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VOLUME 8 NUMBER 3 • SEPTEMBER 2011
CDE WATCH
SA JOURNAL OF DIABETES & VASCULAR DISEASE
The Sanofi-Aventis
Insuman award went
to Dr Bruno Pauly.
The Sanofi-Aventis
award for the centre
with the best glycaemic
control, and compris-
ing sponsorship to the
2012 ADA meeting in
Philadelphia, went to
Dr Jacques van Staden
from George.
The Sanofi-Aventis award for good clinical
practice, and comprising sponsorship to the
2012 ADA meeting in Philadelphia, went to
Dr Louis Minders from the Bluff, Durban.
Sanofi-Aventis recognises excellence in clinical care at CDE centres in
South Africa
Treating the untreatable type 2
patient
Dr L Distiller, CDE Houghton and honor-
ary visiting professor, University of Cardiff
School of Medicine
A small sub-group of type 2 diabetes
patients are severely insulin resistant. Severe
insulin resistance is defined as an insulin
requirement of more than 200 units per 24
hours for more than two consecutive days
(or alternatively, a dose of > 3 U (2U)/kg
body weight).
There are many causes of this syndrome,
including severe infection or steroid use;
endocrinopathies such as Cushing’s, Werner
and HAIR-AN syndromes; genetic defects of
the insulin receptor gene (type A syndrome,
lephrechaunism, Rabson-Mendenhall syn-
drome); and insulin receptor antibodies.
However, these are all rare. For practical
purposes, in the majority of these patients,
severe insulin resistance is associated with
obesity and type 2 diabetes.
Once the obvious causes of high insulin
usage have been excluded, such as lifestyle
issues, poor injection technique, and not
using the prescribed insulin dosages, these
patients present with a very difficult treat-
ment conundrum. Most of these patients
have inadequate glycaemic control despite
massive doses of insulin. Providing adequate
amounts of insulin can be logistically difficult
because of the large volumes needed per
injection. This often results in injection site
problems. In addition, the absorption rate of
insulin is reduced with high-volume doses.
Theoretically, several options are available
in the treatment of these patients. While the
majority of themwill already be onmetformin,
the addition of another insulin sensitiser such
as pioglitazone could be considered. However,
this may result in only a marginal reduction in
insulin dose and may promote further weight
gain. The addition of a DPP-4 inhibitor has
also been suggested. While this might cause
a reduction in HbA
1c
levels by up to 0.8% and
have no effect on weight, the effect on insulin
doses is minimal.
Although GLP-1 agonists are not regis-
tered for use with insulin, there is evidence
that their use may not only result in some
weight reduction, but also in a reduction
in insulin dosage of up to 10%. However,
no studies have been undertaken in the
severely insulin resistant and neither the
weight reduction not the reduction in insu-
lin dosage seems to be sustained for more
than a year.
Bariatric surgery may be a therapeutic
option for the obese, severely insulin-resist-
ant patient. Although there is some anec-
dotal evidence for this form of therapy in
these patients, no studies have been under-
taken.
There is a need for a study of bariatric
surgery for the morbidly obese in South
Africa
Dr Ray Moore, Durban
Overall, the most effective way of treat-
ing these patients appears to be with the
use of highly concentrated insulin in the
form of U-500 regular human insulin.
Using this formulation will result in much
smaller volumes per injection, less day-
to-day variation in absorption and less
absorption variation from different injec-
tion sites than with U-100 regular or NPH
insulin.
More importantly, the peak and dura-
tion of action of U-500 approaches that of
human NPH insulin. It can therefore often
be used as a twice-daily injection. While no
prospective studies have been done to con-
firm the efficacy of this approach, a number
of small retrospective analyses of the use of
U-500 insulin in the severely insulin-resistant
patient have been reported, with extremely
good results.
In conclusion, the use of U-500 regu-
lar insulin is probably the safest and most
conservative option for the treatment of
these patients. Bariatric surgery may be
considered as an alternative provided the
patient is fit enough, wants this option and
can afford it, bearing in mind that there are
no outcomes studies in the severely insulin-
resistant patient.
The efficacy/role of a GLP-1 analogue
added to insulin in severely insulin-resistant
patients has not yet been adequately evalu-
ated, but the combination of U-500 insulin
and a GLP-1 analogue may prove to be the
best approach.
These patients with severe insulin
resistance are being missed during
the stepped-up care of diabetes. This
may well be an opportunity for early
exenatide use
Dr Adri Kok
Metformin – discovered, lost and
rediscovered
Dr Gregory Hough, Port Elizabeth
In a challenging talk on metformin, Dr
Hough noted its discovery in the 1920s, its
loss to diabetes as the newly discovered insu-
lin took front stage, its resurrection in 1958
in the UK, and its approval for use in type 2
diabetes in the United States in 1994.
