VOLUME 10 NUMBER 4 • NOVEMBER 2013
149
SA JOURNAL OF DIABETES & VASCULAR DISEASE
REPORT
TABLE OF CONTENTS
Insulin: friend or foe?...............................................................................................................................145
Novel and emerging basal insulin preparations.........................................................................................146
Diabetic nephropathy: countdown to disaster? The Ascending Star lecture...............................................146
Neuropathy: a diagnosis?.........................................................................................................................147
The debate renewed… Is bariatric surgery a ‘cure’ for diabetes?...............................................................147
2013 UPDATE FROM THE CENTRES
FOR DIABETES AND ENDOCRINOLOGY
15th Postgraduate Forum in Diabetes Management
August 2013
Contributor:
P Wagenaar
SUMMARIES
CDE WATCH
Insulin: friend or foe?
Dr Aslam Amod, endocrinologist, Centre
for Diabetes, Endocrinology and Metabolic
Disease, Life Healthcare Chatsmed Garden
Hospital, Durban
Insulin can be a friend. It can protect and save
lives, but it can cause harm and even kill. This
was Dr Aslam Amod’s cautionary message
to delegates at the 15th CDE postgraduate
forum in diabetes management, which took
place at the Birchwood Hotel and Confer-
ence Centre, Boksburg, in August.
There is no disputing that the discovery
of insulin has changed the lives of type 1
diabetes patients forever. ‘It was one of the
most dramatic moments in medicine, and
for type 1 diabetes patients, insulin therapy
remains the only available option. It is to
all intents and purposes, hormone replace-
ment therapy with numerous benefits,
including near normalisation of metabo-
lism and improved long-term survival. But
type 2 diabetes is another animal entirely
and different for different people.’
Ascertaining the role of insulin in type 2
diabetes begs the questions, ‘Why, when
and in whom? Should it be introduced at
diagnosis, as an early elective option or as
a last resort? How does it compare with
other therapies in respect of benefit and
risk, both glucose related and non-glucose
related? Based on pathophysiology, can
we define specific subgroups and disease
stages where it is indicated?’
The profound heterogeneity of type
2 diabetes makes answering those ques-
tions a challenge. ‘Reality and randomised
controlled trials are very different from
each other’, said Dr Amod. ‘Yet all diabe-
tes patients are lumped together, despite
a multitude of different disease pathways,
discordant expert opinion and a lack of
simple measures of beta-cell function.’
Turning to the evidence base, Dr Amod
cited the 1978 UGDP study, which showed
no difference in fatal cardiac events after
14 years in insulinised versus non-insulinised
patients. ‘The Kumamoto study found that
while insulin had a beneficial effect on
microvascular complications, it had no effect
on macrovascular parameters. This was
borne out by the UKPDS, which again found
only microvascular benefit, but no macro-
vascular or mortality benefit. Insulin was
not superior to the sulphonylureas in this
study.
The DIGAMI-2 study, which focused on
the prevention of secondary complications
following acute myocardial infarction (MI),
found that insulin actually increased the risk
of stroke and re-infarction. The ACCORD
study showed that insulin had no effect
on rates of major cardiovascular events,
death or microvascular complications. In
the VADT studies, insulin was associated
with increased mortality and no significant
reduction in cardiovascular events, while
ORIGIN showed no difference between
standard care and early insulin therapy.
‘This means that in 2013, we have no
formal evidence base that insulin improves
the long-term prognosis of patients with
type 2 diabetes compared to other thera-
pies’, continued Dr Amod. ‘The glucose
hypothesis central to type 1 diabetes is not
upheld when we look at the cardiovascular
disease and mortality associated with type
2 diabetes. Many alternative treatments
are available and the long-term survival
improvement we see is not due to insulin.
There is no evidence that it preserves beta-
cell function and it is associated with only
partial normalisation of metabolism.’
Further to the UKPDS finding that inten-
sive glucose-lowering in the early stages
of type 2 diabetes has a long-term ‘legacy
effect’, the use of insulin has increased dra-
matically. ‘But there have been no improve-
ments in HbA
1c
levels, and in fact HbA
1c
levels are worse with insulin than with other
therapies. Given the absence of benefit, it
begs the question, “Can insulin be harm-
ful?” Epidemiologically it has traditionally
been associated with a two- to three-fold
greater mortality rate than other therapies,
and recent surveys suggest that patients on
insulin have a worse prognosis. In terms of
pathophysiology, endogenous and exog-
enous insulin are different, with the latter
carrying a much higher peripheral:portal
gradient risk. “Lean and thirsty” patients
will do well, but the “obese and hungry”
will not. Many of the latter just continue
to put on weight, something known as the
“insulin sink syndrome”.’
Insulin has been shown to be pro-ather-
ogenic
in vitro
, which might explain the
absence of microvascular benefit. No ran-
domised, controlled trials have shown car-
