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96
VOLUME 8 NUMBER 2 • JUNE 2011
REPORTS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
lower predisposing genetic component is
needed today to result in the development of
diabetes than was required in the 1930s. ‘The
predisposing reactive genotype leads in fact to
a faster tempo of
β
-cell loss in the presence of
increasing insulin resistance’, Dr Segal pointed
out.
In adolescents, it is the ongoing weight gain
that predicts the development of type 2 diabe-
tes, rather than glucose, insulin or C-peptide
levels. ‘This is because the BMI is a reliable
reflection of insulin resistance over time’, Dr
Segal argued. ‘If the ACCELERATOR theory is
correct, the occurrence of type 1 and type 2
diabetes will converge over time, and this has
already occurred in African-American females.’
‘But the added weight is in fact a bystander
injury. It is our high-fat and refined-carbohy-
drate intake that is hammering the
β
-cell. This
high-fat, high-carbohydrate intake is also caus-
ing oxidative stress and release of inflamma-
tory cytokines.
Evidence is emerging linking the trillions of
bacteria living in our gut to the development
of obesity and diabetes. These gut organisms,
collectively known as the gut microbiome, are
so vastly altered that in fact these microbiota
can promote a ‘leaky gut’, an increase in sys-
temic inflammation, and show an increased
capacity for energy harvesting.
‘So not only are overweight people taking
in a calorie excess, their gut is harvesting more
nutrients than the lean individual’, Dr Segal
pointed out. Signals from the gut can promote
the diversion of calories into fat storage and
suppress fat burning.
The perfect storm is however created in the
gut lining, which has been shown in type 1 dia-
betes to develop leaks. This results in increased
permeability to dietary antigens, changing
mucosal immunity and it contributes to the
pathogenesis of type 1 diabetes.
In conclusion, Dr Segal noted that in future
we may find ways of rebalancing our gut
by altering the foods we eat. In the interim,
rebalancing the gut microbiota by returning
to a high-fibre, low-fat, reduced refined-car-
bohydrate diet may contribute to slowing the
advance of both type 1 and type 2 diabetes
worldwide.
The liver in diabetes
Is the fatty liver, as a source of ectopic fat,
responsible for increased cytokines, raised
insulin resistance and the development of the
metabolic syndrome, diabetes and increased
cardiovascular risk? The answer may well be
that the liver is both the target organ and the
initiator of increased cardiovascular risk.
Dr Chris Kassanides, gastro-enterologist,
from Morningside Hospital, Johannesburg
and chairman of the Gastrointestinal Foun-
dation of South Africa explored the relation-
ships between non-alcoholic fatty liver disease
(NAFLD), diabetes and the metabolic syn-
drome.
‘The prevalence of non-alcoholic fatty liver
disease is on the increase as average BMIs
increase worldwide, but are all these patients
with fatty livers at risk of progressive liver dis-
ease? This diagnosis of non-alcoholic steato-
hepatitis (NASH), a progressive disease, can
only be confirmed by liver biopsy and is char-
acterised by raised liver transaminases’, Dr Kas-
sianides pointed out.
‘It is clear that we cannot biopsy all patients
with fatty livers. However, a recent prospective
study of outpatients at a medical centre that
did exactly that, provides us with some impor-
tant insights.
5
The prevalence of NAFLD in this popula-
tion was 46%, and NASH was defined in
12% of the total cohort. The NAFLD patients
were more likely to be male, older (54 years),
hypertensive and diabetic. ‘Importantly, in the
diabetic patient group (16% of the cohort),
NAFLD was found in 74% and NASH in 22%
of patients.’
There are numerous clinical scores/corre-
lates that can be used to ‘diagnose’ NAFLD
and NASH. ‘In practice, if you have a patient
with features of the metabolic syndrome and
NAFLD, marked by increased liver transami-
nases, you need to biopsy them to assess fur-
ther liver damage, liver fibrosis or cirrhosis’, Dr
Kassiandides stressed.
‘The value of doing the liver biopsy is to dif-
ferentiate the patient who has the potential to
progress from NAFLD to more serious disease,
allowing you to intensify your lifestyle advice’,
Dr Kassianides concluded.
NAFLD contributes to worsening
ischaemic heart disease
‘While it is difficult to separate NAFLD from the
metabolic syndrome, a number of studies have
highlighted the increased cardiovascular risk in
NAFLD patients’, Dr Abelson said. Also, in clini-
cally manifest cardiovascular disease, there is a
higher incidence of NAFLD.
In a study of carotid artery intima–media
thickness (IMT) in NAFLD patients, very high
carotid IMT was seen.
6
Management of NAFLD is lifestyle modifi-
cation, which is the cornerstone of therapy to
reduce insulin resistance. ‘Although there are
no data from randomised clinical trials, weight
loss, diet and exercise are key. Bariatric surgery
is defined as the best therapy for the morbidly
obese.
Patients should be treated with statins and
either an ACE inhibitor or ARB for accompa-
nying hypertension. In a recent post-
ad hoc
study of the GREACE study of atorvastatin to
lower LDL, patients with modestly abnormal
liver enzyme levels showed reductions of some
50%, and there were significantly fewer car-
diovascular events in statin-treated patients.
7
‘The figures are highly significant and stress
the fact that these patients should not be
denied statin therapy. A small study has pro-
vided some evidence that ezetimibe is useful in
NASH patients’, Dr Abelson noted.
‘There is more to women than just
levels’
‘Despite the 2007 publication of a new algo-
rithm for women at risk of cardiovascular dis-
ease, which stratified women into high risk
(10-year predicted risk for coronary heart dis-
ease
>
20%), and “at risk” being the presence
of one or more cardiovascular disease risk fac-
tors, cardiovascular mortality in women is not
decreasing’, Dr Naomi Rapeport, physician at
Milpark Hospital, Johannesburg noted.
‘We also know now that hormone replace-
ment therapy should not be used for primary
or secondary intervention in women with
coronary artery disease. Yet many women are
not being treated with statins, for example,
because the traditional Framingham cardiovas-
cular score underestimates women’s vascular
risk.’
‘Myocardial infarction (MI) is occurring
in younger women, and post-MI in-hospital
mortality is higher in women than in men. In
the African cohort of myocardial infarction
patients in the INTERHEART study, the mean
age of women having their first MI was 56
years of age.’
The American Heart Association has
recently (February 2011)
8
released new effec-
‘We have little understanding of the role of
the good bacteria of the gut but an excel-
lent understanding of the pathological bac-
teria’ – Dr Segal
‘Hepatitis C virus (HCV) rates are approxi-
mately double in diabetes patients. Because
the combination of hepatitis C and insu-
lin resistance increases the propensity to
develop end-stage liver disease, screening
diabetic patients for HCV is very important’
– Dr Kassianides
‘Fatty liver is your liver telling you your heart
is not happy!’
‘Some studies have shown that NAFLD is an
independent risk factor for ischaemic heart
disease, others have not; so the jury is still
out’ – Dr Abelson
