Sustained Effectiveness of an Advanced Hybrid Closed Loop System in a Cohort of Children and Adolescents With Type 1 Diabetes: A 1-Year Real-World Study.

OBJECTIVE: To investigate glucose metrics and identify potential predictors of the achievement of glycemic outcomes in children and adolescents during their first 12 months of MiniMed 780G use. RESEARCH DESIGN AND METHODS: This multicenter, longitudinal, real-world study recruited 368 children and adolescents with type 1 diabetes (T1D) starting SmartGuard technology between June 2020 and June 2022. Ambulatory glucose profile data were collected during a 15-day run-in period (baseline), 2 weeks after automatic mode activation, and every 3 months. The influence of covariates on glycemic outcomes after 1 year of MiniMed 780G use was assessed. RESULTS: After 15 days of automatic mode use, all glucose metrics improved compared with baseline (P < 0.001), except for time below range (P = 0.113) and coefficient of variation (P = 0.330). After 1 year, time in range (TIR) remained significantly higher than at baseline (75.3% vs. 62.8%, P < 0.001). The mean glycated hemoglobin (HbA1c) over the study duration was lower than the previous year (6.9 ± 0.6% vs. 7.4 ± 0.9%, P < 0.001). Time spent in tight range (70-140 mg/dL) was 51.1%, and the glycemia risk index was 27.6. Higher TIR levels were associated with a reduced number of automatic correction boluses (P < 0.001), fewer SmartGuard exits (P = 0.021), and longer time in automatic mode (P = 0.030). Individuals with baseline HbA1c >8% showed more relevant improvement in TIR levels (from 54.3 to 72.3%). CONCLUSIONS: Our study highlights the sustained effectiveness of MiniMed 780G among youths with T1D. Findings suggest that even children and adolescents with low therapeutic engagement may benefit from SmartGuard technology.

Maintaining a gluten-free diet is associated with quality of life in youths with type 1 diabetes and celiac disease.

AIM: Conflicting findings have been reported on whether in youths, the double diagnosis of type 1 diabetes (T1D) and celiac disease (CD) substantially impacts quality of life QoL, compared to subjects with T1D only. METHODS: In this study, 86 youths with double diagnosis and their parents were compared to 167 subjects with T1D only. QoL was assessed through the KINDL questionnaire. Anti-tissue transglutaminase antibodies and dietary interviews evaluated the degree of maintaining a gluten-free diet (GFD). RESULTS: We found that having CD in addition to T1D has little effect on overall QoL. However, analysis of the degree of maintaining GFD revealed significantly lower total QoL scores in groups with T1D + CD not strictly maintaining GFD compared to T1D only (p = 0.0014). The multivariable linear regression model confirmed the importance of maintaining GFD on QoL in subjects (p = 0.0066) and parents (p = 0.023). CONCLUSION: The coexistence of T1D and CD and the adoption of a GFD resulted in poor QoL levels, as in youth as in their parents, when difficulties implementing the GFD are present. Psychological support should consider the importance of maintaining GFD not only to prevent potential complications in the future but also to improve actual QoL in different subdomains.

Satisfaction with continuous glucose monitoring is associated with quality of life in young people with type 1 diabetes regardless of metabolic control and treatment type.

AIMS: While continuous glucose monitoring (CGM) and associated technologies have positive effects on metabolic control in young people with type 1 diabetes (T1D), less is known about their impact on quality of life (QoL). Here, we quantified CGM satisfaction and QoL in young people with T1D and their parents/caregivers to establish (i) the relationship between QoL and CGM satisfaction and (ii) the impact of the treatment regimen on QoL. METHODS: This was a cross-sectional study of children and adolescents with T1D on different treatment regimens (multiple daily injections, sensor-augmented pumps and automated insulin delivery). QoL was assessed with the KINDL instrument, and CGM satisfaction with the CGM-SAT questionnaire was evaluated in both youths with T1D and their parents. RESULTS: Two hundred and ten consecutively enrolled youths with T1D completed the KINDL and CGM-SAT questionnaires. The mean total KINDL score was greater than neutral in both subjects with T1D (3.99 ± 0.47) and parents (4.06 ± 0.40), and lower overall CGM-SAT scores (i.e., higher satisfaction) were significantly associated with higher QoL in all six KINDL subscales (p < 0.05). There were no differences in KINDL scores according to delivery technology or when participants were grouped according to optimal and sub-optimal glucose control. CONCLUSIONS: Higher satisfaction with recent CGMs was associated with better QoL in all dimensions. QoL was independent of both the insulin delivery technology and glycaemic control. CGM must be further disseminated. Attention on perceived satisfaction with CGM should be incorporated with the clinical practice to improve the well-being of children and adolescents with T1D and their families.

The real-life management of glucose homeostasis abnormalities in pediatric onco-hematological diseases: data from a national survey.

Glycemic abnormalities are a frequent finding in pediatric oncological patients, both during treatment and after its discontinuation. Moreover, impaired glucose tolerance (IGT), impaired fasting glycemia (IFG) and diabetes mellitus (DM) are not rarely diagnosed in non-oncological hematological diseases. To explore the current pediatric Italian approach to the diagnosis and the management of the glycemic alterations in this clinical setting and, thus, to identify and enforce current clinical needs, we submitted an online 23-items survey to all the Italian Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) centers, and surveys were descriptively analyzed. Thirty-nine AIEOP centers were involved in the study. In 2021, among 75278 children and adolescents affected by an oncological or a hematological disease, 1.2 and 0.65% developed DM, while IGT or IFG were widespread in 2.3 and 2.8%, respectively. The main causes of DM were the use of corticosteroids in patients with cancer and the iron overload in patients with thalassemia. Venous fasting plasma glycemia was the most used tool to detect glycemic abnormalities. The performance of oral glucose tolerance test (OGTT) was extremely limited, except when IFG occurred. Despite the diagnosis of DM, ∼45% of patients with cancer and 30% of patients with one hematological disease did not receive an appropriate treatment. In the other cases, insulin was the drug of first choice. Emerging technologies for diabetes care (glucose sensors and insulin pumps) are not largely used yet. The results of our study support the standardization of the care of the glycemic abnormalities during or after onco-hematologic diseases in the pediatric age. Despite the scarce data in pediatric literature, proper guidelines are needed.

Glycemic variability and Time in range are associated with the risk of overweight and high LDL-cholesterol in children and youths with Type 1 Diabetes.

INTRODUCTION: Reducing cardiovascular risk factors (CVRFs) exposure in children and youths with type 1 diabetes (T1D) is critical for cardiovascular diseases (CVD) prevention. Long-term exposure to hyperglycaemia, measured by HbA1c, had been recognized as the main factor affecting CVRFs profile. To date, the possible association between short-term glycaemic control and variability measured by continuous glucose monitoring (CGM) metrics and CVRFs has not been explored. The aim of this study was to test the hypothesis that CGM metrics independently contribute to CVRFs exposure in children and youths with T1D. METHOD: BMI, blood pressure (BP), lipid profile, and CGM data of 895 children and youths with T1D were analysed. Binary multivariable logistic regression analyses were performed to test independent associations between CVRFs (BMI percentile>85th, LDL-c>100 mg/dL, BP>90th percentile) and CGM metrics according to sex and adjusting for confounding factors. RESULTS: In both sexes, metrics of hypoglycaemia and glycaemic variability (coefficient of variation [%CV]) positively correlated with BMI percentile. LDL-c positively correlated with mean glucose and metrics of hyperglycaemia. A negative correlation was found between LDL-c and time in range (TIR). No significant correlations were found between CGM metrics and BP percentiles. In both sexes, TIR<70% was significantly associated with LDL-c>100 mg/dL (OR 3.2 in males, 2.1 in females). In females, CV>36% was significantly associated with overweight (OR 2.1). CONCLUSIONS: CGM metrics of glycaemic control and variability were significantly associated with the risk of overweight in females and high LDL-c in both sexes.

Satisfaction with continuous glucose monitoring is positively correlated with time in range in children with type 1 diabetes.

AIMS: Continuous glucose monitoring (CGM) can improve glucometrics in children with type 1 diabetes (T1D), and its efficacy is positively related to glucose sensor use for at least 60% of the time. We therefore investigated the relationship between CGM satisfaction as assessed by a robust questionnaire and glucose control in pediatric T1D patients. METHODS: This was a cross-sectional study of children and adolescents with T1D using CGM. The CGM Satisfaction (CGM-SAT) questionnaire was administered to patients and demographic, clinical, and glucometrics data were recorded. RESULTS: Two hundred and ten consecutively enrolled patients attending 14 Italian pediatric diabetes clinics completed the CGM-SAT questionnaire. CGM-SAT scores were not associated with age, gender, annual HbA1c, % of time with an active sensor, time above range (TAR), time below range (TBR), and coefficient of variation (CV). However, CGM satisfaction was positively correlated with time in range (TIR, p < 0.05) and negatively correlated with glycemia risk index (GRI, p < 0.05). CONCLUSIONS: CGM seems to have a positive effect on glucose control in patients with T1D. CGM satisfaction is therefore an important patient-reported outcome to assess and it is associated with increased TIR and reduced GRI.

Glycemia Risk Index as a Novel Metric to Evaluate the Safety of Glycemic Control in Children and Adolescents with Type 1 Diabetes: An Observational, Multicenter, Real-Life Cohort Study.

Glycemia risk index (GRI) is a novel composite metric for the evaluation of the safety of glycemic management and control. The aim of this study was to evaluate GRI and its correlations with continuous glucose monitoring (CGM) metrics by analyzing real-life CGM data in 1067 children/adolescents with type 1 diabetes (T1D) using four different treatment strategies (intermittently scanned CGM [isCGM]-multiple daily injections [MDIs]; real-time CGM-MDIs; rtCGM-insulin pump; hybrid closed-loop [HCL] therapy). GRI was positively correlated with high blood glucose index, low blood glucose index, mean glycemia, its standard deviation, coefficient of variation, and HbA1c. The four treatment strategy groups showed significantly different GRI with the lowest value in the HCL group (30.8) and the highest in the isCGM-MDIs group (68.4). These findings support the use of GRI for the assessment of the glycemic risk and the safety of specific treatment in pediatric subjects with T1D.

Psychological consequences of the COVID-19 pandemic in people with type 1 diabetes: A systematic literature review.

OBJECTIVE: A comprehensive picture of the data on the impact of COVID-19 on the mental health of individuals with type 1 diabetes (T1D) is currently lacking. The purpose of this systematic review was to synthesize extant literature reporting on the effects of COVID-19 on psychological outcomes in individuals with T1D and to identify associated factors. METHODS: A systematic search was conducted with PubMed, Scopus, PychInfo, PsycArticles, ProQuest, and WoS using a selection procedure according to the PRISMA methodology. Study quality was assessed using a modified Newcastle-Ottawa Scale. In all, 44 studies fulfilling the eligibility criteria were included. RESULTS: Findings suggest that during the COVID-19 pandemic, people with T1D had impaired mental health, with relatively high rates of symptoms of depression (11.5-60.7%, n = 13 studies), anxiety (7-27.5%, n = 16 studies), and distress (14-86.6%, n = 21 studies). Factors associated with psychological problems include female gender, lower income, poorer diabetes control, difficulties in diabetes self-care behaviors, and complications. Of the 44 studies, 22 were of low methodological quality. CONCLUSIONS: Taking appropriate measures to improve medical and psychological services is needed to support individuals with T1D in appropriately coping with the burden and difficulties caused by the COVID-19 pandemic and to prevent mental health problems from enduring, worsening, or having a long-term impact on physical health outcomes. Heterogeneity in measurement methods, lack of longitudinal data, the fact that most included studies did not aim to make a specific diagnosis of mental disorders limit the generalizability of the findings and have implications for practice.

Prevalence and Multidimensional Model of Disordered Eating in Youths With Type 1 Diabetes: Results From a Nationwide Population-Based Study.

OBJECTIVE: The aim of this study was to report nationwide data of the prevalence of disordered eating behaviors (DEBs) in adolescents with type 1 diabetes (T1D) and to evaluate a multidimensional model of eating problems, analyzing how psychopathological problems are associated with DEBs and with metabolic control. METHODS: This study was carried out using a cross-sectional design with a sample of 1,562 patients with T1D (812 male), aged 11-19 years. Participants were recruited from multiple pediatric diabetes centers (N = 30) located in northern, central, and southern Italy, and they individually completed the Diabetes Eating Problem Survey-Revised (DEPS-r) and the Youth Self-Report (YSR). Sociodemographic and clinical data were also gathered. Multiple-group structural equation modeling was used to investigate the relationships between internalizing/externalizing symptoms, DEBs, and glycosylated hemoglobin (HbA1c) values. RESULTS: A total of 29.7% of the participants reported DEBs (DEPS-r scores ≥20), 42.4% reported insulin manipulation (IM). The prevalence of DEBs was higher for female participants (p ≤ .001). The model explains 37% of the variance in disordered eating, 12% in IM, and 21% in HbA1c values. Body mass index, externalizing symptoms, and internalizing symptoms were significantly and positively associated with DEBs, which in turn were significantly and positively associated with HbA1c values (all p ≤ .001). Externalizing (p ≤ .001) and internalizing (p ≤ .01) symptoms were also directly associated with HbA1c values. CONCLUSION: Given the relevant prevalence of DEBs, their significant positive association with psychopathological symptoms, and their relationship with worse diabetes outcomes, regular psychological screening and support is needed to ensure the best care of adolescents with T1D.

Italian translation and validation of the CGM satisfaction scale questionnaire.

AIMS: Patient-reported outcomes (PROs) are increasingly important for assessing patient satisfaction with diabetes technologies. PROs must be assessed with validated questionnaires in clinical practice and research studies. Our aim was to translate and validate the Italian version of the continuous glucose monitoring (CGM) Satisfaction (CGM-SAT) scale questionnaire. METHODS: Questionnaire validation followed MAPI Research Trust guidelines and included forward translation, reconciliation, backward translation, and cognitive debriefing. RESULTS: The final version of the questionnaire was administered to 210 patients with type 1 diabetes (T1D) and 232 parents. The completion rate was excellent, with almost 100% of items answered. The overall Cronbach's coefficient was 0.71 and 0.85 for young people (patients) and parents indicating moderate and good internal consistency, respectively. Parent-young people agreement was 0.404 (95% confidence interval: 0.391-0.417), indicating moderate agreement between the two assessments. Factor analysis identified that factors assessing the "benefits" and "hassles" of CGM accounted for 33.9% and 12.9% of score variance in young people and 29.6% and 19.8% in parents, respectively. DISCUSSION: We present the successful Italian translation and validation of the CGM-SAT scale questionnaire, which will be useful for assessing satisfaction with Italian T1D patients using CGM systems.

The Pathogenic Diagnosis in Pediatric Diabetology: Next Generation Sequencing and Precision Therapy.

In pediatric diabetology, a precise diagnosis is very important because it allows early and correct clinical management of the patient. Monogenic diabetes (MD), which accounts for 1-6% of all pediatric-adolescent diabetes cases, is the most relevant example of precision medicine. The definitive diagnosis of MD, possible only by genetic testing, allows us to direct patients to more appropriate therapy in relation to the identified mutation. In some cases, MD patients can avoid insulin and be treated with oral hypoglycemic drugs with a perceptible impact on both the quality of life and the healthcare costs. However, the genetic and phenotypic heterogeneity of MD and the overlapping clinical characteristics between different forms, can complicate the diagnostic process. In recent years, the development of Next-Generation Sequencing (NGS) methodology, which allows the simultaneous analysis of multiple genes, has revolutionized molecular diagnostics, becoming the cornerstone of MD precision diagnosis. We report two cases of patients with clinical suspects of MD in which a genetic test was carried out, using a NGS multigenic panel, and it clarified the correct pathogenesis of diabetes, allowing us to better manage the disease both in probands and other affected family members.

Lifestyle and physical fitness in adolescents with type 1 diabetes and obesity.

Background: The association between Type 1 Diabetes Mellitus (T1DM) and obesity (Ob) is no longer unexpected due to unhealthy lifestyle mostly in adolescents. We compared clinical-biochemical characteristics, adherence to the Mediterranean Diet (MD), lifestyle habits and physical fitness across different weight categories of T1DM adolescents from Campania Region. As second aim, we assessed the relationship among lifestyle and physical fitness in these patients. Methods: 74 adolescents (35M; 39F; 13-18 y), with T1DM diagnosed at least 6 mo before the study, were enrolled at the Regional Center for Pediatric Diabetology of Vanvitelli University of Naples. Height, weight, Body Mass Index (BMI), BMI z-score, and Clinical Biochemical health-related parameters were determined. MD adherence, physical activity (PA) amount and sedentary habits were assessed by questionnaires. Handgrip strength, 2-Min Step test (2-MST) cardiorespiratory endurance and Timed up and go test (TUG) for agility and balance were used for physical fitness evaluation. Results: Our sample included 22 normal weight (NW), 37 overweight (OW) and 15 with Obese (Ob) adolescents. Across the three groups, adolescents showed similar Clinical-Biochemical parameters, MD adherence, PA amount, mostly walking (9.3 h/w), daily video exposure (8.5 h/d) and similar handgrip or 2-MST performance. Better performance was observed in NW compared to OW or Ob for TUG (7 vs 8 vs 9 s; p < 0.05). A positive correlation was found between TUG test and BMI, while no correlation was found between HbA1c (glycated haemoglobin) and BMI z score or 2-MST. Conclusions: T1DM adolescents did not meet the recommendations for active lifestyle, despite a medium/good adherence to MD, in particular in NW and OW youths. Sedentary habits correlated with a poor HbA1c. Further, reduced agility and balance were observed in adolescents with obesity compared to NW participants.Future research should be aimed to examine wider samples and to design health promotion interventions for T1DM adolescents.

Euthyroid sick syndrome and its association with complications of type 1 diabetes mellitus onset.

OBJECTIVE: To evaluate (i) the prevalence and association of euthyroid sick syndrome (ESS) [decreased FT3 and/or FT4 and normal/decreased TSH] with severity indexes of type 1 diabetes mellitus (T1DM) onset such as diabetic ketoacidosis (DKA) and kidney damage [acute kidney injury (AKI) based on KDIGO criteria, acute tubular necrosis (ATN), renal tubular damage (RTD)], (ii) relationship between clinical/metabolic parameters at T1DM onset and thyroid hormones, and (iii) ESS as a prognostic indicator of delayed recovery from kidney damage. METHODS: A total of 161 children with T1DM onset were included. RTD was defined by abnormal urinary beta-2-microglobulin and/or neutrophil gelatinase-associated lipocalin (NGAL) and/or tubular reabsorption of phosphate <85% and/or fractional excretion of Na>2%. ATN was defined by RTD+AKI. RESULTS: Of 161 participants, 60 (37.3%) presented ESS. It was more prevalent in case of more severe T1DM presentation both in terms of metabolic derangement (DKA) and kidney function impairment (AKI, RTD and ATN). Only ATN, however, was associated with ESS at adjusted analysis. FT3 inversely correlated with serum triglycerides and creatinine, and urinary calcium/creatinine ratio and NGAL. Participants with euthyroidism showed earlier recovery from AKI than those with ESS. ESS spontaneously disappeared. CONCLUSIONS: ESS is associated with T1DM onset severity and spontaneously disappears. ESS delayed the recovery from AKI. IMPACT: This is the first longitudinal study describing in detail the relationship between clinical/metabolic factors at type 1 diabetes mellitus (T1DM) onset and thyroid hormones, with particular attention to the relationship between diabetic ketoacidosis (DKA)-related kidney function impairment and euthyroid sick syndrome (ESS). Participants with more severe T1DM onset presentation both in terms of metabolic derangement and kidney function impairment had an increased prevalence of ESS. Children with ESS had a slower recovery from acute kidney injury compared with those without ESS. ESS spontaneously disappeared in all participants.

Adolescents with type 1 diabetes vs. hybrid closed loop systems: a case series of patients' behaviour that challenges the algorithm.

OBJECTIVES: Hybrid closed loop systems (HCL) improve the management of type 1 diabetes (T1DM). T1DM adolescent patients represent a risk category also if they are in an automated insulin infusion delivery therapy. CASE PRESENTATION: We describe a series of four cases in which adolescent patients have adopted incorrect behaviours in the managing of HCL systems, challenging the algorithm skills. Two patients performed fabricated sensor calibrations. The other two did not perform pre-prandial insulin boluses correctly. Despite these behaviours, the algorithm corrected the glucose values in three out of four patients. Only in one case, where fabricated calibrations were too frequent, the automatic system failed to restore the glycemic balance. CONCLUSIONS: Fabricated calibrations seem to be more important than uncorrected insulin boluses to challenge the HCL systems.

Eating Problems in Youths with Type 1 Diabetes During and After Lockdown in Italy: An 8-Month Follow-Up Study.

Eighty-five youths with T1D and 176 controls aged 8-19 years were asked to complete online questionnaires (ChEAT and EAT-26) measuring disordered eating behaviors (DEBs) during (baseline) and after (8-month follow-up) the lockdown. DEB symptoms in all participants (especially younger than 13 years), glycemic control, and zBMI were found unchanged from baseline to follow-up (all p > .05). After 8 months, the ChEAT/EAT-26 critical score frequency decreased significantly in controls (p = .004), as was the score for the ChEAT/EAT-26's Oral Control subscale in both groups (T1D: p = .005; controls: p = .01). Participants with T1D, especially those older than 13 years, had higher ChEAT/EAT-26 Dieting scores (p = .037) and lower ChEAT/EAT-26 Oral Control scores (p = .046) than controls. Unchanged DEB symptoms suggest that the COVID-19 restrictions did not significantly affect participants' eating behaviors and that a general adaptation to the challenges of lockdown and other pandemic containment measures occurred in both T1D and control participants.

Corrigendum: The silent epidemic of diabetic ketoacidosis at diagnosis of type 1 diabetes in children and adolescents in italy during the covid-19 pandemic in 2020.

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The Silent Epidemic of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes in Children and Adolescents in Italy During the COVID-19 Pandemic in 2020.

Aim/Hypothesis: To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019. Methods: Forty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019. Results: Overall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, p<0.001). DKA and severe DKA increased during the early pandemic period by 10.4% (p=0.004) and 8% (p=0.002), respectively, and the increase continued throughout 2020. Immigrant background increased and high household income decreased the probability of presenting with DKA (OR: 1.55; 95%CI, 1.24-1.94; p<0.001 and OR: 0.60; 95 CI, 0.41-0.88; p=0.010, respectively). Conclusions/Interpretation: There was an increase in the frequency of DKA and severe DKA in children newly diagnosed with type 1 diabetes during the COVID-19 pandemic in 2020, with no apparent association with the severity of COVID-19 infection severity or containment measures. There has been a silent outbreak of DKA in children during the pandemic, and preventive action is required to prevent this phenomenon in the event of further generalized lockdowns or future outbreaks.

Very low birth weight newborn with diabetes mellitus due to pancreas agenesis managed with insulin pump reservoir filled with undiluted insulin: 16-month follow-up.

BACKGROUND: When very low doses of insulin are used insulin dilution, a procedure prone to errors, is recommended. CASE PRESENTATION: We managed a neonate with pancreas agenesis with insulin pump therapy from the first days of life to 16 months of age without insulin dilution. Predictive low glucose suspend mode first and then closed loop control were used. No episodes of severe hypoglycemia were observed. CONCLUSIONS: Though limited to a single patient with pancreas agenesis we believe that the use of pump should be warranted in patients with permanent neonatal diabetes mellitus and intestinal malabsorption, even with undiluted insulin.