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VOLUME 8 NUMBER 2 • JUNE 2011
95
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REPORTS
Serving diabetes and cardiology: round three of the South African
diabetologist/cardiologist debate
T
he diabetes/cardiology debate was made
possible by an annual unrestricted edu-
cational grant by Servier, in line with their
long-term commitment to continuing medical
education in South Africa.
Insulin resistance is protective when
secondary to excessive weight gain
‘When patients accumulate visceral fat, insulin
resistance develops as a secondary phenom-
enon to protect against further weight gain.
This hypothesis and its pathophysiological
view cannot be substantiated by peer-reviewed
research’, Dr Amod pointed out. ‘But it makes
physiological sense to resist the effects of an
anabolic hormone (insulin).’
‘The hypothesis is supported by the fact
that 30% of obese, relatively insulin-resistant
individuals are in fact metabolically normal,
have no evidence of increased cardiovascular
risk, and do not derive cardiovascular benefit
from weight loss. On the contrary, overcoming
insulin resistance either with exogenous insu-
lin therapy or thiazolidenediones (glitazones)
produces weight gain, as it overcomes the pro-
tective aspect of insulin resistance’, Dr Amod
stressed.
‘So, while we need to understand insulin
resistance, it should not be the primary target
of our intervention. The role of insulin resist-
ance as a protective mechanism in the over-
weight situation may be the reason why the
insulin-sensitising glitazones show poorer-
than-expected outcomes in clinical studies of
hetero-genous type 2 diabetic patients’, he
added.
In conclusion, Dr Amod stressed that type 2
diabetes is a diagnosis of exclusion. ‘For the cli-
nician and patient, it is less important to label
the particular type of diabetes as type 1, 2 or
1.5, than it is to understand the pathophysiol-
ogy of the disease in each patient.’
New facts in the paediatric diabetic
environment
In a journey to look at childhood obesity differ-
ently and in the context of the increase in both
type 1 and type 2 diabetes, Dr David Segal,
paediatric endocrinologist with academic com-
mitments at Wits Medical Faculty and also in
private practice at CDE, Parktown, explored
the available medical literature and interpreted
new data to provide concepts for clinical inter-
vention.
He targeted two main features of modern
obesity, neuro-economics (the cost–benefit
of obtaining food), and the consequences of
increased fat and carbohydrate intake, which
is challenging the
β
-cell and altering the gut
microbiota so that food transition and absorp-
tion is altered. ‘While genetic studies have
added to our knowledge of the gene control
of appetite, satiety and feedback mechanisms,
they have failed to give us a practical option to
control obesity’, he said.
The field of neuro-economics applied
to food calculates the price-cost in energy
expended, and risk and effort to procure the
food that we eat, and relates it to demand,
which is ever present as appetite, and supply,
which in urban areas is plentiful at the near-
est supermarket. ‘In neuro-economic terms
our food is very cheap and it is extra-ordinarily
palatable, thereby stimulating excess demand.
This demand will remain consistently high
unless we can increase the energy-risk cost or
reduce the palatability.’
1
In a study on the burden of diabetes among
the youth, the SEARCH study
2
has shown the
rising prevalence of type 2 diabetes in different
racial groups in six states in the USA. Among
younger children up to nine years of age, type
1 diabetes accounted for approximately 80%
of the diabetes cases, while among the older
group (10 to 19 years), type 2 diabetes ranged
from 6% in the non-Hispanic white to 76%
(1.74% cases/1 000) among American Indians.
Interestingly, the only group to show, in the
15- to 19-year-old category, the same preva-
lence (3/1 000) for both type 1 and type 2
diabetes was the African-American female
population. ‘Type 2 diabetes in adolescents is
associated with increased obesity, with a five-
year lead time between occurrence of obesity
(BMI
≥
30 kg/m
2
) and the development of dia-
betes’, Dr Segal noted.
In evaluations of the rising trend of child-
hood type 1 diabetes, there is an association
with rising childhood obesity. Up to the 1950s,
diabetes was seen as a single disorder with an
aggressive presentation in the young. ‘In the
1960s, 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 antibodies.
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 hypothesis, which pro-
poses that weight and associated insulin resist-
ance accelerate loss of
β
-cells in both type 1
and type 2 diabetes, and the only thing that
distinguishes 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 adult-
hood) and type 2 diabetes’, Dr Segal said.
Because of environmental pressures, a
‘Acabose is not used widely enough and
is very effective even in impaired glucose
tolerance if titrated slowly to avoid side
effects’ – Dr Amod
‘Dr Jekyll is insulin resistance as a second-
ary protective phenomenon against weight
gain. Mr Hyde is brought to the fore when
pancreatic beta-cell failure occurs and dia-
betes mellitus emerges’ – Dr Amod
‘DPP-4 and GLP-1 should be used early
in type 2 diabetes treatment but not for
patients with a high HbA
1c
(more than
8.5%)’ – Dr Amod
‘Good glycaemic control is important in
the early years for cardiovascular benefit
over the next two decades. In young type
2 diabetes patients, I aim for a lower HbA
1c
of below 6.5%, using early combination
therapies, which are least likely to cause
hypoglycaemia’ – Dr Amod
‘Weight gain is an ongoing assault on the
β
-cell’ – Dr Segal
‘A large component of obesity is genetic
and inflammatory but the gut biome plays
a role’ – Dr Segal
