Comparison of the Clinical Utility of Two Insulin Resistance Indices: IRI-HOMA and IRI-Belfiore in Diagnosing Insulin Resistance and Metabolic Complications in Children Based on the Results Obtained for the Polish Population.

Background: Recognizing insulin resistance (IR) in children remains challenging due to uncertain IRI-HOMA cut-offs and unclear recommendations for evaluating IR based on OGTT. In our study, we compare the effectiveness of IRI-HOMA and IRI-Belfiore (OGTT-based) in detecting IR and its metabolic complications in children. Methods: The analysis included 553 children who were hospitalized at the Department of Endocrinology and Metabolic Diseases of the Polish Mother's Memorial Hospital Research Institute (PMMH-RI) in Lodz, Poland, between 2002 and 2018 due to various reasons-of these, 67.5% were girls. All underwent OGTT for glucose and insulin assessment. IR diagnosis relied on IRI-HOMA and IRI-Belfiore. IR based on IRI-HOMA was evaluated using three criteria: (A) >2.5; (B) >2.67 in boys and >2.22 in girls before puberty and >5.22 and >3.82 during puberty, respectively; (C) >95th percentile according to charts for IRI-HOMA in children. Results: Prepubertal children exhibited significantly lower IRI-HOMA and IRI-Belfiore than their pubertal counterparts (p < 0.00005). IRI-HOMA and IRI-Belfiore values positively correlated with age and BMI SDS value (p < 0.000001 for all calculations). As many as 26% to 46.9% of children with normal IRI-HOMA showed elevated IRI-Belfiore, with notably higher levels of triglycerides, a lower HDL cholesterol fraction, and a lower HDL/total cholesterol ratio in this subgroup. Conclusions: A notable proportion of children exhibited elevated IRI-Belfiore levels despite having normal IRI-HOMA values. This suggests the possibility of peripheral IR preceding hepatic IR in children-omitting an OGTT may therefore lead to overlooking cases of IR. Children diagnosed with IR via OGTT displayed significantly poorer lipid profiles compared to those without IR (characterized by normal values in both IRI-HOMA and IRI-Belfiore). This underscores the ability of OGTT-derived IR indices to identify individuals at risk of developing complications associated with obesity and IR before the onset of metabolic syndrome (MS) symptoms. If IR is already detected in children based on fasting glucose and insulin levels (IRI-HOMA), further evaluation may not be warranted, as OGTT results often simply confirm the diagnosis.

The incidence of insulin resistance based on indices calculated using the HOMA and Belfiore methods and its impact on the occurrence of metabolic complications in prepubertal children born small for gestational age.

INTRODUCTION: Children born small for gestational age (SGA) are predisposed to obesity, insulin resistance (IR), and lipid disorders. The HOMA-IR index is commonly used to assess IR (IRIHOMA), calculated from fasting glucose and insulin. However, sometimes, during the oral glucose tolerance test (OGTT), elevated and prolonged postprandial insulin secretion is observed despite normal fasting insulin levels. IRIBelfiore is an IR index that analyses glucose and insulin levels during OGTT according to the method proposed by Belfiore. THE AIM OF THE STUDY: was to assess the frequency of IR based on IRIHOMA and IRIBelfiore results in SGA children aged 6-8 years, after catch-up phenomenon, to determine the usefulness of IRIBelfiore in diagnosis of IR and in predicting future metabolic complications. MATERIAL AND METHODS: In 129 SGA normal-height children, aged 6-8 years, height, weight, waist circumference, blood pressure, as well as lipids, IGF-1, cortisol, C-peptide, leptin, adiponectin, and resistin concentrations were measured. The glucose and insulin concentrations were evaluated at 0, 60, and 120 minutes of OGTT. RESULTS: IRIHOMA was normal in all children, while elevated IRIBelfiore was found in 22.5% of them. Children with IR diagnosed by IRIBelfiore were taller, had higher blood pressure, higher leptin, and lower HDL-cholesterol concentrations. CONCLUSIONS: It seems worth recommending IRIBelfiore derived from OGTT as a valuable diagnostic tool for identifying IR in SGA prepubertal children. Abnormal IRIBelfiore is related to higher blood pressure and lower HDL-cholesterol concentration in this group.

Osteoporosis as the First Sign of Cushing's Disease in a Thin 16-Year-Old Boy-A Case Report.

Cushing's disease (CD) is an extremely rare diagnosis in children. In this report, we present the case of an almost 16-year-old, short and thin boy with CD, the first symptoms of which were spinal pain and vertebral fractures as a result of osteoporosis. In light of his growth retardation and short stature, the boy underwent diagnostics, which excluded growth hormone (GH) deficiency, hypothyroidism and celiac disease. Finally, based on cortisol profile results, dexamethasone suppression tests and bilateral sampling during catheterization of the inferior petrosal sinuses, CD was diagnosed.

The Variability of Vitamin D Concentrations in Short Children with Short Stature from Central Poland-The Effects of Insolation, Supplementation, and COVID-19 Pandemic Isolation.

The aim of the study was to investigate the effects of seasonal variability of insolation, the implementation of new recommendations for vitamin D supplementation (2018), and the SARS-CoV-2 pandemic lockdown (2020) on 25(OH)D concentrations in children from central Poland. The retrospective analysis of variability of 25(OH)D concentrations during the last 8 years was performed in a group of 1440 children with short stature, aged 3.0-18.0 years. Significant differences in 25(OH)D concentrations were found between the periods from mid-2014 to mid-2018, from mid-2018 to mid-2020, and from mid-2020 to mid-2022 (medians: 22.9, 26.0, and 29.9 ng/mL, respectively). Time series models created on the grounds of data from 6 years of the pre-pandemic period and used for prediction for the pandemic period explained over 80% of the seasonal variability of 25(OH)D concentrations, with overprediction for the first year of the pandemic and underprediction for the second year. A significant increase in 25(OH)D concentrations was observed both after the introduction of new vitamin D supplementation guidelines and during the SARS-CoV-2 pandemic; however, the scale of vitamin D deficiency and insufficiency was still too high. Time series models are useful in analyzing the impact of health policy interventions and pandemic restrictions on the seasonal variability of vitamin D concentrations.

GH-secreting pituitary adenoma in the course of McCune­Albright syndrome in a 21-year-old patient complicated by hepatocellular carcinoma.

Not required for Clinical Vignette.

The prevalence of hypothyroxinemia in premature newborns.

Congenital hypothyroidism diagnosed by TSH assessment in bloodspot screening may be overlooked in preterm newborns due to immaturity of the hypothalamus-pituitary-thyroid axis in them. The purpose of the study was to determine the prevalence and causes of hypothyroxinemia in preterm newborns, determined by TSH and FT4 serum concentration measurement, performed on the 3-5th day of life. We assessed TSH, FT4 and FT3 serum concentration on the 3-5th day of life in preterm children born at our centre within three consecutive years. We assessed the incidence of hypothyroxinemia, and its cause: primary hypothyroidism, secondary hypothyroidism or low FT4 syndrome - with normal TSH concentration, its dependence - among others - on gestational age (GA), birth body weight (BBW) and being SGA. A total of 525 preterm children were examined. FT4 concentration was decreased in 14.9% of preterm newborns. The most frequent cause of hypothyroxinemia was low FT4 syndrome (79.5%). More than 92% cases of hypothyroxinemia occurred in children born before the 32nd week and/or with BBW below 1500 g. Thus, every fourth child in these groups had a reduced FT4 concentration. Neonates with hypothyroxinemia were significantly lighter than those with normal FT4. In older and heavier neonates with hypothyroxinemia, serious congenital defects were observed. Neither IVH nor SGA nor twin pregnancies predispose children to hypothyroxinemia. Among newborns with untreated hypothyroxinemia in whom TSH and FT4 assessment was repeated within 2-5 weeks, a decreased FT4 concentration was confirmed in 56.1% of cases. As hypothyroxinemia affects 25% of newborns born before the 32nd week of gestation and those in whom BBW is less than 1500g, it seems that in this group of children the newborn screening should be extended to measure serum TSH and FT4 concentration between the 3-5th day of life. In older and heavier neonates, additional serum TSH and FT4 assessment should be limited to children with severe congenital abnormalities but not to all SGA or twins. Despite the fact that the most common form of preterm hypothyroxinemia is low FT4 syndrome, it should be emphasized that FT4 remains lowered on subsequent testing in more them 50% of cases.

Bone Turnover Markers and Bone Mineral Density in Children with Hypophosphatemic Rickets.

Hypophosphatemic rickets is a rare disease that results in bone deformities. However, little is known about bone turnover and bone mass disorders in this disease. This retrospective study included 12 children aged 1-16 years diagnosed with hypophosphatemic rickets. Parameters of calcium-phosphate metabolism and bone turnover markers were analysed. Bone mineral density was assessed with the use of dual-energy X-ray absorptiometry, and indices of quantitative ultrasound examination of tibiae and radial bones were analysed. In the majority of patients, hypophosphatemia and hyperphosphaturia were present. The assessed bone turnover markers showed increased bone formation. Increased pyridinoline levels were found in 5 out of 12 patients. Bone mineral density was decreased only in one patient. Decreased values of quantitative ultrasound examination were observed in all the analysed patients. Conclusions: (1) Bone metabolism disturbances, reflected in the increased values of bone turnover markers and worse bone quality, were found in the group of patients with hypophosphatemic rickets. (2) It is crucial to determine bone turnover markers, dual-energy X-ray absorptiometry findings and indices of quantitative ultrasound examination in order to monitor progress of the disease, as well as treatment effects.

Strong Positive Correlation between TSH and Ghrelin in Euthyroid Non-Growth Hormone-Deficient Children with Short Stature.

The growth processes in children depend on the proper functioning of some hormones and growth factors. Recently, a positive correlation between ghrelin and TSH (thyroid stimulating hormone) in patients with hyper- and hypothyroidism was proved. Moreover, in hypothyroid rats with high ghrelin concentration, growth hormone (GH) and insulin-like growth factor I (IGF-I) secretion was suppressed. We analyzed these relationships in euthyroid prepubertal children with idiopathic short stature (ISS). The analysis comprised concentration of ghrelin, GH in stimulating tests and during the night, as well as IGF-I, TSH, free thyroxine (FT4) and free triiodothyronine (FT3) in 85 children with ISS (36 girls, 49 boys) aged 9.65 ± 3.02 years (mean ± SD). A strong positive correlation between ghrelin and TSH was confirmed (r = +0.44, p < 0.05). A higher ghrelin but lower nocturnal GH and lower IGF-I were observed in children with higher normal TSH concentration than those in children with lower normal TSH. Interestingly, alterations of TSH level were without any impact on FT4 and FT3 concentrations. Summing up, in ISS prepubertal euthyroid children, ghrelin and TSH secretion are closely related. On the other hand, the higher the TSH, the lower the nocturnal GH and IGF-I levels. The contribution of the above findings in deterioration of growth processes requires further studies.

Comparison of nocturnal and morning ghrelin concentration in children with growth hormone deficiency and with idiopathic short stature.

Ghrelin - a growth hormone (GH) secretagogue - presents a circadian rhythm with higher nocturnal than diurnal concentration (similar to GH). However, daily ghrelin production depends on food intake and nutritional state; it is increased in the fasting state and decreased after a meal. Since most past research concerning short stature children has relied on the morning ghrelin concentration for analyses, we decided to assess ghrelin concentration at the 60th and 90th minute after falling asleep and in the morning at 06:00 h, shortly after waking up from nighttime sleep (after 12 h of fasting). We compared these ghrelin concentrations to determine differences between nocturnal and morning ghrelin release in short children, both with idiopathic short stature (ISS) and growth hormone deficiency (GHD). We also analyzed the correlation between the nocturnal and morning ghrelin concentrations with nocturnal GH concentrations, measured at the same time points, as well as with maximal GH concentration, achieved by stimulation tests, and with the insulin-like growth factor I (IGF-I). The ghrelin and GH concentration 60th and 90th minute after falling asleep, as well as fasting morning ghrelin and IGF-I concentrations, were measured in 19 (n = 10 ISS and n = 9 GHD) prepubertal short children (7 girls and 12 boys), aged 10.36 ± 3.06 y. Differences between the nocturnal and morning ghrelin concentrations were analyzed by the Wilcoxon matched-pairs signed-rank test. Typical regression and correlation analyses were used to assess relationships among parametric data for other analyses. The Wilcoxon test showed ghrelin concentration is significantly higher in the morning than both at the 60th and 90th minute after falling asleep time points (in ISS and GHD). A significant correlation was observed: a) positive - between nocturnal ghrelin (both at the 60th and 90th minute) and morning ghrelin concentrations; b) positive - between ghrelin at the 60th minute and nocturnal GH concentrations (both at the 60th and 90th minute); c) negative - between ghrelin at the 60th minute and IGF-I concentrations; and d) negative - between body mass index and ghrelin concentrations at the 60th and 90th minute. We conclude: 1) in short children, both with GHD and with ISS, morning ghrelin level reflects its nocturnal concentration; however, it is significantly higher than the nocturnal ones. There is no significant difference between the measurement of ghrelin concentration at night at the 60th or 90th minute after falling asleep; 2) morning ghrelin concentration is affected by the hunger and satiety; therefore, it appears that nocturnal measurements better reflect the pool of hormone responsible for stimulation of GH and IGF-I secretion, especially since positive correlation between nocturnal ghrelin and nocturnal GH secretion was noted; 3) it seems that a higher body mass index is an additional independent factor, associated mainly with lower nocturnal (but not morning) ghrelin secretion.

[Impact on the development of parental awareness of excess weight in children]. / WpLyw SwiadomoSci rodzicÓw na rozwÓj nadmiaru masy ciaLa u dzieci.

UNLABELLED: A lot of publications emphasize the special role of parents' eating habits and their lifestyle on the prevalence of excess body weight in children. AIM: The aim of this study was to answer the question whether parents of children who are overweight and obese are aware of this problem and what factors affect their perception of the excess body weight degree in their offspring. MATERIALS AND METHODS: The study included 137 children aged 6,5- 13,5 years. 23 respondents were overweight and 76 obese. Compared group consisted of 113 children. All patients underwent physical examination with anthropometric measurements. Parents were asked to complete a questionnaire, where they evaluated the degree of excess body weight of their child. We also asked about both parents' weight and body height, their education and chronic diseases occurring in the family. RESULTS: In the group of obese children 56.2% of the respondents came from families where one parent had excess body weight while 32.9% of them from families where this problem affected both parents. In 51.3% of patients with a body mass index (BMI) above 95 centil, parents wrongly assessed the degree of excess body weight of their child, in overweight group this proportion accounted for 8.7%. There was a statistically significant (p = 0.007) correlation between the degree of children's excess body weight and the ability of parents to estimate that. Parents' education had no influence on the incidence of excess body weight in children and their ability to determine its extent. In the group of obese and overweight children only 4% of parents recognized obesity as a chronic disease. CONCLUSIONS: Parents of children who are overweight and obese have lower awareness about their child's weight in comparison to parents of children with normal weight. There is a statistical correlation between parents' perception of excess body weight and the development of obesity in children.

[The estimation nourishment methods of newborns and infants hospitalized in the Department of Pediatric Propedeutics and Bone Metabolism Diseases and analysis of factors which determinate the way of alimentation among these children]. / Ocena sposobu zywienia noworodków i niemowlat hospitalizowanych w Klinice Propedeutyki Pediatrii i Chorób Metabolicznych kosci oraz analiza czynników wplywajacych na wybór sposobu karmienia dzieci.

UNLABELLED: Despite so many advantages of natural feeding, according to the research led in Poland between 2000 and 2005, in the sixth month of life only 8% of infants were strictly breast-fed. The aim of the study was to analyze the factors which have the influence on choosing the way of feeding of children hospitalized in the Department of Pediatric Propedeutics and Bone Metabolism Diseases. MATERIAL AND METHODS: The inquiry was established among parents of newborns and infants up to 1 year old, hospitalized in the Department of Pediatric Propedeutics and Bone Metabolism Diseases between January and May 2008. The research was led on the group of 93 children (39 newborns and 54 infants). The inquiry consists of questions about the cause and duration of hospitalization, perinatal interview, ways of nourishment and parents' personal data. RESULTS: At the time of leading the inquiry 27 children (29%) were fed strictly naturally, 36 (38.7%) were bottle-fed, 23 (24.73%) were fed in the mixed way, 6 (6.5%) were fed by the stomach tube and 1 child (1.1%) was fed parenterally. 44.1% of parents obtained information about breast-feeding from media, whereas only 3 (3.2%) got it from medical staff. The most common reason for giving up breast feeding was the lack (or too little amounts) of mother's milk. The doctor appeared to be the main person who decided to introduce formula-feeding. Among children naturally-fed 21 (77.8%) were given formula in the first twenty-four hours after the labour. The factors which appeared to influence the choice of the way of alimentation, in statistically important way (p < 0.05), were: birth weight, points in Apgar scale, moment of the delivery, mother's age and whether she was breast-fed as a child. CONCLUSIONS: In the researched group only 29% of children, up to 1 year old, were fed strictly naturally. The results suggest that the medical staff (especially doctors) has too little influence on promoting breast feeding as the most appropriate way of alimentation. The health care system (perinatal, labour and basic care) concerning mother and child, doesn't promote natural feeding.