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Diabetes and Cardiovascular Risk
and VADT was observed within six to eight months, whereas the the vast majority of patients with type 2 diabetes. The evidence
decline in ADVANCE occurred over three years. Almost certainly as from the glucose control arm suggests that clinicians should
a consequence of the different strategies for intensive glucose consider a pragmatic and progressive glucose control strategy to
control utilised, the rate of severe hypoglycaemia (using comparable improve microvascular renal disease and long-term cardiovascular
definitions) in ACCORD and VADT was more than six times that risk. These findings add to the compelling evidence for a
observed in ADVANCE (approximately 16.1% over 3.5 years in multifactorial approach that includes statin therapy, smoking
ACCORD and 15.1% over 5.6 years in VADT compared with 2.7% over cessation, BP lowering and glucose control. Widespread
five years in ADVANCE).
2,4,5
There were also significant differences in implementation of a comprehensive management strategy
the mean weight gain in these three studies. In the ACCORD and addressing all cardiovascular risk factors is essential for combating
VADT trials, the mean weight gain from baseline was 3.5 and 4kg in the global epidemic of diabetes with its ever-increasing burden of
those on intensive glucose lowering, respectively, whereas in the cardiovascular disease. n
ADVANCE trial there was no weight gain among patients in the
intensive glucose lowering arm (see Figure 4).
2,4,5
Sophia Zoungas is a Senior Research Fellow in the
Cardiovascular and Renal Divisions of the George
A recent report from the UKPDS
19
has also provided a strong
Institute for International Health at the University of
indication that the reason for the apparent lack of effect on
Sydney, and a senior lecturer within the School of
macrovascular outcomes in ADVANCE, ACCORD and VADT could be
Public Health at Monash University in Melbourne. Her
major research interests are the impact of glycaemic
because the full effects of glucose lowering do not evolve until
control on cardiovascular outcomes and other
many years after the intervention has commenced. The post-trial
complications in type 2 diabetes. She is Study
follow-up study demonstrated that the differences in HbA
Coordinator of ADVANCE-ON, the post-trial follow-up
1c
study of the ADVANCE trial.
between the two originally assigned intervention groups (intensive
treatment with sulfonylurea and insulin versus conventional
John Chalmers is Emeritus Professor of Medicine at
treatment) were lost within one year of the study ending, yet
the University of Sydney and Senior Director of the
relative risk reductions were maintained at 10 years for diabetes-
George Institute for International Health in Sydney.
related outcomes (9%; p=0.004) and microvascular disease (24%;
His research has focused on the prevention of
cardiovascular diseases in high-risk groups, including
p=0.001), and new significant benefits on cardiovascular outcomes
those with diabetes, elevated blood pressure and
and all-cause mortality emerged.
19
These positive findings of a
previous stroke. Professor Chalmers was the principal
‘legacy’ effect of intensive glucose control urgently require
investigator for the ADVANCE and PROGRESS trials
and one of the founders of the Blood Pressure
confirmation in other larger studies of more diverse populations
Lowering Treatment Trialists’ Collaboration.
with long-standing diabetes. If the effects observed in the post-
UKPDS trial are indeed confirmed, this will have enormous
Anushka Patel is Director of the Cardiovascular
implications for the management of type 2 diabetes. Division at the George Institute, a consultant
cardiologist at Royal Prince Alfred Hospital and an
Conclusions
Associate Professor of Medicine at the University of
Sydney. She was Study Director and a member of the
The results of ADVANCE provide additional guidance to help Steering Committee of the ADVANCE study. Dr Patel
prevent many of the devastating vascular complications of type 2
has an MSc in epidemiology from Harvard University
and a PhD in medicine from the University of Sydney.
diabetes. The findings of the BP-lowering arm of the study provide
a strong basis for clinicians to recommend routine BP lowering for
1. Patel A, MacMahon S, Chalmers J, et al., Effects of a fixed 8. Adler AI, Stratton IM, Neil HA, et al., Association of systolic intensive blood-pressure lowering and low-dose aspirin in
combination of perindopril and indapamide on blood pressure with macrovascular and microvascular patients with hypertension: principal results of the
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randomised controlled trial, Lancet, 2007;370(9590):829–40. 9. Lewington S, Clarke R, Qizilbash N, et al., Age-specific 15. Turnbull F, Neal B, Algert C, et al., Effects of different
2. Patel A, MacMahon S, Chalmers J, et al., Intensive blood relevance of usual blood pressure to vascular mortality: blood pressure-lowering regimens on major
glucose control and vascular outcomes in patients with a meta-analysis of individual data for one million adults cardiovascular events in individuals with and without
type 2 diabetes, N Engl J Med, 2008;358(24):2560–72. in 61 prospective studies, Lancet, 2002;360(9349): diabetes mellitus: results of prospectively designed
3. UK Prospective Diabetes Study (UKPDS) Group, Intensive 1903–13. overviews of randomized trials, Arch Intern Med,
blood-glucose control with sulphonylureas or insulin 10. HOPE (Heart Outcomes Prevention Evaluation) Study 2005;165(12):1410–19.
compared with conventional treatment and risk of Investigators, Effects of an angiotensin-converting- 16. Nathan DM, Buse JB, Davidson MB, et al., Medical
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4. Gerstein HC, Miller ME, Byington RP, et al., Effects of 11. Tuomilehto J, Rastenyte D, Birkenhager WH, et al., Effects therapy: a consensus statement of the American Diabetes
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5. Duckworth W, Abraira C, Moritz T, et al., Glucose control 1999;340(9):677–84. 17. Stratton IM, Adler AI, Neil HA, et al., Association of
and vascular complications in veterans with type 2 12. Kloner RA, Neutel J, Roth EM, et al., Blood pressure control glycaemia with macrovascular and microvascular
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Thromb Vasc Biol, 2000;20(3):823–9. 13. United Kingdom Prospective Diabetes Study Group. Tight complications in overweight patients with type 2 diabetes
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baseline major risk factors to coronary and all-cause microvascular complications in type 2 diabetes: UKPDS 19. Holman RR, Paul SK, Bethel MA, et al., 10-year follow-up
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46 EUROPEAN ENDOCRINOLOGY
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