Glucometrics and device satisfaction in children and adolescents with type 1 diabetes using different treatment modalities: A multicenter real-world observational study.

AIMS: To analyze metabolic outcomes, diabetes impact and device satisfaction in children and adolescents with type 1 diabetes in Italy who used different treatment modalities for diabetes care in a real-life context. METHODS: In this multicenter, nationwide, cross-sectional study, 1464 participants were enrolled at a routine visit. The following treatment modalities were considered MDI + SMBG; MDI + CGM; Sensor Augmented Pump Therapy; predictive management of low glucose; Hybrid Closed Loop (HCL); Advanced Hybrid Closed Loop (AHCL). Health related quality of life was evaluated by the Italian version of the Diabetes Impact and Device Satisfaction Scale (DIDS) questionnaire. RESULTS: Patients treated with AID systems were more likely to have HbA1c ≤ 6.5 %, higher percentage of time with glucose levels between 70 and 180 mg/dL, lower percentage of time with glucose levels above 180 mg/dL, higher device satisfaction, and reduced impact of diabetes. All the therapeutic modalities with respect to MDI + CGM, except for MDI + SMBG, contributed to increase the device satisfaction. HCL and AHCL respect to MDI + CGM were associated with lower diabetes impact. CONCLUSION: Real-life use of automated insulin delivery systems is associated with reduced type 1 diabetes impact, increased device satisfaction, and achievement of glycemic goals.

Adjustment of octreotide dose given via insulin pump based on continuous glucose monitoring (CGM) in a child with congenital hyperinsulinism.

OBJECTIVES: CHI is a relevant cause of persistent and severe hypoglycemia and the ABCC8 gene mutation is one of most common cause of the disease. Two main types of CHI have been described, diffuse and focal form. Octreotide is a medication utilized in case of diazoxide-unresponsive forms of CHI. For those CHI focal forms where is decided either to manage medically or until resolutive surgery is completed, octreotide can be administered as subcutaneous injection or as continuous subcutaneous infusion via insulin pump. However, it is unclear how to adjust the drug's daily basal pattern when a pump is used. CASE PRESENTATION: We present a case of an infant with a diazoxide-unresponsive focal form of CHI, due to ABCC8 mutation ABCC8, treated with octreotide. To better evaluate the glycemic trend, a CGM was placed. In order to achieve a better personalization of the therapy we utilized an insulin pump for octreotide administration. CONCLUSIONS: The adoption of the CGM and insulin pump, allowed a better personalization of the therapy and a reduction of acute carbohydrate intake, promoting a good auxological growth before resolutive surgery. What is new? Octreotide administered with an insulin pump in patient with CHI allows a wide modulation of the daily therapy. The CGM allows a continuous and a less painful control of the glycemic trend in a patient with CHI. Different basal rates, given via insulin pump may allow a better personalization of the therapy. Prevention of hypoglycemia reduces the acute introduction of carbohydrates, promoting normal growth..

A Risk Profile for Disordered Eating Behaviors in Adolescents with Type 1 Diabetes: A Latent Class Analysis Study.

(1) Background: This multi-center study aimed to identify a risk profile for disordered eating behaviors (DEBs) in youth with type 1 diabetes (T1D) based on their dietary intake, lipid profile, body mass index (BMI-SDS), and glycometabolic control. (2) Methods: Adolescents aged 11 to 18 years from five centers across Italy were recruited. Lipid profile, HbA1c, BMI-SDS, and dietary intake data were collected. The risk for developing DEBs was assessed via the Diabetes Eating Problems Survey-R (DEPS-R) questionnaire. A latent class analysis (LCA) was performed using a person-centered approach. (3) Results: Overall, 148 participants aged 11-18 (12.1, ±3.34), 52% males with a mean diabetes duration of 7.2 (±3.4), were enrolled. Based on the results of the DEBS-R score, LCA allowed us to highlight two different classes of patients which were defined as "at-risk" and "not at-risk" for DEB. The risk profile for developing DEBs is characterized by higher BMI-SDS (23.9 vs. 18.6), higher HbA1c (7.9 vs. 7.1%), higher LDL cholesterol (99.9 vs. 88.8 mg/dL), lower HDL cholesterol (57.9 vs. 61.3 mg/dL), higher proteins (18.2 vs. 16.1%), and lower carbohydrates (43.9 vs. 45.3%). Adolescents included in the "at-risk" class were significantly older (p = 0.000), and their parents' SES was significantly lower (p = 0.041). (4) Conclusions: This study allowed us to characterize a risk profile for DEBs based on dietary behavior and clinical parameters. Early identification of the risk for DEBs allows timely intervention and prevention of behavior disorders.

Trends and cyclic variation in the incidence of childhood type 1 diabetes in two Italian regions over 33 years and during the COVID-19 pandemic.

AIM: There is conflicting evidence about the impact of the COVID-19 pandemic on the incidence of type 1 diabetes. Here, we analysed long-term trends in the incidence of type 1 diabetes in Italian children and adolescents from 1989 to 2019 and compared the incidence observed during the COVID-19 pandemic with that estimated from long-term data. MATERIALS AND METHODS: This was a population-based incidence study using longitudinal data from two diabetes registries in mainland Italy. Trends in the incidence of type 1 diabetes from 1 January 1989 to 31 December 2019 were estimated using Poisson and segmented regression models. RESULTS: There was a significant increasing trend in the incidence of type 1 diabetes of 3.6% per year [95% confidence interval (CI): 2.4-4.8] between 1989 and 2003, a breakpoint in 2003, and then a constant incidence until 2019 (0.5%, 95% CI: -1.3 to 2.4). There was a significant 4-year cycle in incidence over the entire study period. The rate observed in 2021 (26.7, 95% CI: 23.0-30.9) was significantly higher than expected (19.5, 95% CI: 17.6-21.4; p = .010). CONCLUSION: Long-term incidence analysis showed an unexpected increase in new cases of type 1 diabetes in 2021. The incidence of type 1 diabetes now needs continuous monitoring using population registries to understand better the impact of COVID-19 on new-onset type 1 diabetes in children.

Rethinking Carbohydrate Intake and Time in Range in Children and Adolescents with Type 1 Diabetes.

The aim of this study was to evaluate the association between macronutrient intake and time in range (TIR) of 70-180 mg/dL in children and adolescents with type 1 diabetes (T1D). A multi-center study recruited patients with T1D using continuous glucose monitoring (CGM) between January 2019 and January 2020 from centers across Italy. Diet intake was recorded using three-day weighed food diaries. Nutrients were evaluated as percentages of total intake. TIR was considered at target if the percentage of readings was higher than 70%. Clinical and nutritional factors associated with TIR at target were analyzed using multiple correspondence analysis and multiple logistic regression. Data from 197 participants (53% male, median age 11.6 years, median HbA1c 55.2 mmol/mol, median TIR 60%) were analyzed. Macronutrient intake was 45.9% carbohydrates, 16.9% protein, 37.3% fat, and 13.1 g/day fiber (median values). TIR > 70% was observed in 28% of participants; their diet contained more protein (17.6%, p = 0.015) and fiber (14.4 g/day, p = 0.031) than those not at target. The probability of having a TIR > 70% was significantly higher with 40-44% consumption of carbohydrates compared with 45-50% consumption of carbohydrates and with the use of a carbohydrate counting system. Based on these results, a five percent reduction in the percentage of carbohydrate intake can help children and adolescents with T1D achieve the goal of a TIR > 70%. Both a lower and higher percentage of carbohydrate intake appears to reduce the probability of reaching the target TIR > 70%. These results require validation in other populations before being used in clinical practice.

Socioeconomic Inequalities Increase the Probability of Ketoacidosis at Diagnosis of Type 1 Diabetes: A 2014-2016 Nationwide Study of 2,679 Italian Children.

This study aims to compare the frequency of Diabetic Ketoacidosis (DKA) at diagnosis in 2014-2016 with the one previously reported in 2004-2013; and to assess the association between family socioeconomic status and DKA at type 1 diabetes (T1D) diagnosis in children <15 years of age from 2014 to 2016. Methods: This nationwide, population-based, observational study included 2,679 children diagnosed with T1D from 54 Italian centers for pediatric diabetes during 2014-2016. The ISPAD criteria for DKA were used as a standard reference. The overall and by age frequency of DKA between the two time periods were compared. The association between family socioeconomic status and DKA was assessed using multiple logistic regression analysis. Results: Nine hundred and eighty nine children had DKA (36.9, 95% CI: 35.1-38.8). The frequency of DKA was significantly lower in 2014-2016 in comparison to 2004-2013 (40.3, 95% CI: 39.3-41.4, p = 0.002). The probability of having DKA at diagnosis was lower in mothers with a high level of education (OR = 0.69, 95% CI: 0.51-0.93) or a high level of occupation (OR = 0.76, 95% CI: 0.58 0.99), and in fathers with a high level of occupation (OR = 0.72, 95% CI: 0.55-0.94). Children living in Southern Italy had a higher probability of diagnosis with severe DKA than children living in Central Italy. Conclusion: There was a decrease in the frequency of DKA in children diagnosed with T1D under 15 years of age during 2014-2016. However, DKA frequency remains unacceptably high. This study demonstrated that socioeconomic inequalities, measured as low education and occupational levels, were associated with an increased probability of DKA at T1D diagnosis.

Time In Range in Children with Type 1 Diabetes Using Treatment Strategies Based on Nonautomated Insulin Delivery Systems in the Real World.

Background: Glucose sensors consist of real-time continuous glucose monitoring (rtCGM) and intermittently scanned CGM (isCGM). Their clinical use has been widely increasing during the past 5 years. The aim of this study is to evaluate percentage of time in range (TIR) in a large group of children with type 1 diabetes (T1D) using glucose sensors with nonautomated insulin delivery systems, in a real-world setting. Methods: An 11-center cross-sectional study was conducted during January-May 2019. Children with T1D <18 years, all using rtCGM or isCGM for >1 year, treated with multiple daily injections (MDI) or nonautomated insulin pump (IP), were recruited consecutively. Clinical data, HbA1c measurement, and CGM downloaded data were collected by each center and included in a centralized database for the analysis. Glucose metrics of four treatment strategies were analyzed: isCGM-MDI, rtCGM-MDI, isCGM-IP, and rtCGM-IP. Results: Data from 666 children with T1D (51% male and 49% female), median age 12 years, diabetes duration 5 years, were analyzed. An rtCGM was used by 51% of the participants, and a nonautomated IP by 46%. For isCGM-MDI, rtCGM-MDI, isCGM-IP, and rtCGM-IP, the median TIR 70-180 mg/dL values were 49%, 56%, 56%, and 61% (P < 0.001), respectively; HbA1c 7.6%, 7.5%, 7.3%, and 7.3% (P < 0.001), respectively. Use of rtCGM was associated with significant lower time below target range <70 mg/dL and reduced the percentage coefficient of variation of glucose (%CV), independently by the insulin delivery system used. Conclusions: Among nonautomated insulin delivery strategies, simultaneous use of rtCGM and IP was associated with higher percentage of TIR, lower time above range >180 mg/dL and lower HbA1c. If there are no barriers, an upgrade of the treatment strategy with a higher performing technology should be offered to all children who do not achieve blood glucose metrics within the suggested range.

Weekend-Based Parent-Group Intervention to Reduce Stress in Parents of Children and Adolescents with Type 1 Diabetes: A Pilot Study.

Diagnosis of type 1 diabetes (T1D) in a child is often associated with anger, denial, fear, and depression from the parents. The aim of the study was to improve parents' adaptation to the diagnosis of diabetes of their child. Sixty-two parents (29 mothers, 33 fathers) of 36 children with type 1 diabetes (mean age = 11.3-3.3 years; diabetes duration > 1 year; HbA1c = 57 ± 11 mmol/mol) participated in a three-day educational working group pilot intervention study. Intervention was based on the reexamination of the traumatic event of diagnosis of T1D through spatial and time-line anchorage, retracing of the future, emotional awareness, and interactive discussion. Relaxing technique, diaphragmatic breathing, and guided visualization were used by 2 psychologists and 1 pediatric endocrinologist. The study was approved by EC and participants filled a consent form. At baseline and after intervention, parents filled in a questionnaire including Diabetes-Related Distress (DRD), Parent Health Locus of Control Scale (PHLOC), Parent Stress Index Short Form (PSI-SF), Hypoglycemia Fear Survey-Parents (HFS-P) and Hypoglycemia Fear Survey-Parents of Young Children (HFS-P-YC), and Health Survey Short Form-36 (SF-36). Three months after the intervention, both parents reported a reduction in the "difficult child" subscale of the PSI-SF (p < 0.05) and increased scores of social functioning of the SF-36 (p < 0.05). DRD score was significantly reduced in mothers (p = 0.03), while the "parental distress" subscale of the PSI-SF was significantly improved in fathers (p = 0.03). This weekend-based parent group intervention seems to reduce stress and improve social functioning of parents of children and adolescents with type 1 diabetes.

Disordered eating behaviors in adolescents with type 1 diabetes: A cross-sectional population-based study in Italy.

OBJECTIVE: To evaluate the association of clinical, metabolic and socioeconomic factors with disordered eating behaviors (DEB) among adolescents with type 1 diabetes screened using the Diabetes Eating Problem Survey-Revised (DEPS-R). METHODS: A cross-sectional, population-based study involved 163 adolescents with type 1 diabetes, aged 11-20 years, recruited from the registry for type 1 diabetes of Marche Region, Italy, who completed the DEPS-R (response rate 74.4%). Clinical characteristics, lipid profile, HbA1c , family profile of education and occupation were evaluated. The Italian version of DEPS-R was validated, and the prevalence of DEB estimated. The association of demographic, socioeconomic, and clinical factors with DEB was evaluated by multiple correspondence analysis and multiple logistic regression. RESULTS: The prevalence of DEPS-R-positive (score ≥20) was 27% (95% CI 17-38) in boys and 42% (95% CI 31-53) in girls. A clinical profile of DEPS-R-positive was identified: overweight, little time spent in physical activity, low socioeconomic status, poor metabolic control, skipping insulin injections. Furthermore, the probability of DEPS-R-positive increased 63% for every added unit of HbA1c , 36% for every added number of insulin injections skipped in a week and decreased about 20% for every added hour/week spent in physical activity. Overweight youth were six times more likely to be DEPS-R-positive. DISCUSSION: A specific clinical profile of DEPS-R-positive was identified. A multidisciplinary clinical approach aimed to normalize eating behaviors and enhance self-esteem should be used to prevent the onset of these behaviors, and continuous educational programs are needed to promote healthy behaviors and lifestyles.

The role of socio-economic and clinical factors on HbA1c in children and adolescents with type 1 diabetes: an Italian multicentre survey.

OBJECTIVE: To identify the role of the family's socio-economic and clinical characteristics on metabolic control in children and adolescents with type 1 diabetes. METHODS: In this cross-sectional, multicentre study, 768 subjects with type 1 diabetes under 18 years of age were consecutively recruited from January 2008 to February 2009. Target condition was considered for HbA1c values <7.5% (<58 mmol/mol). A multiple correspondence analysis (MCA) was performed to analyze the association between the socio-economic and clinical characteristics of the participants. A logistic regression analysis was performed to identify factors associated with the subjects metabolic control. In both analyses, the family's socio-economic status was represented, measured by the Hollingshead Four-Factor Index of Social Status (SES) or by parental years of education. RESULTS: A total of 28.1% of subjects reached target HbA1c values. The MCA identified a strong association between at-target condition and several factors: high levels of SES or high levels of parental education, the use of the carbohydrate counting system, the use of insulin pumps, the use of the insulin delivery system over a short period of time, a normal body mass index. The logistic regression analysis showed that SES and the mother's years of education were significantly associated with the target condition [odds ratio (OR): 1.01, 95% confidence interval (CI): 1.01-1.03, p = 0.029; OR: 1.05, 95% CI: 1.01-1.10, p = 0.027, respectively). CONCLUSIONS: Personal, clinical, and family characteristics were found to be associated with HbA1c target. Their identification can be crucial in addressing strategies to optimize metabolic control and improve diabetes management.

Peripheral Precocious Puberty due to Functioning Adrenocortical Tumor: Description of Two Cases.

BACKGROUND: Adrenocortical tumors (ACTs) represent less than 0.2% of all childhood neoplasms. Frequent clinical manifestations are virilization, hypercortisolism, and peripheral precocious puberty (PPP). CASES: We describe two cases in which ACTs were responsible for virilization (case 1) and PPP (case 2) in prepubertal girls. In both cases an ACT diagnosis was made after 5-6 months from the first appearance of clinical signs. Surgery was performed within 1 month of diagnosis, and the benign nature of tumors was histologically confirmed. Despite complete tumor resection, virilizing features persisted. SUMMARY AND CONCLUSIONS: Adrenocortical tumors should be considered early in the assessment of PPP. There is often a significant delay between the onset of symptoms and accurate diagnosis but early treatment is essential to limit the clinical manifestations of androgen overproduction.

Organization and regional distribution of centers for the management of children and adolescents with diabetes in Italy.

BACKGROUND: The incidence of type 1 diabetes in childhood is increasing by 3 % per year, placing growing demands on healthcare professionals and medical expenditures. Aim of this study wars to assess the organization of care to children with diabetes in Italy. METHODS: During 2012 a structured questionnaire was sent to all of the members of Italian Society of Paediatric Endocrinology and Diabetology (ISPED). Questions examined organizational structure of Centers, personnel dedicated to the care of children with diabetes, number of subjects followed, local legal legislation supporting centres. RESULTS: A total of 68 centers taking care to 15,563 children and adolescents with diabetes under 18 years of age were identified with a prevalence of 1.4 per 1,000 people. A wide variation in the organizational background was also reported. Fourty-four centers were organized as outpatient departments, 17 as simple units, 5 as complex units and 2 as simple departmental structures. Most centers had a multidisciplinary team. Ten out of twenty Italian regions had introduced supportive regional legislation, but it was fully applied only in six of them. CONCLUSION: Great differences between regions were found in organizational structures, staffing levels and supportive legislation. The national legislation on diabetes was broadly implemented throughout the country regions. Further efforts are needed to improve standards and consistency of pediatric diabetes care in Italy.

Environmental and genetical aspects of the link between pregnancy, birth size, and type 2 diabetes.

Exposure of the fetus to the intrauterine milieu can have profound effects on the health of the offspring in adulthood. These observations are highly reproducible in many populations worldwide although the mechanisms behind them remain elusive. The 'thrifty phenotype' hypothesis proposes that poor fetal nutrition leads to programming of metabolism and an adult phenotype that is adapted to poor but not plentiful nutrition. Results of a series of studies demonstrate the powerful influence of the mother's metabolic state on whether the emerging adult develops obesity and hyperinsulinemia. Importantly, these attributes can be passed on to the next generation non-genetically and can be reversed and prevented. Such hypothesis has been expanded on by the "Developmental Origins of Health and Disease" (DOHaD) hypothesis which describes the origin of adult disease in terms of fetal developmental 'plasticity' or the ability of the fetus to respond to poor in-utero conditions. A wealth of epidemiological evidence has provided a convincing link between a sub-optimal gestational environment and an increased propensity to develop adult onset metabolic disease. In this paper the factors that participate in the programming of the fetus and infants that lead to endocrine dysfunction in postnatal life are reviewed.

Sporadic congenital nonautoimmune hyperthyroidism caused by P639S mutation in thyrotropin receptor gene.

Germline mutations of thyrotropin receptor (TSHR) gene determining a constitutive activation of the receptor were identified as a molecular cause of familial or sporadic congenital nonautoimmune hyperthyroidism (OMIM: 609152) (Nat Genet 7:396-401, 1994; N Engl J Med 332:150-154, 1995; Acta Endocrinol (Copenh) 100:512-518, 1982). We report the case of an Italian child subjected to the first clinical investigation at 24 months for an increased growth velocity; biochemical investigation showed high FT4 and FT3 serum values and undetectable thyrotropin in the absence of anti-thyroid antibodies; the thyroid gland was normal at ultrasound examination. Treatment with methimazole was started at the age of 30 months when her growth velocity was high and the bone age was advanced. DNA was extracted from her parents', brother's, and the patient's blood. Exons 9 and 10 of the TSHR gene were amplified by polymerase chain reaction and subjected to direct sequencing. In proband, a heterozygous substitution of cytosine to thymine determining a proline to serine change at position 639 (P639S) of the TSHR was detected while the parents and brothers of the propositus, all euthyroid, showed only the wild-type sequence of the TSHR gene. This mutation was previously described as somatic in patients affected by hyperfunctioning thyroid nodules and as germline in a single Chinese family affected by thyrotoxicosis and mitral valve prolapse. This constitutively activating mutation is able to activate both the cyclic AMP and the inositol phosphate metabolic pathways when expressed in a heterologous system. In conclusion, we describe the first case of sporadic congenital nonautoimmune hyperthyroidism caused by de novo germinal P639S mutation of TSHR.

Age-period-cohort analysis of 1990-2003 incidence time trends of childhood diabetes in Italy: the RIDI study.

OBJECTIVE: To investigate age-period-cohort effects on the temporal trend of type 1 diabetes in children age 0-14 years in Italian registries. RESEARCH DESIGN AND METHODS: This report is based on 5,180 incident cases in the period 1990-2003 from the Registry for Type 1 Diabetes Mellitus in Italy (RIDI). Multilevel (random intercept) Poisson regression models were used to model the effects of sex, age, calendar time, and birth cohorts on temporal trends, taking into account the registry-level variance component. RESULTS: The incidence rate was 12.26 per 100,000 person-years and significantly higher in boys (13.13 [95% CI 12.66-13.62]) than in girls (11.35 [10.90-11.82]). Large geographical variations in incidence within Italy were evident; incidence was highest in Sardinia, intermediate in Central-Southern Italy, and high in Northern Italy, particularly in the Trento Province, where the incidence rate was 18.67 per 100,000 person-years. An increasing temporal trend was evident (2.94% per year [95% CI 2.22-3.67]). With respect to the calendar period 1990-1992, the incidence rates increased linearly by 15, 27, 35, and 40% in the following time periods (P for trend < 0.001). With respect to the 1987-1993 birth cohort, the incidence rate ratio increased approximately linearly from 0.63 (95% CI 0.54-0.73) in the 1975-1981 cohort to 1.38 (1.06-1.80) in the 1999-2003 cohort. The best model, however, included sex, age, and a linear time trend (drift). CONCLUSIONS: Large geographical variations and an increasing temporal trend in diabetes incidence are evident among type 1 diabetic children in Italy. Age-period-cohort analysis shows that the variation over time has a linear component that cannot be ascribed to either the calendar period or the birth cohort.