Increased prevalence of cardiovascular risk factors in children and adolescents with type 1 diabetes and hypertension: The SWEET international database.

AIMS: To investigate the prevalence of modifiable cardiovascular risk factors (CVRFs), including dyslipidaemia, obesity and high glycated haemoglobin (HbA1c) concentration, in patients with type 1 diabetes (T1D), and to evaluate their association with blood pressure (BP) categories. METHODS: We analysed 21 634 children and adolescents with T1D from the SWEET international database with office BP values assessed at a three or more visits within a year from 2010 to 2021. Participants were classified into a normotensive group, a group with elevated BP (90 to 94th percentile) or a hypertensive group (≥95th percentile), based on the median BP for the visits within the last treatment year. The prevalences of dyslipidaemia [cholesterol ≥ 5.18 mmol/L (200 mg/dL)  and/or HDL cholesterol ≤ 1.036 mmol/L (40 mg/dL)  and/or LDL cholesterol ≥ 2.59 mmol/L (100 mg/dL)], obesity (body mass index ≥2 standard deviation score) and elevated HbA1c [≥ 75 mmol/mol (9%)] were evaluated in patients within each BP group. RESULTS: Patients with hypertension/elevated BP had less favourable lipid profiles, and a higher prevalence of obesity and HbA1c ≥ 75 mmol/mol than normotensive patients. A total of 38.4% of hypertensive patients and 36.0% of those with elevated BP had one CVRF, 15.1% and 10.1%, respectively, had two CVRFs, and 2.3% and 0.8%, respectively, had three CVRFs. Patients with hypertension/elevated BP had a higher prevalence of one or more CVRFs versus normotensive patients (P < 0.001). Obesity was the CVRF most strongly related to hypertension. Girls had a higher prevalence of one or more CVRFs than boys. Similar results were found in patients aged ≥13 years with hypertension compared to those aged <13 years. CONCLUSIONS: The prevalence of modifiable CVRFs is higher in children and adolescents with T1D who have elevated BP/hypertension than in those with normotension, suggesting that they are more vulnerable to future morbidity and mortality requiring early detection and intervention.

COVID-19 vaccination in adolescents and young adults with type 1 diabetes: Glycemic control and side effects.

BACKGROUND: Two vaccines against SARS-CoV-2 are approved by the World Health Organization (WHO) for minors aged 12 years and over. Currently, people with both type 1 diabetes (T1D) and type 2 diabetes (T2D) are prioritized for vaccination. OBJECTIVE: To evaluate possible glycemic control modification, insulin dose adjustment and adverse effects after COVID-19 vaccination in young T1D individuals, users of different technology levels. METHODS: Thirty-nine T1D individuals, who received a whole vaccination cycle of either Moderna or Pfizer- BioNTech vaccines, were enrolled, 24 of whom using advanced hybrid closed loop systems (AHCLs) and 15 using intermittently scanned continuous glucose monitoring (isCGM). Symptoms after each dose and the following variables were considered: time in range 70-180 mg/dl (TIR), time in different glucose ranges, mean glucose levels, coefficient of variation (CV), total daily dose (TDD) and bolus proportion RESULTS: No significant differences in TIR, time in different glucose ranges, mean glucose levels, TDD, bolus proportion, were observed before and after any dose nor before and after the whole vaccination cycle. CV was significantly lower after the whole vaccination cycle (CV pre-vaccination 35.1 ± 6.9% vs. CV post-vaccination 33.5 ± 6.3%; p 0.031) in subjects treated by AHCLs. Side effects after the vaccination were mild and more frequent after the second dose. No severe adverse reactions were reported. CONCLUSIONS: COVID-19 vaccination was safe and not associated with significant perturbation of glycemic control in adolescents and young adults with T1D. This information could be of clinical use when counseling families about SARS-CoV-2 vaccination in young people with T1D.

Long-term effectiveness of advanced hybrid closed loop in children and adolescents with type 1 diabetes.

BACKGROUND: Advanced hybrid closed loop (AHCL) systems are the newest tool to improve metabolic control in type 1 diabetes (T1D). Long-term glycemic control of children and adolescents with T1D switching to MiniMed™ 780G in a real clinical setting was evaluated. METHODS: Time in range (TIR) and in different glucose ranges, glycemic variability indexes, HbA1c and basal-bolus insulin distribution were evaluated in 44 subjects (mean age 14.2 ± 4.0 years, 22 males) during manual mode period, first 14 days (A14d) and first month after auto-mode activation (A1M), first 14 days after 3 months (A3M) and 6 months (A6M) in auto-mode. RESULTS: Mean TIR at A14d was 76.3 ± 9.6% versus 69.3 ± 12.6% in manual mode (p < 0.001), and this improvement was maintained over 6 months. Subjects with TIR >70% and >80% in manual mode were 45% and 23%, respectively, and increased to 80% (p = 0.041) and 41% (p = 0.007) at A14d. Basal-bolus distribution changed in favor of bolus, and auto-correction boluses inversely correlated with TIR. HbA1c was 7.2 ± 0.7% (55 mmol/mol) at baseline and significantly improved after 3 months (6.7 ± 0.5%, 50 mmol/mol, p < 0.001) and 6 months (6.6 ± 0.5%, 49 mmol/mol, p < 0.001). TIR was higher in individuals >13 years at all time periods (p < 0.001). Glycemic target <120 mg/dl was associated with better TIR. CONCLUSIONS: AHCL MiniMed™ 780G allowed rapid and sustained improvement of glycemic control in young T1D patients, reaching recommended TIR. Teenagers showed good technology adherence with optimal TIR, maintained better over time compared to younger children. Stricter settings were associated with better metabolic control, without increase in severe hypoglycemia occurrence.

Effectiveness of a closed-loop control system and a virtual educational camp for children and adolescents with type 1 diabetes: A prospective, multicentre, real-life study.

AIM: To evaluate the impact of a virtual educational camp (vEC) on glucose control in children and adolescents with type 1 diabetes using a closed-loop control (CLC) system. MATERIALS AND METHODS: This was a prospective multicentre study of children and adolescents with type 1 diabetes using the Tandem Basal-IQ system. Insulin pumps were upgraded to Control-IQ, and children and their parents participated in a 3-day multidisciplinary vEC. Clinical data, glucose metrics and HbA1c were evaluated over the 12 weeks prior to the Control-IQ update and over the 12 weeks after the vEC. RESULTS: Forty-three children and adolescents (aged 7-16 years) with type 1 diabetes and their families participated in the vEC. The median percentage of time in target range (70-180 mg/dL; TIR) increased from 64% (interquartile range [IQR] 56%-73%) with Basal-IQ to 76% (IQR 71%-81%) with Control-IQ (P < .001). After the vEC, more than 75% of participants achieved a TIR of more than 70%. The percentage of time between 180 and 250 mg/dL and above 250 mg/dL decreased by 5% (P < .01) and 6% (P < .01), respectively, while the time between 70 and 54 mg/dL and below 54 mg/dL remained low and unaltered. HbA1c decreased by 0.5% (P < .01). There were no episodes of diabetic ketoacidosis or severe hypoglycaemia. CONCLUSIONS: In this study of children managing their diabetes in a real-world setting, more than 75% of children who participated in a vEC after starting a CLC system could obtain and maintain a TIR of more than 70%. The vEC was feasible and resulted in a significant and persistent improvement in TIR in children and adolescents with type 1 diabetes.

Blood pressure measurement methodology and technology in the SWEET diabetes centers: An international SWEET database survey.

INTRODUCTION: The accuracy of blood pressure (BP) measurement is a prerequisite for the reliable diagnosis and management of hypertension. OBJECTIVES: This survey evaluated the use of office and out-of-office BP measurements and the antihypertensive pharmacological treatment in expert pediatric diabetes centers. METHODS: A questionnaire was distributed in 78 reference pediatric diabetes centers of the SWEET international consortium. The methodology, devices, indications, and interpretation of office BP measurements (OBPM), 24-hour ambulatory BP monitoring (ABPM) and home BP monitoring (HBPM), and the preference for antihypertensive drug treatment was assessed. A grading score was developed to evaluate centers for overall BP measurement performance. RESULTS: Fifty-two centers responded. The average score for OBPM methodology was 72.5%, for technology 77.5% and the overall center score was 74.75%.The majority of the centers used appropriate methodology and technology, however, there was heterogeneity among them. Manual auscultatory or automated devices specifically validated for children were used by 26/52 centers. ABPM was recommended by 35/52 centers (27/35 had health insurance coverage) and HBPM by 18/52 centers. The BP measurement methodology and devices used for ABPM and HBPM were frequently inadequate. Angiotensin converting enzyme inhibitors were the most frequently prescribed drugs for treating hypertension. CONCLUSIONS: The majority of SWEET pediatric diabetes centers use adequate methodology and devices for BP measurement. ABPM is recommended by two thirds of the centers, whereas HBPM is less widely used. Further improvement in the quality of office and out-of-office BP measurements and harmonization among centers is necessary according to current guidelines.

Association of diabetic ketoacidosis and HbA1c at onset with year-three HbA1c in children and adolescents with type 1 diabetes: Data from the International SWEET Registry.

OBJECTIVE: To establish whether diabetic ketoacidosis (DKA) or HbA1c at onset is associated with year-three HbA1c in children with type 1 diabetes (T1D). METHODS: Children with T1D from the SWEET registry, diagnosed <18 years, with documented clinical presentation, HbA1c at onset and follow-up were included. Participants were categorized according to T1D onset: (a) DKA (DKA with coma, DKA without coma, no DKA); (b) HbA1c at onset (low [<10%], medium [10 to <12%], high [≥12%]). To adjust for demographics, linear regression was applied with interaction terms for DKA and HbA1c at onset groups (adjusted means with 95% CI). Association between year-three HbA1c and both HbA1c and presentation at onset was analyzed (Vuong test). RESULTS: Among 1420 children (54% males; median age at onset 9.1 years [Q1;Q3: 5.8;12.2]), 6% of children experienced DKA with coma, 37% DKA without coma, and 57% no DKA. Year-three HbA1c was lower in the low compared to high HbA1c at onset group, both in the DKA without coma (7.1% [6.8;7.4] vs 7.6% [7.5;7.8], P = .03) and in the no DKA group (7.4% [7.2;7.5] vs 7.8% [7.6;7.9], P = .01), without differences between low and medium HbA1c at onset groups. Year-three HbA1c did not differ among HbA1c at onset groups in the DKA with coma group. HbA1c at onset as an explanatory variable was more closely associated with year-three HbA1c compared to presentation at onset groups (P = .02). CONCLUSIONS: Year-three HbA1c is more closely related to HbA1c than to DKA at onset; earlier hyperglycemia detection might be crucial to improving year-three HbA1c.

Association of celiac disease in patients with multiple sclerosis in Tuscany.

Background and study purpose: to describe the comorbidity of celiac disease among a large cohort of multiple sclerosis patients in Tuscany. METHODS: the association of celiac disease among multiple sclerosis adult patients (n=2050) was retrospectively evaluated. RESULTS: 13 patients were diagnosed with celiac disease, the female:male ratio was 3.3:1 and the median age at diagnosis was 34.2 years (SD 13). Seventy-seven per cent of subjects complained about gastrointestinal symptoms. IgA anti- transglutaminase was positive in 85 % of cases and there was 70 % of villous atrophy. CONCLUSIONS: the frequency of celiac disease among multiple sclerosis patients examined was lower than in the general population, 0.6 % vs 1 %)(p = 0.65).

Adjusting insulin doses in patients with type 1 diabetes who use insulin pump and continuous glucose monitoring: Variations among countries and physicians.

AIMS: To evaluate physicians' adjustments of insulin pump settings based on continuous glucose monitoring (CGM) for patients with type 1 diabetes and to compare these to automated insulin dose adjustments. METHODS: A total of 26 physicians from 16 centres in Europe, Israel and South America participated in the study. All were asked to adjust insulin dosing based on insulin pump, CGM and glucometer downloads of 15 patients (mean age 16.2 ± 4.3 years, six female, mean glycated haemoglobin 8.3 ± 0.9% [66.8 ± 7.3 mmol/mol]) gathered over a 3-week period. Recommendations were compared for the relative changes in the basal, carbohydrate to insulin ratio (CR) and correction factor (CF) plans among physicians and among centres and also between the physicians and an automated algorithm, the Advisor Pro (DreaMed Diabetes Ltd, Petah Tikva, Israel). Study endpoints were the percentage of comparison points for which there was full agreement on the trend of insulin dose adjustments (same trend), partial agreement (increase/decrease vs no change) and full disagreement (opposite trend). RESULTS: The percentages for full agreement between physicians on the trend of insulin adjustments of the basal, CR and CF plans were 41 ± 9%, 45 ± 11% and 45.5 ± 13%, and for complete disagreement they were 12 ± 7%, 9.5 ± 7% and 10 ± 8%, respectively. Significantly similar results were found between the physicians and the automated algorithm. The algorithm magnitude of insulin dose change was at least equal to or less than that proposed by the physicians. CONCLUSIONS: Physicians provide different insulin dose recommendations based on the same datasets. The automated advice of the Advisor Pro did not differ significantly from the advice given by the physicians in the direction or magnitude of the insulin dosing.

Type 1 diabetes, sport practiced, and ankle joint mobility in young patients: What is the relationship?

BACKGROUND/OBJECTIVE: It is known that patients with diabetes can develop limited joint mobility (LJM) and that this can depend on the metabolic control maintained and the duration of the disease. The aims of this study were to verify the presence of ankle joint mobility (AJM) deficits in both plantar and dorsiflexion in young type 1 diabetic patients (T1D) considering also the possible role of sport practiced as a further factor, able to modify AJM. METHODS: AJM was evaluated by an inclinometer in 82 T1D patients (M/F: 48/34), mean age 12.9 ± 2.6 years, body mass index (BMI) 19.7 ± 3.6 kg/m2 , duration of diabetes 5.6 ± 3.3 years, mean HbA1c 7.5 ± 1.0% and in 226 healthy controls (M/F: 146/80), age-, gender-, and BMI-matched practicing different sports (soccer, volleyball, basketball, and dance). RESULTS: The patients' ankle range of motion was significantly lower than that in controls (132.7 ± 22.3° vs 126.1 ± 17.9°; P < .017). In particular, ankle plantar flexion was significantly lower in the patients group (31.6° ± 7.9° vs 28.5° ± 6.6°; P < .002). Soccer players showed lower AJM in both groups: patients (120.1 ± 15.9° vs 127.3 ± 18.1) and controls (119.4 ± 21.1° vs 142.0 ± 18.1; P < .0001) than subjects practicing other sports or who were sedentary. In both groups, patients and controls, age, sex, duration of disease, hemoglobin 1Ac, and BMI have not been shown to be correlated to the mobility assessed. CONCLUSIONS: The results of this study, in addition to confirming the negative effect of diabetes on AJM of young T1D patients, suggest that during these evaluations the sport-related effect should be considered because it can induce significant changes of AJM.

The influence of treatment, age at onset, and metabolic control on height in children and adolescents with type 1 diabetes-A SWEET collaborative study.

OBJECTIVE: To describe the association between height, demographics, and treatment in youths with type 1 diabetes participating in an international network for pediatric diabetes centers (SWEET). METHODS: Data were collected from 55 centers with documented patients' height. All subjects below 20 years of age, diabetes duration >1 year, and without celiac disease were included. World Health Organization growth charts were used to calculate height and body mass index z-scores. Multiple hierarchic regression models adjusting for known confounders were applied. RESULTS: Data on 22 941 subjects (51.8% male) were analyzed with a median and interquartile range for age 14.8 years (11.2, 17.6), diabetes duration 5.6 years (3.1, 8.9), and height z-score 0.34 (-0.37, 1.03). Children were taller in the youngest age groups: adjusted height z-scores of 0.31 (±0.06) and 0.39 (±0.06), respectively; with shorter diabetes duration (<2 years: 0.36 [±0.06]; 2-<5 years: 0.34 [±0.06]; ≥5 years: 0.21 [±0.06]) and if they were pump users: 0.35 ± 0.05 vs 0.25 ± 0.05 (>three injections/day and 0.19 ± 0.06 [0-3 injections daily]), respectively. High hemoglobin A1c (HbA1c) and low to normal weight were associated with a lower height z-score. Trends were identical in all models except for gender. No gender differences were found except in the final height model where females exhibited higher z-score than males. CONCLUSION: For youths treated at centers offering modern diabetes management, major growth disturbances are virtually eliminated. For children with a young age at onset, high HbA1c, injections, and/or non-intensive diabetes, treatment still requires attention in order to attain normal growth.

The changing landscape of neonatal diabetes mellitus in Italy between 2003-2022.

CONTEXT: In the last decade Sanger method of DNA sequencing has been replaced by next generation sequencing (NGS). NGS is valuable in conditions characterized by high genetic heterogeneity such as neonatal diabetes mellitus (NDM). OBJECTIVE: To compare results of genetic analysis of patients with NDM and congenital severe insulin resistance (c.SIR) identified in Italy in 2003-2012 (Sanger) versus 2013-2022 (NGS). METHODS: We reviewed clinical and genetic records of 104 cases with diabetes onset before 6 months of age (NDM+c.SIR) of the Italian dataset. RESULTS: Fiftyfive patients (50 NDM + 5 c.SIR) were identified during 2003-2012 and 49 (46 NDM + 3 c.SIR) in 2013-2022. Twenty-year incidence was 1:103,340 (NDM) and 1:1,240,082 (c.SIR) live births. Frequent NDM/c.SIR genetic defects (KCNJ11, INS, ABCC8, 6q24, INSR) were detected in 41 and 34 probands during 2003-2012 and 2013-2022, respectively. We identified a pathogenic variant in rare genes in a single proband (GATA4) (1/42 or 2.4%) during 2003-2012 and in 8 infants (RFX6, PDX1, GATA6, HNF1B, FOXP3, IL2RA, LRBA, BSCL2) during 2013-2022 (8/42 or 19%, p= 0.034 vs 2003-2012). Notably, five among rare genes were recessive. Swift and accurate genetic diagnosis led to appropriate treatment: patients with autoimmune NDM (FOXP3, IL2RA, LRBA), were subjected to bone marrow transplant; patients with pancreas agenesis/hypoplasia (RFX6, PDX1) were supplemented with pancreatic enzymes and the individual with lipodystrophy caused by BSCL2 was started on metreleptin. CONCLUSIONS: NGS substantially improved diagnosis and precision therapy of monogenic forms of neonatal diabetes and congenital SIR in Italy.

The Assessment of Ankle Range-of-Motion and Its Relationship with Overall Muscle Strength in a Cross-Section of Soccer Players.

Soccer (football) practice can induce a limitation of ankle range of motion (ROM) that is a possible risk factor for injury and other negative consequences over time. The main objective of this research was to investigate the effects of soccer practice on ankle ROM throughout the entire period of a sports career of soccer players (SP). Furthermore, the relationship between ankle ROM and muscle strength in SP of different ages was studied. A total of 204 SP (range 6.7−45.1 years) and 87 controls (range: 7.5−45.2 years) matched for age, body mass index (BMI), and gender, were assessed. Ankle ROM in both plantar flexion (APF) and dorsiflexion (ADF) in addition to handgrip strength (HGS) were evaluated using an inclinometer and the Jamar hydraulic hand dynamometer, respectively. The comparison between SP and control groups showed a significant reduction in ankle ROM of both APF (26.3 ± 7.2° vs. 32.6 ± 7.4°; d = −0.90; p < 0.001) and ADF (95.5 ± 15.6° vs. 105.5 ± 15.8°; d = −0.66; p < 0.001). In SP, the results of the ANOVAs test indicate that age had a significant effect on ADF (F = 4.352, p = 0.038, partial eta-squared (ηp2) = 0.015) but not on APF (F = 0.430, p = 0.746, ηp2 = 0.001). Moreover, considering only the SP, a weak inverse correlation between ADF and HGS group ADF was found (rs = −0.27; p < 0.001). Factors such as the non-linear trend of growth in young SP could hinder the definition of the relationship between ankle ROM, age, and muscle strength. However, the appropriate consideration of age and muscle strength could facilitate the management of ankle ROM in PF of different ages.

Glycemic Control, Basal/Bolus Distribution, BMI and Meal Management in Children and Adolescents with Type 1 Diabetes and Advanced Hybrid Closed Loop.

Evidence about the impact of advanced hybrid closed loop (AHCL) on body mass index (BMI) and eating habits in children with type 1 diabetes (T1D) is lacking. This real-world study aimed at evaluating glycemic control, BMI, meals and basal/bolus distribution in young subjects with T1D treated by AHCL. Glycemic metrics, HbA1c, basal/bolus distribution, meals/day, BMI, total daily dose (TDD), and carbohydrates/kg (CHO/kg) have been evaluated in 83 subjects, aged 13 ± 4.5 years, in manual mode, 3 and 6 months after auto-mode. Time in range (TIR) increased after 3 months, exceeding the target of 70% and was maintained at 6 months. While coefficient of variation (CV) did not change, the glucose management indicator (GMI) decreased in auto-mode (6.7 ± 0.3 vs. 7.1 ± 0.5%; p < 0.001), as well as HbA1c. Basal proportion decreased in favor of boluses (38.3 ± 7.3 vs. 43.6 ± 10.9%; p < 0.001). Meals increased at 3 and 6 months (4.4 ± 1.2 vs. 5.0 ± 1.5, p 0.002 and 5.1 ± 1.7, p < 0.001), as well as TDD/kg, without changes in BMI and CHO consumed. No differences in meal composition have arisen from food diaries. In conclusion, AHCL ensured the achievement and maintenance of target TIR in young T1D subjects. The number of meals, TDD, and insulin bolus proportion increased over time, but BMI remained stable.

HLA-DQ typing in the diagnostic algorithm of celiac disease.

OBJECTIVE: celiac disease (CD) is an immune-mediated chronic inflammatory disease associated with HLA-DQ2 and DQ8 molecules. We evaluated the role of HLA in the CD diagnostic algorithm in order to contribute to the development of practical indications for the use of HLA typing. MATERIAL AND METHODS: we selected 317 subjects typed for DR-DQ genes. CD was present in 123 patients, and 89 were included in the study; a control sample of 70 healthy individuals was recruited. RESULTS: 64% of patients with CD carried DQ2 heterodimer (α5ß2), 13.5% carried DQ8 heterodimer without DQ2, 21.4% only showed ß2 chain and 1.1% were positive for DQ2 α5 chain. The only presence of α5 chain did not predispose to CD, while DQB1*02 allele resulted more frequent than in other reports, pointing out the intrinsic correlation between ß2 chain and CD. In the case-control study we observed a progression of increased risk, ranging from 1:7 for HLA-DQ2 homozygous to 1:85 for DQ8 heterozygous subjects. Overall, 8,6% of first degree family members were affected, exclusively in presence of HLA-DQ2, -DQ8 or DQB1*02, and CD was significantly more frequent among siblings than parents. Finally, considering the different patterns of clinical presentation among the HLA-DQ risk classes identified we found no relationship between CD clinical presentation and HLA-DQ risk categories. CONCLUSIONS: our results strengthen the evidence that HLA-DQ status strongly influences the development of CD and demonstrate that knowledge of a patient's HLA-DQ genotype allows to establish clinically relevant genetic risk profiles.

DR4/DQ2 haplotype confers susceptibility to T1DM with early clinical disease onset: A retrospective analysis in a tertiary-care hospital in Italy.

INTRODUCTION: T1DM is the most frequent form of diabetes in children. It has a multifactorial pathogenesis in which genetic, environmental and immunological factors are involved. Among genetic explanations a major role is attributed to second class HLA genes, with the greatest risk associated with the simultaneous presence of the haplotypes DR3DQ2 and DR4DQ8. Based on results obtained in other countries, the aim of this research is to verify a possible association between the haplotype DRB1 * 04: 05-DQA1 * 03-DQB1 * 02 and the onset of T1DM among Italian children with possible genotype-phenotype correlations. Greater knowledge of genes which increase or decrease susceptibility is important for genome analysis. MATERIALS AND METHODS: 165 patients with type 1 diabetes treated at the Diabetology Unit of the Meyer Children's University Hospital, were clinically analyzed. Data relating to age at diagnosis, pancreatic anti-beta cell autoimmunity, comorbidities with date of diagnosis and family history were retrospectively collected from medical data. A case-control study was conducted to investigate the HLA types of the patients compared to a control group of 819 Tuscan donors enrolled in the National Bone Marrow Donor Register. Typing was carried out using the Eurospital "DIABEGEN" kit, currently in use at the immunology laboratory of the Meyer Children's University Hospital. RESULTS: Mean age at diagnosis was 9.3 years; most children (97%) had anti-pancreatic beta cell autoimmunity; the anti-insulin antibody (IAA) was more frequent among children with early clinical disease onset (0-5 years of age). From the case control comparison performed on HLA typing, it emerged that the greatest risk for the development of type 1 diabetes is conferred by the haplotypes DR3DQ2 and DR4DQ8, but in addition to these haplotypes, already known in other countries, we identified another haplotype, DR4DQ2 (DRB1 * 04: 05-DQA1 * 03-DQB1 * 02) which appears to predispose children to type 1 diabetes (p value 2.80E-08) and it is associated with early clinical disease onset (p-value = 0.002). CONCLUSIONS: We report a new haplotype which increases susceptibility to type 1 diabetes among Italian children and which is associated with early clinical disease onset. Given the central role attributed to genetic factors in the pathogenesis of T1DM and to the II class HLA genes, this new haplotype ought to be recognized as a risk factor and included in tests routinely carried out to identify patients with a genetic predisposition to type I diabetes in Italy. These findings could have practical implications in research and prevention programs.

The Importance of Office Blood Pressure Measurement Frequency and Methodology in Evaluating the Prevalence of Hypertension in Children and Adolescents With Type 1 Diabetes: The SWEET International Database.

OBJECTIVE: The prevalence of hypertension is higher in children and adolescents with type 1 diabetes (T1D) compared with those without. This retrospective analysis of a large cohort of children and adolescents with T1D from the SWEET (Better control in Pediatric and Adolescent diabeteS: Working to crEate CEnTers of Reference) international consortium of pediatric diabetes centers aimed to 1) estimate the prevalence of elevated office blood pressure (BP) and hypertension and 2) investigate the influence of BP measurement methodology on the prevalence of hypertension. RESEARCH DESIGN AND METHODS: A total of 27,120 individuals with T1D, aged 5-18 years, were analyzed. Participants were grouped into those with BP measurements at three or more visits (n = 10,440) and fewer than 3 visits (n = 16,680) per year and stratified by age and sex. A subgroup analysis was performed on 15,742 individuals from centers providing a score indicating BP measurement accuracy. RESULTS: Among participants with BP measurement at three or more visits, the prevalence of hypertension was lower compared with those with fewer than three visits (10.8% vs. 17.5% P < 0.001), whereas elevated BP and normotension were higher (17.5% and 71.7% vs. 15.3% and 67.1%, respectively; both P < 0.001). The prevalence of hypertension and elevated BP was higher in individuals aged ≥13 years than in younger ones (P < 0.001) and in male than female participants (P < 0.001). In linear regression models, systolic and diastolic BP was independently determined by the BP measurement methodology. CONCLUSIONS: The estimated prevalence of elevated BP and hypertension in children and adolescents with T1D is ∼30% and depends on the BP measurement methodology. Less frequent BP evaluation may overestimate the prevalence of hypertension.

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.

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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Retrospective Evaluation on the Use of a New Polysaccharide Complex in Managing Paediatric Type 1 Diabetes with Metabolic Syndrome (MetS).

BACKGROUND: Children and adolescents affected by type 1 diabetes have an increased risk of being overweight or obese and of suffering from cardiometabolic symptoms. AIMS: To retrospectively evaluate the effects of a new complex of polysaccharide macromolecules, Policaptil Gel Retard® (PGR), on auxological and metabolic parameters, glycaemic variability and control parameters in paediatric patients with type 1 diabetes and metabolic syndrome (MetS). PATIENTS AND METHODS: Data for 27 paediatric patients with a diagnosis of type 1 diabetes in conjunction with obesity and MetS of at least 5 years' standing were collected and retrospectively studied. Of these, 16 (median age 12.9, range 9.5-15.8 years) had been adjunctively treated with PGR and 11 (median age 12.6, range 9.4-15.6 years) had not been treated with PGR. Auxological, metabolic and glycaemic control and variability parameters and insulin dosing were compared after 6 months in the two groups. RESULTS: PGR significantly reduced BMI standard deviation score (SDS) (p < 0.005), waist SDS (p < 0.005), HbA1c (p < 0.05) and daily mean insulin dose requirement (p < 0.005). A significant improvement was also observed in the metabolic and glycaemic variability parameters of mean daily blood glucose (BG) levels (p < 0.005), SD of daily BG levels (p < 0.0001), mean coefficient of variation (p < 0.05), LBGI (p < 0.0001), HBGI (p < 0.0001), J-index (p < 0.005), total cholesterol (p < 0.005), HDL-cholesterol (p < 0.005) and LDL-cholesterol (p < 0.005) and triglycerides (p < 0.05). CONCLUSIONS: PGR produces a good auxological and metabolic response in obese patients with MetS who are affected by type 1 diabetes. It led to a significant reduction in BMI SDS, waist SDS and an improvement in glucose control and variability as well as in other MetS parameters. The use of polysaccharide compounds, especially if associated with appropriate dietary changes, may help achieve treatment targets in type 1 diabetes and reduce the risk that patients develop metabolic syndrome.

Cocreation of Massive Open Online Courses to Improve Digital Health Literacy in Diabetes: Pilot Mixed Methods Study.

BACKGROUND: Self-management education is a fundamental aspect in the health care of people with diabetes to develop the necessary skills for the improvement of health outcomes. Patients are required to have the competencies to manage electronic information resources-that is, an appropriate level of digital health literacy. The European project IC-Health aimed to improve digital health literacy among people with diabetes through the cocreation of massive open online courses (MOOCs). OBJECTIVE: We report the preliminary results obtained in 3 participating countries in the IC-Health project (Italy, Spain, and Sweden) regarding (1) experience of the participants during the cocreation process of MOOCs, (2) perceived changes in their digital health literacy level after using MOOCs, and (3) a preliminary assessment of the acceptability of MOOCs. METHODS: The cocreation of the MOOCs included focus groups with adults and adolescents with diabetes and the creation of independent communities of practice for type 1 diabetes and type 2 diabetes participants aimed to co-design the MOOCs. Quantitative measures of the acceptability of MOOCs, experience in the cocreation process, and increase in digital health literacy (dimensions of finding, understanding, and appraisal) were assessed. RESULTS: A total of 28 participants with diabetes participated in focus groups. Adults and adolescents agreed that the internet is a secondary source of health-related information. A total of 149 participants comprised the diabetes communities of practice. A total of 9 MOOCs were developed. Acceptability of the MOOCs and the cocreation experience were positively valued. There was a significant improvement in digital health literacy in both adults and adolescents after using MOOCs (P<.001). CONCLUSIONS: Although the results presented on self-perceived digital health literacy are preliminary and exploratory, this pilot study suggests that IC-Health MOOCs represent a promising tool for the medical care of diabetes, being able to help reduce the limitations associated with low digital health literacy and other communication barriers in the diabetes population.