Dehydroepiandrosterone sulphate levels at 7 years old are positively associated with more advanced pubertal development between 10 and 13 years old in girls.

OBJECTIVE: We aimed to explore the association between dehydroepiandrosterone sulphate (DHEAS) levels at age 7, pubertal development between ages 10 and 13, and age at menarche. DESIGN AND PARTICIPANTS: This is a longitudinal study of 603 individuals (301 girls, 302 boys) from the Generation XXI cohort. MEASUREMENTS: Evaluation of the participants at ages 7, 10 and 13 included anthropometry and Tanner staging. Pubertal development between ages 10 and 13 was categorized using latent class analysis, based on Tanner stages. The association between DHEAS at age 7 and pubertal development between ages 10 and 13 was conducted with binomial logistic regression, adjusted for BMI z-score. The variation of age at menarche in relation to DHEAS levels at age 7, controlling for maternal age at menarche, birth weight z-score and BMI z-score, was estimated fitting a linear regression model. RESULTS: Pubertal development at ages 10-13 was categorized into two classes-Class 1 had a higher probability for the lower Tanner stage (less advanced sexual maturation) and Class 2 had a higher probability for the higher Tanner stage (more advanced sexual maturation). In girls, taking Class 1 as a reference, Class 2 was positively associated with BMI z-score and DHEAS. In boys, Class 2 was positively associated with BMI, but not with DHEAS. DHEAS levels at age 7 were negatively associated with age at menarche, after adjustment for maternal age at menarche, birth weight and BMI. CONCLUSION: In girls, but not in boys, DHEAS at age 7 was positively associated with more advanced pubertal development between ages 10 and 13, and with earlier age at menarche.

Persistent weight gain between 0 and 4 years of age is associated with higher dehydroepiandrosterone sulphate levels at 7 years old: Data from the Generation XXI birth cohort.

OBJECTIVE: To assess the influence of longitudinal weight gain from 0 to 4 years old on dehydroepiandrosterone sulphate (DHEAS) levels at 7 years old. DESIGN: DHEAS levels were measured at 7 years old in a subsample of 587 children from the Generation XXI birth cohort. Weight trajectories (0-4 years of age) were identified using model-based clustering and categorized as "normal weight gain," "weight gain during infancy," "weight gain during childhood" and "persistent weight gain." MEASUREMENTS: Differences in DHEAS levels at age 7 between the four weight trajectories were analysed through analysis of covariance (ANCOVA), adjusted for birth weight (BW) and body mass index (BMI). RESULTS: In the crude analysis, compared with the "normal weight gain" trajectory (5.53 (95% CI: 5.10-5.98] µmol/L), DHEAS levels were significantly higher in children in the "persistent weight gain" (8.75 [95% CI: 7.23-10.49] µmol/L, p < .001] and in children in the "weight gain during infancy" trajectories (7.68 [95% CI: 6.22-9.49] µmol/L, p = .021] and marginally significantly higher in children in the "weight gain during childhood" trajectory (6.89 (95% CI: 5.98-8.00) µmol/L; p = .052). In BW- and BMI-adjusted model, a statistically significant difference in DHEAS levels was found between the "persistent weight gain" (7.93 [95% CI: 6.43-9.86] µmol/L) and the "normal weight gain" trajectories ([5.75 [95% CI: 5.32-6.23] µmol/L; p = .039). CONCLUSION: Higher DHEAS levels are found in 7-year-old children following a trajectory of persistent weight gain from 0 to 4 years, independently of their BW or current BMI, highlighting the impact of exposure to overweight in the first years of life on prepubertal adrenal androgen production.

Association of dehydroepiandrosterone sulfate, birth size, adiposity and cardiometabolic risk factors in 7-year-old children.

BACKGROUND: Low birth size (BS) and obesity have been associated with higher dehydroepiandrosterone sulfate (DHEAS) levels in childhood, insulin acting as a mediator, despite contradictory findings. To further explore these issues, we studied the associations between DHEAS, BS, adiposity, maternal characteristics, and cardiometabolic risk indicators, in participants of Generation XXI, a population-based birth cohort. METHODS: A sample of 700 children (mean age 7.1 yr) was randomly selected. Data on maternal characteristics, BS, body mass index (BMI), waist-to-height ratio, body fat (dual-energy X-ray absorptiometry), insulin, lipid profile, and high-sensitivity C-reactive protein were analyzed in relation to DHEAS. RESULTS: DHEAS was negatively associated with BS and positively associated with all adiposity indicators, with no sex differences. DHEAS was positively associated with insulinemia independently of the child's BS or BMI. No significant association was found between DHEAS, maternal characteristics, lipid profile, or high-sensitivity C-reactive protein. Including insulin in the model did not affect the association between BS and DHEAS but reduced the magnitude of the BMI effect by 24% for boys and 30% for girls. CONCLUSION: Higher DHEAS levels at 7 years old were associated with lower BS and higher adiposity. DHEAS levels were positively associated with insulinemia independently of BS or BMI. IMPACT: Low birth weight and obesity have been associated with higher dehydroepiandrosterone sulfate (DHEAS) levels in prepuberty. Insulin has been suggested as a mediator, despite previous studies failing to show an association between DHEAS and insulin levels. In a randomly selected population of 700 7-year-old children from the Generation XXI birth cohort, higher DHEAS levels were associated with a lower birth size and higher adiposity, with no sex differences. DHEAS was positively related to insulinemia independently of the child's birth size or body mass index. No association was found between DHEAS and other cardiometabolic risk factors.

Association between dehydroepiandrosterone sulphate levels at 7 years old and bone mineral density at 10 years old: a prospective cohort study.

We aimed to explore the effect of dehydroepiandrosterone sulphate (DHEAS) at age 7 on areal bone mineral density (aBMD) at age 10 and to distinguish the direct and indirect effects (explained by sexual maturity and by aBMD at age 7), for each sex, after adjustment for body mass index (BMI) z-score. In a subsample of 274 children (139 girls, 135 boys) from Generation XXI cohort, aBMD was assessed with dual-energy X-ray absorptiometry (DXA) scan at ages 7 and 10. The increase in aBMD at age 10 for each 10 µg/dL increase in DHEAS levels at age 7 was estimated using path analysis. Both the direct and the indirect effects were calculated. In girls, higher DHEAS levels at age 7 were associated with higher aBMD at age 10. No direct effect was observed. The indirect effect via higher aBMD at age 7 explained 61% of the total effect, and the indirect effect via higher Tanner stage explained 21%. After adjustment for BMI, the total effect remained statistically significant, explained in 33% by the indirect effect of DHEAS on Tanner stage and Tanner stage on aBMD. In boys, no effect of DHEAS on aBMD was observed. CONCLUSION: An indirect effect of DHEAS at age 7 on aBMD at age 10 was found in girls, but not in boys, as higher DHEAS levels were associated with more advanced sexual maturation at age 10, and more advanced sexual maturation to higher aBMD. No direct effect of DHEAS on aBMD was observed. WHAT IS KNOWN: • Conditions associated with elevated DHEAS, adrenarche's biomarker, are accompanied by advanced bone maturity. • Whether adrenal androgens influence bone mineralization in childhood remains puzzling, and longitudinal data is scarce. WHAT IS NEW: • In girls, but not in boys, higher DHEAS at age 7 was associated with higher aBMD at age 10. • This was partially explained by the indirect effect of DHEAS at age 7 on sexual maturity at age 10, as DHEAS at age 7 was positively associated with sexual maturity at age 10, which was further associated with aBMD.

Pituitary incidentalomas in paediatric age are different from those described in adulthood.

PURPOSE: Guidelines on pituitary incidentalomas evaluation and management are limited to adults since there are no data on this matter in the paediatric population. We aim to analyse the morphologic characteristics, hormonal profile and follow-up of these lesions in children. METHODS: We have searched for pituitary incidentalomas in the neuroimaging reports and electronic medical records of the Paediatric Endocrinology Clinic of our centre. Patients with 18 years-old or less were included. RESULTS: Forty-one incidentalomas were identified, 25 of them (62.4%) in females. The mean age at diagnosis was 12.0 ± 4.96 years-old. Headaches were the main reason that led to image acquisition (51.2%) and MRI was the imaging method that detected the majority of the incidentalomas (70.7%). The most prevalent lesion was pituitary hypertrophy (29.3%), which was mainly diagnosed in female adolescents (91.7%), followed by arachnoid cysts (17.1%), pituitary adenomas (14.6%) and Rathke's cleft cysts (12.2%). Most patients (90.2%) did not present clinical or laboratorial findings of hypopituitarism or hormonal hypersecretion. Four patients presented endocrine dysfunction: three had growth hormone deficiency and one had a central precocious puberty. Twenty-three patients (56.1%) underwent imagiological revaluation during a median follow-up time of 24.6 months (interquartile range 5.07). None of them presented dimensional progression. CONCLUSIONS: To the best of our knowledge, this is the first series of pituitary incidentalomas in pediatric age. Comparing our series with those conducted in adults, we have observed a higher preponderance of pituitary hypertrophy over adenomas, a lower prevalence of hormonal hyper/hyposecretion and lower risk of dimensional progression during follow-up.

Bilateral frontoparietal polymicrogyria: a novel GPR56 mutation and an unusual phenotype.

Loss of function of GPR56 causes a specific brain malformation called the bilateral frontoparietal polymicrogyria (BFPP), which has typical clinical and neuroradiological findings. So far, 35 families and 26 independent mutations have been described.We present a Portuguese 5-year-old boy, born from nonconsanguineous parents, with BFPP. This patient has a novel GPR56 mutation (R271X) and an unusual phenotype, because he presents hot water epilepsy.To the best of our knowledge, this is the first reported case of BFPP evolving hot water epilepsy.

Treatment modalities and outcomes in pediatric Cushing's disease - report of three cases and literature review.

OBJECTIVES: Cushing's disease (CD) is a diagnostic and therapeutic challenge, especially in pediatric patients. CD, primarily caused by adrenocorticotropic hormone-secreting pituitary adenomas, manifests typically with growth retardation and weight gain. There are no published guidelines for pediatric patients. CASE PRESENTATION: We report three pediatric patients diagnosed with CD in a Portuguese tertiary hospital. All patients presented with hypercortisolism features. All patients underwent transsphenoidal pituitary surgery (TSS) as a first-choice treatment; however, it was unsuccessful in one patient and the other patients experienced recurrence. Patients were submitted to different approaches so basal serum cortisol levels could be achieved. Two of three patients achieved remission. CONCLUSIONS: TSS remains the first-line treatment yet challenging due to microadenomas and technical complexities. Medical therapy with agents like metyrapone or ketoconazole, pituitary radiotherapy, or bilateral adrenalectomy are, usually, second-line interventions, unless there is a contraindication to surgery. Our findings support the finding that a shorter hypothalamic-pituitary-adrenal axis recovery time increases the risk of recurrence of CD. Our cases illustrate the intricate management and variable outcomes of pediatric CD, underscoring the importance of multidisciplinary care and continuous surveillance.

Carotid Intima-Media Thickness and Cardiometabolic Profile in Turner Syndrome: A Cross-Sectional Study.

INTRODUCTION: Turner syndrome (TS), one of the most common chromosomal abnormalities in females, often results in adult cardiovascular and metabolic complications. Information on pediatric age is scarce. This study aimed to compare the presence of cardiometabolic risk factors in children with TS and healthy controls. METHODS: This is a cross-sectional study comparing patients with TS to age-matched healthy controls, regarding cardiometabolic risk factors including lipid profile, fasting glucose, insulin resistance, body composition, body mass index, blood pressure, and carotid intima-media thickness (cIMT). RESULTS: We included nine TS patients and nine controls with a median age of 13 years (9-14 years). Three TS patients and three controls were prepubertal. All TS patients received growth hormone treatment (GHT), median treatment of six years (3-10 years); four patients underwent treatment with estradiol. No statistically significant differences were detected between TS patients and controls regarding body mass index (BMI), cholesterol levels, and insulin resistance. cIMT indexed to body surface area showed no significant differences between TS patients and controls (0.37 vs 0.35 mm/m2, respectively, p=0.605). TS patients had lower body fat levels (7.2% vs 34.9%, p=0.004). On the other hand, TS patients had higher levels of systolic (z-score 1.04 vs -0.08, p=0.001) and diastolic (z-score 1.08 vs 0.33, p=0.031) blood pressure (BP) and aspartate (AST) and alanine (ALT) aminotransferase levels (26 vs 20 U/L, p=0.008 and 19 vs 14 U/L, p=0.004, respectively). CONCLUSION: Patients with TS, all submitted to GHT, had lower body fat levels compared with controls, despite similar BMI. Although we found no differences in cIMT between the two groups, young girls with TS had higher BP and transaminase levels. Early anthropometric, cardiovascular, and analytical monitoring of patients with TS is essential to detect abnormalities and prevent further complications.

Dehydroepiandrosterone sulfate levels at 7 years old and cardio-metabolic factors at 10 and 13 years old - the generation XXI birth cohort.

OBJECTIVES: Premature adrenarche is often linked to a cluster of endocrine-metabolic risk factors. Our objective was to explore the association of dehydroepiandrosterone sulfate (DHEAS) levels at age 7 with cardio-metabolic traits at ages 10 and 13, independently of adiposity and pubertal stage. METHODS: Longitudinal study of 603 individuals (301 girls/302 boys) from the Generation XXI birth cohort. DHEAS at age 7 was measured by immunoassay. Anthropometrics, pubertal staging, blood pressure, and metabolic outcomes were evaluated at ages 7, 10, and 13. Pearson correlations between DHEAS and cardio-metabolic traits (insulin, HOMA-IR, triglycerides, LDL-cholesterol, high-sensitivity C-reactive protein, and systolic and diastolic blood pressure) were computed. Path analysis was used to estimate the effect of DHEAS at age 7 on cardiometabolic traits at ages 10 and 13, adjusted for body mass index (BMI) z-score and Tanner stage. RESULTS: DHEAS at age 7 correlated positively with insulin and HOMA-IR at ages 7 and 10 in both sexes, and at age 13 in girls, but not in boys. In girls, DHEAS levels at age 7 directly influenced HOMA-IR at age 13, controlling for BMI and Tanner stage. In boys, DHEAS at age 7 did not influence HOMA-IR at ages 10 and 13. DHEAS at age 7 did not influence the other cardio-metabolic outcomes analyzed. CONCLUSIONS: DHEAS levels in mid-childhood have a positive longitudinal association with on insulin-resistance that persists, in girls, but not in boys, at least until age 13. No association was found regarding dyslipidemia, hypertension, or low-grade inflammation.

Glycemic Control and Metabolic Parameters in Children and Adolescents With Type 1 Diabetes.

AIM: The association between glycemic control and metabolic status is poorly defined in children and adolescents with T1D, besides being biologically plausible. We aimed to evaluate the association between glycemic control and body mass index (BMI), blood pressure (BP), and lipid profile in children and adolescents with T1D. METHODS: Observational cross-sectional study including children and adolescents (5-18 years old) followed in our outpatient clinic with the diagnosis of T1D for at least a year. We used linear regression models (unadjusted and adjusted to sex and age) to evaluate the association between glycated hemoglobin (A1c) and time in range (TIR), several prespecified metabolic parameters, and prespecified demographic and clinical characteristics. We considered a p-value of <0.05 to be statistically significant. RESULTS: A total of 144 patients were included, 51% of whom were female. The population had a mean age of 12.7±3.4 years old. We report a positive association between A1c and BMI, systolic and diastolic BP, total- and LDL-cholesterol and triglycerides. Females and patients diagnosed at a younger age presented with higher A1c values. There is a tendency for a negative association between TIR and the former parameters. Higher A1c levels and lower TIR were associated with higher glycemic variability and were treated with a higher basal insulin per Kg dose. CONCLUSION: Our results support an important association between worse glycemic control and an unhealthier metabolic profile in children and adolescents with T1D. We can hypothesize that a good glycemic profile is needed to achieve good metabolic control at a young age.

Treatment of Isolated Idiopathic Growth Hormone Deficiency in Children and Thyroid Function: Is the Need for LT4 Supplementation a Concern in Long-Term Therapy?

Introduction Recombinant human growth hormone (rhGH) replacement therapy might be able to induce hypothyroidism, but this is a controversial issue. Previous studies evaluated the effects of rhGH replacement therapy on thyroid function, but little information is available in the subset of children with isolated idiopathic growth hormone deficiency (GHD). Our aim was to assess the effects of rhGH replacement therapy on thyroid function in children with isolated idiopathic GHD. Methods Retrospective analysis of the medical files of 64 children with confirmed GHD treated with rhGH. After review, 56 children with isolated idiopathic GHD and treated with rhGH for at least one year were included. Auxological (weight standard deviation score [SDS], height SDS, growth velocity [GV] SDS) and biochemical (free thyroxine [FT4], thyroid-stimulating hormone [TSH], and insulin-like growth factor 1 [IGF-1]) parameters were recorded before, during, and after treatment with rhGH. Results FT4 and TSH levels decreased significantly during rhGH therapy in children with isolated idiopathic GHD. Twenty-one percent (n=12) of the children developed hypothyroidism, on average 47 months after initiation of rhGH. Higher baseline FT4 levels were protective against the need for levothyroxine (LT4) (OR=0.8, CI 0.592-0.983; p=0.036). Hypothyroidism was reversed after interruption of rhGH, except in one patient; FT4 levels returned to baseline in the first year after completing the treatment. Final height SDS of the children who developed hypothyroidism was not different from their counterparts without hypothyroidism (-1.24 [-1.52 to -1.10] vs -1.13 [-1.78 to -0.74], p=1.000). Predicted adult height (PAH) SDS in patients who completed rhGH treatment was similar in both LT4 supplemented (n=7; final Ht SDS -1.16 [-1.31 to -1.10] vs PAH -1.00 [-1.42 to -0.48]; p=0.398) and not supplemented patients (n=25; final Ht SDS -1.46 [-1.83 to -0.78] vs PAH SDS -0.88 [-1.35 to -0.56]; p=0.074). Conclusions Our results show that patients with isolated idiopathic GHD may transiently need LT4 during GH treatment. Properly supplemented patients achieved PAH.

Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: An Update on Genetic Analysis of CYP21A2 Gene.

Congenital Adrenal Hyperplasia is a group of genetic autosomal recessive disorders that affects adrenal steroidogenesis in the adrenal cortex. One of the most common defects associated with Congenital Adrenal Hyperplasia is the deficiency of 21-hydroxylase enzyme, responsible for the conversion of 17-hydroxyprogesterone to 11-deoxycortisol and progesterone to deoxycorticosterone. The impairment of cortisol and aldosterone production is directly related to the clinical form of the disease that ranges from classic or severe to non-classic or mild late onset. The deficiency of 21-hydroxylase enzyme results from pathogenic variants on CYP21A2 gene that, in the majority of the cases, compromise enzymatic activity and are strongly correlated with the clinical severity of the disease. Due to the exceptionally high homology and proximity between the gene and the pseudogene, more than 90% of pathogenic variants result from intergenic recombination. Around 75% are deleterious variants transferred from the pseudogene by gene conversion, during mitosis. About 20% are due to unequal crossing over during meiosis and lead to duplications or deletions on CYP21A2 gene. Molecular genetic analysis of CYP21A2 variants is of major importance for confirmation of clinical diagnosis, predicting prognosis and for an appropriate genetic counselling. In this review we will present an update on the genetic analysis of CYP21A2 gene variants in CAH patients performed in our department.

Clinicopathological features of neonatal subcutaneous fat necrosis and its implications.

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Wolfram syndrome: Portuguese research.

INTRODUCTION: Wolfram syndrome (WFS) is a neurological and endocrinological degenerative disorder, also known as DIDMOAD (Diabetes Insipidus, early-onset Diabetes Mellitus, progressive Optic Atrophy, and Deafness) syndrome. It is an autosomal recessive disorder, mostly involving the Wolfram syndrome 1 gene (WFS1). The phenotypic pleiomorphism, rarity, and molecular complexity complicate the follow-up of these patients. MATERIAL AND METHODS: We aimed to describe the clinical characteristics and the follow-up of 11 patients with this disorder. We retrospectively analysed all WFS patients diagnosed between 1990 and 2020 in the Centro Hospitalar São João, a tertiary hospital in Northern Portugal. RESULTS: Eleven patients were included. Four patients had all 4 components of DIDMOAD. The presentation was diabetes mellitus (DM) in 9 patients, optic atrophy (OA) in another patient, and diabetes insipidus (DI) in another one. The median age of DM and OA diagnosis was 6 and 14 years, respectively. Nine patients had diabetes mellitus, and the other 2 patients had impaired glucose tolerance. All patients had OA. Four patients presented DI, all of them diagnosed in adolescence. Four patients had hearing impairment, 5 had urological abnormalities, 5 had neurological disorders, and 8 had psychiatry disorders. Eight patients had a broad spectrum of recessive mutations in WFS1. CONCLUSION: The information obtained in this study can facilitate further research in an attempt to improve prevention strategies for this devastating disease.

Neonatal presentation of growth hormone deficiency in CHARGE syndrome: the benefit of early treatment on long-term growth.

CHARGE syndrome is a complex disorder involving multiple congenital anomalies and is caused by heterozygous mutations in the CHD7 gene. Growth retardation is a characteristic finding and about 10% of cases present growth hormone (GH) deficiency. GH treatment of short stature in CHARGE syndrome has shown some benefit, but normal height is rarely attained. We report a girl with CHARGE syndrome due to a de novo frameshift mutation in the CHD7 gene (c.2509_2512delCATT), in whom recurrent hypoglycaemia led to the diagnosis of GH deficiency in the second month of life. Early initiation of treatment with recombinant GH resulted in normal growth over ten years of follow-up. This case is the youngest reported CHARGE patient to be diagnosed and treated for GH deficiency and demonstrates that GH deficiency in CHARGE syndrome may manifest early in life through hypoglycaemia, before growth retardation is noted, and can be successfully treated with recombinant GH.

Juvenile breast hypertrophy.

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Neonatal diabetes - same disease, same gene, different outcomes.

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Clinical, biochemical and gender characteristics of 97 prepubertal children with premature adrenarche.

Background Premature adrenarche (PA) is defined as the appearance of clinical signs of androgen action associated with levels of dehydroepiandrosterone sulfate (DHEAS) ≥40 µg/dL, before age 8 years in girls and 9 years in boys, without breast or testicular enlargement. The aim of this study was to characterize a population of prepubertal Caucasian children with PA and to compare them with regard to gender and body mass index (BMI) (normal BMI vs. overweight/obesity). Methods We performed a cross-sectional study of Portuguese Caucasian prepubertal children followed, due to PA, in pediatric endocrinology clinics of a university hospital. Results Eighty-two girls and 15 boys were included (mean age at evaluation: 7.4 ± 1.3 years). The mean birth weight was 2990 ± 689 g; only two children were small for gestational age. Girls presented premature pubarche at a younger age (median [interquartile range (IQR)] 6 (5-6) years vs. 7 (7-8) years in boys; p < 0.001). No gender differences were found for gestational age, birth weight, maternal age at menarche, anthropometry, bone age advancement or androgen levels. The majority of the subjects were overweight or obese (59%). Overweight/obese PA children were taller and had a more advanced bone age than normal-BMI PA children. Overweight/obese children presented higher levels of DHEAS and androstenedione. Bone age advancement and DHEAS were correlated (r = 0.449; p = 0.05). Conclusions We found no evidence of reduced fetal growth. Girls presented premature pubarche at a younger age. No major gender differences in androgen levels were found in prepuberty. Obese and overweight PA children tend to be taller, have a more advanced bone age and higher levels of androgens than normal-BMI PA children.

Arterial stiffness in children and adolescents with and without continuous insulin infusion.

Background Arterial stiffness is a consequence of aging, but there are several diseases that contribute to this process. The evaluation of pulse wave velocity (PWV) allows a dynamic evaluation of vascular distensibility and the detection of atherosclerosis at an early stage. It was intended to evaluate the PWV in children and adolescents with type 1 diabetes mellitus (T1DM) and to compare their outcome according to the type of treatment used. Methods Forty-eight patients were randomly selected. Inclusion criteria: T1DM, under intensive insulin therapy (multiple daily insulin administrations [MDI] or continuous insulin infusion system [CIIS]). Exclusion criteria: existence of another chronic pathology or microvascular complications. Echocardiography was performed and three measurements of PWV were done, with their mean calculated. Results Most of the children and adolescents presented a PWV ≥ the 75th centile. There was a statistically significant difference for hemoglobin A1c (HbA1c) (7.8 in CIIS vs. 9 in MDI, p < 0.05). There were not statistically significant differences in the PWV between the two groups. This can be attributed to the fact that children with CIIS are those who previously presented greater glycemic instability. There was a significant correlation between PWV and disease duration (Pearson's correlation coefficient [r] = 0.314, p = 0.036). Conclusions This study showed that in children and adolescents with T1DM, there is an important prevalence of arterial stiffness, translated by an increase in PWV. This increase in PWV appears to exist even in very young children with little disease evolution time.