure, but with gastrointestinal side effects, especially in the
early stages of treatment. However, due to their mechanisms of
action GLP-1 agonists and DPP-4 inhibitors are not associated with
hypoglycaemia when given as monotherapy. While these agents
increase the pharmacotherapeutic options in diabetes, clinical trials
that assess their long-term safety and efficacy are ongoing.
12
Bariatric surgery in extremely obese patients
Current indications for bariatric surgery are BMI
≥
40 or
≥
35 kg/m
2
with comorbid conditions when the risks for obesity-
associated morbidity and mortality are high and conventional
therapies have failed.
13
In extremely obese patients bariatric surgery has demonstrated
a significant excess weight reduction, and an improvement in
comorbidities such as diabetes, dyslipidaemia and hypertension.
Compared with conventionally treated patients, 10 years after
bariatric surgery the incidence of type 2 diabetes is reduced by
75%, and recovery from diabetes is three- to four-fold higher.
14
Surgical bypass procedures appear to result in a greater metabolic
improvement than restrictive procedures.
15,16
The implications of
different bariatric procedures on the secretion and action of several
gut hormones and their impact on beta-cell function and insulin
resistance have been recently reviewed
17,18
and are summarised in
Table 1.
17
The main mechanisms leading to metabolic improvement
(summarised in Fig. 1) are as follows:
•
Weight loss.
Abdominal visceral fat has a high lipolytic activity,
releasing large amounts of free fatty acids to the liver and
systemic circulation.
19
Free fatty acids impair insulin action at
target tissues,
20
and cause beta-cell apoptosis.
21
Furthermore,
insulin resistance is associated with increased blood pressure
and triglyceride levels and decreased HDL cholesterol.
22
Weight
loss is the cornerstone in preventing and treating diabetes and
its related metabolic disorders. In a multicentre randomised
controlled trial that compared intensive lifestyle intervention
versus standard therapy in 5 145 overweight type 2 diabetic
patients, lifestyle changes resulted in a modest but significant
loss of weight at one year (8.6 vs 0.7%;
p
<
0.001), which was
Correspondence to: Dr Rodolfo Lahsen
Diabetology Unit, Internal Medicine Department and Center of Nutrition and
Obesity Surgery, Clinica Las Condes, Las Condes, Santiago, Chile.
Tel: +562 6108000
Fax: +562 6108097
e-mail: rlahsen@clc.cl
Dr Marcos Berry
Bariatric Surgery Unit, Clinica Las Condes, Las Condes, Santiago, Chile.
S Afr J Diabetes Vasc Dis
2011;
8
: 76–79.
Abbreviations and acronyms
BMI
body mass index
DPP-4
dipeptidyl peptidase-4
PYY
peptide YY
GLP-1
glucagon-like peptide-1
GIP
glucose-dependent insulinotropic peptide/gastric inhibitory
polypeptide
GADA
glutamic acid decarboxylase antibodies
HDL
high-density lipoprotein
ICA
islet cell antibodies
