Andrew Advani

Abstract

Recent upswings in the use of continuous glucose monitoring (CGM) technologies have given people with diabetes and healthcare professionals unprecedented access to a range of new indicators of glucose control.

Some of these metrics are useful research tools and others have been welcomed by patient groups for providing insights into the quality of glucose control not captured by conventional laboratory testing. Among the latter, time in range (TIR) is an intuitive metric that denotes the proportion of time that a person’s glucose level is within a desired target range (usually 3.9–10.0 mmol/l [3.5–7.8 mmol/l in pregnancy]).

For individuals choosing to use CGM technology, TIR is now often part of the expected conversation between patient and healthcare professional, and consensus recommendations have recently been produced to facilitate the adoption of standardised TIR targets.

At a regulatory level, emerging evidence linking TIR to risk of complications may see TIR being more widely accepted as a valid endpoint in future clinical trials. However, given the skewed distribution of possible glucose values outside of the target range, TIR (on its own) is a poor indicator of the frequency or severity of hypoglycaemia.

Here, the state-of-the-art linking TIR with complications risk in diabetes and the inverse association between TIR and HbA1c are reviewed. Moreover, the importance of including the amount and severity of time below range (TBR) in any discussions around TIR and, by inference, time above range (TAR) is discussed.

This review also summarises recent guidance in setting ‘time in ranges’ goals for individuals with diabetes who wish to make use of these metrics.

For most people with type 1 or type 2 diabetes, a TIR >70%, a TBR <3.9 mmol/l of <4%, and a TBR <3.0 mmol/l of <1% are recommended targets, with less stringent targets for older or high-risk individuals and for those under 25 years of age.

As always though, glycaemic targets should be individualised and rarely is that more applicable than in the personal use of CGM and the data it provides.

Abbreviations

CGM

Continuous glucose monitoring (or continuous glucose monitor)

CSII

Continuous subcutaneous insulin infusion

DIAMOND

Multiple Daily Injections and Continuous Glucose Monitoring in Diabetes (study)

GMI

Glucose management indicator

isCGM

Intermittently scanned continuous glucose monitor

MARD

Mean absolute relative difference

PRO

Patient-reported outcome

rtCGM

Real-time continuous glucose monitor

SMBG

Self-monitoring of blood glucose

TAR

Time above range

TBR

Time below range

TIR

Time in range

 

Some items from the article

Read more on 

https://link.springer.com/article/10.1007/s00125-019-05027-0

 

Introduction

When the Diabetes Control and Complications Trial (DCCT)

first demonstrated that intensive glucose lowering reduces the

risk of long-term diabetes complications, intensive glucose

control involved self-monitoring of blood glucose (SMBG)

at least four times daily, a weekly blood glucose check at

03:00 hours and regular laboratory measurement of HbA1c [1].

 

Today, over a quarter of a century on, emphases on

individualised care and advances in glucose monitoring

technology have provided access to a wealth of alternative indices

of glucose control quality that are available to individuals

who have the means and desire to make use of continuous

glucose monitoring (CGM) technologies. Among these metrics,

time in range (TIR) has surfaced as a measure that is preferred

by patients because of its bearing on daily life [2]. Concurrently,

evidence is beginning to emerge indicating that TIR can predict

the risk of long-term diabetes complications [3, 4] and pregnancy

outcomes [5, 6]. However, for clinicians and researchers who

are most familiar with evidence supported by blood glucose

measurement and HbA1c, it may be difficult to know how to

interpret TIR, where to position TIR relative to other glucose

metrics and what TIR goals to discuss with patients.

 

In this short review, I summarise the state-of-the-art for TIR, emphasising

that TIR is largely determined by the extent of hyperglycaemia

and that any discussions around TIR goals should include

consideration of time below range (TBR) as well. I summarise

recent guidance for healthcare professionals in helping patients

interpret TIR goals and I consider the obstacles currently limiting

the broad application of TIR in diabetes management.

 

 

Evidence linking TIR to the risk of long-term

diabetes complications

Aside from being reflective of the day-to-day experience of

individuals with diabetes [2], evidence has recently come

to light indicating that TIR itself can predict the future risk

of diabetes complications [3, 4]. For instance, retrospective

analysis of CGM data collected over three consecutive

days from 3262 individuals with type 2 diabetes revealed

a significant inverse association of TIR with all stages of

retinopathy after adjusting for age, sex, BMI, diabetes

duration, blood pressure, lipids and HbA1c [4]. Data associating

TIR with a reduced risk of complications has also

recently been reported for participants in the DCCT.

During the course of that study, participants conducted

seven-point profile testing of blood glucose concentrations

for 1 day every 3 months. Although not computed with the

aid of a CGM device, investigators derived TIR from the

seven-point profiles and discerned that for every 10%

lowering of TIR the adjusted hazard rate for the retinopathy

outcome in the DCCT was increased by 64% (95% CI

51, 78) and the adjusted hazard rate for the microalbuminuria

outcome was increased by 40% (95% CI 25, 56) [3]. This

evidence is important because it begins to build the case that

CGM metrics could be considered acceptable endpoints for

clinical trials and accordingly used to inform regulatory decisions

in the future [3, 23].

 

Summary

In summary, among the host of possible metrics now available

to patients and healthcare professionals making use of

CGM technology, TIR has emerged as an intuitive metric

that may correlate better with PROs and that itself is associated

with the risk of long-term complications. However,

when engaged in discussions of TIR it is imperative that

healthcare professionals include an indicator of hypoglycaemia

and its severity in the conversation (i.e. TBR <3.9 mmol/l and

TBR <3.0 mmol/l). Based on current evidence, a TIR of >70%

would appear to be a reasonable target for most individuals,

roughly equating to an HbA1c of ≤53 mmol/mol (7.0%), if

it can be achieved with a TBR <3.9 mmol/l of <4% and a

TBR <3.0 mmol/l of <1%. As is always the case, though,

glycaemic goals should be individualised and rarely does

a better opportunity present itself to individualise treatment

goals than with the personal use of CGM in diabetes

self-management.

 

SUMMARY

TIR is a key metric of the quality of glucose control

 

Evidence is beginning to emerge linking lower TIR

to increased risk of long-term diabetes complications

and adverse pregnancy outcomes

 

TIR correlates inversely with HbA1c and is largely

indicative of the extent and magnitude of hyperglycaemia

 

Discussions on TIR should include discussions on

TBR

 

Recent consensus recommendations suggest

targets of TIR >70%, with TBR (<3.9 mmol/l) <4%

and TBR (<3.0 mmol/l) <1% for most individuals

with type 1 or type 2 diabetes, although targets

should be individualised

 

Different targets should be considered for older or

high-risk individuals, paediatric

 

Nyhetsinfo

www red DiabetolpogNytt