SA JOURNAL OF DIABETES & VASCULAR DISEASE
DRUG TRENDS
VOLUME 8 NUMBER 1 • MARCH 2011
39
or C-peptides. ‘This is because the BMI is a reli-
able 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 which is hammering the
b
-cell.
This high fat, high carbohydrate intake is also
causing oxidative stress and the release of
inflammatory 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 this 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 an excess in calories, 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 stor-
age 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 contributing 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, rebal-
ancing thegutmicrobiotaby returning toahigh-
fibre, low-fat, reduced refined carbohydrate
diet may contribute to slowing the advance of
both type 1 and type 2 diabetes worldwide.
Carefully consider the routine use
of aspirin in primary prevention of
CVD in low-risk diabetic patients
Any benefit of aspirin in primary prevention
of cardiovascular disease (CVD) in low-risk
diabetic patients is minimal and may well be
out weighed by the side effects, especially the
increase in gastrointestinal bleeds. This view
was expressed by Prof Brynne Ascott-Evans,
Division of Diabetes and Endocrinology, Stel-
lenbosch University, and substantiated primar-
ily from evidence published in a meta-analysis
by the Anti-Thrombotic Trialists (ATT) collabo-
ration
5
and specific trials in diabetic patients
from Scotland (POPADAD) and Japan (JPAD).
In the ATT meta-analysis, only 5% of
patients were diabetic, and the trials included
were older studies with a mixed bag of patients
and doses. ‘However, individualised data for
each patient in the various studies were utilised
in the meta-analysis.’
The ATT study found that there was a sig-
nificant 12% drop in any serious vascular
event on aspirin (primarily due to a signifi-
cant drop in non-fatal myocardial infarction).
However, aspirin usage did not affect mortality
in this meta-analysis. In the subgroup of dia-
betic patients, the benefit of reduced vascular
events was not significant, but haemorrhage
and extra-cranial bleeds were increased.
Referring to two modern studies,
6,7
POPA-
DAD (Prevention Of Progression of Arterial
Disease And Diabetes) in asymptomatic type
1 and type 2 diabetes who were given 100
mg aspirin and followed for 6.7 years (mean),
and JPAD in healthy type 2 diabetics with no
vascular disease clinically or on ECG and were
followed for 4.4 years, the benefits of aspirin
therapy were not statistically significant. In
POPADAD there was no statistically significant
difference in death from coronary artery dis-
ease and stroke, while increased gastrointes-
tinal bleeds affected four per 1 000 patients
on aspirin. In the JPAD study, the hazard ratio
for atherosclerotic events was reduced by 20%
in aspirin users, but the number of events was
small and the difference was not statistically
significant.
In the 2010 position paper of the ADA, AHA
and the ACC Foundation,
8
diabetic patients
from the ATT meta-analysis were pooled with
those from POPADAD, JPAD and an older large
retinopathy study (where patients received 650
mg aspirin daily and which contributed 50%
of the total study population of 7 500 patients
in this new meta-analysis). Nonetheless, only a
15% relative risk reduction (RRR) in stroke was
seen, which was not statistically significant.
There was a risk of haemorrhagic stroke of
1:10 000 per year and a gastrointestinal tract
(GIT) bleed risk of 3:10 000 per year. However,
it must be remembered that patients at higher
risk of bleeding were not included in these
cohorts of diabetic patients.
The consensus view was that aspirin (81–
162 mg) should be recommended for diabetic
patients with a 10-year cardiovascular disease
risk above 10%, and for those below 5% no
aspirin should be given. ‘In essence, the 10%
risk can be simply assessed as diabetic men
(above 50 years of age) and women (above 60
years of age) with at least one additional major
risk factor’, Prof Brynne Ascott-Evans pointed
out.
He concluded that these recent studies re-
affirm that cheap and seemingly fairly safe
interventions, e.g. aspirin, do not necessarily
benefit patient cohorts that are the target.
Treatment should be individualised.
The obese very insulin-resistant
type 2 diabetic patient: what are
the treatment options?
Treating the obese, extremely insulin-resistant
type 2 diabetic patient with a long duration of
illness is very difficult and published research
provides little guidance for treatment of this
patient population. This view was expressed
by Dr Larry Distiller, CDE Houghton, and sup-
plemented by an appeal to the endocrinolo-
gists present to join a planned clinical study
of these patients in order to evaluate prospec-
tively the value of concentrated insulin (U-500)
and other techniques to improve outcomes in
these patients.
‘These patients are injecting large volumes
Dr Larry Distiller
Prof Brynne Ascott-Evans
