Home' Australian Pharmacist : Australian Pharmacist August 2012 Contents 630 Australian Pharmacist August 2012 I ©Pharmaceutical Society of Australia Ltd.
Diabetic neuropathy and
enhanced glucose control
By Dr Hanan Khalil
Dr Hanan Khalil is the Director
of the Centre for Chronic Disease
Management, a collaborating centre
of the Joanna Briggs Institute, Faculty
of Medicine, Nursing and Health
Sciences, Monash University, and a
reviewer for the consumer group of the
This evidence summary represents the
best available evidence on the e ect of
improved glucose control on diabetic
neuropathy in both type 1 and type 2
diabetes. For the full review, please refer
to: Callaghan BC, Little AA, Feldman EL, et
al. Enhanced glucose control for preventing
and treating diabetic neuropathy. Cochrane
Database of Systematic Reviews 2012, Issue 6.
Art. No.: CD007543. DOI: 10.1002/14651858.
Peripheral neuropathy is caused by
chronically high blood sugar and diabetes.
It leads to numbness, loss of sensation,
and sometimes pain in feet, legs or hands.
It is the most common complication
About 60% to 70% of all patients with
diabetes will eventually develop peripheral
neuropathy, although not all su er pain. Yet
this nerve damage is not inevitable. Various
studies have shown that patients with
diabetes can reduce their risk of developing
peripheral neuropathy by keeping their
blood sugar levels as close to normal
Managing hyperglycaemia has been the
major target intervention for the prevention
of diabetes-related complications such as
neuropathy.4 Hyperglycaemia control has to
be weighed with the risks of hypoglycaemia
episodes which have their own risks
This short evidence summary reviews the
bene ts and harms of enhanced glycemic
control for preventing and treating
Characteristics of the studies
and the interventions
The studies included in the above
mentioned review were all randomised
controlled trials examining the e ect
of enhanced glycaemia control in type
1 and 2 diabetes on the presence and
severity of diabetic neuropathy. The type
of participants included any females or
males who were diagnosed with type 1 or
2 diabetes. The interventions considered
for this review included subcutaneous
insulin administration, continuous insulin
infusion, oral anti-diabetic agents, lifestyle
modi cations such as diet and exercise, or
Quality of the research
All studies were evaluated according
to methodological quality to assess the
robustness of the ndings as well as the
heterogeneity of the included studies. The
overall methodological quality of reporting
was moderate to high.
• Several databases such as The Cochrane
Neuromuscular Disease Group
Specialised Register (30 Jan 2012),
CENTRAL (2012, Issue 1), MEDLINE (1966
to Jan 2012) and EMBASE (1980 to Jan
2012) for randomised controlled trials
of enhanced glucose control in diabetes
mellitus were searched.
• Seventeen randomised studies addressed
whether enhanced glucose control
prevents the development of neuropathy
with a total of 7,897 patients.
• Seven of these studies were conducted in
people with type 1 diabetes, eight in type
2 diabetes, and two in both types.
• The primary outcome measure
was annual development of clinical
neuropathy de ned by a clinical scale.
• A meta-analysis of the two studies that
reported on the incidence of clinical
neuropathy in type 1 diabetes revealed a
signi cantly reduced risk of developing
clinical neuropathy in those with
enhanced glucose control, an annualised
RD of -1.84% (95%(CI) -1.11 to -2.56).
• In a similar analysis of four studies that
reported on the incidence of neuropathy
in type 2 diabetes, the annualised RD
of developing clinical neuropathy was
-0.58% (95% CI 0.01 to -1.17).
• Most secondary outcomes were
signi cantly in favour of intensive
treatment in both type 1 and 2 diabetes
• Both types of diabetic patients also had
a signi cant increase in severe adverse
events including hypoglycaemic events
with enhanced glucose control.
Implications for practice and
In both types of diabetes, enhanced glucose
control was associated with a reduction in
the incidence of developing neuropathy.
However, the exact glucose control target
remains to be de ned and potential adverse
events must be balanced in the decision of
adjusting glucose control. Further research
is needed to nd the optimal glucose level
without increasing side e ects such as
weight gain and hypoglycaemia.
According to high quality evidence,
enhanced glucose control is associated with
a reduction in the incidence of neuropathy
in diabetes. The reduction is the incidence
of neuropathy is more pronounced in type 2
diabetes than in type 1 diabetes.
1. Callaghan BC, Little AA, Feldman EL, et al. Enhanced glucose
control for preventing and treating diabetic neuropathy.
Cochrane Database of Systematic Reviews 2012, Issue 6. Art.
No.: CD007543. DOI: 10.1002/14651858.CD007543.pub2.
2. Brownlee M. The pathobiology of diabetic complications.
3. Ismail-Beigi F, Craven T, Banerji MA, et al. ACCORD trial
group. Effect of intensive treatment of hyperglycaemia on
microvascular outcomes in type 2 diabetes: an analysis of the
ACCORD randomised trial. Lancet 2010;376(9739):419--30.
4. Shichiri M, Kishikawa H, Ohkubo Y, et al. Long-term results of
the Kumamoto study on optimal diabetes control in type 2
diabetic patients. Diabetes Care 2000;23(Suppl 2):B21--9.
5. UK Prospective Diabetes Study (UKPDS) Group. Intensive
blood-glucose control with sulphonylureas or insulin
compared with conventional treatment and risk of
complications in patients with type 2 diabetes (UKPDS 33).
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