The TARGET trial

Even with benefits from new technologies such as insulin pumps and continuous glucose monitoring, achieving optimal glycaemic control for people with T1D remains a challenge.

A primary clinical treatment goal of intensive insulin therapy for type 1 diabetes (T1D) is to minimise excessive glucose excursions (hyper- and hypoglycaemia), which exacerbate the risk of chronic vascular complications, disability and premature death.

Those on intensive insulin therapy have 10-fold higher risk for developing cardiovascular disease compared to those without diabetes. Effective lifestyle-based approaches to improve blood glucose control could further assist in preventing or delaying the onset of the serious vascular complications of T1D.

The TARGET trial will test the effects of exercise and breaking up sitting time to manage T1D.

Exercise recommendations for people with T1D have largely been based on studies showing benefits for those with and without type 2 diabetes (T2D). This is because exercise training studies in those with T1D have largely failed to demonstrate improved glycaemic control (HbA1c). A lack of observed glycaemic benefit is at least in part related to the therapeutic challenge of matching subcutaneous insulin delivery to the varying insulin requirements of exercise.

Fear of exercise-related hypoglycaemia has been identified as the strongest barrier to exercise in adults with T1D, and epidemiological evidence suggests that those with T1D are just as inactive as their counterparts in the general population.

Research project leader Professor David Dunstan said there was a need to identify practical and feasible lifestyle strategies that can help to optimise glycaemia and reduce the risk of diabetic complications.

“We’re looking at emerging alternatives to the conventional notion of health-enhancing bouts of exercise,” Professor Dunstan said.

“Reducing and breaking up sitting time shows promise. We know that prolonged unbroken sitting time is detrimentally associated with cardiometabolic risk biomarkers, T2D, cardiovascular disease and all-cause mortality.

“Recent experimental studies, including several from our own group, have also shown that prolonged sitting is associated with acute elevations in postprandial glucose and insulin responses, and these adverse effects are attenuated with frequent breaks in sitting.”

However, Professor Dunstan said these studies have focussed on those who are healthy or overweight without diabetes, or on those with T2D. Although T1D and T2D are distinct conditions, chronic sustained hyperglycaemia is unequivocally associated with increased risk of vascular disease in both forms of diabetes.

“The TARGET trial aims to evaluate the effect of reducing prolonged sitting on glycaemia and vascular risk factors in T1D, and whether it could decrease the risk of serious diabetes complications,” he said.

In a randomised cross-over trial for adults with T1D, the research team (which includes physiologists and experienced T1D clinicians/researchers) will compare the acute cardiometabolic effects of three rigorously controlled experimental conditions (each of 7 hours duration):

• prolonged uninterrupted sitting
• prolonged sitting interrupted with regular short bouts of light walking
• prolonged sitting interrupted with regular short bouts of simple resistance activities.

Professor Dunstan said findings from this trial would help to identify new options for the lifestyle management of T1D, which can be examined in more depth in subsequent studies.