PCCJ_diabetes_supplement 10/14/09 8:50 AM
JOURNAL REVIEW
Tight control of type 2 diabetes reduces heart
attacks and heart disease events
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Tight control of glucose reduces the risk of heart
attack and coronary heart disease events in
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patients with type 2 diabetes, according to a large
meta-analysis.
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Intensive glucose control has previously been
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shown to reduce microvascular events in people
with type 2 diabetes, but the effects on
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macrovascular disease have been less clear with
individual trials failing to show consistent benefits
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Review warns of high risk of type 2 diabetes in
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women suffering gestational diabetes
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Women who have gestational diabetes mellitus
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(GD) during pregnancy have a more than seven-fold
increased risk for the development of type 2
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diabetes after delivery that persists for their
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lifetime, a systematic review and meta-analysis
has warned.
Gestational diabetes – defined as glucose
intolerance that is first detected during pregnancy
– affects up to 1 in 20 pregnancies. It has previously
been known that women with gestational diabetes
are at increased risk of developing type 2 diabetes,
but the size of the risk and the timescale have not
been known. UK researchers conducted a meta-
analysis of 20 cohort studies that included nearly
700,000 women; 10,859 of these developed type 2
diabetes.
Analysis showed that women with gestational
diabetes were around seven-and-a-half times more
likely to develop type 2 diabetes after pregnancy
than those with normal blood sugar control during
pregnancy (risk ratio 7.43), rising to an increased
risk of 9.34 for women with the longest follow-up.
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and some even suggesting possible harm. To look at
this, researchers analysed five prospective
randomised controlled trials, including a total of
33,040 participants, that compared intensive
glucose-lowering regimens with standard
treatment. Those treated intensively had
haemoglobin A1c (HbA1c) concentrations of
6.6%-7.0%, while controls had HbA1c values
between 7.3% and 8.4%. Overall, patients treated
intensively with combinations of oral drugs or oral
drugs plus insulin had HbA1c concentrations that
were, on average, 0.9% lower than controls
(6.6% vs 7.5%).
Results showed that patients whose glucose
levels were tightly controlled benefited from a 17%
reduction in non-fatal myocardial infarction (odds
ratio 0.83) and a 15% reduction in coronary heart
disease events (OR 0.85). However, there was no
difference in the rates of stroke (OR 0.93) or all-
cause mortality (OR 1.02).
The downside of intensive glucose management
© iStock.com/Emiliano Rodriguez
Women with gestational diabetes also had increased
blood pressure and lipid levels.
The authors conclude that further studies are
needed to establish features for the identification of
a mother with GD at particularly high risk of
developing type 2 diabetes. They add: “The increase
in relative risk of type 2 diabetes reported in this
meta-analysis might help motivate mothers to
attend screening programmes, and healthcare
professionals to increase uptake to these
PCCJ
doi:10.3132/pccj.2009.039
was that patients gained 2.5 kg more in weight than
those on standard treatment and experienced
higher rates of hypoglycaemia (38.1% vs 28.6%) and
serious hypoglycaemia (2.3% vs 1.2%).
The findings suggest that strict glucose control should
be part of effective diabetes management,
significantly reducing coronary events compared with
standard control. The study authors estimate that
treating 200 patients with type 2 diabetes intensively
for five years would prevent around two non-fatal
heart attacks and three coronary heart disease events.
These benefits are not as large as those associated
with tight control of blood pressure or lipids, but they
seem too important to ignore. Aiming for an HbA1c of
7% seems to be reasonable. However, we need to be
alert to the risk of hypoglycaemia, particularly in older
people.
Ray KK, Seshasai SR, Wijesuriya S et al. Lancet
2009; 373: 1765-72.
programmes or perhaps suggest the best time for
reassessment. Since the risk of type 2 diabetes seems
to be maintained for several years, consideration of
whether any form of continuous assessment would
lead to health gains is important.”
The high risk of developing type 2 diabetes in
women with gestational diabetes confirms the need
for long-term follow-up of these women and
underlines the importance of the six-week post-birth
diabetes check. This check could provide a useful
opportunity to alert women to symptoms of future
diabetes, to provide advice on diet and exercise, and
consider treatments to delay or prevent onset of
diabetes. Early identification and treatment of
cardiovascular risk factors could also help to reduce
premature cardiovascular and renal diseases in this
group of women.
Bellamy L, Casas J-P, Hingorani AD, Williams D.
Lancet 2009; 373: 1773-79.
VOLUME 2, SUPPLEMENT 1, JULY/AUGUST/SEPTEMBER 2009
PCCJ_diabetes_supplement 10/14/09 8:50 AM
Metabolic changes leading to diabetes
begin several years before diagnosis
© iStock.com/Jacob Wackerhausen
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Changes in blood glucose, insulin sensitivity and
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insulin secretion begin several years before the
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onset of type 2 diabetes, according to latest results
from the Whitehall II study, which indicate the
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scope for prevention.
The prospective study followed up 6,538 UK civil
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servants (71% male) without type 2 diabetes at
baseline for almost 10 years. Over this time 505
cases of diabetes were diagnosed. The researchers
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then looked back at blood glucose levels both
before a meal (fasting) and after a standard glucose
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test, insulin sensitivity (the capacity of tissues such
as muscle and liver to adequately respond to
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insulin), and the function of the insulin-producing
beta-cells of the pancreas.
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Results showed that changes in glucose
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concentrations and insulin sensitivity followed
QOF improves diabetes care
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Significant improvements in the care of patients with
diabetes have been achieved since the introduction of
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the Quality and Outcomes Framework (QOF) but
patients not included in the indicators may miss out,
a study of UK general practices has shown.
The study compared a range of measures in the
care of patients with diabetes in 147 general practices
in the three years before the introduction of the QOF
with the three years afterwards. Results showed
significant improvements in outcome measures during
the entire six-year period, with consecutive annual
improvements before the introduction of incentives.
However, the study authors cautioned that the current
diagnostic case definition for the QOF does not
capture up to two-thirds of people with type 1 diabetes
and one-third of people with type 2 diabetes.
After the introduction of the QOF, existing trends of
improvement in glycaemic control, cholesterol levels,
and blood pressure were attenuated, particularly in
PCCJ VOLUME 2, SUPPLEMENT 1, JULY/AUGUST/SEPTEMBER 2009
Page 3
linear trends in non-diabetics, except for insulin
secretion that did not change during follow-up. In
those developing diabetes, there was a linear
increase in fasting glucose, followed by a steep
increase (from 5.79 mmol/L to 7.4 mmol/L) starting
three years before diagnosis of diabetes. Post-meal
glucose levels also showed a rapid increase starting
three years before diagnosis.
Insulin sensitivity decreased steeply during the
five years prior to diagnosis. Finally, pancreatic beta-
cell function increased between four and three years
prior to diagnosis – presumably as the body tried to
compensate for rising glucose levels – but then
decreased in the three years up to diagnosis.
These findings show the opportunities for screening
and prevention of type 2 diabetes. Although most
prevention studies focus on people with prediabetes,
they suggest that prevention might be more effective
before this metabolically unstable period. More
research is needed to successfully identify people at
this stage of disease development. If a person could
be kept on the linear part of the fasting glucose (or
post-load glucose) trajectory, the onset of diabetes
might be substantially delayed.
Tabák AG, Jokela M, Akbaraly TN et al. Lancet
2009; 373: 2215-21.
people with diabetes who did not meet the QOF case
definitions. The introduction of QOF seemed to lead
to an increase in the number of patients with type 2
diabetes with HbA1c levels of 7.5% (odds ratio 1.05,
p=0.02). However, there was no improvement in the
management of patients with type 1 diabetes, and
no reduction in the number of patients with type 2
diabetes who had HbA1c levels greater than 10%.
The management of people with diabetes has
improved since the late 1990s, but the impact of the
QOF on care has not been straightforward. Targets
need to be made more challenging if people are to
benefit. Many patients whose care may be
suboptimal may not currently be captured in the
Quality and Outcomes Framework assessment.
Calvert M, Shankar A, McManus RJ et al. BMJ
2009; 338: b1870.
JOURNAL REVIEW
Study shows no increase in
cardiovascular morbidity or
mortality with rosiglitazone
Adding the insulin sensitiser rosiglitazone to
glucose-lowering therapy in patients with type 2
diabetes does not increase overall cardiovascular
morbidity or mortality compared with standard
treatment, according to a recent study.
The multicentre, open-label RECORD study
randomly assigned 4,447 patients with type 2
diabetes on metformin or sulphonylurea
monotherapy with average HbA1c values of 7.9% to
addition of rosiglitazone or a combination of
metformin plus sulphonylurea. The mean HbA1c
achieved in the rosiglitazone group was lower than
in the control group at five years.
Results showed similar rates of cardiovascular
hospitalisation or cardiovascular death (321 people
in the rosiglitazone group and 323 in controls) over
an average of 5.5 years of follow-up (hazard ratio
0.99). The risk of cardiovascular death was reduced
by 16% (HR 0.84) and stroke by 28% (HR 0.72) with
rosiglitazone, while the risk of myocardial infarction
was increased by 14% (HR 1.14).
The risk of heart failure was also increased, with
61 hospitalisations and deaths in the rosiglitazone-
treated group and 29 in controls (HR 2.10). Upper
and distal lower-limb fracture rates were also higher,
mainly in women, with rosiglitazone.
This study provides reassurance that addition of
rosiglitazone to metformin or sulphonylurea
monotherapy does not increase the risk of
cardiovascular morbidity or mortality in patients with
type 2 diabetes, as had been suggested in some
previous studies. However, the findings confirm that
rosiglitazone increases the risk of heart failure and
some fractures, mainly in women.
Home PD, Pocock SJ, Beck-Nielsen H et al. Lancet
2009; 373: 2125-35.
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