CARDIOVASCULAR JOURNAL OF AFRICA • Vol 22, No 3, May/June 2011
AFRICA
161
Drug Trends in Cardiology
Serving diabetes and cardiology: round three of the
South African diabetologist/cardiologist debate
The diabetes/cardiology debate was made
possible by an annual unrestricted educa-
tional 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 second-
ary phenomenon 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 meta-
bolically 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 insulin
therapy or thiazolidenediones (glitazones)
produces weight gain, as it overcomes the
protective aspect of insulin resistance’, Dr
Amod stressed.
‘So, while we need to understand insu-
lin resistance, it should not be the primary
target of our intervention. The role of
insulin resistance as a protective mecha-
nism in the overweight 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 exclu-
sion. ‘For the clinician 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 pathophysiology of the
disease in each patient.’
New facts in the paediatric
diabetic environment
In a journey to look at childhood obesi-
ty differently and in the context of the
increase in both type 1 and type 2 diabe-
tes, Dr David Segal, paediatric endocri-
nologist with academic commitments at
Wits Medical Faculty and also in private
practice at CDE, Parktown, explored the
available medical literature and inter-
preted new data to provide concepts for
clinical intervention.
He targeted two main features of
modern obesity, neuro-economics (the
cost–benefit of obtaining food), and the
consequences of increased fat and carbo-
hydrate intake, which is challenging the
β
-cell and altering the gut microbiota
so that food transition and absorption is
altered. ‘While genetic studies have added
to our knowledge of the gene control of
appetite, satiety and feedback mecha-
nisms, they have failed to give us a practi-
cal 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 appe-
tite, and supply, which in urban areas is
plentiful at the nearest 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 chil-
dren up to nine years of age, type 1 diabe-
tes 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 prevalence (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
diabetes’, Dr Segal noted.
In evaluations of the rising trend of
childhood 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 pres-
entation in the young. ‘In the 1960s,
‘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
secondary protective phenomenon
against weight gain. Mr Hyde is
brought to the fore when pancreatic
beta-cell failure occurs and diabetes
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 hypo-
glycaemia’ – Dr Amod
‘Weight gain is an ongoing assault on
the
β
-cell’ – Dr Segal
