150
VOLUME 10 NUMBER 4 • NOVEMBER 2013
REPORT
SA JOURNAL OF DIABETES & VASCULAR DISEASE
diovascular benefits for insulin, while the
weight gain associated with intensive insu-
lin therapy has a greater negative impact
on patient longevity than diabetes itself.
In addition, insulin increases the risk of
severe hypoglycaemic episodes three-fold,
and severe hypoglycaemia is a stronger risk
factor for a cardiovascular event than a
previous MI.
‘Insulin can transform well-selected
patients, but how do you select them,
given that there is no one set of criteria?
In the absence of these, all insulin use must
be empirical. It has not been shown to
improve prognosis and the case for early
elective insulin therapy is not established.
We also need to move away from look-
ing at it as the “ultimate treatment” and
must never stop thinking about the bigger
picture when it comes to diabetes manage-
ment. Patients on insulin might not need
to remain on it forever’, he concluded.
‘Whether insulin is a friend or foe in type 2
diabetes ultimately lies with clinicians and
individual patients and will depend on mul-
tiple factors. Individualisation of treatment
remains key.’
Novel and emerging basal insulin
preparations
Dr Stan Landau, specialist physician, Centre
for Diabetes and Endocrinology, Johannes-
burg
Basal insulins form the backbone of insu-
lin therapy in type 2 diabetes and their use
has increased dramatically in recent years.
Though well tolerated, safe and easy to
administer, those currently available still
have limitations and even in the era of
the analogues, glargine and detemir, only
41% of patients achieve HbA
1c
levels below
7%. In addition, neither agent provides full
24-hour peakless insulin cover, neither has
eliminated the risk of nocturnal hypoglycae-
mia, and successful treatment still requires
careful individual titration, given persistent
intra-patient variability.
‘We need to improve glycaemic control.
Hypoglycaemia, which is an insulin prob-
lem, limits our treatment mandate and
simply putting patients on insulin does not
automatically equate to an improvement in
glycaemic control. Hypoglycaemia is associ-
ated with worse cardiovascular outcomes
and hypoglycaemic episodes are dangerous
even in low-risk patients. Ideally, we need an
insulin with a flat action profile, reduced or
no variability in its glucose-lowering effect,
reduced risk of hypoglycaemia and a longer
duration of action’, observed Dr Landau.
Several new agents not yet available in
South Africa show some promise in this
regard. ‘Insulin degludec is an analogue
with an exceptionally flat and stable 24-hour
profile that, irrespective of dose, is gradu-
ally delivered into the peripheral system in
a sustained manner. Its HbA
1c
outcomes are
equivalent to glargine, against which it has
been compared in non-inferiority trials.
Amendments to the insulin molecule
allow it to be used flexibly, so the timing of
doses is less critical than with glargine and
detemir. Intervals of between eight and
40 hours have been observed in trials
involving both type 1 and type 2 diabetes
patients. This is an advantageous devel-
opment for people with diabetes who do
shift work, travel frequently or who are in
institutional care. In addition, it is one of
only two basal insulins that can be co-for-
mulated with aspart or GLP-1.’
In respect of safety, data show it to be
safe in both chronic kidney disease and liver
disease. There are no tolerability issues, it is
effective across different ethnic profiles and
is not affected by body mass index (BMI)
or duration of diabetes. A major benefit is
that it lowers nocturnal hypoglycaemia.
Lilly basal insulin LY2605541 is the
second long-acting basal insulin. It has a
preferential hepatic mode of action and
weight loss may be a reasonable expecta-
tion. Dr Landau cautioned, however, that
most of the data so far are animal data
and current knowledge is largely abstract.
‘There are no data in individuals with type
2 diabetes; only healthy volunteers, and it
is not without concerns. Phase 2 data have
indicated that it may raise triglyceride levels
and cause deranged hepatic function.’
Other agents are on the way too,
including insulin glargine U3000, which
also diminishes nocturnal hypoglycaemia,
FT-105 and the so-called ‘smart insulins’,
which comprise glucose-responsive mol-
ecules with attached insulin.
Despite their promise, Dr Landau feels
that modern insulins require ‘deconstruc-
tion’ and that it is mainly secondary out-
comes that differentiate the newcomers
from what’s currently available. ‘Everything
depends on how we use the material, not
the material itself and new is not necessarily
superior. Insulin isn’t always what it seems
and control is worsening despite increased
insulin usage. Changing a patient’s brand
of insulin is only one consideration when
one is trying to prevent hypoglycaemia’, he
concluded.
Diabetic nephropathy: countdown
to disaster? The Ascending Star
lecture
Dr Julien Trokis, Diabetes Care Centre,
Stellenryk
Diabetes is the most common cause of
end-stage renal disease (ESRD). Chronic
kidney disease (CKD) is underdiagnosed
and undertreated and opportunities for
early intervention are often missed due to
lack of awareness. Various modifiable risk
factors can be addressed: these include
hypertension, lipids, smoking and obesity.
The financial burden is considerable and
in 2007, dialysis cost the USA US$35.3 bil-
lion. ‘Diabetes patients with CKD cost three
times as much to treat as those without.
The life expectancy of patients receiving
treatment for ESRD is considerably reduced,
with only 51% still alive after three years’,
said Dr Trokis.
Abnormal albuminuria is the most pow-
erful risk factor for decline in glomerular
filtration rate (GFR). It heralds the onset of
worsening function, together with raised
cardiovascular and all-cause mortality risk,
with the former surpassing the latter at all
stages. ‘While microalbuminuria is revers-
ible, when macroalbuminuria is present, we
can only slow disease progression’, warned
Dr Trokis. ‘As GFR drops, cardiovascular risk
climbs. Cardiovascular mortality is the hidden
danger beneath the surface of CKD.’
Undiagnosed CKD is common in diabetes
and a failure to screen patients is an impor-
tant factor. ‘We therefore need to screen
more actively. Guidelines recommend annual
screening for microalbuminuria, starting at
diagnosis in type 2 diabetes patients, and
five years after diagnosis in type 1 patients.
Serum creatinine levels should be measured
at least annually and used to estimate GFR.’
Healthcare professionals need to be
aware that there is sometimes discord-
ance between GFR and albuminuria and
that both albuminuria and retinopathy may
be absent in diabetes patients with CKD.
‘We need to shatter the myth that we can
always rely on the presence of one of them
to raise our suspicion that nephropathy
may be present.’
Various studies have shown that inten-
sive glycaemic control reduces the incidence
and rate of progression of diabetic nephrop-
