CARDIOVASCULAR JOURNAL OF AFRICA • Vol 24, No 7, August 2013
AFRICA
291
Reports from the American Diabetes Association’s 73rd scientific
sessions, 21–25 June 2013, Chicago, Illinois
Intensive HbA
1c
management
in type 1 diabetes sees pers-
istent benefit
Preliminary results of the latest data from
the Diabetes Control and Complications
trial (DCCT) and Epidemiology of
Diabetes Interventions and Complications
(EDIC) trial were published as abstracts
and presented at the recent ADA
meeting. The 10-year DCCT, which
began in 1983, demonstrated a consistent
beneficial effect of intensive therapy on
reducing complications compared with
conventional therapy.
The DCCT revealed that intensive
therapy, lowering HbA
1c
levels to 7% rather
than the 9%, which was standard practice
at the time in patients with type 1 diabetes,
diminished a range of complications by
about 35 to 75%, establishing intensive
therapy as the standard of care. Improved
glucose control was achieved with
frequent insulin injections or insulin
pump therapy, guided by frequent self-
monitoring of blood glucose with finger-
prick testing.
The trial was extended into EDIC (now
running for a total of 30 years); 95% of
trial patients who are still alive continue
to participate in the trial. While the initial
DCCT results were dramatic, the effect of
intensive therapy in reducing the longer-
term consequences of complications,
including kidney failure, loss of vision,
amputations and heart disease, were
unknown.
Over 18 years, those patients who had
intensive management and maintained
an HbA
1c
target of 7% had a 46% lower
risk of retinopathy, a 39% reduced risk of
microalbuminuria, and a 61% lower risk
of macroalbuminuria (
p
<
0.0001 for all).
The long-term consequences of intensive
therapy have shown a 50% reduction
in risk for developing impaired kidney
function. Intensive therapy also reduced
the incidence of heart disease and stroke
by almost 60%.
Researchers also reported new data
on musculoskeletal complications,
particularly cheiroarthropathy, which
presentswith peri-articular skin thickening
of the hands and limited joint mobility.
Cheiroarthropathy typically results from
the accumulation of advanced glycation
end-products in the collagen, and includes
carpal tunnel syndrome, adhesive
capsulitis, Dupuytren’s contracture,
flexor tenosynovitis (or ‘trigger finger’),
and prayer sign (or trouble holding the
hands flat when palm-to-palm).
Researchers found that a third of
about 1 200 patients (33%) had at least
one type of this complication, with the
most common being adhesive capsulitis,
followed by carpal tunnel and then prayer
sign. Another 20% of patients had at
least two complications, and a further
10% had at least three. About 3% had
four or more complications. Risk factors
for these conditions included older age,
female gender, longer duration of disease,
and higher HbA
1c
levels over time.
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New therapeutic targets for
type 2 diabetes
Recent years have seen a dramatic
expansion in the range of pharmacological
therapy for type 2 diabetes. A range
of new therapeutic targets were under
discussion.
Beta-cells
The beta-cell plays a crucial role in type 2
diabetes, with beta-cell pathways offering
multiple potential drug targets. Free fatty
acid receptor 1 (FFAR-1 or GPR40)
is one of the most promising targets.
Free fatty acids are both metabolic
fuels and signalling pathways that are
highly expressed in the beta-cells, the
hypothalamus and the gut.
The investigational compound
TAK-875 has shown reductions in HbA
1c
levels similar to those with glimepiride;
with significantly fewer incidents of
hypoglycaemia and no effect on weight,
insulin sensitivity, blood pressure or
pulse. The compound has also shown no
significant drug-related adverse events.
Insulin receptors
The most important cause of insulin
resistance is obesity and treating obesity
is probably the most effective way to
treat insulin resistance. Other approaches
include enhancing insulin receptor activity
and modulating signalling downstream
from the receptor. Enhancement and
activation of insulin receptors has met
with success in rodent models, but none of
these compounds appear to be appropriate
for human use. Other investigative agents
potentiate insulin receptor activity to
increase glucose uptake.
Targeting inflammation
Reducing inflammation in adipose
tissue and skeletal muscle with salsalate
has positive metabolic consequences,
including a decrease in numbers
of white blood cells, neutrophils and
lymphocytes, and HbA
1c
levels. Another
target is the nuclear factor kappa-B, or
NF-kB, a pathway that acts as a master
regulator of inflammatory signalling in
both adipose tissue and skeletal muscle.
Pharmacological intervention in this
pathway appears to have beneficial effects
on the metabolism and inflammation.
Targeting glucose absorption and
excretion
One of the approaches to targeting glucose
absorption and excretion is to enhance the
activity of sodium glucose co-transporter
2 (SGLT-2) in order to boost renal glucose
excretion. Dapagliflozin and canagliflozin
have been approved for use by the Federal
Drug Administration, and positive phase
3 data on empagliflozin were presented
at the meeting. These agents can be
used with other antiglycaemics but safety
questions remain.
Look AHEAD: lifestyle inter-
vention in type 2 diabetes
offers microvascular benefit
but does not lower risk of
cardiovascular disease
Look AHEAD (Action for Health in
Diabetes) is the longest and largest
randomised, controlled trial to examine
the effects of an intensive lifestyle-
intervention programme in overweight
and obese participants with type 2
diabetes. Investigators presented 11-year
results of lifestyle interventions designed
