DRUG TRENDS
SA JOURNAL OF DIABETES & VASCULAR DISEASE
40
VOLUME 8 NUMBER 1 • MARCH 2011
of insulin, with resulting problems at the injec-
tion sites and reduced patient compliance.
Their HbA
1c
levels are often high (
>
10%) and
lifestyle change is poorly supported’, Dr Dis-
tiller pointed out.
The use of U-500 produced by Eli Lilly and
available on request for named patients under
a Section 21 approval is a useful tool to help
these patients. ‘Although U-500 is not com-
mercially available anywhere in the world,
there are a few retrospective studies that guide
its use in these special patients’, Dr Distiller
said.
9
The studies used both insulin pumps and
injections and showed improved HbA
1c
levels
(reduction from 10–8.4%), small weight gain
equivalent to the improved glucose control
(average of 4 kg) and no severe hypoglycaemic
events.
‘As one unit of U-500 equals five units by
volume of regular insulin, using this concen-
trated insulin requires in-depth understand-
ing by the healthcare professional and the
patient. This insulin is much more stable, and
in the obese patient reaches peak levels after
about eight and a half hours and offers dura-
tion of action of 24 hours’, Dr Distiller noted.
The application form for use can be obtained
from Lilly and it takes about two weeks to pro-
cess. As the insulin is affordable, there are not
any funder-related problems’, Dr Distiller con-
cluded.
Cancer: the forgotten
‘complication’ of diabetes
‘The most appropriate causative factor related
to the observed increased cancer occurrence in
type 2 diabetes is the presence of insulin resist-
ance and hyperinsulinaemia’, Dr Stan Landau
CDE, Houghton, stated and set out to show
data supporting this concept. ‘It is important
to clarify the issues around cancer and type 2
diabetes as, based on epidemiological data, a
patient with both these conditions is exposed
to a 40% increase in the risk of death com-
pared to an age- and cancer-matched patient
without diabetes’, he noted.
10
While cancer
is a leading cause of death, specific cancers
such as lung, breast and colon are dominant in
prevalence, while others such as lung, stomach
and liver cancer are the main causes of cancer
deaths.
The complete pathophysiological path-
ways of both diabetes and cancer are incom-
pletely understood, adding to the complexity
of evaluating the relationship between these
two disease states. ‘In terms of epidemiological
studies, we know that simple elevation of glu-
cose levels is associated with increased cancer
occurrence. Also, that as impaired glucose tol-
erance (IGT) moves into the diabetic ranges,
cancer rates increase.’
Data from the European Prospective Inves-
tigation into Cancer and nutrition (EPIC) stud-
ies and the DECODE study
11
are adding to the
quite solid basis of evidence that links increased
blood sugar to cancer provocation. Specifically
in the DECODE study of European populations,
there were significant increases in deaths from
cancer of the stomach, colon–rectum and liver
in men with pre-diabetes and diabetes, and
increased deaths from cancers of the liver and
pancreas in women.
A further pathway to increased cancer risk
may relate to the chronic inflammatory nature
of diabetes, which produces excessive reactive
oxygen species.
‘The most appropriate causative associa-
tion in my view is that of insulin resistance
and hyperinsulinaemia, which leads to a 35%
increased risk of cancer; likely due to insulin
growth factor-1 (IGF-1) release, which stimu-
lates cell proliferation of the mitogenic path-
way in a susceptible genetic environment.
However, there are no prospective clinical data
linking IGF-1 stimulation to mitogenic devel-
opment, only laboratory-based studies. In my
view, the insulin supply hypothesis as opposed
to the glucose supply hypothesis is more likely
and is the major contributor to increased
cancer risk’, Dr Landau noted.
‘When we assess the cancer risk of diabetes
treatment using insulins, we raise a multiplicity
of variables: duration of insulin therapy, adher-
ence, insulins in multiple treatment protocols
over time, all of which complicate any determi-
nation of a specific insulin therapy and cancer
risk. Insulin is certainly a mitogenic hormone
but to prove that insulin analogues are related
to cancer provocation, one would need more
than the present
in vitro
studies of IGF activity.’
Currently, the only prospective data on an
insulin analogue (glargine) compared to NPH
insulin with regard to cancer risk comes from
a study of ocular complications in diabetic
patients using these therapies.
12
This study
over a five-year period found no greater risk of
cancer or cancer death in the glargine-treated
compared to the NPH insulin-treated group.
In conclusion, Dr Landau expressed the
view that better understanding is required and
that ‘no evidence of risk’ does not equal ‘no
risk’ and prospective trials of specific insulins
and specific cancer types in specific diabetic
populations will be required to clarify the real
cancer risks in type 2 diabetes.
Future diabetic therapies and unmet
clinical needs in type 2 diabetes
Unmet clinical needs including increasing
HbA
1c
levels reflecting poorer glucose con-
trol over time, reduced
β
-cell function, which
decreases by about 4% annually, and an ina-
bility to significantly reduce the macrovascular
consequences of diabetes, are being targeted
by newer medications. ‘But will they fulfil this
promise?’ Dr Ray Moore, from Durban asked.
His answer seems to indicate some improve-
ment on the pharmaceutical front, but no real
panacea.
‘There are new formulations of older drugs
such as slow-release gliclazide (Diaglucide MR,
Diamicron MR), sustained-release metformin
(Glucophage XR), and combinations of oral
anti-diabetic medications such as glucovance
(metformin and glibenclamide). These drugs
Dr Ray Moore
Dr Stan Landau
