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34
VOLUME 9 NUMBER 1 • MARCH 2012
REPORT
SA JOURNAL OF DIABETES & VASCULAR DISEASE
of safe agents will improve adherence and
reduce the need for home glucose monitor-
ing. This in turn would limit the number of
patients needing up-referral to secondary
and tertiary care. Dr Amod also pointed out
that increasing evidence of caloric restriction
improving insulin resistance and
β
-cell func-
tion raises the question of including weight-
loss therapies in guidelines for the treatment
of the diabetic patient.
In essence, Dr Amod emphasised that the
source mechanism of diabetic disease should
be the first consideration when determining
therapeutic options to be employed in the
management of the patient.
Contributors to the guideline review include
endocrinologists and diabetelogists, as well as
members of DESSA, DSA, FCPSA, CMSA and the
National Department of Health. Observers from
funders and the pharmaceutical industry were
also included. The draft document is currently up
for comment, to be finalised early in 2012.
Early bariatric surgery benefits
derive from acute caloric restriction
Dr Laura Blacking, Gauteng, presented an
unbiased view of bariatric surgery, drawing
from recent surgical reviews, which contrast
early and long-term results, together with a
cluster of established and emerging surgical
techniques.
Not giving up on the ‘lifestyle works’
concept, a small new study of acute calorie
restriction (600 kCal/day)
8
was cited as pro-
viding exciting evidence that the unexpected
early remission results from bariatric surgery
are explained by this phenomenon.
‘In this study from Newcastle-upon-Tyne,
UK, Dr Lim and co-workers showed reversal
of insulin resistance, and
β
-cell normalisation
in overweight/obese (BMI 33.6 ± 1.2 kg/m²)
patients with type 2 diabetes of less than
four years’ duration and not yet on insulin
therapy when exposed to a 600-kCal/day
diet for eight weeks. ‘These patients still
had pancreatic function, as did the patients
who benefitted most on a long-term
basis from bariatric surgery’, Dr Blacking
noted.
In a recent study
9
of factors influencing
the durability of remission of type 2 diabe-
tes after Roux-en-Y gastric bypass, the study
found that while early remission of type 2
diabetes occurred in 89% of post surgery
patients, durable remission over a five-year
period occurred in 57% of patients. Durable
resolution of type 2 diabetes was greatest
in patients who were fairly well controlled
on diet or oral hypoglycaemic agents.
‘This study emphasises that durable
remission correlated most closely with an
early stage of type 2 diabetes’, Dr Black-
ing stressed. ‘In our experience, motivated
patients with weight loss also do better
from alternative therapies, such as hypno-
therapy with virtual gastric banding’.
‘In my view, we need to target the brain
to achieve successful weight loss’, Dr Black-
ing stressed. ‘The requirement from interna-
tional guidelines is insufficiently emphasised
that successful bariatric surgery requires
a lifelong commitment to lifestyle change
and follow up by a multidisciplinary team
is essential. We need centres of excellence
that offer this level of multidisciplinary care
at both a pre- and post-operative level’, she
concluded.
The long memory of diabetes:
epigenetics provides new insights
Diabetes complications under the
spotlight
‘Epigenetics provides us with an insight as
to how the environment interacts with our
genomes and emphasises the fact that our
behaviour may impact both on our own
lives as well as future generations.’
Dr Brian Kramer, CDE, Johannesburg,
reviewed the development of the concept
of the long-term hyperglycaemic memory
of diabetes, as first explored in dogs by Dr
RL Engerman, an ophthalmologist from the
University of Wisconsin, USA.
10
He observed
that progression of retinopathy continued
during good glycaemic control following a
period of profound, poor glycaemic con-
trol.
‘This memory effect has also been
shown in diabetic patients in the DCCT-EPIC
study. This emphasises the need for early
metabolic control in both type 1 and type
2 diabetes if we are hoping to reduce dia-
betic complications’, Dr Kramer noted. The
explanation for the ongoing damage relates
to both the role of advanced glycation end-
products (AGES), which continue to drive
the production of reactive oxygen species,
and to the altered up or down regulation
of genes due to changes in the epigenetic
environment.
The abnormal genetic regulation relates
to histone functioning, which is exposed to
the altered cellular environment. ‘Tightly
packed methylated histones restrict the
availability of the DNA to be transcripted,
while the acetylated histones allow unfold-
ing, gene transcription and the production
of gene products’, Dr Kramer explained.
Research has shown that stress, nutri-
tion, smoking and alcohol consumption
can also change the environment of the
histones; changes that can be passed on to
generations of cells. ‘Our investigation of
polymorphisms is probably misplaced and
the epigenetic environment may provide a
new target for better therapeutic agents’,
Dr Kramer noted.
Even transient periods of 15 minutes of
hyperglycaemia are sufficient to alter the
epigenetic environment. Chronic exposure
also alters the balance of histone methylase
and demethylase enzymes, changing the
genetic environment and gene expression.
11
‘We really need better markers of glycae-
mic control than HbA
1c
level, which does not
describe exposure to glycaemia as well as
we would like’, Dr Kramer concluded.
Peripheral neuropathy: focusing on
painful, diffuse, distal, symmetric
polyneuropathy (DSM)
Dr Kaplan, Cape Town, presented a review of
the physiology of pain with a special empha-
sis on painful diabetic neuropathy. He then
discussed clinical and therapeutic aspects of
treating neuropathy, and particularly painful
diabetic neuropathy.
Diabetic neuropathy occurs in 30 to 60%
of diabetic patients, varying from 54 to
59% in type 1 diabetes patients and some-
what lower in type 2 patients (37–54%). In
50% of cases of diabetic neuropathy, pain
is present, which can occur early, even in
patients with impaired glucose tolerance.
The incidence of painful diabetic neuropa-
thy progresses with duration of the diabe-
tes, with a peak after 15 years.
Distal symmetric polyneuropathy is the
most common form of neuropathy. Typi-
cally, it starts as a loss of sensation, affect-
ing the feet more than the hands. As the
neuropathy progresses, pain may become
the dominant symptom. Often, pain occurs
in the setting of a normal clinical examina-
tion. It is important to exclude other causes
of neuropathy and pain, such as claudica-
tion, osteoarthritis and fibromyalgia.
‘It is important to note that there may be
few signs to relate to the patient’s complaint
of pain – examination of patient reflexes
such as vibrational, temperature, sensory
and soft touch measures may be normal’, Dr
Kaplan said. ‘Typically, patients complain of
‘Sugar and high-fat foods are as addic-
tive as alcohol and smoking.