A government funding initiative is set to dramatically improve the management of type 1 diabetes
Diabetes testing has come a long way since the early urine tests of the 1930s and the blood glucose colour charts of the 1960s.
Now continuous glucose monitoring (CGM) looks poised to again dramatically shift the management of diabetes.
In the last few years, the accuracy and precision of these continuous glucose monitors has improved and the body of research analysing their impact on hard clinical outcomes across different subgroups has grown.
Thanks to the federal government coming good on their election promise, Australian children and under-21s with type 1 diabetes will soon have access to CGM devices under the National Diabetes Services Scheme (NDSS).
As a result, around 4000 children and young adults will be able to get a device that takes constant readings of their glucose levels, alerting them if their blood glucose becomes too high or too low.
Patients and the parents of children with type 1 diabetes talk with enthusiasm about the relief that devices like this bring, alleviating the stress of having to wake during the night to do a fingerprick test, or the anxiety many parents feel when their child is at school or out with friends beyond their supervision.
Up until now, one of the major barriers to the widespread adoption of CGM has been the cost. The sensors, need to be replaced weekly with most systems.
Patients also need new transmitters once or twice a year, which has meant the average family would have out-of-pocket costs of around $3000 to $4000 per year.
Without the scheme, CGM has simply been unaffordable for many Australians without private health insurance.
CGM allows individuals to gain back control as their self-management improves, and allows clinicians to give more appropriate advice.
Associate Professor Sof Andrikopoulos, CEO of the Australian Diabetes Society, commends the government on its $54 million promise to the NDSS. “Continuous glucose management is really important in management of diabetes,” says the head of Islet Biology and Metabolism Research Group at Austin Health.
Going from a spot check of blood glucose only a handful of times a day, to continuous reading of glucose levels leads to a better understanding of the patient’s variability over the day.
CGM allows individuals to gain back control as their self-management improves, and allows clinicians to give more appropriate advice, the endocrinologist adds. “Understanding what happens to your blood glucose in a particular circumstance, whether it’s with food, with exercise, with fasting or with distress is really critical in being able to manage that situation when you encounter it in the future.”
“That information [from CGM] can then lead to significant modification in the management of diabetes for that person – whether that be lifestyle or whether that be the way they manage their diabetes with insulin,” he says.
It will also ensure detection of both hyper and hypoglycaemic episodes, both of which are critical to manage if you want to stabilise blood glucose levels, Professor Andrikopoulos said.
This provides a clearer picture of what the blood glucose is doing, for example how long the patient has had high or low glucose levels. Instead of a snapshot, CGM gives context to the reading.
“Glucose variability is an important component and an important indicator of complications in type 1 and in type 2 diabetes, so knowing your variability and being able to manage that variability is quite important,” Professor Andrikopoulos says.
Who should use it?
To date, CGM has primarily been used in people with type 1 diabetes who have severe hypoglycaemic events and those who are unaware they are having a hypoglycaemic event.
Around one in four people with type 1 diabetes have some sort of impairment with hypoglycaemic awareness, which increases their risks of severe hypoglycaemia. A study of Australian adults with type 1 diabetes found that 8.5% had experienced impaired hypoglycaemic awareness as well as severe hypoglycaemia in the six months prior.1
In their proposal for a trial of affordable access to CGM for type 1 diabetes, Australian diabetes groups such as Diabetes Australia and the Australian Diabetes Society noted that as many as one in 13 people with type 1 diabetes die from hypoglycaemia.
Much of the evidence of the effectiveness of CGM has involved its use in tandem with a continuous subcutaneous insulin infusion pump.
As a result, many patients and their families live with significant fear of the possibility of one happening.
“Many patients are concerned about severe, nocturnal hypoglycaemia, and CGM should be considered for high-risk patients, given the morbidity and possible mortality associated with severe nocturnal hypos,” Associate Professor Neale Cohen, general manager of Diabetes Services at the Baker IDI, explained in an article in Australian Family Physician.2 “High-risk groups include patients with hypoglycaemia unawareness and particularly ‘frequent flyers’ with regular severe hypos.”
As well as providing an early warning for patients with type 1, and their carers, CGM can also help to reassure and free people from the anxiety that might be happening without their knowledge.
How they work
Subcutaneous CGM requires the glucose sensor to be inserted into the subcutaneous abdominal fat, and, in most devices, replaced weekly.
The sensor is connected to a transmitter that wirelessly sends the data to either a meter or an insulin pump. Readings are displayed on the meter, and are updated at one or five-minute intervals.
Because the sensors measure glucose levels in interstitial fluid, there is a delay of around 10 to 15 minutes between the results of a blood-glucose test and the CGM sensor reading.
For this reason, experts recommend using a fingerprick test two or more times a day to calibrate the device, and when the patient suspects their blood-glucose level is rising or falling rapidly.
Accuracy is another reason to fall back on the fingerprick test before treating hyper or hypoglycaemia.
While CGM is traditionally thought of as a tool for people with type 1 diabetes, it also has been shown to have value in helping manage complex type 2 diabetes and gestational diabetes.
Studies on the mean absolute relative difference (MARD), or the discrepancies between readings from the CGM and a reliable reading such as a laboratory one, can sometimes be 20% or more.
Technology has improved significantly over the last decade, meaning the differences between the CGM and the actual blood glucose levels are shrinking.
A 2017 systematic review found that most subcutaneous CGM devices had a MARD that ranged between 7% and 15.6%.3
Ultimately the trends and speed of change are the most useful aspect of the monitors rather than the glucose level itself. But the useability and reliability of CGM is likely to improve as advances in technology occur.
A new device, released late last year includes a fully implantable sensor that needs replacing only once every three months. This device is among the newer generation of CGM devices that send information straight to an app that the patient, and potentially their doctor, can access on a smart phone or computer.
Some newer technologies also trigger a “low glucose suspend” feature on the patient’s insulin pump which temporarily halts the input of insulin if the CGM detects glucose levels getting too low.
The evidence
Much of the evidence of the effectiveness of CGM has involved its use in tandem with a continuous subcutaneous insulin infusion (CSII) pump.
Two out of every five young people with type 1 diabetes now use CSII, which mimics the body’s normal insulin delivery by providing short-acting insulin over 24 hours which can be increased around meals and snacks.
However, despite the increasing popularity of implantable insulin pumps, multiple daily insulin injections remain the gold-standard for people with type 1 diabetes.
Results from two studies published earlier this year found that CGM improves glucose control in patients with type 1 diabetes, even in patients who manage their diabetes with multiple injections of insulin.
Both the 24-week DIAMOND4 and the 26-week GOLD4 studies found
CGM reduced the number of hyper- and hypoglycaemic events among these patients.
The randomised controlled DIAMOND trial of 158 adult patients with type 1 diabetes found CGM led to an average of 1% improvement in HbA1c after 24 weeks compared to baseline, while patients in the self-monitoring blood glucose group achieved only a 0.4% improvement.
It also found CGM was associated with more time spent in the target glucose range compared to traditional fingerprick testing.
And, in the GOLD trial, 161 adults with type 1 diabetes and a HbA1c of at least 7.5% were tested to see whether CGM was superior to self-monitoring blood glucose in reducing blood glucose levels.
After 26 weeks, the randomised crossover trial found patients using CGM had a mean HbA1c level of 7.9% compared to 8.3% in the self-monitored blood glucose group.
Researchers also found that patients in the CGM group spent almost an hour less each day outside of the target range, had reduced glucose variability and had improved quality of life.
“Subjective well-being and treatment satisfaction were greater during CGM than conventional therapy,” they said.
Despite the promising results, experts warn that more evidence is needed before CGM is more widely adopted.
“Additional clinical trials are needed to determine the long-term effect of CGM and whether this approach translates to improved health outcomes and to determine the potential utility of real-time CGM for patients with type 1 diabetes encountered in usual clinical practice and in patients with type 2 diabetes who require insulin injections,” wrote Dr Mayer Davidson from the Charles R Drew University of Medicine and Science, US in an accompanying editorial.
New funding arrangements
Under the new scheme, patients will need a letter from their endocrinologist, diabetes educator or a practice nurse stating the individual meets the eligibility criteria, in order to claim the device under government subsidy.
The diabetes groups have been pushing for this government funding for young people with type 1 diabetes, because this is the group most likely to benefit the most, long-term and possibly the most difficult group to stabilise in terms of glucose levels.
Research shows that hyper- and hypoglycaemia can negatively impact on the brain development of young children.
But while CGM is traditionally thought of as a tool for people with type 1 diabetes, it also has been shown to have value in helping manage complex type 2 diabetes and gestational diabetes.
At the moment, CGM for type 2 diabetes is largely confined to specialist clinics, but Professor Cohen says research supports its use in primary care to better manage patients on complex therapies who are not achieving adequate control of their glucose levels.
This is particularly useful for patients who don’t test their glucose frequently, he says. And for those people in whom a hypo could be particularly dangerous such as professional drivers or people who work in isolation in remote areas.
CGM can also help women with gestational diabetes, who need intensive glucose control to avoid complications such as cardiac and neural tube defects, as well as malformations of the renal and urinary tract, gastrointestinal and skeletal systems, Professor Cohen says.
The future
Once the government funding becomes a reality, it is expected that CGM will be widely adopted by young Australians currently on insulin.
If this kind of monitoring is found to be practical and effective among this group, clinicians and policy-makers will have the ammunition to mount a case for broader coverage across the diabetes population, Professor Andrikopoulos says.
And at some point, in the not-too-distant future, he hopes to see these devices being affordable for everybody with diabetes, including those with type 2 and gestational diabetes.
References
1. Diabetes Res Clin Pract 2014; Mar;103(3):430-6
2. Aust Fam Physician 2015; May;44(5):284-7
3. Sensors 2017; online 14 January
4. JAMA 2017; online 24 January
