The association of chronic complications with time in tight range and time in range in people with type 1 diabetes: a retrospective cross-sectional real-world study.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the association of chronic complications with time in tight range (TITR: 3.9-7.8 mmol/l) and time in range (TIR: 3.9-10.0 mmol/l) in people with type 1 diabetes. METHODS: The prevalence of microvascular complications (diabetic retinopathy, diabetic nephropathy and diabetic peripheral neuropathy [DPN]) and macrovascular complications according to sensor-measured TITR/TIR was analysed cross-sectionally in 808 adults with type 1 diabetes. Binary logistic regression was used to evaluate the association between TITR/TIR and the presence of complications without adjustment, with adjustment for HbA1c, and with adjustment for HbA1c and other confounding factors (sex, age, diabetes duration, BMI, BP, lipid profile, smoking, and use of statins and renin-angiotensin-aldosterone system inhibitors). RESULTS: The mean TITR and TIR were 33.9 ± 12.8% and 52.5 ± 15.0%, respectively. Overall, 46.0% had any microvascular complication (34.5% diabetic retinopathy, 23.8% diabetic nephropathy, 16.0% DPN) and 16.3% suffered from any macrovascular complication. The prevalence of any microvascular complication, diabetic retinopathy, diabetic nephropathy and a cerebrovascular accident (CVA) decreased with increasing TITR/TIR quartiles (all ptrend<0.05). Each 10% increase in TITR was associated with a lower incidence of any microvascular complication (OR 0.762; 95% CI 0.679, 0.855; p<0.001), diabetic retinopathy (OR 0.757; 95% CI 0.670, 0.856; p<0.001), background diabetic retinopathy (OR 0.760; 95% CI 0.655, 0.882; p<0.001), severe diabetic retinopathy (OR 0.854; 95% CI 0.731, 0.998; p=0.048), diabetic nephropathy (OR 0.799; 95% CI 0.699, 0.915; p<0.001), DPN (OR 0.837; 95% CI 0.717, 0.977; p=0.026) and CVA (OR 0.651; 95% CI 0.470, 0.902; p=0.010). The independent association of TITR with any microvascular complication (OR 0.867; 95% CI 0.762, 0.988; p=0.032), diabetic retinopathy (OR 0.837; 95% CI 0.731, 0.959; p=0.010), background diabetic retinopathy (OR 0.831; 95% CI 0.705, 0.979; p=0.027) and CVA (OR 0.619; 95% CI 0.426, 0.899; p=0.012) persisted after adjustment for HbA1c. Similar results were obtained when controlling for HbA1c and other confounding factors. CONCLUSIONS/INTERPRETATION: TITR and TIR are inversely associated with the presence of microvascular complications and CVA in people with type 1 diabetes. Although this study was not designed to establish a causal relationship, this analysis adds validity to the use of TITR and TIR as key measures in glycaemic management. TRIAL REGISTRATION: ClinicalTrials.gov NCT02601729 and NCT02898714.

Assessing the feasibility of time in tight range (TITR) targets with advanced hybrid closed loop (AHCL) use in children and adolescents: A single-centre real-world study.

AIMS: Time in Tight Range (TITR) is a novel glycaemic metric in monitoring type 1 diabetes (T1D) management. The aim of this study was to assess the attainability of the TITR target in children and adolescents using the advanced hybrid closed loop (AHCL). METHODS: The 2128-day CGM data from 56 children and adolescents with T1D using AHCL (Minimed-780G) were analysed. Time in Range (TIR) (3.9-10 mmol/L), TITR (3.9-7.7 mmol/L), and other glycaemic parameters were separately analysed in terms of whole day, daytime (06.00-23:59), and nighttime (00.00-05.59) results. The participants were divided into two groups by autocorrection rate where Group 1 had a rate of <30% and Group 2 had a rate of ≥30. RESULTS: All glycaemic parameters indicated a better glycaemic outcome in the nighttime with higher TIR and TITR values compared with daytime (for TIR 87.5 ± 9.5% vs. 78.8 ± 8%, p < 0.001, and TITR 68.2 ± 13.5% vs. 57.5 ± 8.8%, p < 0.001). The rates of TITR >50% and >60% were 87% and 52%, respectively. When those with TITR >60% (n: 29) and those without (n: 27) were evaluated in terms of hypoglycaemia, no statistically significant difference was found in time below range (TBR) 3-3.9 mmol/L (0.3% vs. 2.1%, p: 0.084) and TBR < 3 mmol/L (0.47% vs. 0.3%, p: 0.298). Group 1 had a significantly higher TIR and TITR compared to Group 2 (82.6 ± 6.1% vs. 75.6 ± 8.6%, p: 0.008 and 62.1 ± 7.5% vs. 53.8 ± 7.5%, p: 0.002, respectively). CONCLUSIONS: Most children and adolescents on AHCL achieved the 50% target for TITR whereas more than half achieved the >60% target. A target of >50% for TITR seems realistic in children with T1D using AHCL.

Evaluation of time in tight range and the glycaemia risk index in adults with type 1 diabetes using an advanced hybrid closed loop system: A 1-year real-world assessment.

AIM: To assess the long-term glycaemic outcomes, with additional metrics, in adults with type 1 diabetes (T1D) using the Tandem t:slim X2 with Control-IQ technology advanced hybrid closed-loop (AHCL) system. METHODS: This was a single-centre, retrospective study involving 56 T1D patients who transitioned to the Tandem t:slim X2 with Control-IQ system. The primary and secondary endpoints consisted of variations in time in tight range (TiTR; 70-140 mg/dL) and the glycaemia risk index (GRI), respectively. Additional standardized continuous glucose monitoring (CGM) metrics, mean sensor glucose, coefficient of variation, the glucose management indicator (GMI), HbA1c and insulin daily dose, were also evaluated. Variables were measured at baseline and at 15 days, 3 months, 6 months and 1 year after Tandem t:slim X2 Control-IQ initiation. Glucose outcomes are expressed as mean (standard deviation). RESULTS: Use of Tandem t:slim X2 with Control-IQ over 1 year was associated with an increase in mean TiTR, from 38.11% (17.05%) to 43.10% (13.20%) (P = .059), and with a decline in the GRI, from 41.03 (25.48) to 28.55 (16.27) (P = .008). CGM metrics, including time in range and time above range, showed consistent improvements. Mean sensor glucose, the GMI and HbA1c decreased significantly over time. After an initial increase, insulin daily dose remained stable throughout the 12 months. CONCLUSIONS: The results highlight the sustained effectiveness of Tandem t:slim X2 with Control-IQ in improving glycaemic outcomes over 1 year and support the use of this technology for the management of T1D.

During an 18-month course of automated insulin delivery treatment, children aged 2 to 6 years achieve and maintain a higher time in tight range.

AIMS: To investigate whether the positive effects on glycaemic outcomes of 3-month automated insulin delivery (AID) achieved in 2- to 6-year-old children endure over an extended duration and how AID treatment affects time in tight range (TITR), defined as 3.9-7.8 mmol/L. RESEARCH DESIGN AND METHODS: We analysed 18 months of follow-up data from a non-randomized, prospective, single-arm clinical trial (n = 35) conducted between 2021 and 2023. The main outcome measures were changes in time in range (TIR), glycated haemoglobin (HbA1c), time above range (TAR), TITR, and mean sensor glucose (SG) value during follow-up visits (at 0, 6, 12 and 18 months). The MiniMed 780G AID system in SmartGuard Mode was used for 18 months. Parental diabetes distress was evaluated at 3 and 18 months with the validated Problem Areas in Diabetes-Parent, revised (PAID-PR) survey. RESULTS: Between 0 and 6 months, TIR and TITR increased, and HbA1c, mean SG value and TAR decreased significantly (p < 0.001); the favourable effect persisted through 18 months of follow-up. Between 3 and 18 months, PAID-PR score declined significantly (0 months: mean score 37.5; 3 months: mean score 28.6 [p = 0.06]; 18 months: mean score 24.6 [p < 0.001]). CONCLUSIONS: Treatment with AID significantly increased TITR and TIR in young children. The positive effect of AID on glycaemic control observed after 6 months persisted throughout the 18 months of follow-up. Similarly, parental diabetes distress remained reduced during 18 months follow-up. These findings are reassuring and suggest that AID treatment improves glycaemic control and reduces parental diabetes distress in young children over an extended 18-month follow-up.

Is It Time to Move Beyond TIR to TITR? Real-World Data from Over 20,000 Users of Continuous Glucose Monitoring in Patients with Type 1 and Type 2 Diabetes.

The growing use of continuous glucose monitoring (CGM) has been supported by expert consensus and clinical guidelines on glycemic management in diabetes with time in range (TIR 70-180 mg/dL) representing a key CGM-derived glucose metric. Time in tight range (TITR) has also been proposed for clinical use, spanning largely normal glucose levels of 70-140 mg/dL. However, keeping such narrow glucose ranges can be challenging, and understanding the factors modulating TITR can help achieve these tight glycemic targets. Our real-life study aimed to evaluate the relationship between average glucose (AG) and TIR/TITR in a large cohort (n = 22,006) of CGM users, divided into four groups: self-identified as having type 1 diabetes (T1D) treated with insulin using multiple daily injections (MDI) or pumps; type 2 diabetes (T2D) on MDI or insulin pumps; T2D on basal insulin only; and T2D not on insulin treatment. The T2D groups, regardless of treatment type, displayed the highest TIR and TITR values, associated with lowest glycemic variability measured as glucose coefficient of variation (CV; 23-30%). The T1D group showed the lowest TIR and TITR, associated with the highest CVs (36-38%). Overall, higher CV was associated with lower TIR and TITR for AG values below 180 and 140 mg/dL, respectively, with the reverse holding true for AG values above these thresholds. The discordance between AG and TIR/TITR was less pronounced in T2D compared with T1D, attributed to lower CV in the former group. It was also observed that TITR has advantages over TIR for assessing glycemia status and progress toward more stringent A1C, particularly when approaching normal glucose levels. The data detail how CV affects the AG relationship with TIR/TITR, which has implications for CGM interpretation. In many instances TITR, rather than TIR, may be preferable to employ once AG falls below 140 mg/dL and near-normal glucose levels are required clinically.

A Comparison of Continuous Glucose Monitoring-Measured Time-in-Range 70-180 mg/dL Versus Time-in-Tight-Range 70-140 mg/dL.

Objective: To evaluate the relationship between continuous glucose monitoring (CGM)-measured time-in-range 70-180 mg/dL (TIR) and time-in-tight-range 70-140 mg/dL (TITR). Methods: TIR and TITR were calculated from CGM data collected using blinded or unblinded Dexcom sensors from 9 studies with 912 participants with type 1 diabetes (T1D) and 2 studies with 184 participants with type 2 diabetes (T2D). The TIR-TITR relationship was assessed overall and stratified by coefficient of variation (CV) and by time below range <70 mg/dL (TBR). Results: The correlation between TIR and TITR was 0.94. TITR was higher for a given TIR for T2D compared with T1D. However, after adjusting for the differences in CV or TBR, both of which were higher with T1D than T2D, the differences were minimized. The TIR-TITR relationship was nonlinear, with a higher ratio of TITR:TIR observed as TIR increased ranging from 0.42 when TIR was 20% to 0.66 when TIR was 80%. Similarly, as TITR increased, the ratio of TIR:TITR decreased, varying from 2.6 with TITR of 10% to 1.3 for TITR of 70%. The TIR-TITR relationship varied according to CV and TBR, such that the higher the CV or higher the amount of TBR the greater was TITR for a given TIR. Conclusions: TIR and TITR are highly correlated, although the relationship is nonlinear. With knowledge of TIR, TITR can be estimated with reasonable precision.

Long-Term Improvements in Glycemic Control with Dexcom CGM Use in Adults with Noninsulin-Treated Type 2 Diabetes.

Aims: The objective of this real-world, observational study was to evaluate change in continuing glucose monitoring (CGM) metrics for 1 year after CGM initiation in adults with noninsulin-treated type 2 diabetes (T2D). Methods: Data were analyzed from Dexcom G6 and G7 users who self-reported: T2D, ≥18 years, gender, no insulin use, and had a baseline percent time in range (TIR) 70-180 mg/dL of ≤70%. Outcomes were change in CGM metrics from baseline to 6 and 12 months overall and for younger (<65 years) and older (≥65 years) cohorts. Additional analyses explored the relationship between use of the high alert feature and change in TIR and time in tight range (TITR) 70-140 mg/dL. Results: CGM users (n = 3,840) were mean (SD) 52.5 (11.2) years, 47.9% female, mean TIR was 41.7% (21.4%), and 12.4% of participants were ≥65 years. Significant improvement in all CGM metrics not meeting target values at baseline was observed at 6 months, with continued improvement at 12 months. Mean baseline TIR increased by 17.3% (32.1%) from 41.7% (21.4%) to 59.0% (28.9%), and mean glucose management indicator decreased by 0.5% (1.2%) from 8.1% (0.9%) to 7.6% (1.1%) (both P < 0.001). Participants who maintained or customized the high alert default setting of 250 mg/dL had a greater increase in TIR and TITR compared with participants who disabled the alert. Days of CGM use over 12 months were high in 84.7% (15.9%). Conclusion: In this large, real-world study of adults with suboptimally controlled T2D not using insulin, Dexcom CGM use was associated with meaningful improvements in glycemic control over 12 months. Use of the high alert system feature was positively associated with glycemic outcomes. High use of CGM over 12 months suggests benefits related to consistent CGM use in this population.

Time in Range, Time in Tight Range, and Average Glucose Relationships Are Modulated by Glycemic Variability: Identification of a Glucose Distribution Model Connecting Glycemic Parameters Using Real-World Data.

Background: Time in range (TIR), time in tight range (TITR), and average glucose (AG) are used to adjust glycemic therapies in diabetes. However, TIR/TITR and AG can show a disconnect, which may create management difficulties. We aimed to understand the factors influencing the relationships between these glycemic markers. Materials and Methods: Real-world glucose data were collected from self-identified diabetes type 1 and type 2 diabetes (T1D and T2D) individuals using flash continuous glucose monitoring (FCGM). The effects of glycemic variability, assessed as glucose coefficient of variation (CV), on the relationship between AG and TIR/TITR were investigated together with the best-fit glucose distribution model that addresses these relationships. Results: Of 29,164 FCGM users (16,367 T1D, 11,061 T2D, and 1736 others), 38,259 glucose readings/individual were available. Comparing low and high CV tertiles, TIR at AG of 150 mg/dL varied from 80% ± 5.6% to 62% ± 6.8%, respectively (P < 0.001), while TITR at AG of 130 mg/dL varied from 65% ± 7.5% to 49% ± 7.0%, respectively (P < 0.001). In contrast, higher CV was associated with increased TIR and TITR at AG levels outside the upper limit of these ranges. Gamma distribution was superior to six other models at explaining AG and TIR/TITR interactions and demonstrated nonlinear interplay between these metrics. Conclusions: The gamma model accurately predicts interactions between CGM-derived glycemic metrics and reveals that glycemic variability can significantly influence the relationship between AG and TIR with opposing effects according to AG levels. Our findings potentially help with clinical diabetes management, particularly when AG and TIR appear mismatched.

Future of Time-in-Range Goals in the Era of Advanced Hybrid Closed-Loop Automated Insulin Delivery Systems.

The concept of maintaining blood glucose levels within the 70-180 mg/dL range, known as time-in-range, has raised questions regarding its representation of true physiological euglycemia. Some have speculated that focusing on the time spent within the 70-140 mg/dL range, introduced as time in tight range (TITR) through the International Consensus statement, could serve as a more precise metric for assessing normoglycemia in individuals with type 1 diabetes. This article delves into the current status of TITR as an emerging marker and explores how advanced hybrid closed-loop systems may offer a promising avenue for achieving this higher level of glycemic control.

12-Month Time in Tight Range Improvement with Advanced Hybrid-Closed Loop System in Adults with Type 1 Diabetes.

INTRODUCTION: Time in tight range (TITR) is an emerging and valuable metric for assessing normoglycemia. The latest advancement in automated insulin delivery (AID) systems, the advanced hybrid closed-loop (AHCL) systems, are particularly noteworthy for managing type 1 diabetes (T1D) and enhancing glycemic control. METHODS: In a real-world clinical setting, we carried out a retrospective evaluation of TITR in 42 adult subjects with T1D using the AHCL Minimed™ 780G system over a 12-month period. RESULTS: Within just 14 days of activating the automatic mode, the AHCL Minimed™ 780G system showed rapid improvement in TITR, and in the other continuous glucose monitoring (CGM) metrics. This improvement persisted over 12 months, achieving the proposed 45-50% range for effective glycemic control. CONCLUSION: The AHCL Minimed™ 780G system significantly enhances TITR, demonstrating continuous improvement throughout a 12-month follow-up period.

Utility of time in tight range (TITR) in evaluating metabolic control in pediatric and adult patients with type 1 diabetes in treatment with advanced hybrid closed-loop systems.

PURPOSE: To analyze the time in tight range (TITR), and its relationship with other glucometric parameters in patients with type 1 diabetes (T1D) treated with advanced hybrid closed-loop (AHCL) systems. METHODS: A prospective observational study was conducted on pediatric and adult patients with T1D undergoing treatment with AHCL systems for at least 3 months. Clinical variables and glucometric parameters before and after AHCL initiation were collected. RESULTS: A total of 117 patients were evaluated. Comparison of metabolic control after AHCL initiation showed significant improvements in HbA1c (6.9 ± 0.9 vs. 6.6 ± 0.5%, p < 0.001), time in range (TIR) (68.2 ± 11.5 vs. 82.5 ± 6.9%, p < 0.001), TITR (43.7 ± 10.8 vs. 57.3 ± 9.7%, p < 0.001), glucose management indicator (GMI) (6.9 ± 0.4 vs. 6.6 ± 0.3%, p < 0.001), time below range (TBR) 70-54 mg/dl (4.3 ± 4.5 vs. 2.0 ± 1.4%, p < 0.001), and time above range (TAR) > 180 mg/dl (36.0 ± 7.6 vs. 15.1 ± 6.4%, p < 0.001). Coefficient of variation (CV) also improved (36.3 ± 5.7 vs. 30.6 ± 3.7, p < 0.001), while time between 140-180 mg/dl remained unchanged. In total, 76.3% achieved TITR > 50% (100% pediatric). Correlation analysis between TITR and TIR and GRI showed a strong positive correlation, modified by glycemic variability. CONCLUSIONS: AHCL systems achieve significant improvements in metabolic control (TIR > 70% in 93.9% patients). The increase in TIR was not related to an increase in TIR 140-180 mg/dl. Despite being closely related to TIR, TITR allows for a more adequate discrimination of the achieved control level, especially in a population with good initial metabolic control. The correlation between TIR and TITR is directly influenced by the degree of glycemic variability.

Exploring the Continuous Glucose Monitoring in Pediatric Diabetes: Current Practices, Innovative Metrics, and Future Implications.

Continuous glucose monitoring (CGM) systems, including real-time CGM and intermittently scanned CGM, have revolutionized diabetes management, particularly in children and adolescents with type 1 diabetes (T1D). These systems provide detailed insights into glucose variability and detect asymptomatic and nocturnal hypoglycemia, addressing limitations of traditional self-monitoring blood glucose methods. CGM devices measure interstitial glucose concentrations constantly, enabling proactive therapeutic decisions and optimization of glycemic control through stored data analysis. CGM metrics such as time in range, time below range, and coefficient of variation are crucial for managing T1D, with emerging metrics like time in tight range and glycemia risk index showing potential for enhanced glycemic assessment. Recent advancements suggest the utility of CGM systems in monitoring the early stages of T1D and individuals with obesity complicated by pre-diabetes, highlighting its therapeutic versatility. This review discusses the current CGM systems for T1D during the pediatric age, established and emerging metrics, and future applications, emphasizing the critical role of CGM devices in improving glycemic control and clinical outcomes in children and adolescents with diabetes.