Time in rANge vs. Time in nOrmal Glycemia for Better Glycemic Control

This multinational, multicenter, randomized controlled trial aims to evaluate the clinical impact of targeting Time in Normal Glycemia (TING; 70-140 mg/dL) compared to the current standard, Time in Range (TIR; 70-180 mg/dL), in children and adolescents with Type 1 Diabetes (T1D).

Background and Rationale Managing glucose levels in pediatric T1D is essential for preventing long-term complications. While the international consensus currently recommends maintaining a TIR \>70%, recent technological advances-such as automated insulin delivery (AID) systems and next-generation continuous glucose monitors (CGM)-now make it feasible to target narrower, more physiological glucose ranges. TING (70-140 mg/dL) has emerged as a potential new clinical metric for improved metabolic compensation. However, there is no definitive evidence yet that aiming for this tighter range leads to better long-term outcomes than the standard TIR without increasing treatment burden or psychological stress.

Study Objectives The primary objective is to determine if setting TING as the glycemic target improves CGM-derived glycemic metrics compared to the standard TIR approach.

Secondary objectives include:

Evaluating changes in HbA1c. Assessing differences in Quality of Life (QoL) and treatment burden using standardized patient and caregiver questionnaires.

Monitoring the safety and incidence of acute complications, such as severe hypoglycemia and diabetic ketoacidosis (DKA).

Study Design and Population The study will enroll 120 children and adolescents (ages 5.0-17.99) across three tertiary pediatric diabetes centers in the Czech Republic, Israel, and Poland. All participants must be using AID systems and have used a CGM for at least 70% of the time in the month prior to enrollment.

From the target population, we aim to recruit 25% of individuals newly diagnosed.

Intervention and Methods

Participants will be randomized 1:1 into two groups:

TING Group (Intervention): Will follow a target glucose range of 70-140 mg/dL (3.9-7.8 mmol/L).

TIR Group (Control): Will follow the standard target range of 70-180 mg/dL (3.9-10.0 mmol/L).

Both groups will receive structured education from a multidisciplinary team regarding CGM interpretation, glycemic targets, and self-management. In the TING group, CGM hyperglycemia targets will be lowered by at least 10% from baseline.

Timeline and Endpoints The study duration is 12 months. Data collection includes CGM metrics, insulin dose data, and HbA1c at 3-month intervals (Months 0, 3, 6, 9, and 12). A telephone check-up will occur 6 weeks after baseline to assess early adherence and treatment satisfaction.

Primary Endpoint: Change in TIR (70-180 mg/dL) between baseline and 12 months.

Secondary/Exploratory Endpoints: Percentage of time in TING, time in hypoglycemia (Levels 1 and 2), glycemic variability, and various QoL scores (PAID, INSPIRE, Hypoglycemia/Hyperglycemia Fear Surveys) .

Impact If targeting TING is proven beneficial and acceptable, the results of this trial could inform future clinical guidelines and redefine optimal glycemic targets for pediatric diabetes care globally.

• Diabetes-Related Emotional Distress in Pediatric Participants (PAID-Teen [Срок оценки: At enrollment, 6 months and 12 months]
• Participant Perceptions of Diabetes Technology - INSPIRE Patient Scale [Срок оценки: At enrollment, 6 months and 12 months]
• Quality of Life (QoL) Related to Diabetes Technology - INSPIRE Parent/Caregiver Scale [Срок оценки: At enrollment, 6 months and 12 months]
• Parent/Caregiver Fear of Hypoglycemia (HFS-P) [Срок оценки: At enrollment, 6 months and 12 months]
• Parent/Caregiver Fear and Behaviors Related to Hyperglycemia (HAQ) [Срок оценки: At enrollment, 6 months and 12 months]
• Diabetes-Related Emotional Distress in Parents/Caregivers (PAID-PR) [Срок оценки: At enrollment, 6 months and 12 months]