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VOLUME 9 NUMBER 3 • SEPTEMBER 2012
ADA WATCH
SA JOURNAL OF DIABETES & VASCULAR DISEASE
increase lung cancer in previous smokers.
This aspect needs further study.
New bolus insulins
Julio Rosenstock presented different combi-
nation therapies in his discussion on co-for-
mulations. He answered in the affirmative
the question whether there is a place for
co-formulations. The main reason for the
use of co-formulations is to simplify insulin
usage.
He prefers basal insulin plus boluses,
either one or more, according to the require-
ments of the patients. He supported this
with a comparative study comparing pre-
mix insulin, which gave a 1.8% reduction in
HbA
1
c
level with an average of 7 kg weight
gain and more incidents of hypoglycaemia,
compared to a basal-plus-one regimen,
which gave a –2.1% reduction in HbA
1
c
level
in type 2 diabetes patients, with a 5.2-kg
weight increase. A basal-plus-three (full
basal–bolus) gave a 6.9-kg weight increase
with a 2.2% reduction in HbA
1
c
level.
Dr Rosenstock stated that if one can get
away with a basal-plus-one regimen in a
type 2 diabetes patient, one will probably
have the best reduction in HbA
1
c
level with
the least weight gain. The pre-mix regimen
gives less flexibility and more incidents of
hypoglycaemia.
In the future, combinations of GLP-1
analogues with degludec insulin are in the
pipeline and they will probably be given
as a once-daily dosing, with additional
short-acting insulin if necessary. This has
been compared to NovoMix and has been
shown to cause fewer incidents of hypogly-
caemia.
Dr Rosenstock also discussed the use
of hyaluronidase with short-acting insulin,
improving the onset of action and shorten-
ing the duration of action of short-acting
analogues. He also discussed the possibil-
ity of using pramlintide with lispro insulin,
which gives less weight increase and even
some weight loss with equivalent diabetes
control.
Further combinations, which will be
used in the future, are basal insulin plus
GLP-1 analogue and metformin. Dr Rosen-
stock feels this combination has the poten-
tial to lower HbA
1
c
levels as well as promote
weight loss.
Preserving beta-cells
In a diabetes-care symposium, a study was
presented by Dr Ildiko Lingray on preserva-
tion of beta-cell function after 3.5 years of
follow up after a short period of intensive
diabetes therapy. Newly diagnosed type
2
diabetes patients were randomised and
put on three months of intensive insulin
therapy, with normalisation of HbA
1
c
levels.
After three months they were randomised
to triple oral therapy with gliburide
(
according to glucose levels), metformin
(1
g bid) and pioglitazone (45 mg), versus
NovoMix-30, twice a day with metformin
1
g bid.
All the patients were confirmed to be
GAD antibody negative in 42 months of
follow up after a three-month randomi-
sation period. Failure or endpoint was
defined as reaching an HbA
1
c
level of
8%
and the study was analysed with
intention-to-treat analysis.
Fifty-eight patients were randomised,
29
to each group. The initial HbA
1
c
level
was 10.6 ± 2.8%. This was brought down
within three months to 5.9% on average
(
in the normal range) and then randomisa-
tion took place. The patients on the insulin
gained 4 kg over the period, whereas those
on the triple therapy gained 10 kg.
The patients’ beta-cell function was
assessed after the treatment period and the
conclusion was that early glycaemic nor-
malisation with combination therapy pre-
served beta-cell function. This was better in
the patients in the insulin group.
Bariatric surgery: gastric bypass
Prof J Cummings focused on the Roux-Y
gastric bypass, reporting on follow up
of a group of patients who had had the
procedure. Between 80 and 85% remission
of type 2 diabetes had occurred after the
gastric bypass. Remission occurred before
the weight loss. The Roux-Y gastric bypass
showed better remission of diabetes
than comparative weight loss with other
methods.
Prof Cummings also discussed a Swedish
obesity study with 20-year follow up after
gastric bypass. The benefits of the bypass
surgery were not related to the degree of
obesity. There was a clear lowering in ghre-
lin levels and an increase in GLP-1 release.
Since food enters the small intestine more
quickly after gastric bypass, it appears
that the gut has control of not only insulin
release, but also insulin sensitivity.
He reported on six patients who had
had gastric bypass with six years of follow
up. Their body mass index was between 30
and 35 kg/m
2
,
which was lower than usual.
The average duration of diabetes was 13
years and 40% of the patients were on
insulin.
The average HbA
1
c
level was 9.7%
before treatment. It dropped to 6.5% and
was stable over the follow up of six years.
Remission of diabetes of 88% occurred.
There was > 400% increase in insulin
sensitivity and beta-cell function and a
recovery of C-reactive protein-measured
insulin release after meals. Dyslipidaemia
also improved, as did the blood pressure
levels.
One of the conclusions was that the
duration of diabetes was not related to the
remission rate and that even people who
had longstanding diabetes could go into
remission. Long follow-up periods of the
patients are useful to assess these proce-
dures.
Islet cell transplantation: numbers
still small, but some success
Dr M Rickels reported on the outcome of
islet cell transplants at the largest centres
in the world, 27 centres in total, between
1999
and 2010. There were 677 cases of
islet cell transplantation and the patients
were assessed on insulin independence.
The results confirmed C-reactive protein
production > 0.3 ng/ml and an HbA
1
c
level
< 6.5%, with preferably normal fasting
glucose levels and the absence of hypogly-
caemia. Of the patients, 85% had islet cell
transplants and 50% also had renal trans-
plants. There was no mortality associated
with the islet cell transplants.
From 1999 to 2003, only 20% of these
patients were insulin independent. With
follow up from 2004 to 2006 this increased
to 37%, and from 2007 to 2010 it had
improved to 44%. In the best centres,
the latest results for insulin independence
could be as high as 60% with the newest
immunosuppressive regimens, the reason
for improved outcomes.
However, small numbers of patients
are currently receiving the transplant. In
the three years from 2007 to 2010, only
208
islet cell transplants were done in all
27
centres, making this largely experimen-
tal therapy, done in brittle type 1 diabetes
patients with recurrent hypoglycaemia and
many complications.
Dr Landi Lombard
