Is time in tight range the metric of the future?
With the increasing use of continuous glucose monitoring (CGM) in people with diabetes, glucose metrics are starting to complement HbA1c in both diabetes care and clinical trials. To reduce the risk of complications, time in tight range (TITR) may be the metric to focus on going forward, according to discussion at recent Advanced Technologies & Treatments for Diabetes (ATTD) conference. Dr Susan Aldridge reports.
TITR is a glucose metric that is increasingly being used in diabetes care to evaluate glucose control. It is defined as a glucose level between 3.9 and 7.8 mmol/l, while the now well-established time in range(TIR) is a glucose level between 3.9 and 10 mmol/l. “TITR describes time in normoglycaemia, while time above tight range is dysglycaemia,” explained Professor Thomas Danne, of the Children’s Hospital Auf der Bult, Hannover, introducing ATTD’s TITR presentations.
Dr Peter Adolfsson, from the Hospital of Halland, Sweden, has been at the forefront of introducing TITR in Sweden, where they have been using it for some time in all of the country’s paediatric type 1 diabetes clinics. He sees the advantage as being giving children a ‘good start’ with their glucose control after diagnosis. Success with TITR depends upon teamwork and coaching strategies. “We are learning from each other, from other teams and from people and families affected with type 1 diabetes,” he said.
The rationale behind the introduction of TITR is the concept of metabolic memory, where high glucose values manifest themselves many years later as diabetes-related complications, such as retinopathy. This means introducing very early and aggressive treatment with the aim of normalising glucose control. Knowledge of metabolic memory can also motivate high and tight goals in glucose control, whether these be HbA1c, TIR or TITR. For instance, national registry data in Sweden shows that higher goals in themselves promote better glucose control.
Technology and TITR
“We are very keen on diabetes technology in Sweden and today we mainly use smart pens or connected pens and intermittent CGM talking to an algorithm,” said Dr Adolfsson. Hybrid closed loop, including advanced systems, are now increasingly being used, while most people with type 1 diabetes use CGM and pumps. And it is this increased use of technology that has driven commitment to TITR and improved HbA1c levels nationally.
National target HbA1c for type 1 diabetes was set to 48 mmol/mol in 2017. “Step by step, we improve by using technology, education and training,” said Dr Adolfsson. “Last year, the mean national HbA1c value was 51.2 mmol/mol and we are now looking for 48 mmol/mol and increasing the percentage reaching this target over time. In my clinic today, I don’t have anyone with an HbA1c value above 70 mmol/mol. It’s possible because of the automated insulin delivery systems today.”
In one study, glucose control in healthy children aged two to nine years, using the Dexcom G4 CGM, showed 89% of them achieving TITR and a later study with the G6 model showed 97% in TITR – so, in other words, most of these children were now achieving normal glycaemia. “The advantage is that the individual can see their TITR at home, so it’s a more understandable metric for them than HbA1c,” said Dr Adolfsson. “You have the potential with technology to reach TITR targets, but keep in mind that staying in a tighter range requires more vigilance and tools. And the target might be different for different ages and types of diabetes.”
He concluded that children with type 1 diabetes who have access to modern diabetes care can achieve an HbA1c of 48 mmol/mol. With CGM, a reasonable treatment target is 50% TITR, which relates to an HbA1c of 48 mmol/mol. “Remember that an early onset of diabetes is associated with a long lifetime of potential complications, necessitating optimal glycaemia control from the start,” he said.
TITR in type 2 diabetes
People with type 2 diabetes can also benefit from TITR as long-term glucose control is important to them too, although they may not be as focused on the daily highs and lows as those with type 1 diabetes are. And, at the moment, far fewer of them use CGM, although that could change. “To me, it is important not only to live long, but also to be aware of living well,” said Professor Tadej Battelino of the University of Ljubljana. “And the higher the HbA1c, the higher the risk of dementia. Elevated glucose is harmful and that is why we need a tight range.”
The TITR metric is now being used in clinical trials in type 2 diabetes. For example, a sub-study (SURPASS-3 CGM) of the SURPASS-3 trial of weekly tirzepatide (the dual GIP/GLP-1 receptor agonist) versus daily insulin degludec in type 2 diabetes measured TITR. At 52 weeks, those on 15 mg and 10 mg tirzepatide (but not 5 mg) spent significantly more TITR than those on insulin degludec. These findings complement those of the main SURPASS-3 trial, which showed greater HbA1c reductions for tirzepatide.
“TITR is obviously relevant in early type 2 diabetes, especially where insulin therapy is involved,” concluded Professor Battelino. There is also potential for TITR in monitoring response to changes in therapy. And it could also be useful in detecting early hyperglycaemia in prediabetes and obesity to allow prompt intervention to prevent type 2 diabetes. It’s to be hoped that as CGM becomes the standard of blood glucose monitoring, TITR will be found to play a major role in the prevention of diabetes complications.
To learn more, enrol on the EASD e-Learning course ‘Time in range’.
Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.
