Position statement of the Australian Diabetes Society: individualisation of glycated haemoglobin targets for adults with diabetes mellitus.
ABSTRACT Tight glycaemic control reduces the risk of development and progression of organ complications in people with type 1 or type 2 diabetes. In this position statement, the Australian Diabetes Society recommends a general target glycated haemoglobin (HbA(1c)) level of </= 7.0% for most patients. This position statement also provides guidelines for the individualisation of glycaemic targets to a tighter or lesser degree, with a recommended target HbA(1c) level of </= 6.0% in some people, or up to </= 8.0% in others. Individualisation of the HbA(1c) target is based on patient-specific factors, such as the type of diabetes and its duration, pregnancy, diabetes medication being taken, presence of cardiovascular disease, risk of and problems from hypoglycaemia, and comorbidities. Management of diabetes also includes: adequate control of other cardiovascular risk factors, including weight, blood pressure and lipid serum levels; antiplatelet therapy; and smoking cessation.
- [Show abstract] [Hide abstract]
ABSTRACT: Aim To assess the cost-effectiveness of an automated telephone-linked care intervention, Australian TLC Diabetes, delivered over 6 months to patients with established Type 2 diabetes mellitus and high glycated haemoglobin level, compared to usual care. Methods A Markov model was designed to synthesize data from a randomized controlled trial of TLC Diabetes (n = 120) and other published evidence. The 5-year model consisted of three health states related to glycaemic control: ‘sub-optimal’ HbA1c ≥58 mmol/mol (7.5%); ‘average’ ≥48-57 mmol/mol (6.5- 7.4%) and ‘optimal’ <48 mmol/mol (6.5%) and a fourth state ‘all-cause death’. Key outcomes of the model include discounted health system costs and quality-adjusted life years (QALYS) using SF-6D utility weights. Univariate and probabilistic sensitivity analyses were undertaken. Results Annual medication costs for the intervention group were lower than usual care [Intervention: £1076 (95%CI: £947, £1206) versus usual care £1271 (95%CI: £1115, £1428,) p = 0.052]. The estimated mean cost for intervention group participants over five years, including the intervention cost, was £17,152 versus £17,835 for the usual care group. The corresponding mean QALYs were 3.381 (SD 0.40) for the intervention group and 3.377 (SD 0.41) for the usual care group. Results were sensitive to the model duration, utility values and medication costs. Conclusion The Australian TLC Diabetes intervention was a low-cost investment for individuals with established diabetes and may result in medication cost-savings to the health system. Although QALYs were similar between groups, other benefits arising from the intervention should also be considered when determining the overall value of this strategy.Diabetes research and clinical practice 01/2014; · 2.74 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: To reduce the congenital malformations that occur in pregnancies complicated by diabetes, it is essential to achieve and maintain a good metabolic control before conception. In this context, measuring HbA1c is considered as the gold standard for monitoring metabolic control in diabetes and various different HbA1c levels have been recommended as optimal in the preconception period for diabetic women planning a pregnancy. An analysis of key studies published on this issue until now clearly shows that HbA1c levels correlate closely with the occurrence of congenital malformations and other neonatal complications characteristic of pregnant diabetic women. HbA1c is therefore one of the key markers to use in monitoring metabolic control, and the most reasonable approach would seem to be to use a standardized measurement method and aim for HbA1c levels resembling normal values as closely as possible, with a view to preventing episodes of hypoglycemia.Acta Diabetologica 09/2010; 47(3):187-92. · 4.63 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The diabetes epidemic imposes a substantial burden on health systems and economy all over the world. Over the last two decades many health systems adopted healthcare quality and performance measures for DM most notably hemoglobin A1C (HbA1c). This article raises concerns regarding the significance of HbA1c as a performance measure and emphasizes the need for individualized therapy. This article is protected by copyright. All rights reserved.Diabetes/Metabolism Research and Reviews 02/2014; · 2.97 Impact Factor
MJA • Volume 191 Number 6 • 21 September 2009
The Medical Journal of Australia ISSN: 0025-
729X 21 September 2009 191 6 339-344
©The Medical Journal of Australia 2009
microvascular disease in type 1 and type 2 diabetes, respectively.1,2
In the DCCT, tight glycaemic control, achieving a mean HbA1c
level of 7.0% (v 9.2% in the conventional-therapy arm), reduced
retinopathy by 47%–76%, nephropathy by 39%–54%, and clinical
neuropathy by 60% in participants with type 1 diabetes.1 In the
UKPDS, intensively treated people with newly diagnosed type 2
diabetes (mean age, 53 years) had a median HbA1c level of 7.0%
over 10 years (v 7.9% with standard treatment) and a 12%
reduction in diabetes-related end points, mainly in microvascular
events.2 Additionally, in an obese subgroup of the intensive-
therapy group, metformin used as first-line therapy reduced the
incidence of myocardial infarction and mortality.3 The effect was
not statistically significant in participants primarily assigned to
treatment with sulfonylureas or insulin.2
In 2008 and 2009, results of several large studies designed to
examine the effect of even tighter glycaemic control on cardiovas-
cular outcomes were published, as well as results of the long-term
follow-up of UKPDS. The conflicting results of these studies have
raised questions about the appropriateness of existing HbA1c
targets, and created confusion among clinicians. This has
prompted the Australian Diabetes Society (ADS) to develop recom-
mendations for HbA1c levels, with a focus on the individualisation
of targets. These will complement the soon-to-be-released National
Health and Medical Research Council (NHMRC)-approved Evid-
ence based guideline for blood glucose control in type 2 diabetes, which
recommends a general HbA1c target level of ?7.0%.4 The ADS
recommendations are shown in Box 1 and Box 2.
A more detailed version of this position statement is available on
the ADS website (http://www.diabetessociety.com.au/downloads/
positionstatements/HbA1ctargets.pdf). The process used to
develop the document is outlined in Box 3. Our recommendations
serve as a guide to assist patient management, and it is not our
intention for them to be applied dogmatically.
ype 1 and type 2 diabetes are associated with increased
microvascular and macrovascular disease, disability and pre-
mature mortality. There is strong evidence from randomised
controlled trials that better glycaemic control can reduce some of
these diabetic complications. Improving glycaemic control is a
principal goal of diabetes management. Most authorities have
recommended a glycated haemoglobin (HbA1c) target level of
?7.0%, largely based on the results of the Diabetes Control and
Complications Trial (DCCT) and United Kingdom Prospective Dia-
betes Study (UKPDS), which demonstrated that intensive glucose
control substantially reduced onset and delayed progression of
Type 2 diabetes
Key recent studies of tight glycaemic control
In the Action to Control Cardiovascular Risk in Diabetes
(ACCORD) study, 10251 adults with type 2 diabetes (mean age,
62 years; disease duration, 10 years) were randomly allocated to
intensive therapy (target HbA1c level, <6.0% using any anti-
diabetic agent) or conventional therapy (target HbA1c level, 7.0%–
7.9%).5 All participants had an established or increased risk for
cardiovascular disease (CVD). At 1 year, the intensive-therapy
group achieved a median HbA1c level of 6.4%, and the convention-
ally treated group, 7.5%.
After 3.5 years of follow-up, the intensive regimen was discon-
tinued because of an unexpected increase in all-cause mortality (a
secondary end point) in this arm (5.0% v 4.0%; hazard ratio [HR],
1.22; 95% CI, 1.01–1.46; P=0.04). At this point, the pre-specified
primary outcome, which was the first occurrence of non-fatal
myocardial infarction, non-fatal stroke or cardiovascular death,
was showing a non-significant trend favouring intensive control
(6.9% v 7.2%; HR, 0.90; 95% CI, 0.78–1.04; P=0.16). No cause
for the increased mortality in the intensive-therapy group was
identified, though the incidence of hypoglycaemia requiring assist-
ance was higher (10.5% v 3.5%; P<0.001). On post-hoc subana-
lysis, increased mortality was observed in the intensive-therapy
group among participants with known CVD or HbA1c levels
>8.5% at baseline. Weight gain >10kg was also more common in
the intensive-therapy group.
The increased mortality in the intensive-therapy group has
raised questions about the appropriateness of an HbA1c target level
near the normal range in patients with, or at high risk of, CVD.
Position statement of the Australian Diabetes Society:
individualisation of glycated haemoglobin targets
for adults with diabetes mellitus
N Wah Cheung, Jennifer J Conn, Michael C d’Emden, Jenny E Gunton, Alicia J Jenkins, Glynis P Ross, Ashim K Sinha,
Sofianos Andrikopoulos, Stephen Colagiuri and Stephen M Twigg
• Tight glycaemic control reduces the risk of development and
progression of organ complications in people with type 1 or
type 2 diabetes.
• In this position statement, the Australian Diabetes Society
recommends a general target glycated haemoglobin (HbA1c)
level of ?7.0% for most patients.
• This position statement also provides guidelines for the
individualisation of glycaemic targets to a tighter or lesser
degree, with a recommended target HbA1c level of ?6.0%
in some people, or up to ?8.0% in others.
• Individualisation of the HbA1c target is based on patient-
specific factors, such as the type of diabetes and its duration,
pregnancy, diabetes medication being taken, presence
of cardiovascular disease, risk of and problems from
hypoglycaemia, and comorbidities.
• Management of diabetes also includes: adequate control
of other cardiovascular risk factors, including weight, blood
pressure and lipid serum levels; antiplatelet therapy; and
MJA 2009; 191: 339–344
340MJA • Volume 191 Number 6 • 21 September 2009
The Action in Diabetes and Vascular Disease: Preterax and Dia-
micron Modified Release Controlled Evaluation (ADVANCE) trial
randomly allocated 11140 people with type 2 diabetes (mean age,
66 years; mean duration of disease, 8 years) and major macrovas-
cular or microvascular disease, or at least one other risk factor, to
intensive or standard glycaemic control.6 The intensive-therapy
group was treated with modified-release gliclazide (Diamicron MR,
Servier), with the suggested sequential addition of metformin, a
thiazolidinedione, acarbose and insulin as required to achieve a
target HbA1c level ?6.5%. The standard-therapy group was
treated in accordance with local guidelines.
After 5 years, the mean HbA1c level was 6.5% in the
intensive-therapy group and 7.3% in the standard-therapy
group. Intensive control resulted in a reduction in the
primary outcome of combined major microvascular and
macrovascular events (18.1% v 20.0%; HR, 0.90; 95% CI,
0.82–0.98; P = 0.01), which was solely due to fewer microvas-
cular events, mainly nephropathy.
There were no differences in major macrovascular events or
mortality. Severe hypoglycaemia was more common in the inten-
sive-therapy group (2.7% of participants having at least one
episode v 1.5%; HR, 1.86; 95% CI, 1.42–2.40; P<0.001), with
this contributing to increased hospitalisation (44.9% v 42.8%; HR,
1.07; 95% CI, 1.01–1.13; P=0.03).
Veterans Affairs Diabetes Trial
The Veterans Affairs Diabetes Trial (VADT) recruited 1791 partici-
pants (mean age, 60 years; 97% male; mean duration of disease, 12
years) with suboptimally controlled type 2 diabetes to receive
either intensive or standard treatment.7 The HbA1c target level was
<6.0% for the intensive-therapy group, and 8.0%–9.0% for the
standard-therapy group. Stable median HbA1c levels of 6.9% and
8.4%, respectively, were achieved.
1 Recommended glycated haemoglobin (HbA1c) target ranges for adults with type 2 diabetes
targetRationale for recommendation
?7.0%* UKPDS demonstrated improved outcomes with median HbA1c ?7.0%;
result supported by NHMRC systematic review.
Specific clinical situations
Diabetes of short duration† and
no clinical cardiovascular disease
• Requiring lifestyle
modification ± metformin
?6.0%* UKPDS showed early treatment of diabetes to be beneficial.
In epidemiological studies, the threshold level of HbA1c, beyond which increased
mortality and cardiovascular events occur, lies between 5.0% and 6.0%.
Risk of hypoglycaemia is negligible with lifestyle modification or metformin.
UKPDS showed early treatment of diabetes to be beneficial.
Risk of hypoglycaemia increases with use of most antidiabetic agents other than
metformin, hence we do not recommend a target HbA1c ?6.0% for this group.
ADVANCE demonstrated reduced microvascular disease with target HbA1c
UKPDS demonstrated improved outcomes with median HbA1c of 7.0% in people
with newly diagnosed diabetes, including among those treated with insulin.
Observational data (albeit mainly in type 1 diabetes) demonstrate a relationship
between HbA1c and adverse pregnancy outcomes when HbA1c levels exceed a
threshold between 5.0% and 6.0%.
UKPDS demonstrated improved outcomes with median HbA1c of 7.0%.
ACCORD indicated that attempts for even tighter control in people with
relatively long duration of diabetes and cardiovascular disease were associated
with increased mortality.
We therefore do not routinely recommend tighter control in this group.
Severe hypoglycaemia is associated with significant morbidity and mortality.
Risks of tight glycaemic control outweigh the benefits for such patients.
• Requiring any antidiabetic
agents other than
metformin or insulin
• Requiring insulin
Pregnancy or planning pregnancy
Diabetes of longer duration† or
clinical cardiovascular disease
Recurrent severe hypoglycaemia
or hypoglycaemia unawareness
Patients with major comorbidities
likely to limit life expectancy‡
Tight glycaemic control will be of no benefit, as diabetic complications take
many years to develop.
ACCORD=Action to Control Cardiovascular Risk in Diabetes study. ADVANCE=Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release
Controlled Evaluation trial. NHMRC=National Health and Medical Research Council. UKPDS=United Kingdom Prospective Diabetes Study.
*Achievement of HbA1c targets must be balanced against risk of severe hypoglycaemia, especially among older people. †In an older adult, long duration might be
considered to be >10–20 years, but for a person who develops type 2 diabetes at a young age, it may be considerably longer. ‡Examples of major comorbidities
include chronic medical conditions, such as chronic kidney disease stages 4 or 5; heart failure stages III or IV (New York Heart Association grading); incurable
malignancy; and moderate to severe dementia. §Where practical, suggest blood glucose target level <15 mmol/L to help minimise risk of infection.
MJA • Volume 191 Number 6 • 21 September 2009
After a median follow-up of 5.6 years, no difference was
demonstrated in the primary outcome of time to the first occur-
rence of any one of myocardial infarction, stroke, cardiovascular
death, congestive heart failure, surgery for vascular disease, inop-
erable coronary artery disease or amputation for ischaemia (HR,
0.88; 95% CI, 0.74–1.05; P=0.14).
There was no difference in all-cause mortality (HR, 1.07; 95%
CI, 0.81–1.42; P=0.62). Severe hypoglycaemia was three times
more likely in the intensive-therapy group, and weight gain was
The 10-year observational post-trial monitoring of the original
randomised UKPDS cohorts has provided additional data about
longer-term type 2 diabetes outcomes.8 Upon completion of the
UKPDS, all study participants were advised to aim for lower blood
glucose levels than previously targeted, with 3277 patients enter-
ing post-trial monitoring.
Although the difference in HbA1c levels between the intensive-
and standard-therapy groups was lost within 1 year of completing
the original study, the previously demonstrated reductions in risk
of diabetes end points and microvascular disease persisted at 20
years. A reduction in myocardial infarction (15%; P=0.01) and all-
cause mortality (13%; P=0.007) emerged among patients ori-
ginally under intensive treatment with sulfonylureas or insulin
compared with participants in the standard-treatment group, and
even greater reductions were observed in those originally treated
with metformin (21% in any diabetes end point; 33% in myocar-
dial infarction; 27% in all-cause mortality). Therefore, the benefits
of better glycaemic control from the time of diagnosis of type 2
diabetes persisted and strengthened. Furthermore, the cardiovas-
cular benefits may take many years to become evident.
Key studies compared
ACCORD showed an overall detrimental effect of tight glycaemic
control on mortality; ADVANCE and VADT did not show any
overall effect, either positive or detrimental, of tight glycaemic
control on mortality; and UKPDS showed a reduction in all-cause
A limitation of ACCORD, ADVANCE and VADT is that, com-
pared with UKPDS, they recruited older participants at increased
risk of CVD with poorly controlled diabetes. These patients may
have had suboptimal control for many years, resulting in irrevers-
ible end-organ damage. Instituting tight control in such patients
may have outcomes very different from those of maintaining
excellent control from the outset, especially when other risk factors
are addressed. Therefore, these three studies do not provide
guidance for the management of younger patients, patients with
lower risk of CVD or patients with longstanding, well controlled
type 2 diabetes. In contrast, UKPDS indicates that maintaining
good glycaemic control after achieving it early in the disease
process is beneficial. However, as the cardiovascular benefits were
only observed in the post-trial monitoring period of UKPDS,
appropriate trials in newly presenting young patients are much
Other recent epidemiological and observational data
Epidemiological and observational studies have shown a
continuum of risk of diabetic complications and mortality with
increasing HbA1c levels. The threshold for increased risk lies
within or at the upper limit of the normal range for HbA1c.
Published in 2004, the European Prospective Investigation of
Cancer in Norfolk (EPIC-Norfolk) Study prospectively followed
10132 individuals aged 40–79 years for an average of 6 years.9 A
2 Recommended glycated haemoglobin (HbA1c) target ranges for adults with type 1 diabetes
Rationale for recommendation
DCCT/EDIC showed that achieving a mean HbA1c of 7.0% is associated
with improved outcomes.
Specific clinical situations
Better pregnancy outcomes (borderline significance) were achieved for
intensive-therapy group of DCCT (mean HbA1c of 7.4%).
Observational data demonstrate a relationship between HbA1c and adverse
pregnancy outcomes when HbA1c levels exceed a threshold between 5.0%
and 6.0%, but there is a heightened risk of hypoglycaemia at such low levels.
Therefore, for most women, we recommend a target HbA1c ?7.0%.
Severe hypoglycaemia is associated with significant morbidity and mortality.
Risks of tight glycaemic control outweigh the benefits for such patients.
Patients with major
to limit life expectancy
and avoidance of
Tight glycaemic control will be of no benefit, as diabetic complications
take many years to develop.
DCCT=Diabetes Control and Complications Trial. EDIC=Epidemiology of Diabetes Interventions and Complications study.
*Achievement of HbA1c targets must be balanced against risk of severe hypoglycaemia. †An HbA1c level ?6.0% is desirable if it can be achieved safely.
‡Where practical, suggest blood glucose target level <15 mmol/L to help minimise risk of infection.
342 MJA • Volume 191 Number 6 • 21 September 2009
continuous increase in cardiovascular events and all-cause mortal-
ity was observed with increasing baseline HbA1c levels from 5.0%
upwards in men, even in the absence of diabetes. Among women,
this was significant at HbA1c levels >6.0%.
Also published in 2004, a meta-analysis of prospective cohort
studies in people with type 2 diabetes estimated that for every
1.0% increase in the level of HbA1c, there was an 18% (95% CI,
10%–26%) higher risk of CVD.10 For people with type 1 diabetes,
the risk increased by 15% (95% CI, 8%–43%).
Follow-up UKPDS data, published in 2000, showed that each
1.0% reduction in the HbA1c level was associated with a 37%
decrease in risk of microvascular complications, 14% decrease in
risk of myocardial infarction, and 14% decrease in risk of all-cause
mortality, with no threshold effect.11
The main concern arising from the ACCORD study is that tight
glycaemic control in individuals with or at high risk of CVD
increases the risk of death. When the results of ACCORD are
considered together with those of the other trials mentioned
above, there remains a clear benefit of maintaining an HbA1c level
?7.0% for most patients. However, the risk–benefit balance is
complex, and the following conclusions can also be drawn:
• Tight glycaemic control early in the diabetes disease process is
desirable and is likely to yield the greatest benefit for the preven-
tion of microvascular and macrovascular complications, as well as
overall mortality. There is no evidence that maintenance of tight
glycaemic control (eg, HbA1c levels <6.0%–6.5%) in a patient with
longstanding well controlled type 2 diabetes increases mortality
• Attaining tight glycaemic control in advanced disease yields
little, if any, benefit for macrovascular disease but is effective in
retarding the development and progression of microvascular
• Attempts to achieve tight glycaemic control need to be balanced
against the increased risk of severe hypoglycaemia. In the UKPDS,
the annual incidence of hypoglycaemia was 0.1% among parti-
cipants who were treated with diet alone; 0.3% for those receiving
metformin monotherapy; 1.2% for those taking sulfonylureas;
3.8% for participants taking basal insulin only; and 5.5% for those
taking prandial insulin.12 Caution is necessary when treating older
people or people with CVD. When such patients are taking insulin
or sulfonylureas, a low HbA1c level warns of a heightened risk of
hypoglycaemia. For patients prone to severe hypoglycaemia or
who have hypoglycaemia unawareness, it is prudent to maintain
an HbA1c level >7.0%.
• Intensive correction of HbA1c levels requires caution because
the risk of hypoglycaemia may be increased. This is particularly
important for patients with CVD or a history of diabetes longer
than 10–20 years. Weight gain is also more likely.
In light of these conclusions, practitioners need to individualise
the HbA1c target level, taking into consideration the presence of
CVD, diabetes duration, diabetes medication regimen, comorbid-
ities and problems with severe hypoglycaemia (Box 1). It is
important to remember that the prevention of hypoglycaemia does
not rely purely on adjustment of medication, but also on patient
education, including instruction in blood glucose monitoring.
Type 1 diabetes
Recent data regarding tight glycaemic control
Upon the completion of the DCCT, follow-up of 1394 participants
(96% of DCCT survivors) continued in the observational Epidemi-
ology of Diabetes Interventions and Complications (EDIC) study.
Among the primary aims of EDIC were to examine the long-term
effects of the earlier differences in glycaemic control on both
microvascular disease and CVD. All EDIC participants were
advised about intensive insulin therapy, and returned to their usual
medical practitioner for diabetes care.
Subsequently, the HbA1c levels converged, with the level in the
original intensive-therapy group rising to 8.0% ±1.2% and the
conventional group’s level decreasing to 8.2% ±1.2%. The rate of
progression of retinopathy,13 nephropathy14 and neuropathy15
remained lower in the prior intensive-therapy group, though there
was some attenuation of the effect on retinopathy after 4 to 10
years.16 Over 17 years of follow-up in DCCT and EDIC, particip-
ants in the DCCT intensive-treatment group had a 42% lower risk
of CVD events (P=0.02), and non-fatal myocardial infarction,
stroke or cardiovascular death fell by 57% (P=0.02).16
These long-term results of DCCT/EDIC on both microvascular
and macrovascular outcomes support the target HbA1c level of
? 7.0% for people with type 1 diabetes. Situations where it is
suggested that the HbA1c target level should be less strict are
outlined in Box 2. In particular, it is advisable that HbA1c be
maintained at higher levels (eg, 7.0%–8.0%) for patients who
suffer severe hypoglycaemic episodes or have hypoglycaemia
Pregestational diabetes is associated with serious adverse preg-
nancy outcomes, such as miscarriage, congenital malformation,
pre-eclampsia and perinatal death. There is a continuous relation-
ship between elevated HbA1c levels at conception and these
outcomes, with increased risk at even slight elevations above the
non-pregnant normal range.
A meta-analysis that included 1977 pregnant participants (the
vast majority with type 1 diabetes) from seven prospective cohort
3 Consensus process used to develop this Australian
Diabetes Society position statement
Aim: To develop guidelines for the individualisation of glycated
haemoglobin (HbA1c) targets for the treatment of diabetes mellitus
Method: Australian Diabetes Society (ADS) members were invited to
make submissions to ADS Council regarding their views on HbA1c
targets, with a specific focus on the results of recent clinical trials.
ADS Council prepared a draft position statement, taking into
consideration the submissions. This was reviewed by four eminent
former presidents of ADS, and further changes were made. The final
version of the position statement was prepared by ADS Council.
Guidelines for pregestational and gestational diabetes
management were developed in collaboration with the Council
of Australasian Diabetes in Pregnancy Society.
Levels of evidence: Each of the recommendations was graded
according to the National Health and Medical Research Council
(NHMRC) levels of evidence.
MJA • Volume 191 Number 6 • 21 September 2009
studies found that for every 1 SD increase in the level of HbA1c
(equivalent to 0.5% where the normal range is 4.0%–6.0%), the
risk of congenital malformation increased by 20%.17 Even when
the HbA1c level was only 2 SD above the mean (that is, 6.0%),
there was about a 50% increase in risk (absolute risk, 3%)
compared with participants with HbA1c levels at the population
mean (5.0%). There are no detailed data defining the relationship
between HbA1c level and fetal outcome in type 2 diabetes, beyond
the recognition that high HbA1c levels in early pregnancy are
associated with serious adverse fetal outcomes.18
The only randomised controlled trial data come from the DCCT,
which included 270 pregnant participants with type 1 diabetes.19
Women in the intensive-therapy arm had lower HbA1c levels at
conception than those in the control arm (7.4% ±1.3% v 8.1%
±1.7%). Despite intensification of management during pregnancy
resulting in a convergence in HbA1c levels between the two groups,
eight congenital malformations occurred in the conventional-
therapy group, compared with one in the intensive-therapy group
We recommend that the HbA1c level at conception and during
pregnancy should be ?6.0%. This is achievable for many women
with type 2 diabetes. Although this HbA1c target is also desirable in
women with type 1 diabetes, there is a heightened risk of severe
hypoglycaemia with such tight glycaemic control. Therefore,
unless a lower HbA1c level can be achieved safely, a conservative
target of ?7.0% is recommended for women. Prepregnancy
planning is essential. Other aspects of pregnancy care for women
with pregestational diabetes have previously been outlined in the
Coexistent cardiovascular risk factors
Weight control, antihypertensive therapy, lipid control and
antiplatelet therapy are critical in diabetes management. The
Steno-2 Study addressed multiple risk factors through control of
HbA1c, blood pressure and lipids, and a regimen of aspirin and
angiotensin-converting enzyme (ACE) inhibitor therapy, healthy
diet, physical activity and smoking cessation.21 This long-term
target-driven intervention among people with type 2 diabetes
and microalbuminuria more than halved the risk of CVD,
nephropathy, retinopathy and autonomic neuropathy. The
UKPDS and ADVANCE also demonstrated improved outcomes
with better blood pressure control.22,23 The blood pressure
target is < 130/80mmHg, and for those with ? 1g/day of
proteinuria, < 125/75mmHg. Statin therapy markedly reduces
macrovascular events in type 2 diabetes.24,25 The main lipid
target is a low-density lipoprotein cholesterol level < 2.5 mmol/L
for primary prevention and < 1.8 mmol/L in secondary preven-
tion. For most people with type 2 diabetes, the high absolute
risk for macrovascular disease justifies statin treatment and an
ACE inhibitor (or angiotensin-II receptor blockade), even if
lipids and blood pressure are in the target range. Antiplatelet
therapy (especially aspirin) is indicated for secondary and, in
many cases, primary prevention in those with high absolute
We thank Professor Don Chisholm, Professor Peter Colman and Associate
Professor Jeff Flack for reviewing this position statement and providing
Wah Cheung received a travel grant from GlaxoSmithKline and another from
Eli Lilly to attend conferences. Jennifer Conn received travel grants from
Novo Nordisk. Michael d’Emden received speaker fees, honoraria for
attending advisory board meetings and support to attend meetings of the
Australian Diabetes Association and European Association for the Study of
Diabetes from Eli Lilly, Novo Nordisk, Novartis, Sanofi-Aventis, Bayer and
Merck Sharpe & Dohme. Jenny Gunton received speaker fees from Eli Lilly.
Alicia Jenkins is a member of the Merck Diabetes Advisory Board. She is a
chief investigator of an investigator-initiated study, funded by Medtronic,
about use of glucose sensor-augmented pumps in type 1 diabetes; she has
not received a salary for this work. Glynis Ross received travel grants from
Novo Nordisk to attend meetings, and speaker fees from Medtronic. Ashim
Sinha has received travel grants and speaker fees from Eli Lilly, Novo
Nordisk, GlaxoSmithKline and Sanofi-Aventis. He is also on an advisory
board for Sanofi-Aventis. Stephen Twigg is a paid consultant for the advisory
boards of Eli Lilly, Merck Sharp & Dohme, Novo Nordisk and Sanofi-Aventis.
He receives speaker fees from Merck Sharp & Dohme, and meeting
organiser fees from the Eli Lilly Meeting Faculty. He receives travel assistance
to attend meetings from Sanofi-Aventis, GlaxoSmithKline and Novo Nordisk.
N Wah Cheung, MBBS, FRACP, PhD, Senior Endocrinologist,1 and
Jennifer J Conn, FRACP, MClinEd, BSc(Hons), Consultant
Michael C d’Emden, MBBS, PhD, FRACP, Acting Director and
Jenny E Gunton, MBBS, FRACP, PhD, Endocrinologist1,2,5
Alicia J Jenkins, MD, FRACP, FRCP, Associate Professor6
Glynis P Ross, MBBS(Hons), FRACP, Senior Endocrinologist7,8
Ashim K Sinha, MBBS(Hons), MD, FRACP, Associate Professor and
Director of Diabetes and Endocrinology9
Sofianos Andrikopoulos, PhD, NHMRC Career Development
Stephen Colagiuri, MBBS(Hons), FRACP, Professor of Metabolic
Stephen M Twigg, MBBS(Hons), PhD, FRACP, Associate Professor,2
and Senior Endocrinologist7
1 Department of Diabetes and Endocrinology, Westmead Hospital,
2 Department of Medicine, University of Sydney, Sydney, NSW.
3 Royal Melbourne Hospital, Melbourne, VIC.
4 Royal Brisbane and Women’s Hospital, Brisbane, QLD.
5 St Vincent’s Clinical School, University of New South Wales, Sydney,
6 Department of Medicine, University of Melbourne, St Vincent’s
Hospital, Melbourne, VIC.
7 Department of Endocrinology, Royal Prince Alfred Hospital, Sydney,
8 Bankstown–Lidcombe Hospital, Sydney, NSW.
9 Cairns Base Hospital, Cairns, QLD.
10 Department of Medicine, University of Melbourne, Heidelberg
Repatriation Hospital, Melbourne, VIC.
11 Boden Institute of Obesity, Nutrition and Exercise, University of
Sydney, Sydney, NSW.
1 The Diabetes Control and Complications Trial Research Group. The
effect of intensive treatment of diabetes on the development and
progression of long-term complications in insulin-dependent diabetes
mellitus. N Engl J Med 1993; 329: 977-986.
2 Turner RC, Holman RR, Cull CA, et al. Intensive blood-glucose control
with sulphonylureas or insulin compared with conventional treatment
and risk of complications in patients with type 2 diabetes (UKPDS 33).
Lancet 1998; 352: 837-853.
344MJA • Volume 191 Number 6 • 21 September 2009
3 Turner RC, Holman RR, Stratton IM, et al. Effect of intensive blood-
glucose control with metformin on complications in overweight patients
with type 2 diabetes (UKPDS 34). Lancet 1998; 352: 854-865.
4 Colagiuri S, Dickinson S, Girgis S, Colagiuri R. Evidence based guideline
for blood glucose control in type 2 diabetes. Public consultation draft,
August 2008. http://www.diabetesaustralia.com.au/PageFiles/7852/
(accessed Aug 2009).
5 Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose
lowering in type 2 diabetes. N Engl J Med 2008; 358: 2545-2559.
6 Patel A, MacMahon S, Chalmers J, et al. Intensive blood glucose control
and vascular outcomes in patients with type 2 diabetes. N Engl J Med
2008; 358: 2560-2572.
7 Duckworth W, Abraira C, Moritz T, et al. Glucose control and vascular
complications in veterans with type 2 diabetes. N Engl J Med 2009; 360:
8 Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive
glucose control in type 2 diabetes. N Engl J Med 2008; 359: 1577-1589.
9 Khaw KT, Wareham N, Bingham S, et al. Association of hemoglobin A1c
with cardiovascular disease and mortality in adults: the European pro-
spective investigation into cancer in Norfolk. Ann Intern Med 2004; 141:
10 Selvin E, Marinopoulos S, Berkenblit G, et al. Meta-analysis: glycosylated
hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern
Med 2004; 141: 421-431.
11 Stratton IM, Adler AI, Neil HA, et al. Association of glycaemia with
macrovascular and microvascular complications of type 2 diabetes
(UKPDS 35): prospective observational study. BMJ 2000; 321: 405-412.
12 Wright AD, Cull CA, Macleod KM, Holman RR. Hypoglycaemia in type 2
diabetic patients randomized to and maintained on monotherapy with
diet, sulfonylurea, metformin, or insulin for 6 years from diagnosis:
UKPDS73. J Diabetes Complications 2006; 20: 395-401.
13 White NH, Sun W, Cleary PA, et al. Prolonged effect of intensive therapy
in the risk of retinopathy complications in patients with type 1 diabetes
mellitus. Arch Ophthalmol 2008; 126: 1707-1715.
14 The Diabetes Control and Complications Trial/Epidemiology of Diabetes
Intervention and Complications Research Group. Sustained effect of
intensive treatment of type 1 diabetes mellitus on development and
progression of diabetic nephropathy: the epidemiology of diabetes
interventions and complications (EDIC) study. JAMA 2003; 290: 2159-
15 Martin CL, Waberski B, Albers J, et al. Neuropathy among the diabetes
control and complications trial cohort 8 years after trial completion.
Diabetes Care 2006; 29: 340-344.
16 Nathan DM, Cleary PA, Backlund JYC, et al. Intensive diabetes treatment
and cardiovascular disease in patients with type 1 diabetes. N Engl J
Med 2005; 353: 2643-2653.
17 Guerin A, Nisenbaum R, Rav JG. Use of maternal GHb concentration to
estimate the risk of congenital anomaly in the offspring of women with
prepregnancy diabetes. Diabetes Care 2007; 30: 1920-1925.
18 Clausen TD, Mathiesen E, Ekbom P, et al. Poor pregnancy outcome in
women with type 2 diabetes. Diabetes Care 2005; 28: 323-328.
19 The Diabetes Control and Complications Trial Research Group. Preg-
nancy outcomes in the Diabetes Control and Complications Trial. Am J
Obstet Gynecol 1996; 174: 1343-1353.
20 McElduff A, Cheung NW, McIntyre HD, et al. The Australasian Diabetes
in Pregnancy Society consensus guidelines for the management of type 1
and type 2 diabetes in relation to pregnancy. Med J Aust 2005; 183: 373-
21 Gaede P, Lund-Andersen H, Parving HH, Pedersen O. Effect of a
multifactorial intervention on mortality in type 2 diabetes — STENO 2.
N Engl J Med 2008; 358: 580-591.
22 Turner R, Holman R, Stratton I, et al. Tight blood-pressure control and risk
of macrovascular and microvascular complications in patients with type 2
diabetes: (UKPDS 38). Lancet 1998; 352: 837-853.
23 Patel A, MacMahon S, Chalmers J, et al. Effects of a fixed combination of
perindopril and indapamide on macrovascular and microvascular out-
comes in patients with type 2 diabetes mellitus (the ADVANCE trial): a
randomised controlled trial. Lancet 2007; 370: 829-840.
24 Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary prevention of
cardiovascular disease with atorvastatin in type 2 diabetes in the Collab-
orative Atorvastatin Diabetes Study (CARDS): multicentre randomised
placebo-controlled trial. Lancet 2004; 364: 685-696.
25 Heart Protection Study Collaborative Group. MRC/BHF Heart Protection
Study of cholesterol lowering with simvastatin in 20536 high-risk individ-
uals: a randomised placebo-controlled trial. Lancet 2002; 360: 7-22.
26 Hansson L, Zanchetti A, Carruthers SG, et al. Effects of intensive blood-
pressure lowering and low-dose aspirin in patients with hypertension:
principal results of the Hypertension Optimal Treatment (HOT) random-
ised trial. HOT Study Group. Lancet 1998; 351: 1755-1762.
(Received 21 Apr 2009, accepted 22 Jul 2009)