The ACCORD (Action to Control Cardiovascular Risk in Diabetes) and VADT (Veterans Affairs Diabetes Trial) studies sowed seeds of doubt in the minds of many clinicians in diabetes care by appearing to show that intensive glycaemic control caused deaths in people with type 2 diabetes (ACCORD Study Group, 2008; Duckworth et al, 2009). Caution was exercised when dealing with poor glycaemic control and clinical inertia was evident, irrespective of whether this association was causal or not.
Fang and colleagues have shed more light on this matter, performing a meta-analysis with rigorous methodology on 13 studies of intensive glycaemic control versus conventional treatment (summarised alongside). They conclude that intensive glycaemic control is safe, with a mixed bag of distinct clinical benefits. There was actually no improvement in mortality rates; the relative risk with intensive treatment was a non-significant 0.98. Similarly, cardiac deaths, congestive heart failure and stroke were not improved – but, more importantly, not worsened – by intensive glycaemic control. However, the overall conclusion from the 58160 people studied was that the rate of major adverse cardiac events (MACE) and myocardial infarction were significantly reduced by 8% and 10%, respectively.
There was always a debate whether the rapid improvement in glycaemic control in people with a long duration of diabetes, using multiple agents, was the actual cause of the problem in ACCORD and VADT. The average duration of diabetes in ACCORD was 10 years. In contrast to these trials, better clinical accounts of intensive or improved glycaemic control emerged in trials that enrolled people at the onset of their diabetes, such as the UKPDS (UK Prospective Diabetes Study Group, 1998). It was also clear from the meta-analysis that studies involving multifactorial interventions, such as Steno-2 (Gaede et al, 2008) and UKPDS (which had blood pressure [BP] and glycaemic control arms), had the best outcomes in terms of reducing all diabetes complications, including MACE.
Previous research from the Clinical Practice Research Datalink concluded that all-cause mortality, stroke mortality and coronary mortality were lowest in people who were in the “good control” range for all three major CVD risk factors (Kontopantelis et al, 2015). These were found to be an HbA1c of 56–61 mmol/mol (7.25–7.75%), a total cholesterol of 3.5–4.5 mmol/L, a systolic BP of 135–145 mmHg and a diastolic BP of 82.5–87.5 mmHg. The latest National Diabetes Audit shows that only 18.1% of people with type 1 and 40.2% of those with type 2 diabetes reach these targets in clinical practice in the UK (NHS Digital, 2017). We would serve our patients better by ensuring that the vast majority attain these targets to reduce the risk of all complications of diabetes. It is time to accept this diktat and pursue national diabetes care targets with renewed enthusiasm.
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Vinod Patel highlights the growing evidence base that lifestyle interventions are effective, and encourages persistence even though they can be difficult.
25 May 2023