Endocrine Disrupting Chemicals and Type 1 Diabetes

Type 1 diabetes (T1D) is the most common chronic metabolic disease in children and adolescents. The etiology of T1D is not fully understood but it seems multifactorial. The genetic background determines the predisposition to develop T1D, while the autoimmune process against -cells seems to be also determined by environmental triggers, such as endocrine disrupting chemicals (EDCs). Environmental EDCs may act throughout dierent temporal windows as single chemical agent or as chemical mixtures. They could aect the development and the function of the immune system or of the beta-cells function, promoting autoimmunity and increasing the susceptibility to autoimmune attack. Human studies evaluating the potential role of exposure to EDCs on the pathogenesis of T1D are few and demonstrated contradictory results. The aim of this narrative review is to summarize experimental and epidemiological studies on the potential role of exposure to EDCs in the development of T1D.We highlight what we know by animals about EDCs\u2019 eects on mechanisms leading to T1D development and progression. Studies evaluating the EDC levels in patients with T1D were also reported. Moreover, we discussed why further studies are needed and how they should be designed to better understand the causal mechanisms and the next prevention interventions

Endocrine features of Prader-Willi syndrome: a narrative review focusing on genotype-phenotype correlation

Prader-Willi syndrome (PWS) is a complex genetic disorder caused by three different types of molecular genetic abnormalities. The most common defect is a deletion on the paternal 15q11-q13 chromosome, which is seen in about 60% of individuals. The next most common abnormality is maternal disomy 15, found in around 35% of cases, and a defect in the imprinting center that controls the activity of certain genes on chromosome 15, seen in 1-3% of cases. Individuals with PWS typically experience issues with the hypothalamic-pituitary axis, leading to excessive hunger (hyperphagia), severe obesity, various endocrine disorders, and intellectual disability. Differences in physical and behavioral characteristics between patients with PWS due to deletion versus those with maternal disomy are discussed in literature. Patients with maternal disomy tend to have more frequent neurodevelopmental problems, such as autistic traits and behavioral issues, and generally have higher IQ levels compared to those with deletion of the critical PWS region. This has led us to review the pertinent literature to investigate the possibility of establishing connections between the genetic abnormalities and the endocrine disorders experienced by PWS patients, in order to develop more targeted diagnostic and treatment protocols. In this review, we will review the current state of clinical studies focusing on endocrine disorders in individuals with PWS patients, with a specific focus on the various genetic causes. We will look at topics such as neonatal anthropometry, thyroid issues, adrenal problems, hypogonadism, bone metabolism abnormalities, metabolic syndrome resulting from severe obesity caused by hyperphagia, deficiencies in the GH/IGF-1 axis, and the corresponding responses to treatment

COMPLICANZE MACROVASCOLARI E MORTALITÀ NEL DIABETE TIPO 1

Il diabete mellito è un disturbo metabolico ad eziologia multipla, caratterizzato da iperglicemia cronica dovuta ad una difettosa secrezione o azione (o entrambi) della insulina. Le complicanze che tale condizione implica possano essere tanto dannose quanto costose. I soggetti con diabete tipo 1 (DM1), la forma di più frequente riscontro in età evolutiva, hanno un rischio da 2 a 4 volte superiore a quello della popolazione generale di sviluppare eventi aterosclerotici quali conseguenza di macroangiopatia nel lungo termine. Nello specifi co le complicanze macrovascolari del DM1 includono la malattia coronarica, la malattia vascolare periferica, e lo stroke. La prevenzione delle complicanze vascolari del diabete necessita di una rapida identificazione delle anomalie precoci. Il buon controllo glicemico ovvero il suo miglioramento sono associati ad una migliore funzionalità vascolare cardiaca e periferica. Un approccio multifattoriale che comprende anche la gestione della dislipidemia, dell’ipertensione e degli altri fattori di rischio, può essere efficace nel ridurre il tasso di eventi cardiovascolari

Endothelial and heart dysfunction in children and adolescents with type 1 diabetes

Background/Objectives: Type 1 diabetes (T1D) is an important risk factor for cardiovascular disease (CVD). Even if CVD become mainly manifest in adulthood, the process of atherosclerosis starts in childhood. Ultrasound is a reliable and noninvasive method for detecting early structural and functional atherosclerotic changes in arterial wall and heart. Aim of this study was to determine early ultrasound signs of atherosclerosis and of left ventricular (LV) systolic and diastolic dysfunction in children and adolescents with T1D. Methods: Ninety-four subjects with T1D [12.3±3.53 yrs.; males 59.6%; T1D duration 5.14±3.53 years) were enrolled into the study. Carotid intima-media thickness (cIMT), systolic and diastolic function indices were determined according to standardized scanning protocol and were performed by the same investigator blinded to subjects’ anthropometric (Ht, Wt, BMI, pubertal status, WC, SBP/DBP) and laboratory data (HbA1c, TC, LDL-C, HDL-C, TG). Results: cIMT, LV systolic and diastolic function indices were all in the normal range defined for healthy population. Pubertal subjects, respect to pre-pubertal ones, had significantly higher values of cIMT (0.60±0.09 vs. 0.49±0.08 mm; p<0.001), interventricular septal end-diastole (IVSd) (7.27±1.27 vs. 6.61±1.00 mm; p=0.027), deceleration time (DT) (138.3±31.7 vs. 112.6±20.9 ms; p<0.001), and isovolumetric relaxation time (IVRT) (60.8±14.1 vs. 53.1±9.58 ms; p=0.006). Patients with DKA at T1D onset had significantly higher values of IVSd respect to subjects without DKA 7.40±1.22 vs. 6.80±1.17 mm; p=0.018). Moreover, DBP (Chi-Square=6.13; p=0.047), LV internal dimension at end-iastole (LVIDd) (Chi-Square=7.25; p=0.027), A wave peak (Chi-Square=6.11; p=0.047), and IVRT (Chi-Square=7.29; p=0.026) were significantly different according to mean HbA1c value in the last year. cIMT was higher in subjects with a worse glycemic control (HbA1c ≥9%) (Chi-Square=5.07; p=0.079) and cIMT was significantly correlated with age (R=0.51, p<0.001), WC (R=0.39, p<0.001), SBP (R=0.41, p<0.001), mean HbA1c values of the first 5 years of T1D (R=0.24, p=0.021), TG (R=0.23, p=0.029), and TG/HDL-C ratio (R=0.22, p=0.034). The multivariate regression model was statistically significant for cIMT (R2=0.44, p<0.001) and identify T1D duration (β= -0.23; p=0.024) and LDL-C levels (β=0.20, p=0.031) as predictor factors. Conclusions: cIMT were within normal range but, despite the good glycemic and lipid control, mean values were significantly higher respect to published ones in healthy and T1D children and adolescents. Moreover, LV diastolic function was slightly abnormal. Ultrasound is useful for early detection of subjects with a greater cardiovascular risk who can benefit from targeted therapeutic interventions

IMPATTO DELLA TERAPIA CON ANALOGO DEL GNRH SULLA QUALIT\uc0 DELLA VITA DEI PAZIENTI CON CPP E DELLE LORO FAMIGLIE

OBIETTIVI La qualit\ue0 di vita (QoL) \ue8 un importante componente dello stato di salute del paziente ed \ue8 un indicatore delle conseguenze a lungo termine di malattia cronica. Non sussiste, tuttavia, concordanza tra gravit\ue0 della malattia, trattamento e QoL. Obiettivo del nostro studio \ue8 quello di valutare la QoL dei bambini affetti da pubert\ue0 precoce centrale in trattamento con aGnRH e dopo la terapia e dei loro genitori. METODI Sono stati valutati 56 pazienti (2M) di cui 3 di et\ue0 compresa fra 4-7 aa(G1), 15 fra 8-12aa(G2), 13 fra 13-18aa(G3), 25>18aa(G4) e comparati a 25 controlli(4-18 aa). Tutti sono stati sottoposti al questionario \u201cPaediatric Quality of Life Inventory\u201d (PedsQL) che valuta funzione fisica, emotiva, sociale, scolastica, e ad un questionario messo a punto per valutare lo stress emotivo correlato alla terapia (SET). I genitori di G1, G2, G3 sono stati sottoposti a PedsQL per le scale di funzione emotiva e sociale. RISULTATI Per tutte le scale del PedsQL non sussiste differenza significativa fra G1, G2, G3 e controlli. Dal confronto figli/genitori non emergono differenze significative nei gruppi G1(p= 0.59); G2(p=0.61); G3 (p=0.48). Inoltre, in G2 e G3 non c\u2019\ue8 correlazione fra le 4 scale del PedsQL e durata del trattamento. Comparando SET nei quattro gruppi, si evince come sussista una differenza signifi cativa fra G2 e G4 (p=0.029) e fra G3 e G4 (p=0.011). Per i gruppi G2 e G3 la durata del trattamento non sembra essere correlata con SET n\ue9 nei pazienti (p=0.94; p=0.52) n\ue9 nei genitori (p=0,21; p=0.7). In G4, tuttavia, sussiste una correlazione significativa fra durata della terapia e SET (p:0.021, r 0.47). Inoltre, in G4 SET \ue8 risultato essere maggiore riferendosi al periodo del trattamento rispetto al momento di compilazione del questionario(p<0.001). CONCLUSIONI La terapia con aGnRH, valutata mediante PedsQL, non sembra inficiare la QoL sia dei pazienti in trattamento che dei loro genitori, indipendentemente dalla durata della terapia. Tuttavia \ue8 stato possibile identificare, mediante questionario specifico, come i livelli di stress emotivo siano aumentati nei pazienti in trattamento rispetto agli offtherapy e, in questi ultimi, come sussista una correlazione tra stress emotivo e durata del trattamento

IPERTENSIONE IN BAMBINI ED ADOLESCENTI AFFETTI DA DIABETE DI TIPO 1: ALTA PREVALENZA IDENTIFICATA TRAMITE L’UTILIZZO DEL MONITORAGGIO PRESSORIO AMBULATORIALE

OBIETTIVI - L’ipertensione nei bambini ed adolescenti con diabete di tipo 1 (DM1) è associata ad un aumentato rischio di complicanze cardiovascolari in età adulta. Il monitoraggio pressorio ambulatoriale (24h-ABPM) consente la registrazione dei valori pressori per 24 ore in un ambiente non medico; tuttavia, i dati sulla sua utilità in età evolutiva sono ancora controversi. Gli obiettivi di questo studio sono stati quelli di confrontare la prevalenza di ipertensione utilizzando sia il metodo oscillometrico tradizionale sia il 24h-ABPM ovvero di valutare l’utilità del 24h-ABPM nella diagnosi precoce di ipertensione al fi ne di iniziare un trattamento precoce. METODI - Sono stati reclutati 40 bambini ed adolescenti (52.5% maschi) con DM1 (13.6±2.56 anni; durata DM1 >1 anno) e raccolti dati antropometrici, metabolici (HbA1c, assetto lipidico, funzionalità renale) e pressione arteriosa (sfigmomanometro oscillometrico e 24h-ABPM). L’ipertensione è stata definita come: A) pressione arteriosa sistolica (SBP) superiore al 95° percentile per età, sesso e percentile di altezza con sfigmomanometro oscillometrico; B) SBP superiore al 95° percentile per un tempo >25% con 24h-ABPM. RISULTATI - Utilizzando lo sfigmomanometro oscillometrico durante la visita clinica, sono risultati ipertesi 9 pazienti su 40 (22.5%) mentre, tramite 24h-ABPM, la prevalenza di ipertensione è risultata significativamente maggiore (57.5%; χ2=8.58, p=0.003). I pazienti risultati ipertesi con 24h-ABPM avevano una durata di DM1 più lunga rispetto ai normotesi (8.04±3.22 vs. 5.76±1.85 anni, rispettivamente, p=0.013). Utilizzando le curve ROC abbiamo identificato i 6.5 anni dall’esordio del DM1 come cut-off predittivo di carico SBP >25% (AUC 0.716). L’analisi multivariata ha permesso di identifi care la durata della malattia (β=0.49, SE 0.17, p=0.006) ed il z-score BMI (β=0.41, SE 0.20, p=0.049) come principali fattori predittivi per il carico di SBP >95° percentile. I nostri dati non hanno supportato una relazione tra ipertensione, controllo metabolico, profilo lipidico ed indici di funzionalità renale. CONCLUSIONI - 24h-ABPM ha permesso di identificare una maggiore prevalenza di ipertensione e potrebbe essere introdotta nella comune pratica clinica a distanza di 6 anni dall’esordio del DM1. 24h-ABPM può essere considerato uno strumento utile per identificare precocemente i soggetti con ipertensione che possono beneficiare di un trattamento precoce per prevenire le complicanze renali e cardiovascolari

Health-Related Quality of Life and Diabetes Control in Immigrant and Italian Children and Adolescents with Type 1 Diabetes and in their Parents

Background/Objectives: Type 1 diabetes (T1D) is a chronic metabolic disease that requires daily and complex management for both patients and their caregivers, impairing the quality of life. Aim of this cross-sectional observational study was to determine whether metabolic control and health-related quality of life (HRQOL) of T1D subjects and their parents could be influenced by immigration status. Methods: We enrolled 125 children and adolescents with T1D (12.4\ub13.55 years; males 53.6%; T1D duration 5.61\ub13.50 years) and their parents (102 mothers and 37 fathers). According to patients\u2019 maternal origin, the study population was categorized into Group A (immigrant) and Group B (Italian). The Italian translation of the PedsQL\u2122 3.0 Diabetes Module was used to evaluate the HRQOL. Information on presence of diabetic ketoacidosis (DKA) at T1D onset, insulin therapy (MDI/SAP), and glycosylate hemoglobin (HbA1c), were collected at the same time of the questionnaire. Results: Group A, respect to Group B, had significantly higher frequency of DKA at T1D onset (55.0 vs. 22.3%; Chi-square=13.1; p&lt;0.001) and a significant lower use of SAP (5.0 vs. 22.3%; Chi-Square=5.86; p=0.015). HbA1c values were significantly higher in Group A respect to Group B (72.7\ub117.6 vs. 62.6\ub112.9 mmol/mol; p&lt;0.001). Patients\u2019 HRQOL scores were significantly lower in Group A than in Group B in the following scales: \u201cDiabetes selfsymptoms\u201d (57.9\ub114.6 vs. 66.9\ub112.8; p=0.004), \u201cTreatment barriers\u201d (68.1\ub123.6 vs. 82.9\ub113.0; p=0.001), and \u201cWorry\u201d (52.9\ub126.9 vs. 66.9\ub123.7; p=0.009). Mothers\u2019 HRQOL scores were significantly lower in Group A than in Group B in the following scales: \u201cDiabetes self-symptoms\u201d (56.7\ub118.1 vs. 65.8\ub115.7; p=0.030), \u201cTreatment barriers\u201d (55.9\ub119.8 vs. 71.3\ub119.7; p&lt;0.001), \u201cTreatment adherence\u201d (71.2\ub118.1 vs. 80.6\ub111.2; p=0.018), \u201cCommunication\u201d (58.9\ub131.4 vs. 75.9\ub123.3; p=0.009) scales, and total score (57.2\ub117.1 vs. 68.8\ub112.6; p=0.011). No differences were found in fathers\u2019 data. The multivariate regression model for child HRQOL scales identified the following significant predictive factors: MDI insulin therapy ('=0.438; p=0.008), Italian ethnicity ('=0.018; p=0.004), HbA1c ('=-0.228; p=0.029) for \u201cTreatment barriers\u201d scale; Italian ethnicity ('=0.584; p=0.046) for \u201cWorry\u201d scale. Conclusions: Our results strongly suggest that immigrant status confers significant disadvantages in terms of T1D treatment, glycemic control, and HRQOL in children and adolescents with T1D. Moreover, parents\u2019 HRQOL data suggest that daily T1D management is usually supervised by mothers rather than fathers. Specific challenges and educational interventions should be considered in clinical care of T1D patients with distinct migration background

The Effect of GnRH-Analogue Therapy on the Quality of Life of Patients with Central Precocious Puberty and their Families

Introduction: Quality of life (QoL) is a multidimensional indicator including several functions and represents an important evaluator of patient\u2019s health, especially in chronic diseases. Treatment with aGnRH in Central Precocious Puberty (CPP) is source of stress for patients and families. The aim of our study is to evaluate QoL and levels of therapy-related stress in patients with CPP and in their families during and after treatment. Material and Methods: 56 patients (2 males) with CPP attending a tertiary Endocrinological Outpatient Clinic in 2015 and 2016 were enrolled. The population was divided, according to their age, in 4 categories: G1: 3 patients, 4-7 years; G2: 15 patients, 8-12 years, G3: 13 patients, 13-18 years, G4: 25 patients beyond 18 years. Groups G1 and G2 were on therapy with aGnRH, G3 were off therapy, still on clinical follow up, G4 were off therapy. We also evaluated 30 controls paired for age and level of instruction. Each patient underwent 2 questionnaires: the \u201cPediatric Quality of Life Inventory\u201d (PedsQL) and a tailored \u201cad-hoc\u201d questionnaire to investigate self perception in CPP. Parents also underwent the latter questionnaire. Results and Discussion: No significant differences were detected comparing PedsQL scores among G1, G2 and G3 groups each others nor comparing patients and controls. A difference statistically significant was detected in the evaluation of physical functions between G2 and controls (p: 0.02). In G2 and G3 no significant association was found between the duration of treatment and the 4 functions of PedsQL. For the self perception questionnaire scores, although no significant differences among G1, G2 and G3 themselves nor between patients and their parents were detected, the scores trend showed in patients an amount of stress therapy-related increasing proportionally with age. For G4 a direct correlation was identified between duration of treatment and emotional stress, and lower scores about self-esteem were identified, referring both to the period of therapy and the period of questionnaire\u2019s compilation. Conclusion: In CPP, from the PedsQL, it appears that therapy with aGnRH only affects QoL on physical functions. Levels of emotional stress therapy-related, detected through ad-hoc questionnaire, increase in treated patients, independently from the treatment interruption. In off-therapy patients a decreased self-esteem and an indirect correlation between emotional stress and duration of treatment were found, underlining the effect of therapy in self perception