Type 1 diabetes (T1D) is the most frequent form of diabetes in pediatric age, affecting more than 1.5 million people younger than age 20 years worldwide. Early and intensive control of diabetes ...provides continued protection against both microvascular and macrovascular complications, enhances growth, and ensures normal pubertal development. In the absence of definitive reversal therapy for this disease, achieving and maintaining the recommended glycemic targets is crucial. In the last 30 years, enormous progress has been made using technology to better treat T1D. In spite of this progress, the majority of children, adolescents and young adults do not reach the recommended targets for glycemic control and assume a considerable burden each day. The development of promising new therapeutic advances, such as more physiologic insulin analogues, pioneering diabetes technology including continuous glucose monitoring and closed loop systems as well as new adjuvant drugs, anticipate a new paradigm in T1D management over the next few years. This review presents insights into current management of T1D in youths.
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•Achieving and maintaining the recommended glycemic targets for type 1 diabetes is crucial to avoid complications.•Most youths do not reach the recommended targets for glycemic control.•The development of new advances in therapies will offer new treatment opportunities.•New insulin analogues, diabetes technology and adjuvant drugs showed promising results in improving glycemic control.
Background and aims of the study
Type 1 diabetes (T1D) impacts lung function and exercise capacity in adults, but limited information is available in children. We hypothesize that T1D causes ...alterations in pulmonary function and cardiorespiratory fitness, i.e., exercise capacity, at early stages of the disease, due to the presence of inflammation and vascular damage. Therefore, we aim to investigate pulmonary function before and after exercise in children with T1D as compared to age matched healthy controls.
Method
Twenty-four children with T1D and twenty healthy controls underwent body plethysmography, diffusion lung capacity for carbon monoxide and fractional exhaled nitric oxide at rest and after cardio-pulmonary exercise test.
Results
In children with T1D, baseline total lung capacity and diffusion lung capacity for carbon monoxide were reduced as compared to healthy controls. Children with T1D also showed a reduced exercise capacity associated with poor aerobic fitness. Accordingly, diffusion lung capacity for carbon monoxide tended to increase with exercise in healthy controls, while no change was observed in children with T1D. Fractional exhaled nitric oxide was significantly higher at baseline and tended to increase with exercise in children with T1D, while no changes were observed in healthy controls.
Conclusions
Altered diffusion lung capacity for carbon monoxide, increased fractional exhaled nitric oxide and a poor aerobic fitness to exercise suggests the presence of early pulmonary abnormalities in children with T1D.
Liang-Wang syndrome (LIWAS) is a polymalformative syndrome first described in 2019 caused by heterozygous mutation of the KCNMA1 gene encoding the Ca2+ and voltage-activated K+ channel (BKC). The ...KCNMA1 variant p.(Gly356Arg) abolishes the function of BKC and blocks the generation of K+ current. The phenotype of this variant includes developmental delay, and visceral and connective tissue malformations. So far, only three cases of LWAS have been described, one of which also had neonatal diabetes (ND). We present the case of a newborn affected by LIWAS carrying the p.(Gly375Arg) variant who manifested diabetes in the first week of life. The description of our case strongly increases the frequency of ND in LIWAS patients and suggests a role of BK inactivation in human insulin secretion. The knowledge on the role of BKC in insulin secretion is very poor. Analyzing the possible mechanisms that could explain the association of LIWAS with ND, we speculate that BK inactivation might impair insulin secretion through the alteration of ion-dependent membrane activities and mitochondrial functions in β-cells, as well as the impaired intra-islet vessel reactivity.
The Italian Lombardy region has been the epicenter of COVID-19 since February 2020. This study analyses the epidemiology of pediatric type 1 diabetes (T1D) onset during the first two pandemic waves ...and three previous years.
All the 13 pediatric diabetes centers in Lombardy prospectively evaluated charts of children at T1D onset (0–17 years), during year 2020. After calculating the annual incidence, the data were compared with those of the 3 previous years, using generalized linear models, adjusted for age and sex. Monthly T1D new onsets and diabetic ketoacidosis (DKA) were investigated yearly from 2017 to 2020. Data were extracted from outpatients charts of the pediatric diabetes centers and from the database of the national institute of statistics.
The estimated incidence proportion of T1D was 16/100·000 in 2020, compared to 14, 11 and 12 in 2019, 2018 and 2017, respectively. When adjusting for age and gender, the incidence was significantly lower in 2018 and 2017 compared to 2020 (adjusted incidence ratio: 0.73 and 0.77 respectively, with 95% CI: 0.63 to 0.84, and 0.67 to 0.83; p = 0·002 and p = 0·01), but no difference was found between the years 2020 and 2019. A reduction trend in the percentage of T1D diagnosis during the first wave (March-April) over the total year diagnoses was observed compared to previous years (11·7% in 2020, 17·7% in 2019, 14·1% in 2018 and 14·4% 2017). No difference was observed during the second wave (October-December) (32·8% in 2020, 33·8% in 2019, 34% in 2018, 30·7% in 2017). The proportion of DKA over the total T1D diagnoses during the second wave had higher trend than the first one (41·7% vs 33·3%), while severe DKA over the total DKA appeared higher during the first wave (60% vs 37·1%).
The study suggests an increase in the incidence of pediatric T1D in Lombardy throughout the past five years. Pandemic waves may have affected the clinical presentation at onset.
None.
We performed a cross-sectional study to analyze the retinal vasculature in children, adolescent, and young adults with type 1 diabetes using optical coherence tomography angiography (OCTA). Patients ...underwent funduscopic examination for diabetic retinopathy (DR) screening during an annual visit for the screening of diabetes-related complications which included the evaluation of glycated hemoglobin (HbA1c), microalbuminuria, lipid profile, arterial pressure, and neurological assessment. In addition, OCTA of the retinal vasculature was performed. Quantitative analysis of the OCTA images evaluated the vessel density at the superficial (SCP) and deep (DCP) capillary plexus of the retina. Structural vascular alterations were evaluated qualitatively. Results were compared to those obtained in a group of healthy age-, sex-, and pubertal stage-matched controls. The effect of age, disease duration, age at the disease onset, mean HbA1c since the onset, and lipid profile on vascular density was tested. Fifty-three patients (median age 15.5, IQR 12.4-19.4 years; 57% females) with type 1 diabetes and 48 controls were enrolled. The median (IQR) HbA1c was 7.6% (60 mmol/mol) (6.9-8.1%, 52-65 mmol/mol), and the median (IQR) duration of disease was 6.0 (3.3-10.3) years. Mean vessel density measured with OCTA was lower in patients compared to controls with the temporal sector showing the highest difference both in the SCP (0.55 vs. 0.57, p<0.001) and the DCP (0.63 vs. 0.65, p<0.001). None of the predictors was associated with the superficial and deep vascular densities. Only 2 patients had clinically detectable DR. Microvascular structural changes were found on OCTA in both of these patients and in one without funduscopic alterations. In conclusion, patients with type 1 diabetes without clinically detectable DR had decreased capillary density compared to controls on OCTA images. These findings may provide useful information for the screening and the management of patients with type 1 diabetes. Further studies are needed to confirm our results and their clinical relevance.
•Covid-19 restrictions disrupted physical activities in children with type 1 diabetes.•Diabetes management worsened in glycemia values and insulin delivery.•Active breaks rather than structured ...training may interrupt sedentary in children with type 1 diabetes.
We explored the physical activity (PA) level and the variation in glycaemic control in children with type 1 diabetes (T1D) before and during the lockdown. Then, we proposed an online training program supported by sport-science specialists.
Parents of children with T1D (<18 years) filled out an online survey. Anthropometric characteristics, PA, play, sport and sedentary time and the medical related outcomes were recorded. An adapted online program “Covidentary” was proposed through full-training (FT) and active breaks (AB) modality.
280 youth (11.8 ± 3.3 years) were included in the analysis. We reported a decline in sport (-2.1 ± 2.1 h/week) and outdoor-plays (-73.9 ± 93.6 min/day). Moreover, we found an increase in sedentary time (+144.7 ± 147.8 min/day), in mean glycaemic values (+25.4 ± 33.4 mg/dL) and insulin delivery (71.8% of patients). 37% of invited patients attended the training program, 46% took part in AB and 54% in FT. The AB was carried out for 90% of the total duration, while the FT for 31%. Both types of training were perceived as moderate intensity effort.
A decline of participation in sport activities and a subsequent increase of sedentary time influence the management of T1D of children, increasing the risk of acute/long-term complications. Online exercise program may contrast thepandemic's sedentarylifestyle.
Aims
Abnormalities in the oculomotor system may represent an early sign of diabetic neuropathy and are currently poorly studied. We designed an eye-tracking-based test to evaluate oculomotor function ...in patients with type 1 diabetes.
Methods
We used the
SRLab—Tobii TX300 Eye tracker®
, an eye-tracking device, coupled with software that we developed to test abnormalities in the oculomotor system. The software consists of a series of eye-tracking tasks divided into 4 classes of parameters (Resistance, Wideness, Pursuit and Velocity) to evaluate both smooth and saccadic movement in different directions. We analyzed the oculomotor system in 34 healthy volunteers and in 34 patients with long-standing type 1 diabetes.
Results
Among the 474 parameters analyzed with the eye-tracking-based system, 11% were significantly altered in patients with type 1 diabetes (
p
< 0.05), with a higher proportion of abnormalities observed in the Wideness (24%) and Resistance (10%) parameters. Patients with type 1 diabetes without diabetic neuropathy showed more frequently anomalous measurements in the Resistance class (
p
= 0.02). The classes of Velocity and Pursuit were less frequently altered in patients with type 1 diabetes as compared to healthy subjects, with anomalous measurements mainly observed in patients with diabetic neuropathy.
Conclusions
Abnormalities in oculomotor system function can be detected in patients with type 1 diabetes using a novel eye-tracking-based test. A larger cohort study may further determine thresholds of normality and validate whether eye-tracking can be used to non-invasively characterize early signs of diabetic neuropathy.
Trial:
NCT04608890.
Historically, the lung was not listed and recognized as a major target organ of diabetic injury. The first evidence of diabetic lung involvement was published fifty years ago, with a study conducted ...in a population of young adults affected by type 1 diabetes (T1D). In recent years, there has been mounting evidence showing that the lung is a target organ of diabetic injury since the beginning of the disease-at the pediatric age. The deeply branched vascularization of the lungs and the abundance of connective tissue, indeed, make them vulnerable to the effects of hyperglycemia, in a way similar to other organs affected by microvascular complications. In this review, we focus on pulmonary function impairment in children and adolescents affected by T1D. We also cover controversial aspects regarding available studies and future perspectives in this field.
Hematopoietic stem and progenitor cells (HSPCs) are multipotent stem cells that have been harnessed as a curative therapy for patients with hematological malignancies. Notably, the discovery that ...HSPCs are endowed with immunoregulatory properties suggests that HSPC-based therapeutic approaches may be used to treat autoimmune diseases. Indeed, infusion with HSPCs has shown promising results in the treatment of type 1 diabetes (T1D) and remains the only "experimental therapy" that has achieved a satisfactory rate of remission (nearly 60%) in T1D. Patients with newly diagnosed T1D have been successfully reverted to normoglycemia by administration of autologous HSPCs in association with a non-myeloablative immunosuppressive regimen. However, this approach is hampered by a high incidence of adverse effects linked to immunosuppression. Herein, we report that while the use of autologous HSPCs is capable of improving C-peptide production in patients with T1D,
modulation of HSPCs with prostaglandins (PGs) increases their immunoregulatory properties by upregulating expression of the immune checkpoint-signaling molecule PD-L1. Surprisingly, CXCR4 was upregulated as well, which could enhance HSPC trafficking toward the inflamed pancreatic zone. When tested in murine and human
autoimmune assays, PG-modulated HSPCs were shown to abrogate the autoreactive T cell response. The use of PG-modulated HSPCs may thus provide an attractive and novel treatment of autoimmune diabetes.
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