Diabetic ketoacidosis incidence among children with new-onset type 1 diabetes in Poland and its association with COVID-19 outbreak-Two-year cross-sectional national observation by PolPeDiab Study Group.

BACKGROUND: There are several observations that the onset of coronavirus 19 (COVID-19) pandemic was associated with an increase in the incidence of diabetic ketoacidosis (DKA). However, due to heterogeneity in study designs and country-specific healthcare policies, more national-level evidence is needed to provide generalizable conclusions. OBJECTIVE: To compare the rate of DKA in Polish children diagnosed with type 1 diabetes (T1D) between the first year of COVID-19 pandemic (15 March 2020 to 15 March 2021) and the preceding year (15 March 2019 to 15 March 2020). METHODS: Reference centers in 13 regions (covering ~88% of Polish children) retrospectively reported all new-onset T1D cases in children from assessed periods, including DKA status at admission, administered procedures and outcomes. Secondly, we collected regions' demographic characteristics and the daily-reported number of COVID-19-related deaths in each region. RESULTS: We recorded 3062 cases of new-onset T1D (53.3% boys, mean age 9.5 ± 4.3 years old) of which 1347 (44%) had DKA. Comparing pre- and post-COVID-19 period, we observed a significant increase in the rate of DKA (37.5%-49.4%, p < .0001). The fraction of moderate (+5.4%) and severe (+3.4%) DKA cases increased significantly (p = .0089), and more episodes required assisted ventilation (+2.1%, p = .0337). Two episodes of DKA during 2020/2021 period were fatal. By region, change in DKA frequency correlated with initial COVID-19 death toll (March/April 2020) (R = .6, p = .0287) and change in T1D incidence (R = .7, p = .0080). CONCLUSIONS: The clinical picture of new-onset children T1D in Poland deteriorated over a 2-year period. The observed increase in the frequency of DKA and its severity were significantly associated with the overlapping timing of the COVID-19 epidemic.

The presence of eye defects in patients with Turner syndrome is irrespective of their karyotype.

OBJECTIVE: Published data on eye disorders in patients with Turner syndrome (TS) are limited. We aimed to evaluate the prevalence of eye disorders in patients with TS and assess the association with patient karyotype. DESIGN: Cross-sectional, observational study. PATIENTS: Eighty-two patients with TS. MEASUREMENTS: We evaluated visual acuity (distance and proximity), intraocular pressure, optic system refraction, orthoposition, frontal eye segment, the eye fundus and colour vision. For eye fundus abnormalities, we conducted ultrasound examinations, visual field evaluations and fluorescein angiography. We statistically tested the association between the prevalence of eye disorders and karyotype. RESULTS: 50 (61%) patients had monosomy X; 9 (11%) had mosaicism with a normal 46,XX line; 21 (26%) had structural aberrations; and 2 patients (2%) had other chromosomal abnormalities. Eye disorders were diagnosed in 43 (52%) patients, with 29 (35%) patients having multiple eye defects. Defects related to impaired vision were the most common (44%), followed by strabismus (21%), changes in the posterior eye segment (6%), red-green colour deficiency (5%), changes in the anterior eye segment (5%) and nystagmus (4%). Amblyopia was diagnosed in 13 patients (16%). The most common combinations of ophthalmological defects were hypermetropia and astigmatism with or without other eye problems (12 patients). We found no association between the presence of eye defects and karyotype. CONCLUSIONS: Detection of eye abnormalities is necessary in all patients directly after being diagnosed with TS to prevent irreversible deterioration of eye function and permanent poor vision. All girls with TS, irrespective of their karyotype, should be referred to an ophthalmologist.

Bone markers in craniofacial bone deformations and dysplasias.

Various forms of bony deformations and dysplasias are often present in the facial skeleton. Bone defects can be either localized or general. Quite often they are not only present in the skull but also can be found in other parts of the skeleton. In many cases the presence and levels of specific bone markers should be measured in order to fully describe their activity and presence in the skeleton. Fibrous dysplasia (FD) is the most common one in the facial skeleton; however, other bone deformations regarding bone growth and activity can also be present. Every clinician should be aware of all common, rare and uncommon bony diseases and conditions such as cherubism, Paget's disease, osteogenesis imperfecta and others related to genetic conditions. We present standard (calcium, parathyroid hormone, calcitonin, alkaline phosphatase, vitamin D) and specialized bone markers (pyridinium, deoxypyridinium, hydroxyproline, RANKL/RANK/OPG pathway, growth hormone, insulin-like growth hormone-1) that can be used to evaluate, measure or describe the processes occurring in craniofacial bones.

Physical Activity and Its Potential Determinants in Obese Children and Adolescents under Specialist Outpatient Care-A Pilot Cross-Sectional Study.

(1) Background: this study aimed to assess the physical activity of obese pediatric patients under specialized outpatient care and its potential determinants. (2) Methods: A total of 83 subjects aged 7-18 years with simple obesity and their parents were enrolled. Data were collected with the use of physical activity questionnaires (PAQs) for children and adolescents and additional questions concerning selected socio-demographic characteristics. (3) Results: The mean final PAQ score was 2.09 ± 0.69. The most frequently chosen types of physical activity included walking, gymnastics, and jogging or running. We found a weak correlation inversely proportional between the child's age and mean final PAQ score (r = -0.25; p = 0.02). Younger children were more active during lunchtime at school and after school compared to adolescents (p = 0.03 and p = 0.04). The final PAQ score differed according to the place of residence; the lowest score was obtained by subjects living in cities >100,000 inhabitants (p = 0.025). We found a positive correlation between PAQ-Ch score and the father's physical activity, and between PAQ-A score and the mother's education. (4) Conclusions: The physical activity of obese pediatric patients is low, particularly in adolescents. It seems that age and place of residence have an impact on the physical activity of obese children and adolescents. The PAQs used in this study are useful in physical activity assessment and identification of time segments during the day in which activity might be improved. However, this requires confirmation in a larger group of pediatric patients.

Syndrome of Congenital Insulin Resistance Caused by a Novel INSR Gene Mutation

Mutations in the INSR gene result in rare inherited syndromes causing insulin resistance, such as leprechaunism (Donohue syndrome), Rabson-Mendenhall syndrome and insulin resistance type A. Leprechaunism is an autosomal recessive disorder associated with extreme insulin resistance that leads to hyperinsulinemia, impaired glucose homeostasis, fasting hypoglycemia and postprandial hyperglycemia. Impaired insulin action causes prenatal and postnatal growth retardation. Lipoatrophy, dysmorphic facies, hypertrichosis, macrogenitosomia and hypertrophy of internal organs are also present. A male infant with congenital insulin resistance was born at term after a normal pregnancy with a weight of 1905 g (<3 c), a length of 48 cm (<3 c), and an Apgar score of 10. Intrauterine growth retardation, transient hypoglycemia, pneumonia, urinary tract infection and heart defects [patent foramen ovale (PFO); patent ductus arteriosus (PDA)] were diagnosed after birth. At 5 weeks of age, he was admitted to the regional hospital with severe fever, diarrhea and dehydration. Hyperglycemia was observed (672 mg/dL), and insulin was administered. He was referred to a hospital at 7 weeks of age for suspected neonatal diabetes and hypertrophic cardiomyopathy. The physical examination revealed a loud systolic heart murmur, tachycardia, tachypnea, dysmorphic facies, hypertrichosis, acanthosis nigricans, hypotonia, swollen nipples and enlarged testicles. Glycemic fluctuations (50-250 mg/dL) were observed. The serum insulin concentration was high (maximum 1200 IU/mL) at normoglycemia. Ultrasound of the heart confirmed progressive hypertrophic cardiomyopathy. Leprechaunism was confirmed by genetic analysis of INSR, in which a novel c.320C>G; p. Thr107Arg homozygous missense mutation was found in exon 2.

Silver-Russell syndrome and Turner syndrome in a girl with short stature treated with growth hormone - case report.

INTRODUCTION: Silver-Russell syndrome (SRS) is a rare condition, affects one in 100,000 births. Turner syndrome (TS) is a chromosomal disorder, with an incidence of one in 2,500 females. Patient with SRS and mosaic 45, X/46,X,del(X) karyotypes can have a wide range of phenotypic manifestations. The aim of this article is to present a case report of a patient with an extremely rare and not reported so far genetically confirmed diagnose of Silver-Russell syndrome and Turner syndrome. CASE REPORT: The patient is a 9-years old girl who had a karyotype of 45,X on prenatal amniocytes. After delivery she was small for gestational age and her phenotype was quite consistent with Russell-Silver syndrome: characteristic dimorphic facial skeleton with a triangular face with prominent forehead, thin nose, hypotonia and hemihyperthrophy. The girl was admitted to hospital due to short stature and deep body weight deficiency. Skin fibroblast and DNA analysis showed mosaic karyotype 45,X[14]/46,X,del(X)(p21.2) and hypomethylation of a gene H19 located on chromosome 11p15. At present the patient is treated with growth hormone in our clinic with good therapeutic results. CONCLUSIONS: The diagnosis of one genetic disorder does not rule out the possibility of a second genetic disease. Early diagnosis of coexistence of two different genetic syndromes, although very difficult, may help with quickly, appropriate therapy for patients and prevent them from developing serious complications.

Weight gain in type 1 diabetes during the SARS-CoV-2 pandemic. Does lockdown affect the metabolic control of pediatric patients?

Background and aims: Due to the severe acute respiratory syndrome coronavirus 2 pandemic, governments of many countries decided to implement lockdowns, which included school closures. This major lifestyle change also applied to people with diabetes. The aim of this paper was to analyze how the COVID-19 pandemic and related restrictions influenced the metabolic compensation of diabetes in the pediatric population. Methods: Patients with type 1 diabetes (T1D), treated by one therapeutic team, who in 2020 and 2021 paid at least two in-person visits in the outpatient clinic, were included in the study. The time in range (TIR) and HbA1c, as well as the total daily dose (TDD) of insulin and BMI from the visit before the announcement of the pandemic restrictions (March 2020) and during the lockdown (second visit after 6 months) and within the period of loosened restrictions (two visits in 2021) were analyzed. Results: A total of 185 patients with T1D were included in the study (96 boys), aged 2-18 years (11.5 ± 3.5); 135 of them (72.9%) use CSII and 142 (76.8%) use CGM or FGM. During the first months of the studied period, despite comparable (p>0.05) TIR (57.5 ± 21.4% vs. 59.9 ± 20.5%), improvement of HbA1c was noticed (7.9 ± 1.6% vs. 7.5 ± 1.4%, p=0.0336), whereas in the following months, both HbA1c and TIR were comparable. Also, the TDD increased significantly (from 37.3 ± 18.9 units/day on the first visit up to 46.8 ± 22.7 units/day on the last visit, p=0.0003); however, TDD/kg remained constant (p>0.05) (0.8 ± 0.2 units/kg/day vs. 0.8 ± 0.3 units/kg/day) possibly due to an increased BMI (19.1 ± 3.7 kg/m2 vs. 20.9 ± 4.1 kg/m2, p=0.0001). The percentage of basal insulin in the TDD remained stable (p>0.05) (39.7 ± 11.3% vs. 39.3 ± 13.6%). Furthermore, a significant (p=0.0001) change in the BMI percentile was noticed [from 58.9 ± 26.2 percentiles (%iles) before lockdown vs. 64.6 ± 26.0%iles on the second visit]. However, the BMI percentile returned to baseline (58.1 ± 28.4%iles) at the visit at the end of the observation period. Conclusions: The parameters of metabolic control in pediatric patients with T1D during the pandemic period remained stable; however, weight gain and an increase in daily insulin dose have been observed, possibly due to reduced physical activity.

Prevalence of haplotype DQ2/DQ8 and celiac disease in children with type 1 diabetes.

Type 1 diabetes (T1D) and celiac disease (CD) coexist very often. Identification of the human leukocyte antigen (HLA) DQ2/DQ8 can confirm the genetic predisposition to CD. Negative result of this test allows to exclude CD with a high probability. It was suggested that in individuals with higher risk of CD, including T1D patients, the implementation of genetic testing should reduce the number of patients requiring systematic immunological screening. The aim of this study was to analyze the prevalence of different haplotypes predisposing to CD in children and adolescents with previously diagnosed T1D. MATERIAL AND METHODS: A retrospective analysis was performed on 166 T1D children (91 girls) in whom HLA DQ2/DQ8 alleles were tested. In 9.6% CD was also diagnosed. RESULTS: In 12.7% both HLA DQ2/DQ8 were negative. In 87.3% patients HLA DQ2 and/or DQ8 was positive, including 27.7% patients with both haplotypes DQ2.5 and DQ8 positive. In all CD patients the disease predisposing alleles were positive, while none of the HLA DQ2/DQ8 negative children were diagnosed with CD. CONCLUSIONS: The prevalence of HLA DQ2.5 and the HLA DQ2.5 / HLA DQ8 configuration is higher in patients with T1D, and CD compared to children with T1D alone. The combination of HLA DQ2 and HLA DQ8 most significantly increases the risk of developing CD. The group of HLA DQ2/DQ8 negative patients with improbable CD diagnosis, is relatively small. Most of T1D patients HLA DQ2/DQ8 positive need further regular antibody assessment. In patients with T1D, who are at high risk of developing CD, genetic testing may be considered to select those who require further systematic serological evaluation. Due to its retrospective nature, the study was not registered in the database of clinical trials and the Clinical trial registration number is not available.

Visfatin in juvenile obesity - the effect of obesity intervention and sex.

BACKGROUND: The association of visfatin, an adipocytokine relevant to the development of inflammation and metabolic disorders, with juvenile obesity needs to be re-established as previously used tests occurred to be nonspecific. OBJECTIVE: To evaluate visfatin association with a metabolic profile of 88 overweight/obese and 26 lean children/adolescents as well as changes in its levels following weight reduction programme (diet + enhanced physical activity ± metformin). DESIGN: A case-control and cohort study. RESULTS: Visfatin was higher in obese than lean and overweight individuals (2·07 vs. 1·53 and 1·47 ng mL(-1) , P = 0·034). Of metabolic syndrome components, central obesity combined with either insulin resistance (IR) or hyperinsulinemia (HI) was associated with increases in circulating visfatin. In girls, visfatin correlated with leptin (r = 0·40, P = 0·009) and thiols (r = -0·36, P = 0·009), which explained 24% in visfatin variability. In boys, visfatin correlated with waist circumference (r = 0·36, P = 0·036), BMI% (r = 0·38, P = 0·025), whole body insulin sensitivity index (r = -0·36, P = 0·036), IL-6 (r = 0·38, P = 0·024) and thiobarbituric acid reactive substances (TBARS) (r = 0·52, P = 0·001), of which IL-6 and TBARS were independent predictors of visfatin elevation, explaining 42% in data variability. Visfatin was significantly lower following weight reduction programme than at baseline (1·43 vs. 1·83 ng mL(-1) , P = 0·033). Visfatin reduction correlated neither with changes in metabolic parameters nor was it affected by metformin. ΔVisfatin correlated exclusively with baseline visfatin (r = 0·612, P < 0·0001), which explained 38% in data variability. CONCLUSIONS: Central obesity combined with HI/IR contributes to visfatin elevation. Visfatin association with metabolic/biochemical variables is gender dependent. Diet + enhanced physical activity are effective in visfatin reduction, the degree of which depends on baseline visfatin.

Gender-specific association of serum uric acid with metabolic syndrome and its components in juvenile obesity.

BACKGROUND: Hyperuricemia has been implicated in the pathogenesis of obesity and related metabolic abnormalities. Studies on the association between serum uric acid (sUA) and metabolic syndrome (MetS) in juvenile obesity are scant. The effect of gender has not been evaluated. METHODS: sUA (uricase method), anthropometric and biochemical indices were measured in gender-stratified children/adolescents consisting of 113 overweight/obese and 71 lean individuals. RESULTS: In males, sUA was significantly elevated in overweight as well as obese patients. sUA was strongly associated with obesity indices and reflected sexual development, decreases in high density lipoprotein-cholesterol, and moderately, the number of MetS components. Waist circumference (WC) and Tanner stage explained 40% of sUA variability. Controlling for body mass index (BMI) and other MetS components, sUA was associated with abdominal obesity, explaining 30% of variability in WC. In females, sUA was significantly increased in obesity, high blood pressure (BP), and MetS and corresponded with the number of MetS components, indices of glucose metabolism, triglycerides (TG), and the atherogenecity index. Insulin-resistance (IR) (homeostasis model assessment; HOMA) and high BP explained 29% of sUA variability, whereas sUA, while controlling for BMI, age, and other MetS components, was associated with hypertriglyceridemia, hyperglycemia, high BP, and abdominal obesity. IR mediated the associations with high TG and glucose. CONCLUSIONS: The association between sUA and MetS components in juvenile obesity is gender-specific, with females being related more closely and to more metabolic abnormalities. It may explain why, despite its lower concentrations, sUA is an independent predictor of mortality from all causes and from vascular diseases exclusively in females. Our findings may help in identifying metabolic abnormalities which may possibly be targeted by reducing sUA in males and females.

The effect of a one-year weight reduction program on serum uric acid in overweight/obese children and adolescents.

BACKGROUND: Hyperuricemia may underlie obesity and related disorders, but the impact of weight reduction and metformin on serum uric acid (sUA) in Caucasian children/adolescents is unknown. METHODS: One hundred and thirteen children/adolescents were enrolled (83 completed) into 1-year weight reduction program (diet+exercise) without or with metformin. Anthropometric and biochemical measurements were conducted at baseline and at the end of follow-up (13 ± 3 months). RESULTS: sUA decreased in 86% females and 67% males. Significantly more patients substantially (≥ 10%) reduced their sUA than body mass index (BMI)%. In females, sUA decreased regardless of type of intervention, but more markedly in the metformin group, and ΔsUA correlated positively with ΔBMI%, ΔWHtR (waist-to-height ratio), Δinsulin, ΔHOMA (homeostasis model of assessment), and Δtriglycerides/high density lipoprotein (HDL), but correlated negatively with baseline sUA, HOMA, insulin, and triglycerides/HDL. Of these, metformin treatment, baseline sUA, and ΔBMI% were independent predictors of sUA reduction, explaining 77% of data variability. In males, sUA reduction was significant in the metformin group only, and negatively correlated with ΔWHR (waist-to-hip ratio), ΔWHtR, Δleptin, baseline sUA, and waist circumference. Of these, baseline sUA and ΔBMI% were independent predictors of sUA reduction, explaining 69% of data variability. Except for sUA, females reduced their BMI%, waist circumference, triglycerides, triglycerides/HDL and increased HDL, while males reduced total cholesterol. CONCLUSIONS: A longitudinal weight reduction program encompassing diet/exercise with or without metformin was more efficient in reducing sUA than weight and its effect on sUA and other metabolic parameters differed between genders. Weight loss did not condition sUA reduction, which was strongly dependent on baseline levels. The sUA reducing effects of metformin may contribute to its effects on blood pressure-lowering and endothelial function-improving properties in females.

Circulating adipocyte fatty acid-binding protein, juvenile obesity, and metabolic syndrome.

Adipocyte fatty acid-binding protein (A-FABP) links obesity and metabolic syndrome (MetS) and might be targeted in future therapies. Its utility as a MetS biomarker has been suggested in adults but has not been examined in children/adolescents. Our objectives were to identify metabolic parameters associated with A-FABP elevation in children and adolescents and to evaluate the effect of obesity intervention and A-FABP diagnostic utility. A-FABP and anthropometric, metabolic, and inflammatory indices were measured in 31 lean and 114 overweight/obese children and adolescents and reassessed after obesity intervention (1 year; diet and enhanced physical activity, with or without metformin). A-FABP was significantly higher in overweight/ obese than lean individuals, where it correlated with insulin, waist circumference (WC), and 2-h glucose independent of body mass index (BMI), age, gender, and developmental stage. The pattern of A-FABP associations differed between sexes. As a MetS indicator, A-FABP had 68% accuracy. The weight reduction program was effective in reducing A-FABP, BMI%, WC, triglycerides, and cholesterol. In conclusion, elevation in A-FABP is associated with MetS components independent of BMI status and can be reduced by diet and enhanced physical activity. A-FABP as a single MetS biomarker has a moderate accuracy.

Soluble Klotho Is Decreased in Children With Type 1 Diabetes and Correlated With Metabolic Control.

Klotho concentration may be considered as a prognostic factor in the development of chronic complications of diabetes. Moreover, decrease in sKlotho concentration may contribute to beta cell apoptosis and type 1 diabetes development. The aim of this study was to evaluate if sKlotho protein concentration in children with type 1 diabetes (T1D) and its correlation with classical risk factors of chronic complications of diabetes: dysglycemia and endothelial dysfunction. Material and methods: In a cross-section single center study the levels of soluble Klotho protein in 80 T1D (37 boys) and 34 healthy children (controls, 15 boys). Micro- and macroangiopathy were excluded and renal function was normal in all participants. Serum sKlotho, sICAM-1, sVCAM-1 and E-selectin levels were measured. Results: The concentration of sKlotho was lower in T1D than in the controls (2041.9 ± 1017.6 pg/mL vs. 2790.3 ± 1423.9 pg/mL, p=0.0113). sICAM-1, sVCAM-1 and E-selectin concentrations were comparable in patients and controls. In T1D, sKlotho was not correlated with the duration of diabetes. Klotho and E-selectin were correlated with HbA1c (r=-0.31, P=0.0066 and r=0.25, P=0.0351, respectively), but not with AVBG and blood glucose SD. Correlations of sKlotho with total cholesterol (r=0.31, P=0.0129), HDL-cholesterol (r=0.43, P=0.0011) and LDL-cholesterol (r=0.28, P=0.0412), but not with triglycerides, were found. Likewise, Klotho was not correlated with sICAM-1, sVCAM-1, and E-selectin concentrations. Conclusions: This study reports the significantly lower level of s-Klotho in children with type 1 diabetes, correlated with HbA1c and HDL cholesterol, but not with the adhesion molecules concentrations nor the duration of the disease. Negative correlation between the levels of HbA1c and soluble Klotho may suggest its possible involvement in the development of chronic diabetes complications.

To increase body height and muscle strength - one medicine for two diseases? Case report of a boy with Silver-Russell syndrome and Duchenne muscular dystrophy.

The coexistence of 2 genetic diseases can mutually modify their course. We describe the case of a 10-year-old boy with Sliver-Russell syndrome (SRS) and Duchenne muscular dystrophy (DMD). The patient's short stature, which is part of the clinical picture of both diseases, has been additionally aggravated by the steroid therapy, which is necessary to delay the progression of DMD. From the age of 9 years, the patient was treated with recombinant human growth hormone (rhGH) for 18 months. The following study discusses whether rhGH therapy in a child with SRS and DMD may alleviate or worsen the course of DMD, and how it affects carbohydrate metabolism disorders.

Complex glycerol kinase deficiency - long-term follow-up of two patients.

Complex glycerol kinase deficiency (CGKD) is a rare genetic syndrome which belongs to the group of contiguous gene syndromes and is caused by microdeletion of genes located in Xp21. Patients with CGKD present with features characteristic for adrenal hypoplasia, glycerol kinase deficiency, Duchenne muscular dystrophy and sometimes intellectual disability. We present a long-term follow-up of two unrelated boys with molecular diagnosis of complex glycerol kinase deficiency. Genetic examinations in both patients revealed a deletion on Xp21 chromosome including complete deletion of NR0B1 and GK genes. Additionally in patient 2 IL1RAPL1 genes were deleted. In separate MLPA test DMD gene deletion was diagnosed in both patients as follow: in patient 1 whole gene while in patient 2 the C-terminal region of DMD was deleted. Although the first symptom in both was salt loss syndrome, the course of the disease was different for them. We share our experience resulting from the opportunity of caring for patients with this rare disease from the beginning of their life to the end of pediatric care.

Diagnosis of type 1 diabetes during the SARS-CoV-2 pandemic: Does lockdown affect the incidence and clinical status of patients?

BACKGROUND: Currently, the only effective method to control the spread of the COVID-19 pandemic is social distancing. The lockdown measures during the epidemic may have an impact on the presentation of diabetes and may disturb metabolic control. OBJECTIVES: In order to address the hypothesis that the COVID-19 lockdown affected the incidence rate (IR) of type 1 diabetes (T1D) in the pediatric population of Lower Silesia and the patients' clinical status, the incidence of T1D during the COVID-19 pandemic was analyzed. MATERIAL AND METHODS: Incidence estimates were obtained from the T1D pediatric registry for Lower Silesia which has been maintained since January 1, 2000. The observation was completed on April 30, 2020. RESULTS: A total of 1961 cases were diagnosed (1054 boys, 53.72%). An increase in the T1D IR was observed, from 10.43/100,000/year in 2000 to 22.06/100,000/year in 2019. The seasonality of T1D incidence was also observed, with the highest IR appearing in January and February. There were half as many cases of T1D in March and April 2020 as in the same months in 2019 (p > 0.05). Diabetic ketoacidosis (DKA) occurred in 31.75% of patients in years 2000-2019, comparably (p > 0.05) to 2020 (36.67% patients), including March and April (50% of patients). The duration of hyperglycemia symptoms was 20.2 ±25.4 days, which was comparable to 2020 (13.1 ±10.96 days; p = 0.1675) and March and April of 2020 (9.67 ±5.63 days; p = 0.0831). Glycated hemoglobin (HbA1c) level was 11.79 ±2.63%, which was comparable to March and April of 2020 (13.06 ±2.35%; p = 0.1171), while in all of 2020 it was 13.41 ±2.50% (p = 0.0003). CONCLUSIONS: The IR of T1D in Lower Silesian children in the months of the COVID-19 pandemic was comparable to previous years, while their clinical condition at the time of diagnosis was worse than in previous years.

Clinical evaluation of 31 children with pituitary insufficiency in the course of the pituitary stalk interruption syndrome. The unexpected growth without growth hormone in 2 children.

INTRODUCTION: The pituitary stalk interruption syndrome (PSIS) is one of the complex -forms of congenital pituitary insufficiency. Symptoms resulting from insufficiency of the pituitary gland, in spite of the inborn character of the disease, may appear at various stages of life. The aim of this paper was to present clinical presentation in 31 patients with PSIS confirmed radiologically. RESULTS: In the whole study population during first examination 25.8% children were diagnosed with combined pituitary hormone deficiency (CPHD). During the endocrinological observation (median follow-up 5.1 years, range 0.513.2) of the above-mentioned group 74.2% subjects were diagnosed with CPHD, while 25.8% patients with isolated growth hormone deficiency (GHD). Two children with initially short stature were confirmed with GHD. As a result of the parents' decision, growth hormone therapy was either not started or discontinued. During further follow-up, however, the children achieved normal height. CONCLUSIONS: Children with PSIS present a diverse clinical picture and should be observed because of the risk of further pituitary disorders. In the differential diagnosis of hypoglycemia in the neonatal period and in infancy, hypopituitarism should be considered. The phenomenon of normal growth in patients with confirmed growth hormone deficiency has been observed, although is not fully understood.

Disturbances in the intraventricular conduction system in teenagers with type 1 diabetes. A pilot study.

Body Surface Potential Mapping (BSPM) is a multi-electrode synchronous method for examining electrocardiographic records on the patients' body surface that allows the assessment of changes in the heart conduction system. The aim of the study was to visualize and evaluate changes in the intraventricular system in adolescents with T1D. PATIENTS AND METHODS: Inclusion criteria: age > 12 years, T1D duration >3 years, HbA1c >8%. EXCLUSION CRITERIA: diagnosis of autonomic neuropathy, heart structural defects, heart failure. BSPM data were processed into map plotting to illustrate differences in ventricular activation time (VAT, isochron lines). RESULTS: 33 teenagers (20 boys), mean age 15.0 ± 2.1 years, T1D from 6.8 ± 4.1 years were included. Mean HbA1c was 9.6 ± 2.0%. In the standard ECG recording abnormalities were not present. The distribution of isolines on the group-mean map plotted for T1D patients only initially resembles the course of isolines on the group-map for normal subjects (N = 30), in whom the electrical impulse stimulating the heart ventricles passes through the atrio-ventricular node, then symmetrically excites the branches of His bundle and finally the Purkinje fibers. In T1D patients, after proper onset of intraventricular stimulation, the isolines reflecting the both ventricles reach higher time values, which indicates problems in the propagation of the ventricular depolarization.

Effects of Recombinant Human Growth Hormone Treatment, Depending on the Therapy Start in Different Nutritional Phases in Paediatric Patients with Prader-Willi Syndrome: A Polish Multicentre Study.

Recombinant human growth hormone (rhGH) treatment is an established management in patients with Prader-Willi syndrome (PWS), with growth promotion and improvement in body composition and possibly the metabolic state. We compared anthropometric characteristics, insulin-like growth factor 1 (IGF1) levels, metabolic parameters and the bone age/chronological age index (BA/CA) in 147 children with PWS, divided according to age of rhGH start into four groups, corresponding to nutritional phases in PWS. We analysed four time points: baseline, rhGH1 (1.21 ± 0.81 years), rhGH2 (3.77 ± 2.17 years) and rhGH3 (6.50 ± 2.92 years). There were no major differences regarding height SDS between the groups, with a higher growth velocity (GV) (p = 0.00) and lower body mass index (BMI) SDS (p < 0.05) between the first and older groups during almost the whole follow-up. IGF1 SDS values were lower in group 1 vs. other groups at rhGH1 and vs. groups 2 and 3 at rhGH2 (p < 0.05). Glucose metabolism parameters were favourable in groups 1 and 2, and the lipid profile was comparable in all groups. BA/CA was similar between the older groups. rhGH therapy was most effective in the youngest patients, before the nutritional phase of increased appetite. We did not observe worsening of metabolic parameters or BA/CA advancement in older patients during a comparable time of rhGH therapy.

The broad phenotypic spectrum of 17α-hydroxylase/17,20-lyase (CYP17A1) deficiency: a case series.

CONTEXT: 17α-Hydroxylase/17,20-lyase deficiency (17OHD) caused by mutations in the CYP17A1 gene is a rare form of congenital adrenal hyperplasia typically characterised by cortisol deficiency, mineralocorticoid excess and sex steroid deficiency. OBJECTIVE: To examine the phenotypic spectrum of 17OHD by clinical and biochemical assessment and corresponding in silico and in vitro functional analysis. DESIGN: Case series. PATIENTS AND RESULTS: We assessed eight patients with 17OHD, including four with extreme 17OHD phenotypes: two siblings presented with failure to thrive in early infancy and two with isolated sex steroid deficiency and normal cortisol reserve. Diagnosis was established by mass spectrometry-based urinary steroid profiling and confirmed by genetic CYP17A1 analysis, revealing homozygous and compound heterozygous sequence variants. We found novel (p.Gly111Val, p.Ala398Glu, p.Ile371Thr) and previously described sequence variants (p.Pro409Leu, p.Arg347His, p.Gly436Arg, p.Phe53/54del, p.Tyr60IlefsLys88X). In vitro functional studies employing an overexpression system in HEK293 cells showed that 17,20-lyase activity was invariably decreased while mutant 17α-hydroxylase activity retained up to 14% of WT activity in the two patients with intact cortisol reserve. A ratio of urinary corticosterone over cortisol metabolites reflective of 17α-hydroxylase activity correlated well with clinical phenotype severity. CONCLUSION: Our findings illustrate the broad phenotypic spectrum of 17OHD. Isolated sex steroid deficiency with normal stimulated cortisol has not been reported before. Attenuation of 17α-hydroxylase activity is readily detected by urinary steroid profiling and predicts phenotype severity. SIGNIFICANCE STATEMENT: Here we report, supported by careful phenotyping, genotyping and functional analysis, a prismatic case series of patients with congenital adrenal hyperplasia due to 17α-hydroxylase (CYP17A1) deficiency (17OHD). These range in severity from the abolition of function, presenting in early infancy, and unusually mild with isolated sex steroid deficiency but normal ACTH-stimulated cortisol in adult patients. These findings will guide improved diagnostic detection of CYP17A1 deficiency.