REVIEW
SA JOURNAL OF DIABETES & VASCULAR DISEASE
66
VOLUME 7 NUMBER 2 • JUNE 2010
Dr Amod concluded that treating ‘diabetic pre-hypertensives’ phar-
macologically would mean treating 140 million new patients world-
wide – or 50% of the world’s diabetic population. ‘The consequences
in respect of cost, adverse events and extra doctor visits are therefore
staggering – and also impact on the cost of treating true hypertension,
given the requirement to treat to lower targets. All it will really achieve
is lower traces of albumin in urine samples!’
In the discussion that followed, Dr Amod reiterated his concern that
as yet no study had evaluated whether it made a real difference to treat
to a target of 120 mmHg systolic BP rather than 130 mmHg. ‘I’m happy
to treat to 130 mmHg’, he said, ‘but below that, pharmacotherapy
should not be involved.’
Dr Bihl picked up the point about lower albumin in urine, counter-
ing that this was an important consideration, reflecting a generalised
‘endothelialitis’ and was associated with greater cardiovascular and
renal dysfunction. ‘Pre-hypertension seldom exists in isolation, so treat-
ing a pre-hypertensive diabetic who has microalbuminuria will reduce
his/her cardiovascular risk.’
He agreed with Dr Amod that diagnosing pre-hypertension was a
challenge and that if it were suspected, 24-hour blood pressure moni-
toring was essential to confirm the diagnosis, as office measurements
are often unreliable.
Both doctors agreed that individualisation of treatment thereafter
was critical. ‘All type 2 diabetics will ultimately become cardiac patients
– and it’s easier and more effective to lower blood pressure than blood
sugar, concluded Dr Bihl. ‘It’s also cheaper!’
Promoting early insulin usage in type 2 diabetes
Dr Graham Ellis, endocrinologist, Somerset West
‘The longer we burden our patients with raised HbA
1c
levels, the greater
the risk of micro- and macrovascular damage, devastating the produc-
tive lives of our patients’, Dr Ellis motivated. Many studies, including
the results from the pivotal UKPDS of long-term type 2 diabetes man-
agement,
1
have related increased micro- and macro-vascular events to
increases in HbA
1c
.
‘
In vitro
studies have shown the extensive damage caused by glu-
cotoxicity, mediated by increased free oxygen radicals and oxidative
stress, including damage at a genetic level of the
β
-cells’, Dr Ellis
pointed out.
Oral agents do not offer enough HbA
1c
reduction; metformin mono-
therapy reduces HbA
1c
by about 1.5%, sulphonylureas reduce levels
by between 1 and 2% and thiazolidinediones (mainly pioglitazone) on
average reduce levels by 0.5 and 1.4%.
2
‘We really need to tackle our own treatment inertia, and studies
using NPH insulin nocturnal plus metformin,
3
and the INSIGHT study
4
using insulin glargine at bedtime (normal dosage was 38 units per
day) plus oral agents, compared to oral agents only showed that more
patients reached an HbA
1c
of 6.5% earlier and importantly there was
no difference in hypoglycaemic rates.
‘Weight gain is of course the excuse most often cited for not intro-
ducing insulin. In fact, weight gain with insulin is modest and if com-
pared to optimal sulphonylurea dosages, insulin doesn’t do too badly’,
Dr Ellis said.
Today, clinicians are being told to use expensive GLP-1 agonists to
save and preserve
β
-cell function. In fact, studies using intensive insulin
early on diagnosis of type 2 diabetes has shown preservation of
β
-cell
function.
5,6
So why not use insulin to save
β
-cells?
Furthermore, the evaluation of the ACCORD study with its increased
mortality attributed this to poor glucose control, not to going for too-
low targets and causing hypoglycaemic-related deaths. In fact, patients
who achieved levels of HbA
1c
<
7% within three to six months had a
lower risk of mortality, regardless of whether they were in the stand-
ard/intensive arm.
‘These targets of below 7% are very difficult, if not impossible to
achieve with oral agents only, so early insulin is safe, effective and per-
haps also cost-effective,’ Dr Ellis concluded.
Benefits of early insulin usage is not proven in type 2
diabetes
Dr Ray Moore, Umhlanga Centre for Diabetes and
Endocrinology, Durban
‘There is no current evidence supporting the early use of insulin, as
many of the studies purporting to show some benefit have not taken
into account the general improvement in
β
-cell function following
reduction of glucotoxicity.’
Motivating this point of view, Dr Moore pointed out that in the
UKPDS,
1
improvement in microvascular events was related to improved
glycaemic control and not to the particular medication utilised. ‘Only
metformin, in a relatively small subgroup, was able to define itself as
being of somewhat greater benefit, with a reduction in myocardial
infarction rate over the other agents which did not achieve this’, he
pointed out.
In an instructive study undertaken in the 1980s,
7
which compared
diet alone, insulin and sulphonylurea therapy, it showed that with diet
alone, there was an increase in insulin levels and a drop in blood glucose
levels. ‘Why would one use insulin with its accompanying expensive
monitoring costs, increased hypoglycaemic events (six-fold more than
with sulphonylureas) and weight gain (7 kg on average in the UKPDS
study), if diet, lifestyle and two/three oral agents can achieve the same
results without increased cost and morbidity?’, Dr Moore asked.
Perhaps the only exception to this position is when a patient presents
at diagnosis of diabetes with an HbA
1c
of 10% or more. ‘Start short-
term therapy with insulin, to reduce glucose levels, and then revert to
lifestyle and oral agents’, said Dr Moore.
With regard to insulin usage and cancer risk, it was noted that insu-
lin is a growth factor and in diabetic patients, there is an overall higher
incidence of cancer. ‘It is simplistic to blame only one insulin. What is
needed is a thorough prospective study comparing cancer risks across
treatment modalities’, Dr Moore added.
‘The focal treatment of type 2 diabetes should be lifestyle change
with back-up integrated care. If this is done consistently, diabetes can
be extremely well managed at the primary-care level’, added Dr Larry
Distiller, chairman of this session and organiser of the meeting.
Diabetic dyslipidaemia – current management with
combination therapy
Prof FJ Raal, Lipid Clinic, Witwatersrand University
‘Type 2 diabetes should be considered a coronary artery disease equiva-
lent, and dyslipidaemia should be looked for and aggressively treated
in every diabetic patient. There is an ongoing debate as to which lipid-
modifying drug is the most appropriate for the treatment of diabetic
dyslipidaemia. Statins should be considered first-line therapy following
the disappointing results of the FIELD study and the positive results of
the HPS and CARDS study. The role of combination therapy (statins plus
fibrate and/or niacin) will be increasingly elucidated with the results of
outcome studies.’ This view was strongly presented by Prof Raal.
Results of the first of these outcome studies using combination
therapy, the ACCORD Lipid trial,
8
was announced at the recent 2010
American Cardiology Congress meeting.
This study showed that the combination of fenofibrate and simvas-
tatin did not reduce the rate of fatal cardiovascular events, non-fatal
myocardial infarction or non-fatal stroke, compared with simvastatin
alone. ‘There was a possible benefit in patients with both a high base-
