Editorial :
Hiroshi Bando As to the development of treatment for diabetes,
Continuous Glucose Monitoring (CGM) has been recently prevalent rapidly. By the
analysis of real-time CGM, Ambulatory Glucose Profile (AGP) has been used. It
includes time in range (TIR, 70-180 mg/dL), time above range (TAR,
>181mg/dL), time below range (TBR, <69 mg/dL), Glycemic Variability (GV),
Glucose Management Indicator (GMI), Glycemic variability, Coefficient Of
Variation (CV%) and so on. TIR value indicating approximately 70% seems to
correlate closely with the HbA1c level of 6.7-7.0%. Marked discordance of HbA1c
values has been found between laboratory HbA1c and estimated HbA1c (eA1c) using
GMI from CGM. As to the development of
treatment for diabetes,
Continuous Glucose Monitoring (CGM) has been prevalent rapidly, including both
of real-time CGM (rtCGM) and intermittently scanned CGM (isCGM). Lots of
studies demonstrated remarkable benefits of CGM for diabetes patients [1].
However, absence of clarified glycemic targets was observed from both patients
and diabetes team cooperating together. Consequently, the Advanced Technologies
and Treatments
for Diabetes (ATTD) congress were convened for better management of
practice and research. The objective included the development of clinical
CGM-derived times in glucose ranges, such as above target range, within target
range and below target range. CGM continuously provides diabetic patients and
medical staffs current glucose values and related data in order to make
adequate treatment management [2]. Furthermore, real-time CGM systems can give
attention for higher and lower glucose levels which allow necessary
intervention for additional insulin or carbohydrate
per os [3]. In recent report, T1DM patients with rtCGM
(n=70) were compared with control for impaired hypoglycemia awareness related
to the HypoDE (Hypoglycemia in Deutschland) study. As a result, glucose
threshold at taking rescue carbohydrate was increased from 71mg/dL to 79mg/dL
in the rtCGM group. It suggested earlier awareness for hypoglycemia
with preventing hypoglycemia episodes [3]. For T2DM cases with basal insulin
without prandial insulin (n=175), glucose variability was compared for CGM
group vs traditional blood glucose meter (BGM) group [1]. The comparative
results for 8 months in both groups were as follows: HbA1c changes 9.1 to 8.0%
vs 9.0 to 8.4%, TIR (70-180mg/dL) 59% vs 43%, TAR (>250mg/dL) 11% vs 27% and mean glucose levels
179mg/dL vs 206mg/dL. Consequently, CGM group showed more effective response. According to American Diabetes
Association (ADA), diabetic patients with intensive insulin treatment are
encouraged to check glucose changes by CGM [4]. Glucose profile was captured by
CGM which was optimal method to clarify current glucose
variability [5]. From the data of CGM, Time in Range (TIR) refers the time
period of 70-180 mg/dL during 24 hours. Furthermore, TIR is useful for
estimating insulin response during short-term Continuous Subcutaneous Insulin
Infusion (CSII) treatment. Recently, TIR value was reported to show both of
micro vascular and macro vascular complications [6], neuropathy [7] and micro
albuminuria [8]. For CGM report, Ambulatory
Glucose Profile (AGP) is used [9]. In some studies, lower Coefficient
of Variation (CV%) targets would be adequate for 33% in the case who are
treated by insulin or sulfonylureas [10]. Standardized CGM metrics for clinical
care are as follows [5]: i) Number of days CGM worn (14-days recommended), ii)
Percentage of time CGM (70% recommended), iii) Mean glucose, iv) Glucose
Management Indicator (GMI), v) Glycemic variability (%CV <36%), vi) Time
Above Range (TAR): >250mg/dL level 2, vii) TAR: 181-250mg/dL, level 1, viii)
TIR: 70-180 mg/dL, ix) Time Below Range (TBR): 54-69mg/dL level 1, x) TBR:
<54mg/dL level 2. CGM-based targets for some
patients are recommended. Target
percentages of each factor are shown in the following: TIR >70%, TAR-L2
<5%, TAR-L1 <25%, TBR-L1 <4%, TBR-L2 <1% in type 1 and type 2
diabetes, and TIR >50%, TAR-L2 <10%, TAR-L1 <50%, TBR-L1 <1%, in
older/high-risk of type 1 and type 2 diabetes [5]. TIR and other metrics from CGM
have become standardized factors from international consensus. TIR value of
about 70% correlates closely with HbA1c level of 6.7-7.0% [11]. Several
evidences are found on the relationship of TIR and diabetic
complications, in which each 10% TIR elevation brings risk decrease for
long-term complications. CGM data were collected for 5901
T2DM cases for 5 years, and analyzed for 3 profiles of Glycemic Variability
(GV) [12]. They are i) TIR profile, ii) hypo profile, iii) hyper profile
(N=2271, 1471, 2159, respectively). Comparative data between group i) vs iii)
showed that fasting glucose 167 vs 203 mg/dL, 2-hr post prandial glucose 256 vs
302 mg/dL, and HbA1c 8.6 vs 9.7%. Odds Ratio (OR) of ii) and iii) for i) showed
that non-proliferative Diabetic Retinopathy (PDR) 1.44 and 1.33, macro
albuminuria 1.58 and 1.37, and diabetic kidney disease (DKD) 1.65 and 1.88
compared with i)TIR profile. Especially, ii) showed OR 2.84 for PDR. Recent report showed the
relationship between TIR by CGM and body fat percentage in T2DM [13]. Subjects
were 85 T2DM cases and they received CGM during short-term CSII therapy. As a
result, T2DM cases with higher body fat exhibited lower TIR (p=0.004) and
higher mean blood glucose levels (p=0.001). Thus, weight reduction can be
therapeutic target to obtain better glucose variability for obese cases, which may
get less beneficial effect from intensive insulin
therapy. For CGM study for T1DM, TIR and
CV% were analyzed for 95 cases [14]. Subjects number for HbA1c was 20 for ≤7%,
44 for 7-8%, 31 for >8%. TIR was negatively associated with HbA1C, mean
blood glucose (MBG) and time spent in hyperglycemia (p<0.001), but not with
time in hypoglycemia. The results suggested that TIR would be strongly related
with hyperglycemia and CV% would be reflective of hypoglycemic
risk. Lots of diabetic patients and
related medical staffs have felt marked discordance of HbA1c values, between
laboratory HbA1c and estimated HbA1c (eA1c) using GMI from CGM [15]. According
to latest report, much data from 641 separate offices were analyzed. Subjects
showed T1DM in 91% with mostly history of >20 years and 24.5 days duration
of CGM. As a result, 11% cases discordance <0.1%, 50% vs 22% cases showed
differences ≥0.5% vs ≥1%. Elevated discordance was found with advanced Chronic
Kidney Disease (CKD), in which Estimated Glomerular
Filtration Rate (eGFR) <60 mL/ min/1.73m2). Consequently, substantial
discordance is present between laboratory HbA1c and eA1C in the actual clinical
practice. Hiroshi Bando, Tokushima University/Medical
Research, Nakashowa 1-61, Tokushima 770-0943, Japan Tel: +81-90-3187-2485, E-mail: pianomed@bronze.ocn.ne.jp
Bando H. The importance of Time in Range (TIR) for
Continuous Glucose Monitoring (CGM) in the clinical practice for diabetes
(2021) Edel J Biomed Res Rev 3: 12-13 Diabetes, Glucose, CarbohydrateThe Importance of Time in Range (TIR) for Continuous Glucose Monitoring (CGM) in the Clinical Practice for Diabetes
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