ISPAD ANNUAL CONFERENCE HIGHLIGHTS 2023.

The 49th Annual Conference of the International Society of Pediatric and Adolescent Diabetes (ISPAD), held from October 18 to 21, 2023, in Rotterdam, Netherlands, showcased significant advancements and diversity in paediatric and adolescent diabetes research and clinical innovations. The conference, renowned for its global impact, brought together experts to discuss cutting-edge developments in the field. Highlights from the plenary sessions included ground-breaking research on immunotherapies and diabetes technologies and offering new insights into personalised treatment approaches. Keynote speakers emphasised the importance of early diagnosis, prevention and the potential of novel biomarkers in predicting disease progression. The symposia covered a broad spectrum of topics, from advancements in continuous glucose monitoring technologies to the latest in hybrid closed loop systems which promise to revolutionise diabetes management for young patients.

Safety and efficacy of the structured onboarding steps and initiation protocol for MiniMed™ 780G system among an Egyptian cohort of young people living with type 1 diabetes.

OBJECTIVES: The aim of the current study was to evaluate the safety and efficacy of initiation protocol for MiniMed ™ 780G system among an Egyptian cohort of young people living with type 1 diabetes (T1D). METHODS: A prospective single-arm study including 72 participants with T1D. Five days of structured education and training were provided to all users and continuous glucose monitoring (CGM) was initiated on the first day of the training. Users initiated the pump initially in manual mode, with suspend before low feature, for 3 days before shifting to Auto Mode. RESULTS: The mean HbA1c decreased from 8.72 ± 2.01 % to 6.7 ± 0.4 % (p<0.01). Time in range (70-180 mg/dL) substantially improved from 55.24 % ± 10.35 to 81.7 % ± 5.12 % after spending 84 days in auto mode (p<0.001) with 2.03 % of the time spent below 70 mg/dL. Regarding AHCL compatibility, users spent at least 90 % of time in auto mode. CONCLUSIONS: Young people with T1D successfully initiated the AHCL system, using a tailored structured on-boarding protocol. Structured stepwise initiation protocol and onboarding steps are important prerequisite for participants' adherence and engagement with the system. Patient education together with optimized pump settings are important predictors of glycemic outcomes.

MNX1 mutations causing neonatal diabetes: Review of the literature and report of a case with extra-pancreatic congenital defects presenting in severe diabetic ketoacidosis.

The MNX1 gene encodes a homeobox transcription factor found to be important for pancreatic beta cell differentiation and development. Mutations of the MNX1 gene that cause permanent neonatal diabetes mellitus (PNDM) are rare and have been reported in only two cases. Both cases presented with hyperglycemia, with one case having isolated PNDM while the other had PNDM and multiple neurologic, skeletal, lung, and urologic congenital anomalies resulting in death in early infancy. We describe the genetic and clinical features of a preterm male infant with a homozygous [c.816C > A p.(Phe272Leu)] MNX1 mutation. Our proband is the first case to present in severe diabetic ketoacidosis (DKA), indicating severe insulin deficiency. Unlike the previously reported female case who had the same mutation and presented with isolated PNDM, our proband had hypospadias and congenital umbilical hernia and showed poor growth on follow up. Our case suggests that MNX1 mutations causing NDM can result in a range of extra-pancreatic features and a variable phenotype, similar to other transcription factors causing NDM such as GATA6 and GATA4 mutations. We also cannot exclude the possibility of sex-biased expression of MNX1 gene (which was recently reported for other monogenic/neonatal diabetes genes such as the NEUROD1 and HNF4A in humans) since the two male cases had associated multiple anomalies while the female case had isolated PNDM. Our report further defines the phenotype caused by recessive homozygous MNX1 mutations and explores potential new mechanisms regulating MNX1 gene expression which should be further explored.

Insulin delivery patterns required to maintain postprandial euglycemia in type 1 diabetes following consumption of traditional Egyptian Ramadan Iftar meal using insulin pump therapy: A randomized crossover trial.

OBJECTIVES: During Ramadan, traditional Egyptian Iftar meals have large amounts of high-glycemic index carbohydrate and fat. The efficacy of different bolus regimens on optimizing post prandial glucose (PPG) excursion following this Iftar meal was assessed. METHODS: A randomized controlled trial evaluating 4-h PPG measured by continuous glucose-monitoring was conducted. A total of 25 youth with T1DM using insulin pumps were given the same Iftar meal (fat [45 g], protein [28 g], CHO [95 g]) on seven consecutive days. Insulin to carbohydrate ratio (ICR) was individualized, and all boluses were given upfront 20 min before Iftar. Participants were randomized to receive a standard bolus and six different split boluses delivered over 4 h in the following splits: dual wave (DW) 50/50; DW 50/50 with 20% increment (120% ICR); DW60/40; DW 60/40 with 20% increment; DW 70/30 and DW 70/30 with 20% increment. RESULTS: Standard bolus and split 70/30 with 20% increment resulted in significantly lower early glucose excursions (120 min) with mean excursions of less than 40 mg/dL (2.2 mmol/L) compared to other conditions (p < 0.01). The split 70/30 with 20% increment significantly optimized late PPG excursion (240 min) in comparison to standard bolus (p < 0.01), as well as resulting in a significantly lower post meal glucose area under the curve compared with all other conditions (p < 0.01), with no late hypoglycemia. CONCLUSION: To achieve physiologic PPG profile in traditional Iftar meal, a DW bolus with 20% increment given 20 min preprandial as split bolus 70/30 over 4 h, optimized both early and delayed PPG excursions.

Adherence to Insulin Therapy Among Children with Type 1 Diabetes: Reliability and Validity of the Arabic Version of the 4-Item Morisky Medication Adherence Scale.

Background: Inadequate adherence to insulin is a major concern, necessitating the use of reliable and valid metrics for assessing adherence. Up to date, there are no Arabic validated tools assessing adherence to insulin therapy among children with type 1 diabetes (T1DM). Thus, the aim of this study is to evaluate the psychometric properties of an Arabic version of the four-item Morisky Green Levine Medication Adherence Scale (MGLS-4) as a self-reported measure of adherence to insulin among a cohort of Egyptian children with T1DM. Methods: The MGLS-4 was translated using forward and backward translation. The Cronbach's alpha was used to assess reliability. Criterion validity of the scale was tested by examining the correlation coefficients between the compliance score (level of adherence) and the HbA1c levels. Results: A total of 400 patients completed the Arabic version of MGLS-4. 26.25% of the studied cohort was found to be non-adherent to insulin therapy; non-adherent patients were significantly older (P=0.001). Decreased maternal education level, decreased frequency of blood glucose monitoring and prolonged disease duration best predicted the occurrence of non-adherence among the studied cohort. The internal consistency of the current version showed good reliability (Cronbach's alpha = 0.857). The adherence score and adherence level showed very strong correlation with HbA1c level (rho = 0.830, P < 0.001 and rho = 0.808, P < 0.001, respectively). Conclusion: The Arabic version of MGLS-4 showed good reliability and validity as a self-administered tool for assessing adherence to insulin in pediatric patients with T1DM.

Coping strategies among children and adolescents: validity and reliability of the Arabic version of the Kidcope scale.

Coping strategies adopted by children and adolescents play a crucial role in their mental health. This study aimed to develop the Arabic version of the Kidcope, assess its psychometric properties, and examine age and gender differences in the use of coping strategies by children and adolescents. A total of 800 children and adolescents siblings of patients with type 1 Diabetes mellitus completed the Kidcope scale. The developed Arabic Kidcope was checked for its construct validity, reliability, reproducibility, and confirmed by confirmatory factor analysis (CFA). Age and gender differences in coping styles utilization were assessed by one-way analysis of variance (ANOVA) and student t tests. Kidcope chid version yielded a three factors model by exploratory factor analysis (EFA). Overall, the 15-items revealed good internal consistency, Cronbach's alpha (0.89), and an intra-class correlation coefficient (ICC) of 0.82. EFA identified a two-factor solution for adolescents' Kidcope version. Overall, the 11-items showed acceptable internal consistency, Cronbach's alpha (0.74), and satisfactory (ICC) of 0.84. For both versions, the CFA supported the yielded factors models with good model fit indices. Developmental age changes were apparent for problem-solving, emotional regulation, and distraction coping strategies, and girls showed an enhanced use of adaptive strategies (problem-solving, social support). The Arabic Kidcope version is a reliable and valid tool to measure coping strategies used by children and adolescents.

Glycemic control among children and adolescents with type 1 diabetes during COVID-19 pandemic in Egypt: a pilot study.

BACKGROUND: The COVID-19 pandemic and the consequences of lockdown significantly impacted glycemic control. AIM: To evaluate the impact of the pandemic and lockdown on glycemic control among Egyptian children and adolescents with type 1 diabetes. METHODS: Cross-sectional study conducted through an online questionnaire. The participants were patients with type 1 diabetes and/or their caregivers. RESULTS: A total of 115 valid responses to the questionnaire were received. During the lockdown, almost 64% of patients showed worsening of their HbA1C with significant increment of HbA1c after the lockdown (p < 0.001). Synchronous simple telemedicine service was initiated through phone calls and social media applications, and 97% of the patients and their families were successfully able to continue follow-up. Almost 76% of the patients/caregivers showed moderate stress which was significantly correlated with HbA1C (p < 0.05). Fear of hospital admission and fear from shortage of medical supplies were the main COVID-19-related worries. CONCLUSION: The lockdown negatively impacted glycemic control and initiated a set of COVID-19 worries and stress among patients and their caregivers in Egypt. Telemedicine service, even simple tools, is effective and important for the continuity of care among patients. The limited availability and the fear of shortage of medical supply forced patients to ration glucose monitoring. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13410-021-00968-y.

A Worldwide Perspective on COVID-19 and Diabetes Management in 22,820 Children from the SWEET Project: Diabetic Ketoacidosis Rates Increase and Glycemic Control Is Maintained.

Aims: To investigate the short-term effects of the first wave of COVID-19 on clinical parameters in children with type 1 diabetes (T1D) from 82 worldwide centers participating in the Better Control in Pediatric and Adolescent DiabeteS: Working to CrEate CEnTers of Reference (SWEET) registry. Materials and Methods: Aggregated data per person with T1D ≤21 years of age were compared between May/June 2020 (first wave), August/September 2020 (after wave), and the same periods in 2019. Hierarchic linear and logistic regression models were applied. Models were adjusted for gender, age-, and diabetes duration-groups. To distinguish the added burden of the COVID-19 pandemic, the centers were divided into quartiles of first wave COVID-19-associated mortality in their country. Results: In May/June 2019 and 2020, respectively, there were 16,735 versus 12,157 persons, 52% versus 52% male, median age 13.4 (Q1; Q3: 10.1; 16.2) versus13.5 (10.2; 16.2) years, T1D duration 4.5 (2.1; 7.8) versus 4.5 (2.0; 7.8) years, and hemoglobin A1c (HbA1c) 60.7 (53.0; 73.8) versus 59.6 (50.8; 70.5) mmol/mol [7.8 (7.0; 8.9) versus 7.6 (6.8; 8.6) %]. Across all country quartiles of COVID-19 mortality, HbA1c and rate of severe hypoglycemia remained comparable to the year before the first wave, while diabetic ketoacidosis rates increased significantly in the centers from countries with the highest mortality rate, but returned to baseline after the wave. Continuous glucose monitoring use decreased slightly during the first wave (53% vs. 51%) and increased significantly thereafter (55% vs. 63%, P < 0.001). Conclusions: Although glycemic control was maintained, a significant rise in DKA at follow-up was seen during first wave in the quartile of countries with the highest COVID mortality. Trial Registration: NCT04427189.

Clinical characteristics and outcome of hospitalized children and adolescent patients with type 1 diabetes during the COVID-19 pandemic: data from a single center surveillance study in Egypt.

OBJECTIVES: COVID-19 pandemic significantly impacted the diagnosis of type 1 diabetes and its acute complications. Thus, the study aimed to evaluate the characteristics of pediatric patients with type 1 diabetes hospitalized during the first wave of the pandemic and the prevalence of new onset diabetes among patients with evidence of COVID-19 infection. METHODS: A single-center surveillance study included all patients with diabetes admitted to Children's Hospital, Ain Shams University, in Egypt between May to August 2020. Data were collected to evaluate patients' clinical and laboratory characteristics as well as their outcomes. RESULTS: Thirty-six patients were admitted during the study period. The mean age was 8.4 ± 3.8 years. Patients presented late to the emergency department with a mean delay of 3.05 ± 1.19 days from onset of symptoms. 34/36 patients presented in diabetic ketoacidosis (DKA), 50% presenting in severe DKA. Almost 81% of the patients were newly diagnosed. During the study period, SARS-CoV-2 PCR was found positive in four patients, COVID Ig M antibodies were positive in another two patients; all were symptomatic requiring ICU admission. Four patients showed a picture suggestive of the multi-inflammatory syndrome (MIS-C); cardiac affection was a constant feature. CONCLUSIONS: The pandemic affected both the prevalence and severity of DKA among pediatric patients. The increased prevalence of severe DKA could be partly related to delayed hospital admission or the effect of COVID-19 in triggering DKA. Efforts should be done to continuously raise awareness about diabetes in children as well as the importance of seeking timely medical guidance.

Urinary miRNA-377 and miRNA-216a as biomarkers of nephropathy and subclinical atherosclerotic risk in pediatric patients with type 1 diabetes.

BACKGROUND: Urinary microRNAs (miRNAs) play a role in the pathogenesis of chronic kidney disease (CKD). AIM: To identify the expression of urinary miR-377 and miR-216a in 50 children and adolescents with type 1 diabetes (T1DM) compared with 50 healthy controls and assess their relation to the degree of albuminuria, glycemic control and carotid intimal thickness (CIMT) as an index of atherosclerosis. METHODS: Diabetic subjects were divided into normoalbuminuric and microalbuminuric groups according to urinary albumin creatinine ration (UACR). Urinary miRNAs were assessed using real time polymerase chain reaction. CIMT was measured using high resolution carotid ultrasound. RESULTS: The expression of urinary miR-377 was significantly higher in patients with microalbumiuria (median, 3.8) compared with 2.65 and 0.98 in normoalbuminic patients and healthy controls, respectively (p<0.05). Urinary miR-216a was significantly lower in all patients with type 1 diabetes and the lowest levels were among the microalbumiuric group. Significant positive correlations were found between urinary miR-377 and HbA1C, UACR and CIMT while urinary miR-216a was negatively correlated to these variables. CONCLUSIONS: Urinary miR-377 and miR-216a can be considered early biomarkers of nephropathy in pediatric type 1 diabetes. Their correlation with CIMT provides insights on the subclinical atherosclerotic process that occurs in diabetic nephropathy.

Early Cardiac Involvement and Risk Factors for the Development of Arrhythmia in Patients With ß-Thalassemia Major.

BACKGROUND: Cardiac iron overload is the most serious complication in thalassemia; even patients treated with intensive chelation suffer at a certain point from cardiomyopathy and arrhythmia. AIM: The aim of the study was to identify indicators of cardiac dysfunction in thalassemia as well as risk factors associated with the development of arrhythmia. PATIENTS AND METHODS: A total of 45 patients with ß-thalassemia major were enrolled in this cross-sectional study. Patients were divided into 2 groups according to the absence (group A) or the presence of arrhythmia (group B). Cardiac parameters in thalassemic groups were evaluated using 24-Holter recording, Stress electrocardiogram, and M-mode echocardiography. Serum ferritin and Cardiac T2* were used to assess the iron status. RESULTS: Group B showed significantly higher values of cardiac T2* and serum ferritin (P<0.05). Group B patients had significantly higher maximum heart rate with significant attacks of bradycardia and ST segment changes. In addition, they achieved a lower percentage of maximum age predicted heart rate and lower values of maximum metabolic equivalents (P<0.05). Significantly higher values of the left atrial diameter, the interventricular septum diameter, and the left-ventricle posterior wall diameter (P<0.05) were identified in group B. CONCLUSIONS: The increase in left atrial diameter, interventricular septum diameter, and left-ventricle posterior wall diameter seems to be related to the development of arrhythmia in patients with thalassemia, especially supraventricular arrhythmias.

Budd-Chiari syndrome complicating essential thrombocythemia in an adolescent: favorable outcome of TIPS procedure.

Budd-Chiari syndrome (BCS) is a liver disorder characterized by hepatic venous outflow obstruction, mainly resulting from thrombosis of the terminal part of the hepatic veins or the inferior vena cava. It causes hepatic congestion, ascites, portal hypertension, and collateral circulation between the obstructed and contiguous patent venous territories. BCS is reported complicating myeloproliferative disorders, as well other prothrombotic events. Essential thrombocythemia is one of the most frequent myeloproliferative disorders that cause BCS, and in some cases, it may be the initial presentation. Many treatment options have been proposed for BCS, routine anticoagulation therapy being recommended as the first therapeutic approach.

Plasma osteoprotegerin concentrations in type 1 diabetic patients with albuminuria.

BACKGROUND: Osteoprotegerin (OPG) is a recently identified inhibitor of bone resorption. Recent studies indicate that OPG is also associated with endothelial dysfunction in diabetes. AIM: To investigate the relationship between plasma OPG levels and urinary albumin excretion (UAE) in type 1 diabetes. METHODS: A total of 80 type 1 diabetic subjects and 40 control subjects were enrolled. Diabetic subjects were divided into a normoalbuminuric group and a microalbuminuric group according to urinary albumin excretion rate (UAER). Plasma OPG level was measured by enzyme-linked immunoassay. RESULTS: The plasma OPG levels were significantly elevated in patients with microalbuminuria (176.39±25.05pg/ml) compared with patients with normoalbuminuria (154.73±16.66pg/ml) and control subjects (44.76±8.7pg/ml). The plasma OPG level had a positive correlation with patients' age, duration of disease, HbA1C and UAER. CONCLUSIONS: Plasma OPG levels are significantly associated with UAE in patients with type 1 diabetes. These findings may support the concept that elevated plasma OPG may be associated with diabetic angiopathy.

Oxidant/antioxidant status in children and adolescents with immune thrombocytopenia (ITP) and the role of an adjuvant antioxidant therapy.

BACKGROUND: Free oxygen radicals might have an adverse effect on platelets which might be reflected either on its count and/or degree of bleeding severity. AIM: To assess oxidant-antioxidant systems and evaluate effect of antioxidant therapy on platelet count (PC) and bleeding score (BS) in children and adolescents with ITP. METHODS: Six months prospective randomized single blind study registered as (NCT 01763658) including 39 patients with newly diagnosed (ND) ITP; group 1 (G1) and 39 patients with chronic ITP (G2), each group was randomly allocated (2:1) to one of two subgroups respectively; (G1A and G2A) interventional arm received daily antioxidant therapy, while G1B and G2B; received a placebo. Both groups were compared with healthy controls (n = 39). The primary efficacy endpoints were the difference in the change from baseline to 6 month in ITP specific bleeding assessment tool (ITP-BAT), PC, total antioxidant capacity (TAC), catalase (CAT), reduced glutathione (GSH) and serum malondialdehyde (MDA). RESULTS: Baseline TAC was significantly lower in patients with (ND) ITP compared to patients with chronic ITP (P < 0.05), both showed significantly lower levels than healthy controls (P < 0.001). At end of study both BS and PC significantly improved in patients receiving antioxidant compared to placebo (P < 0.05). Patients with chronic ITP receiving antioxidant showed better improvement. CONCLUSION: Reduced antioxidant mechanisms were reported in patients with ITP. Antioxidant therapy ameliorated the oxidative stress in both ND and chronic ITP groups which might explain the improvement in both BS and PC.

Efficacy and safety of a novel combination of two oral chelators deferasirox/deferiprone over deferoxamine/deferiprone in severely iron overloaded young beta thalassemia major patients.

OBJECTIVE: Minimal data are available on the combined two oral iron chelators in ß-thalassemia major (ß-TM). Comparison of safety, efficacy, compliance, treatment satisfaction, and quality of life (QoL) of two regimens: deferiprone (DFP) and deferoxamine (DFO) versus DFP and deferasirox (DFX) were studied. METHODS: A prospective randomized trial (NCT01511848) was conducted on 96 young ß-TM patients with severe iron overload. Patients were randomized to receive either DFP with DFO (arm 1) or DFP and DFX (arm 2). Efficacy endpoints were the difference between two groups in the change of serum ferritin (SF), liver iron concentration (LIC), cardiac MRI, and quality of life (QoL). RESULTS: In both arms, SF and LIC at 12 months were significantly lower, and geometric mean cardiac T2* was higher compared to baseline. On regression analysis of change in each studied variable against time, significant difference between slopes of the two groups regarding cardiac T2* (P = 0.001 with more improvement in DFP/DFX patients) was found with no significant difference in the slopes of SF and LIC (P = 0.218 and 0.340). CONCLUSION: Both iron chelation combination regimens were equally effective in reducing iron overload and improving QoL.DFP/DFX combination proved superior in improving cardiac T2*, treatment compliance, and patients satisfaction with no greater adverse events.

Therapeutic superiority and safety of combined hydroxyurea with recombinant human erythropoietin over hydroxyurea in young ß-thalassemia intermedia patients.

OBJECTIVE: To assess the efficacy and safety of combined hydroxyurea (HU) and recombinant human erythropoietin (rHuEPO) in ß-thalassemia intermedia (TI) patients compared with single HU therapy. METHODS: An interventional prospective randomized study registered in the ClinicalTrials.gov (NCT01624038) was performed on 80 TI patients (≤ 18 yr) divided into group A (40 patients received combined HU and rHuEPO) and group B (40 patients received single HU therapy). Baseline serum EPO levels were measured, and both groups were followed up for a mean period of 1 yr with regular assessment of transfusion requirements, blood pressure, ferritin, liver and renal functions, hemoglobin, and HbF. Quality of life (QoL) was assessed at the start and end of the study. RESULTS: Transfusion frequency and index were significantly decreased, while QoL was increased in group A compared with group B where 85% of patients showed improvement on combined therapy compared with 50% of patients on HU. Hemoglobin and HbF were significantly increased in both TI groups; however, this was more evident in group A than in group B. Also, 37.5% of patients in group A became transfusion-independent compared with 15% in group B. EPO levels were negatively related to increments of hemoglobin and HbF. Splenectomized patients and those with initial HbF% >40% had the best response to combined therapy. No serious adverse events necessitating discontinuation of therapy in both groups. CONCLUSIONS: HU was effective in management of TI; however, combination with rHuEPO gave a superior therapeutic effect resulting in the best clinical and hematological responses without adverse events.