Time In Range & Glycemic Risk Index- Evolving Dynamics in Diabetes "Digi-Tech" Care

CURRENT MARKET DYNAMICS:

With the recent approval of Abbott Freestyle Libre 3, the recent launch of Senseonics Eversense CGM and expected launch of Dexcom G7, the race for the perfect CGM is heating up -Minus the high costs, these CGMs have contributed significantly towards the overall wellbeing and better management of Patients With Diabetes (PWDs).

CGMs have facilitated self-monitoring of blood glucose levels: Patients/Caregivers/Physicians can monitor blood glucose levels continuously and hence predict the episodes of "Hypo" and "Hyper" glycemia before they happen and can take preventive action to avoid such incidents and can ensure quick correction in case such events happen.

Receiving "real time updates" of blood glucose levels via CGMs, helped in "real time" assessments & diagnosing of real time damage and real time corrective actions - Something that has long been due for managing diabetes

THE PARADIGM SHIFT:

So far, the HbA1c value has been the "gold standard" for evaluating glucose control for decades. It has also been one of best markers for identifying development and worsening of microvascular complications, including diabetic retinopathy and it will continue to stay the standard in evaluating long terms implications of diabetes. Previously with Blood Glucose Monitoring systems which needed finger-sticks every time blood glucose levels were assessed, real time monitoring was not a possibility and average value were the only way to assess glucose control, effect of medicines, and long term complications.

WHY WAS "TIME IN RANGE" NOT INTRODUCED AS STATUTORY GUIDELINES FOR DIABETES BEFORE?

Before the advent of CGMs (Continuous Glucose Monitors), blood glucose levels were being monitored only once or twice in a day, by conventional "finger-prick' devices & real-time 'constant" updates which could depict "blood glucose variability" throughout the day wasn't possible. Hence average blood glucose levels, represented by A1c was the best way to assess blood glucose levels.

However, after the advent and wide scale adoption of CGMs (Continuous Glucose Monitoring Systems) patient & providers started realizing its limitations like the lack of information on glycemic variability or the risk of hypoglycemia, poor/inadequate correlation with average blood glucose levels and underestimation of the degree and impact of high and low blood glucose levels on patients’ quality of life and risk of bad outcomes.

"Time in Range"?as an additional parameter which helps record, notice and implement the daily blood glucose troughs and crests, esp hypoglycemia, which is vital for overall management of PWDs.

WHY "TIME IN RANGE"?

“Time in Range”?(TIR) is the?percentage of time that a person spends with their blood glucose within a target range. The range will vary depending on the person, but general guidelines suggest starting with a range of 70 to 180 mg/dl. (Over time, some people decide to aim for a tighter range, such as 70 to 140 mg/dl.)

In a single number,?Time in Range?captures?how your blood glucose levels change throughout the day or over longer periods of time. The example graphics below show various levels of?Time in Range, from 0% to 100%:?

In essence, Time in Range?captures?the highs, lows, & in-range values that characterize daily life with diabetes & offers a balanced cause & effect relationship understanding of diabetes with specific foods and exercise.

A1c on the other hand, measures average blood sugar over 2-3 months period and fails to capture time spent in various blood glucose ranges throughout the day & therefore PWDs (People with Diabetes) are unable to make daily changes in their regime, to better manage glycemic control

Limitations of A1c can further be highlighted using the illustration below:

The above graphic?represents three different people – all with the same average blood glucose (154 mg/dl) and the same A1C?(7%). However, time spend with high, low, and in-range blood glucose values are markedly different:

1) Person "A" tides through dangerously low and high blood glucose levels. 2) Person "B" reflects moderate variability with reduced fluctuations in blood glucose levels while Person "C" has little variability with all time spent in-range. The time a PWD spends in range improves his/her overall QOL as reflected in his/her energy levels, moods, and overall quality of life when they are “in-range” vs. “out-of-range.”?Time in Range?can capture these differences in a way A1C?cannot.

WHAT ARE RECOMMENDED ADA GUIDELINES FOR TIME IN RANGE?

The International Consensus on Time in Range has recently set targets for different diabetes populations. For the majority of people with type 1 or type 2 diabetes, a TIR (70–180?mg/dL or 3.9–10.0?mmol/L) of >70%, a time below range (TBR) <70?mg/dL (<3.9?mmol/L) of <4% and a TBR <54 (<3.0?mmol/L) of <1% are recommended.

Even though the recommendations for TIR give specific values and percentages, there is a general consensus that?TIR should be personalized based on the individual and their current life circumstances, it may change over time, and that time spent in hypoglycemia?(recommended for most as <4% of time or <1 hour per day) should not be overlooked (Close & Brown, 2017).

For specific Populations, the chart below highlights the "TIR" ranges to be followed

BOTTOMLINE ON "TIME IN RANGE":

TIR "assists & informs"A1C: TIR is easy to comprehend, which is motivating enough for the patients to introduce lifestyle interventions & supports physicians in proper dosage adjustments of diabetes medications (keeping hypoglycemia at bay). It provides additional & real time valuable information that a HbA1C does not,?which enables a physician to introduce important treatment adjustments even for those with a?HbA1C that is in the target range.

TIR is helpful to make adjustments?when no?HbA1C is available (when lab tests are conducted months ago etc) or in cases when?HbA1C value may not be truly representative of the individual’s blood glucose values (e.g., for sickle cell anemia).?For those whose insurance will not cover personal CGM, professional CGM can be used to periodically obtain TIR data.

"TIR" provides targets which are “easily understood and are doable". Period.

WHAT DOES THE FUTURE LIKE LIKE?

The glycemia risk index (or dysglycemia index) is an emerging measurement, currently being researched, that combines seven of your CGM metrics, including TIR, into a numeric score that your healthcare provider can use to quickly identify areas for adjustments within your glucose management.

These 7 parameters include:

• Time in Range
• Time spent in severe hypoglycemia (less than 54 mg/dL)
• Time spent in hypoglycemia (less than 70 mg/dL)
• Time spent in hyperglycemia (greater than 180 mg/dL)
• Time spent in severe hyperglycemia (greater than 250 mg/dL)
• Glucose variability
• And average glucose

It delivers this information as a data point that indicates your exposure to hyperglycemia and hypoglycemia and it may provide another way for your healthcare provider to quickly assess your overall diabetes management and make recommendations based on the score. Read up more on Glycemic risk index in the articles by David C Klonoff et al.

With A1C, TIR and GRI, Diabetes Care & Disease Management is Up for a stir.

Disclaimer: This article represents a fact based research piece and is not in any manner a guidance document and in no manner represents an exhaustive review.

The author represents a CI firm called Intelligience. Please DM her for a detailed analysis of the Diabetes Tech Landscape.

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