Useful Continuous Glucose Monitoring (CGM) With Time in Range (TIR) And Time Above Range (TAR)

Bando H, Kato Y, Aihara A, Kawahito A, Sueki E, Fujii A, Kanazawa S, Ikezoe M and Fukushima N

Published on: 2024-06-29

Abstract

In recent diabetic research and practice, continuous glucose monitoring (CGM) has been prevalent using FreeStyle Libre. Patient is 69-year-old male with type 2 diabetes (T2D) who has Multiple Daily Insulin (MDI). The estimated HbA1c by CGM was 6.4% in May 2024, whereas HbA1c in out clinic was 7.0%. By latest CGM data for 15 days, HbA1c and time in range (TIR) showed 6.4% and 76.7-81.9%, respectively, which were better results than those during half year. Regarding CGM application, glucose variability can be followed in detail by the metrics of TIR, time above range (TAR) and time below range (TBR).

Keywords

Time In Range (TIR); Time Above Range (TAR); Time Below Range (TBR); Continuous Glucose Monitoring (CGM); Multiple Daily Insulin (MDI)

Introduction

For the detail measurements of blood glucose in diabetic patients, continuous glucose monitoring (CGM) have been used for years. The technical developments have been found for evolution of apparatus generation [1]. Real time (rt)-CGM system has improved its usability, accuracy and design for years and played the role in the performance of integrated personalized diabetes management (iPDM) [2]. For future development of diabetic research, rtCGM will be linked to iPDM, associated with enhancing personalized treatment strategies. As the increasing usage of CGM for actually diabetes clinical practice, novel metrics for adequate assessment of glycemic control has showed beyond HbA1c measurement. It is time in range (TIR) that has revealed as a simple and useful metric, which can correlate inversely with HbA1c value and become novel link to the risk for diabetic complications [3]. Consequently, the parameters as TIR, time above range (TAR), time below range (TBR) would be evaluated with the human daily activities as the ambulatory glucose profile (AGP) [4].

In the latest report, clinical efficacy of intermittently scanned continuous glucose monitoring (isCGM) and blood glucose monitoring (BGM) was studied in patients with T2D on multiple insulin injections (MDI) [5]. The protocol included 24-week randomized multicenter-trial and patients with T2D. Consequently, isCGM has showed a greater reduction in HbA1c, when adequate education was provided for the interpretation of CGM graphical patterns. Diabetes research group of authors et al. has continued clinical studies and research for years through Japan low carbohydrate diet promotion association (JLCDPA) [6]. Among them, several reports have been developed for CGM, T2D, low carbohydrate diet (LCD), meal tolerance test (MTT) and related research [7,8]. We have encountered an impressive T2D patient who showed clinical improvement by the application of CGM. Clinical progress and related perspectives will be described in this study.

Medical History

The patient was a 69-year-old male patient with T2D. For his previous history, he had no special health problems, and was diagnosed as T2D more than 20 years ago. He has been treated by several types of oral hypoglycemic agents (OHAs). He began to receive insulin therapy about 7 years ago, and his diabetic conditions have been stable, maintaining about 6.5-7.2% in recent period.

His current treatment included several kinds of OHAs, insulin as MDI and anti-hypertensive agents (AHAs), such as Ipragliflozin L-proline, novo rapid insulin 8-8-8 units a day, Degludec 11 units at night, Valsartan, and Rosuvastatin.

Several Exams

Current case revealed unremarkable physical findings, or unremarkable vital signs, consciousness. His stature showed 172cm in height, and 75kg in weight with body mass index (BMI) 25.4 kg/m². He showed negative findings of lung, heart and abdomen. About diabetic complications, he has been treated as pre-proliferative retinopathy. Diabetic neurological motor or sensory disturbances were not observed.

Biochemistry showed the following data: GOT 14 U/L, GPT 16 U/L, GGT 24 U/L, HbA1c 7.8%, post-prandial glucose 163 mg/dL, Hb 14.0 g/dL, RBC 453 x 10⁶/mcL, WBC 6000 /mcL, LDL 84 mg/dL, HDL 48 mg/dL, TG 104 mg/dL, Cre 1.15 mg/dL, BUN 21 mg/dL, UA 6.0 mg/dL.

Results

His daily glucose variability was measured by the CGM method using the apparatus of FreeStyle Libre. It monitors detail changes in blood glucose every 15 minutes. Consequently, actual glucose variability was obtained for 15 days in May 2024. For 15 days, the changes in blood glucose could be followed (Figure 1), in which blood glucose maintained almost stable range. The estimated HbA1c calculated by the computer was 6.4%. On the other hand, actual HbA1c value in out clinic was 7.0%, associated with some discrepancy. CGM data from 3 days were shown in Figure 2. They showed TIR, TAR and TBR, respectively. The TIR value was 76.7-81.9% for these days.

Figure 1: Blood glucose profile by CGM for 2 weeks using FreeStyle Libre.

Figure 2: Changes blood glucose variability with TIR, TAR and TBR.

Ethical Considerations

The report was described along with the principle of Helsinki Declaration [9]. In addition, some comments were according to the Ethical Guidelines for Human Research. For current study, authors et al. established our ethical committee, which was in Kanaiso Hospital, Tokushima, Japan. They included several professionals, such as hospital director, physician, head nurse, pharmacist, nutritionist, and legal specialty. We discussed in satisfactory manner and concluded the agreement of the protocol. The informed consent was taken from the case by the document.

Discussion

This case was T2D male who has been treated and checked blood glucose variability by FreeStyle Libre. Compared with previous situation, the current results showed decreased values of HbA1c, TAR, and elevated value of TIR that would be better tendency. For last half year, HbA1c and TIR have showed 6.6-6.8% and 80-85%, respectively. In contrast, latest 2 weeks showed HbA1c 6.4% and TIR 76.7-81.9%, respectively. Consequently, HbA1c and TIR seemed to present inverse relationship. For standard perspectives for CGM, time on target (70-180 mg/dL) has showed a negative correlation with HbA1c, while time above target (>180 mg/dl) showed a positive correlation. As for correlation coefficients, it ranges between -0.310 and -0.869 for time on target, and between 0.66 and 0.934 for time above target [10]. Significant relationships exist between time on target and time above target with HbA1c. As higher proportion adequate glucose ranges for higher proportion, HbA1c becomes closer or <7%.

For evaluating CGM measurement, therapeutic effect was compared as the alternatives to HbA1c. CGM data were analyzed from 5910 T2D cases [11]. As a result, three biomarkers were i) mean glucose, ii) %TAR and iii) %TIR. They showed the correlation with HbA1c values, which could be used for evaluation of clinical efficacy. Mean glucose revealed the highest relationship with %TAR (r=0.97 in T2D), and weak relationship with %TIR (r=-0.83 in T2D). There was high correlation between %TAR and %TIR (r= -0.91 in T2D). Consequently, %TAR and %TIR revealed higher relationship with Mean Glucose than with HbA1c. Then, Mean glucose would be the sensitive marker for efficacy, and it revealed consistently higher relationships with %TAR than with %TIR.

Concerning CGM, TIR has been well-known as 70-180mg/dL for better glycemic management. It represents a key CGM-derived metric. Recently, another marker has been proposed, which is time in tight range (TITR) ranging 70-140 mg/dL [12]. However, TITR means narrower glucose ranges, where maintaining such ideal range would be rather challenging. In the real study for average glucose, TIR and TITR (n= 22,006) from CGM data, 4 groups of T1D and T2D were categorized. When analyzing in T2D group, highest TIR and TITR were found, and lowest glycemic variability was observed as 23-30% of glucose coefficient of variation (CV). On the other hand, T1D group showed lowest TIR and TITR, and highest glycemic variability as 36-38% of CV. When diabetic case is approaching normal glucose ranges, TITR seems to be beneficial for assessing glycemic status and progressing to more stringent HbA1c. From previous experience, TITR will be more preferable than TIR, if average glucose has showed below 140mg/dL in clinical situation.

TIR has been recently emerging as a key indicator for satisfactory range of glycemic control. However, few reports are found about the relationship of TIR with renal function or albuminuria. The research was conducted for whether TIR, nocturnal TIR and hypoglycemic events may be related to albuminuria or decreased eGFR in T2D [13]. Research design included 823 T2D cases, and TIR was in the range of 3.9-10.0 mmol/L (70-180 mg/dL). Then, TIR, nocturnal TIR or ACR were analyzed for the correlation among them.?As a result, binary logistic regression showed that TIR and also nocturnal TIR were obviously related to the existence of albuminuria.

For detail analyses of TIR, TAR and TBR in CGM measurement, T2D cases (n=50) aged 25-55 years were investigated, who showed HbA1c up to 8% and are provided only metformin [14]. There were 2 groups for i) average carbo taking (55-60%) vs ii) high carbo taking. The results showed that average glucose 142 mg/dL vs 155 mg/dL, glucose management indicator (GMI) 6.6% vs 7.1%. Another 2 groups were iii) average protein taking (12-15%) vs iv) low protein taking (≤10%). The results showed that TIR 68.2% vs 61.0%, TAR -23.0%, -32.9%, respectively, with significant difference. As carbo-intake increases, TIR decreases and TAR increases (p=0.006). No significant relationships were observed between fat intake and TIR, TAR or TBR. Consequently, current findings suggest that lowering carbo-taking while protein-increasing in the meal may help improving TIR value. Further study will be required for confirming these perspectives.

Some limitation may be present in this study. Current CGM data did not cover all data for 2 weeks or for half year. Then, future clinical progress will be followed up with close attention. When CGM has been applied to T2D cases with the investigation of TIR, TAR and TBR, approximately 0.31% of HbA1c improvement may be expected [15].

In summary, T2D male case showed more improved CGM data with higher TIR and lower HbA1c than those in latest half year. Furthermore, related perspectives were described such as TIR, TAR, TBR and TITR. This article will be hopefully useful reference for diabetic research and practice.

Conflict of interest: The authors declare no conflict of interest.

Funding: There was no funding received for this paper.

International Journal of Case Reports and Clinical Images