A new analysis of UK Prospective Diabetes Study (UKPDS) data shows that a simple blood test which estimates the degree of insulin resistance at the time of diagnosis of type 2 diabetes can help to predict the development of heart failure and death many years later. The analysis was carried out by researchers at OCDEM, led by Dr Gosia Wamil, with Professor Rury Holman as the senior author.
The UKPDS was a landmark randomised, multicentre trial of glycaemic therapies in 5,102 people with newly-diagnosed type 2 diabetes. It ran for twenty years (1977 to 1997) in 23 UK clinical sites, followed by a ten-year, post-trial monitoring programme completed in 2007. Researchers assessed insulin resistance in UKPDS participants using the Homeostasis Model Assessment (HOMA) calculator which estimates steady state beta cell function (HOM2_%B) and insulin resistance (HOMA2_IR) from simultaneous measurements of fasting plasma glucose and insulin.
In the new study, Dr Wamil used UKPDS trial and post-trial monitoring data to show that insulin resistant participants were more likely to develop symptoms of heart failure or die than those who were more insulin sensitive at the time their diabetes was diagnosed. A doubling in HOMA2_IR values was associated with a 14% increased risk of heart failure.
Although insulin resistance is frequently associated with obesity, the new study demonstrated that the link between insulin resistance and heart failure was independent of how obese the participants were.
Dr Wamil said “This is particularly important, because it suggests there may be a different mechanism linking diabetic heart disease with insulin resistance in addition to the known effect of obesity on the development of heart failure.
“These results also suggest there could be a potential role for pharmacotherapies that target insulin signalling pathways for the prevention of heart failure. This hypothesis is also supported by another observation that increased insulin levels predate the development of type 2 diabetes in people with heart failure.
The study highlights the potential utility of HOMA2-IR to facilitate the early identification of people with confirmed insulin resistance who may be at high risk of heart failure. Other studies are under way to establish if treatments which have been shown to particularly effective at reducing heart failure (e g. sodium-glucose co-transporter-2 inhibitors) can induce insulin sensitisation, which might help explain their cardioprotective role.
Read the full paper.