Glucose sensor with predictive alarm for hypoglycaemia: Improved glycaemic control in adolescents with type 1 diabetes.

AIM: Hypoglycaemic events are linked to microvascular and macrovascular complications in people with type 1 diabetes. We aimed to evaluate the efficacy of glucose sensor [real-time continuous glucose monitoring (RT-CGM)] with predictive alarm (PA) in reducing the time spent below the range (%TBR <70 mg/dl) in a group of adolescents with type 1 diabetes (AwD). MATERIALS AND METHODS: This was a crossover, monocentric and randomized study. RT-CGM was set with Alarm on Threshold (AoT) at 70 mg/dl) or PA for hypoglycaemia (20 m before threshold). Twenty AwD were enrolled and randomized to either a PA/AoT or AoT/PA treatment sequence, in a 1:1 ratio. The two groups (PA vs. AoT) were compared using two-way repeated measures ANOVA taking account of the carryover effect. RESULTS: AwD using PA for hypoglycaemia spent less time in severe hypoglycaemia (%TBR2 <54 mg/dl; 0.32 ± 0.31 vs. 0.91 ± 0.90; p < .02) and hypoglycaemia (%TBR <70 mg/dl; 1.68 ± 1.06 vs. 2.90 ± 2.05; p < .02), with better glycaemia risk index (51.3 ± 11.0 vs. 61.5 ± 12.6; p ≤ .01). CONCLUSION: The use of RT-CGM with PA for hypoglycaemia technology in AwD using multiple daily insulin injection treatment could significantly reduce the risk of having hypoglycaemic events resulting in an improved quality of glucose control. CLINICAL TRIAL REGISTRATION NUMBER: NCT05574023.

Evaluation of HbA1c and glucose management indicator discordance in a population of children and adolescents with type 1 diabetes.

BACKGROUND: Glucose management indicator (GMI) is a useful metric for the clinical management of diabetic patients using continuous glucose monitoring (CGM). In adults, a marked discordance between HbA1c and GMI has been reported. To date, no studies have evaluated this discordance in children/adolescents with type 1 diabetes (T1D). METHODS: HbA1c and real-life CGM data of the 12 weeks preceding HbA1c measurement were collected from 805 children/adolescents. The absolute difference between HbA1c and GMI was calculated for both the 12-week and 4-week periods preceding HbA1c measurement and the proportion of discordant patients was defined according to specific thresholds in the entire study population and in subjects stratified by type of CGM, insulin therapy, gender, age and puberty. Regression analyses were performed with HbA1c-GMI discordance as dependent variable and patients' characteristics as independent ones. A new GMI equation for children and adolescent was derived from the linear regression analysis between mean glucose and HbA1c. RESULTS: HbA1c-GMI discordance calculated on the 12-week period was <0.1, ≥0.5 and ≥1.0 in 24.8, 33.9 and 9.2% of the subjects, respectively. No significant differences in the proportion of discordant patients were found comparing patients stratified by type of CGM, insulin therapy, gender, age and puberty. GMI-HbA1c discordance was not significantly explained by age, gender, BMI, type of CGM, insulin therapy, hemoglobin, anemia and autoimmune diseases (R2  = 0.012, p = 0.409). HbA1c-GMI discordance calculated on the 4-week period was comparable. GMI (%) equation derived for this cohort was: 3.74 + 0.022x (mean glucose in mg/dl). CONCLUSIONS: GMI could be meaningfully discordant respect to HbA1c in more than a third of children/adolescents with T1D. This discrepancy should be taken into careful consideration when the two indices are directly compared in daily clinical practice.

Twenty years of the International Society for Pediatric and Adolescent Diabetes Science Schools programs: Assessment of their impact on the participants' personal careers and networking development.

OBJECTIVE: The following report describes the evaluation of the ISPAD Science School for Physicians (ISSP) and for Healthcare Professionals (ISSHP) in terms of their efficiency and success. METHODS: All past attendees from 2000-2019 ISSP and 2004-2019 ISSHP programs were invited to respond to an online survey to assess perceived outcomes of the programs on career development, scientific enhancement, scientific networking, and social opportunities. RESULTS: One-third of the past ISSP (129/428), and approximately 43% of the past ISSHP attendees (105/245) responded to the surveys. Most of ISSP attendees reported that the programs supported their career (82%) by helping to achieve a research position (59%), being engaged with diabetes care (68%) or research (63%) or starting a research fellowship (59%). Responders indicated that ISSP was effective in increasing interest in diabetes research (87%) and enhancing the number (66%) and quality (83%) of scientific productions, and promotion of international collaborations (86%). After the ISSP, 34% of responders received research grants. From the first round of the ISSHP survey (2004-2013), responders reported have improved knowledge (60%), gained more confidence in research (69%), undertaken a research project (63%), and achieved a higher academic degree (27%). From the second round (2014-2019), participants indicated that the program was valuable/useful in workplace (94%) through understanding (89%) and conducting (68%) research and establishing communication from other participants (64%) or from faculty (42%). After the ISSHP, 17% had received awards. CONCLUSIONS: From the participants' viewpoint, both programs were effective in improving engagement with diabetes research, supporting career opportunities, increasing scientific skills, and enhancing networking and research activities.

Sex differences in cardiovascular risk factors of children and adolescents with type 1 diabetes mellitus: A role for diet?

BACKGROUND AND AIMS: Cardiovascular disease is the leading cause of morbidity and mortality in individuals with type 1 diabetes mellitus (T1DM). Cardiovascular risk is higher in women with diabetes than in men. With this study, we wanted to determine whether female children and adolescents with T1DM are more prone to cardiovascular risk factors (CVRFs) and an atherogenic diet than boys. METHODS AND RESULTS: For this cross-sectional study, anthropometric, clinical, biochemical, and dietary intake data of 314 children with diabetes (3-18 years; 178 boys) were analysed according to age and sex. Linear and binary logistic regression was performed to test independent associations between sex, dietary intake, and CVRFs. Low-density lipoprotein -cholesterol (LDL-c), triglyceride (TG), fibre, monounsaturated fatty acid levels (all p < 0.01), and lipid (p = 0.022) intake were higher in the girls than in the boys. Multiple regression analysis showed that LDL was associated with sex, glycated haemoglobin (HbA1c), and lipid intake percentage (R (Kannel, 1979) [2] = 0.130; p = 0.0004) independent of age, pubertal stage, body mass index (BMI), duration of diabetes, energy, and fibre intake. Logistic regression analysis showed that high LDL-c levels were present more often in girls [odds ratio, OR; confidence interval, CI = 2.569 (1.178-5.604); p = 0.018] who had a higher dietary lipid intake percentage [OR (CI) = 1.089 (1.011-1.173); p = 0.025]. CONCLUSIONS: Girls with diabetes have higher LDL-c levels associated with higher dietary lipid intake. Our findings suggest that young people with diabetes, especially girls, may benefit from early dietary interventions to reduce their cardiovascular risk.

Delayed age at menarche in chronic respiratory diseases.

OBJECTIVE: Age at menarche (AAM) is an important indicator of physiological development in women, and delayed AAM has been associated with chronic illnesses. We investigated predictive factors at diagnosis that influence AAM in adolescents with chronic respiratory diseases. STUDY DESIGN: AAM was assessed in 1207 northern Italian female aged 11-24 (1062 healthy, 98 with asthma and 47 with cystic fibrosis [CF]). AAM was defined by recall and status quo methods. We studied anthropometric data, metabolic status, diagnosis parameters, presence of irregular menses. Clinical data of subjects with chronic respiratory illness were compared with that of healthy adolescents. RESULTS: Mean AAM for healthy adolescents was 12.49 ± 1.2 years. Mother's AAM was positively associated with that of their daughters (P < .001). BMI was negatively correlated with AAM (P < .001). 69% of healthy adolescents referred regular menses. AAM in the different groups was 12.79 ± 3.0 years for patients with asthma (P < .05 vs healthy) and 13.24 ± 1.44 years for adolescents with CF (P < .0001 vs healthy). In the asthmatic group, 57% of the patients referred regular menses, and no significant differences were found between AAM and control of the disease (ACT test). In the CF group, no correlation was found between the type of CFTR mutation or FEV1% and AAM. 53% of the patients with CF referred regular menses. CONCLUSIONS: AAM in patients with CF and asthma was significantly higher than in healthy adolescents, and menses abnormalities were observed in the last two groups. Inflammation influences the reproductive function in chronic respiratory disease.

In vivo confocal microscopy study of corneal nerve alterations in children and youths with Type 1 diabetes.

OBJECTIVE: To determine whether children and youths with Type 1 diabetes (T1D) have early alterations of the corneal subbasal nerve plexus detectable with in vivo confocal microscopy (IVCM) and to investigate the role of longitudinally measured major risk factors for diabetes complications associated with these alterations. METHODS: One hundred and fifty children and youths with T1D and 51 age-matched controls were enrolled and underwent IVCM. Corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), corneal fiber total branch density (CTBD), and corneal fiber fractal dimension (CNFrD) were measured. Risk factors for diabetes complications (blood pressure, BMI, HbA1c, lipoproteins, urinary albumin-creatinine ratio) were recorded at IVCM and longitudinally since T1D onset. Unpaired t-test was used to compare variables between the groups. Multiple regression models were calculated using IVCM parameters as dependent variables and risk factors as independent variables. RESULTS: All IVCM parameters, except CTBD, were significantly lower in the T1D patients. Glycometabolic control (HbA1c, visit-to-visit HbA1c variability, and mean HbA1c), and blood pressure were inversely correlated with IVCM parameters. Multiple regression showed that part of the variability in CNFL, CNFD, CTBD, and CNFraD was explained by HbA1c, blood pressure percentiles and age at IVCM examination, independent of diabetes duration, BMI percentile and LDL cholesterol. Comparable results were obtained using the mean value of risk factors measured longitudinally since T1D onset. CONCLUSIONS: Early signs of corneal nerve degeneration were found in children and youths with T1D. Glycometabolic control and blood pressure were the major risk factors for these alterations.

Are we confident that final-year medical students know at least basics about diabetes?: A preliminary report from the multicenter, survey-based Diabetes Know-Me study.

BACKGROUND: We present the results of the pilot study of a multinational "Diabetes Know-Me" project investigating knowledge regarding diabetes of medical students. This is the first collaborative project of the ISPAD JENIOUS group. METHODS: Students of the final year of medical studies from six countries answered a 25-question survey regarding basic knowledge concerning diabetes (1091 surveys handed out, response rate 86%). RESULTS: Among the responders (58% female) 90% confirmed attending diabetology classes; 11% planned to specialize in diabetology. There were significant differences between countries in the median score of correct answers ranging from 10/25 to 22/25. Attending diabetes classes (20 vs. 13/25, p < 0.0001) was the strongest factor associated with improved knowledge about diabetes (other factors analyzed were: gender, familiar/personal experience of diabetes, interest to specialize in diabetology). CONCLUSIONS: Basic knowledge about diabetes remains a challenge. Participating in classes concerning diabetes contributed the most to the diabetes-related knowledge among students of the final year of medical faculties.

Long chain fatty acids metabolism and cardiovascular risk factors in youth with type 1 diabetes.

BACKGROUND AND AIMS: Fatty acids (FAs) and their metabolizing enzymes have been associated with several cardiometabolic outcomes. Whether they correlate with cardiovascular risk in type 1 diabetes (T1D), it is unknown. We investigated whether erythrocyte FAs correlated with cardiovascular risk factors and dietary fats in youth with T1D. METHODS AND RESULTS: We recruited 154 adolescents with T1D (aged 17.3 ± 2 years, 82 boys) and assessed blood pressure, plasma lipids, HbA1c, estimated insulin sensitivity (eIS) and dietary fats based on a 3-days weighed dietary record. Erythrocyte FAs were measured by gas chromatography and desaturase and elongase activities were estimated as product/precursor ratios. Delta-6-desaturase (D6D) activity correlated inversely with eIS (r = -0.32,p = 6.6∗10-5) and directly with triglycerides (r = 0.24, p = 0.003), adjusted for z-BMI, age and gender. No single erythrocyte FA correlated with eIS. Erythrocyte membrane stearic acid (SA) correlated with HbA1c adjusted for confounders and eIS (r = -0.26, p = 0.002). We found some weak (r ≤ 0.20) correlations between erythrocyte membrane FAs and dietary fats, which were not retained by correction for multiple testing. CONCLUSION: In youth with T1D, D6D activity might exert unfavorable effects per se, beyond its role on FAs composition. This is in accordance with previous data associating D6D activity/D6D-enhancing polymorphisms with metabolic syndrome and incident type 2 diabetes, as well as D6D activity with the regulation of cellular red-ox balance. SA was a favorable marker of glycemic control. Future research is needed to clarify the biological pathways linking D6D and SA with the cardiometabolic health of youth with T1D.

Albuminuric and non-albuminuric reduced eGFR phenotypes in youth with type 1 diabetes: Factors associated with cardiometabolic risk.

BACKGROUND AND AIM: Albuminuria and reduced eGFR are hallmarks of Diabetic Kidney Disease in adults. Our aim was to analyze factors associated with albuminuric and non-albuminuric mildly reduced eGFR phenotypes in youths with type 1 diabetes. METHODS AND RESULTS: This multicenter cross-sectional study included 1549 youths (age 5-17 years) with type 1 diabetes enrolled at 14 Italian Pediatric Diabetes Centers. Albuminuria, creatinine, glycosylated hemoglobin (HbA1c), lipids, blood pressure (BP), neutrophils (N) and lymphocytes (L) count were analyzed. Uric acid (UA) was available in 848 individuals. Estimated GFR (eGFR) was calculated using bedside Schwartz's equation. The sample was divided in three phenotypes: 1) normoalbuminuria and eGFR ≥90 mL/min/1.73 m2 (reference category, n = 1204), 2) albuminuric and normal GFR phenotype (n = 106), 3) non-albuminuric mildly reduced GFR (MRGFR) phenotype (eGFR 60-89 mL/min/1.73 m2, n = 239). Albuminuric and non-albuminuric reduced eGFR phenotypes were significantly associated with autoimmune thyroiditis (P =0.028 and P=0.044, respectively). Albuminuric phenotype showed high risk of high HbA1c (P=0.029), high BP (P < 0.001), and low HDL-C (P =0.045) vs reference category. Non-albuminuric MRGFR phenotype showed high risk of high BP (P < 0.0001), low HDL-C (P =0.042), high Triglycerides/HDL-C ratio (P =0.019), and high UA (P < 0.0001) vs reference category. CONCLUSION: Non albuminuric MRGFR phenotype is more prevalent than albuminuric phenotype and shows a worst cardiometabolic risk (CMR) profile). Both phenotypes are associated with autoimmune thyroiditis. Our data suggest to evaluate both albuminuria and eGFR earlier in type 1 diabetes to timely identify young people with altered CMR profile.

Long-term glycemic control and glucose variability assessed with continuous glucose monitoring in a pediatric population with type 1 diabetes: Determination of optimal sampling duration.

BACKGROUND: No studies have assessed if 2-week of continuous glucose monitoring (CGM) data provide good estimation of long-term glycemic control and glucose variability (GV) in pediatric patients with type 1 diabetes (T1D) as in adults. METHODS: Six hundred fifty-four T1D pediatric patients were enrolled and 12-weeks of CGM data, before HbA1c measurement, were collected. Metrics of glycemic control and GV in incremental sampling periods were calculated. The agreement between metrics calculated in the sampling periods and the full 12-week period was assessed with correlation analysis (R2 ), median relative absolute difference (RAD) or absolute difference in the entire study populations and subjects stratified by age, pubertal status, insulin therapy (MDI,CSII), type of CGM (intermittently scanned [isCGM], real-time [rtCGM]), and HbA1c level. RESULTS: Correlations with metrics of the full 12-week period improved by extending the sampling periods. R2 values close to 0.90 using 4-week period were significantly higher than 2-week period, particularly for coefficient of variation, mean glucose SD, percentage of time below the range <70 mg/dL. A significant difference was found comparing the median RAD of 2- and 4-week, especially for mean glucose and coefficient of variation. Similar results were obtained analyzing subjects according to age and pubertal status, whereas in patients with HbA1c ≤7%, using rtCGM and CSII significant correlations were found for 2-week period. CONCLUSIONS: In T1D pediatric subjects, 4-week CGM data better reflects long-term glycemic control and GV in MDI and isCGM users. The 2-week period may be acceptably accurate in CSII and rtCGM users, especially in those with good glycometabolic control.

Nutrition habits of children and adolescents with type 1 diabetes changed in a 10 years span.

BACKGROUND: Diet plays a key role in the treatment of type 1 diabetes (T1D). Dietary habits changed rapidly in the last decades and few data are available on recent dietary changes in children and adolescents with T1D. OBJECTIVE: To test the hypothesis that diet composition changed in a 10-year period in children and adolescents with T1D. METHODS: Two hundred and twenty-nine T1D subjects (M/F:121/108) aged 6 to 16 years were recruited: 114 (group A) enrolled in 2009, not using CGM and/or CSII, and 115 (group B) enrolled in 2019. Anthropometric biochemical (HbA1c, lipid profile), diet, and insulin therapy parameters were compared between the two groups. Multivariate logistic regression analysis was performed with HbA1c as dependent variable (HbA1c > 58 mmol/mol = 1) and nutritional variables and technology use as independent ones. RESULTS: Energy intake of group A was not statistically different from that of group B. Group B had a significantly (P < 0.001) higher protein and lipids intake and lower total carbohydrate and fiber intake than group A. HbA1c was significantly (P < 0.01) lower in group B than in group A. Logistic regression analysis showed that MUFA (OR 0.83, 95%CI:0.693-0.998), fiber intake (OR 0.82, 95%CI:0.699-0.0969), and technology use (OR 0.15, 95%CI:0.031-0.685), adjusted for age, gender, BMI, energy intake and diabetes duration, were associated with a HbA1c higher than 58 mmol/mol) (R2 = 0.27, P < 0.05). CONCLUSIONS: In a 10-year period, diet composition of children and adolescents with T1D changed and glucometabolic control improved. Fiber and MUFA intake showed a positive effect on HbA1c, independent from technology use, supporting the importance of educating children with T1D and families to maintain healthy eating habits.

Cardiovascular risk factors in children and adolescents with type 1 diabetes in Italy: a multicentric observational study.

AIMS: To assess the prevalence of cardiovascular risk factors (CVRFs) and to identify the variables associated with CVRFs in a cohort of children and adolescents with Type 1 Diabetes. METHODS: 2021 subjects, 2-18 year-old, were recruited in 17 Italian Pediatric Diabetes Centers. Anthropometric, blood pressure, biochemical (HbA1c, lipid profile, ACR), insulin therapy, physical activity level, smoking and family socio-economic status data were collected. CVRFs prevalence and their distribution were analyzed according to age and binary logistic regression was performed with positivity for at least one major CVRF (BMI-SDS > +2SD, blood pressure > 90th percentile, LDL cholesterol>100 mg/dL) as dependent variable and age, duration of illness, gender, HbA1c and physical activity, as independent variables. RESULTS: The prevalence of CVFRs not at the recommended target was respectively: 32.5% one CVRF, 6.7% two CVRFs and 0.6% three CVRFs, with no significant differences across the 3 age groups (2-10, 10-15, 15-18 years). In the total sample, HbA1c and inadequate physical activity were associated with a higher probability of having at least one major CVRF. This probability was associated with physical activity in the 2-10-year-old group, with physical activity and HbA1c in the 10-15-year-old group and with HbA1c only in subjects older than 15 years. CONCLUSIONS: More than 30% of subjects had at least a major CVRF. Early detection of CVRFs may be useful to enforce the therapeutic intervention in this subgroup, in order to reduce the risk to develop cardiovascular complications.

Systemic anti-oxidant capacity is inversely correlated with systolic blood pressure and pulse pressure in children with obesity.

BACKGROUND AND AIMS: Oxidative stress leading to endothelial dysfunction is a candidate driver of obesity-related hypertension. We aimed to assess whether the total anti-oxidant capacity (TAC) was associated with blood pressure in children/adolescents with obesity. METHODS AND RESULTS: One hundred and fifty-two children/adolescents with obesity (79 boys; age 11.9+/-2.5 years) underwent blood drawing for the assessment of TAC, lipids and HOMA-IR. Blood pressure was measured and classified according to the latest American Academy of Pediatrics Guidelines. Serum TAC was measured by a commercial kit (Sigma-Aldrich). The average TAC was 1.11+/-0.4 mMol/Trolox equivalents. Systolic blood pressure was predicted by TAC (B = -5.8, p = 0.003), z-BMI (B = 2.39, p = 0.008), height [cm] (B = 0.38, p < 0.001) and diastolic blood pressure (B = 0.56, p < 0.001). Diastolic blood pressure was predicted by age [years] (B = 0.58, p = 0.001), log-HOMA-IR (B = 3.0, p = 0.002), and systolic blood pressure (B = 0.26, p < 0.001), but not by TAC. The pulse pressure was predicted only by TAC (B = - 6.6, p = 0.002), and height [cm] (B = 0.42, p < 0.001). Overall "elevated blood pressure + hypertension" or hypertension alone were not associated with TAC. However, systolic "elevated blood pressure + hypertension" was associated with TAC (OR = 0.4 [0.1-0.9], p = 0.037), and z-BMI (OR = 2.1 [1.3-3.6], p = 0.004). CONCLUSION: The systemic anti-oxidant capacity is inversely associated with systolic blood pressure and pulse pressure in children and adolescents with obesity.

Minor diplotypes of FMO3 might protect children and adolescents from obesity and insulin resistance.

In order to assess whether flavin-containing monooxygenase-3 (FMO3) might be involved in early cardiovascular risk, we assessed adiposity and traditional metabolic variables in children/adolescents grouped according to their genotypes in two FMO3 exonic polymorphisms, rs2266782 (E158K) and rs2266780 (E308G), which are in linkage disequilibrium and have been associated with decreased FMO3 activity. Among 776 children/adolescents (10.8 ± 2.2 years) recruited from the general population (452) and from our obesity outpatient clinic (324), the 68 carrying either the 158K-308G/158K-308E or the 158K-308G/158K-308G diplotype had lower mean z-BMI and prevalence of obesity compared to their 708 peers carrying any of the other diplotypes (0.39 vs 0.80, p = 0.01; OR = 0.39[0.17-0.87], p = 0.018, respectively), and to the sub-sample of 303 children carrying the major diplotype (158E-308E/158E-308E) (0.39 vs 0.87, p = 0.008; OR = 0.35[0.16-0.81], p = 0.014, respectively). They also had lower z-BMI-adjusted lnHOMA-IR compared to all the other children (0.75 vs 0.97, p = 0.001) and those carrying the major diplotype, (0.75 vs 0.98, p = 0.03), as well as lower z-BMI-adjusted iln-triglycerides compared to all the other children (3.98 vs 4.17, p = 0.037). These associations provide the first evidence that FMO3 may be involved in early body weight, insulin sensitivity, and lipid regulation in humans.

Non-adjunctive flash glucose monitoring system use during summer-camp in children with type 1 diabetes: The free-summer study.

BACKGROUND: A factory-calibrated sensor for intermittently scanned continuous glucose monitoring (isCGM) is accurate and safe in children with type 1 diabetes (T1D). Data on isCGM effectiveness as a replacement for self-monitoring of blood glucose (SMBG) in this population is scarce. OBJECTIVE: The aim of this study was to evaluate the non-adjunctive use of isCGM in children with T1D during 2 weeks in a challenging summer-camp setting. METHODS: In this two-arm, parallel, randomized, outpatient clinical trial we enrolled 46 children (25 females, mean ± SD: age 11.1 ± 2.6 years, glycated hemoglobin (HbA1c) 7.4% ± 0.7%): 26 in the isCGM group were blinded for the SMBG and insulin dosing was isCGM-based, whereas 20 in the control group were blinded for isCGM and performed SMBG-based insulin dosing. The primary outcome of intention-to-treat analysis was between-group difference in the proportion of time within range 3.9 to 10 mmol/L (TIR). RESULTS: There was no significant difference in TIR (3.9-10 mmol/L) between the two groups. In participants with suboptimal metabolic control (HbA1c > 7%) we observed a significant reduction in time spent above 10 mmol/L (P < 0.05) and an improvement in TIR (P = 0.05) in the isCGM group. No severe hypoglycemic events or serious adverse events occurred. Overall mean absolute relative difference (MARD) between isCGM and SMBG was 18.3%, with median absolute relative difference (ARD) of 8%. Consensus error grid analysis demonstrated 82.2% and 95.2% of results in zone A, and zone A + B, respectively. CONCLUSION: The non-adjunctive use of isCGM was as safe and effective as SMBG, and reduced time spent in hyperglycemia in a sub-population of children with T1D with suboptimal glycemic control. TRIAL REGISTRATION: NCT03182842.

Aiming for the Best Glycemic Control Beyond Time in Range: Time in Tight Range as a New Continuous Glucose Monitoring Metric in Children and Adolescents with Type 1 Diabetes Using Different Treatment Modalities.

Introduction: To evaluate time in tight range (TITR) 70-140 mg/dL (3.9-7.8 mmol/L), its correlation with standard continuous glucose monitoring (CGM) metrics and the clinical variables that possibly have a substantial impact on its value, in a large cohort of pediatric subjects using different treatment strategies. Materials and Methods: A total of 854 children and adolescents with type 1 diabetes were consecutively recruited in this real world, dual center, cross-sectional study. Participants were categorized into four treatment groups (multiple daily injections [MDI] + real-time CGM, MDI + intermittently scanned CGM, sensor augmented pump, and hybrid closed loop [HCL]). Demographical and clinical data, including CGM data, were collected and analyzed. Results: The overall study population exhibited an average TITR of 36.4% ± 12.8%. HCL users showed higher TITR levels compared to the other treatment groups (P < 0.001). A time in range (TIR) cut-off value of 71.9% identified subjects achieving a TITR ≥50% (area under curve [AUC] 0.98; 95% confidence interval 0.97-0.99, P < 0.001), and a strong positive correlation between these two metrics was observed (r = 0.95, P < 0.001). An increase in TIR of 1% was associated with 1.84 (R2 Nagelkerke = 0.35, P < 0.001) increased likelihood of achieving TITR ≥50%. Use of HCL systems (B = 7.78; P < 0.001), disease duration (B = -0.26, P = 0.006), coefficient of variation (B = -0.30, P = 0.004), and glycated hemoglobin (B = -8.82; P < 0.001) emerged as significant predictors of TITR levels. Conclusions: Our study highlights that most children and adolescents with type 1 diabetes present TITR levels below 50%, except those using HCL. Tailored interventions and strategies should be implemented to increase TITR.