CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 3, May/June 2011
162
AFRICA
scientific evidence saw the emergence of
an auto-immune basis for type 1 diabetes,
with lymphocytic infiltration of the islets,
and an HLA link to diabetes and islet anti-
bodies. We do not have a clue as to what
triggers the immune system to attack the
beta-cell’, Dr Segal said.
An hypothesis which is gaining
credence is the ACCELERATOR hypoth-
esis, which proposes that weight and
associated insulin resistance accelerate
loss of
β
-cells in both type 1 and type 2
diabetes, and the only thing that distin-
guishes these two forms of diabetes is the
rate of progression. There is considerable
evidence that weight gain in early life
can be used to predict, at two years of
age, the risk of islet immunity in children
with first-degree relatives with type 1
diabetes.
3
Also, over the past 20 years, there has
been a steady increase in BMI in girls
and boys at the time of diagnosis of their
type 1 diabetes.
4
‘If we look at HLA risk
markers for diabetes, it is evident that
there are genotypes that are related to the
development of type 1, 1.5 (LADA: latent
autoimmune diabetes in adulthood) and
type 2 diabetes’, Dr Segal said.
Because of environmental pressures,
a lower predisposing genetic component
is needed today to result in the develop-
ment 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 diabetes, 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 diabe-
tes 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-carbohydrate intake that is
hammering the
β
-cell. This high-fat, high-
carbohydrate intake is also causing oxida-
tive stress and release of inflammatory
cytokines.
Evidence is emerging linking the tril-
lions of bacteria living in our gut to
the development of obesity and diabe-
tes. 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 systemic 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 creat-
ed in the gut lining, which has been
shown in type 1 diabetes to develop leaks.
This results in increased permeability
to dietary antigens, changing mucosal
immunity and it contributes to the patho-
genesis 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-carbohydrate 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 develop-
ment of the metabolic syndrome, diabe-
tes 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-enter-
ologist, from Morningside Hospital,
Johannesburg and chairman of the
Gastrointestinal Foundation of South
Africa explored the relationships
between non-alcoholic fatty liver disease
(NAFLD), diabetes and the metabolic
syndrome.
‘The prevalence of non-alcoholic fatty
liver disease is on the increase as aver-
age BMIs increase worldwide, but are
all these patients with fatty livers at
risk of progressive liver disease? This
diagnosis of non-alcoholic steatohepatitis
(NASH), a progressive disease, can only
be confirmed by liver biopsy and is char-
acterised by raised liver transaminases’,
Dr Kassianides 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 important insights.
5
The prevalence of NAFLD in this
population 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 diabet-
ic patient group (16% of the cohort),
NAFLD was found in 74% and NASH in
22% of patients.’
There are numerous clinical scores/
correlates that can be used to ‘diagnose’
NAFLD and NASH. ‘In practice, if you
have a patient with features of the meta-
bolic syndrome and NAFLD, marked by
increased liver transaminases, you need
to biopsy them to assess further liver
damage, liver fibrosis or cirrhosis’, Dr
Kassiandides stressed.
‘The value of doing the liver biopsy
is to differentiate 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 clinically mani-
fest 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
modification, which is the cornerstone
of therapy to reduce insulin resist-
‘A large component of obesity is
genetic and inflammatory but the gut
biome plays a role’ – Dr Segal
‘We have little understanding of the
role of the good bacteria of the gut
but an excellent understanding of the
pathological bacteria’ – Dr Segal
‘Hepatitis C virus (HCV) rates are
approximately double in diabetes
patients. Because the combination
of hepatitis C and insulin resistance
increases the propensity to develop
end-stage liver disease, screening
diabetic patients for HCV is very
important’ – Dr Kassianides
