Band 34, Heft 2

Obesity, a complex, multi-factor and heterogeneous condition, is thought to result from the interaction of environmental and genetic factors. Considering the result of adolescence obesity in adulthood, the role of genetic factors comes to the fore. Recently, many genome-wide association studies (GWAS) have been conducted and many loci associated with adiposity have been identified. In adolescents, the strongest association with obesity has been found in single nucleotide polymorphisms (SNP) in the FTO gene. Besides FTO , GWAS showed consistent effects between variants in MC4R, TMEM18, TNNI3K, SEC16B, GNPDA2 , POMC and obesity. However, these variants may not have similar effects for all ethnic groups. Although recently genetic factors are considered to contribute to obesity, relatively little is known about the specific loci related to obesity and the mechanisms by which they cause obesity.

Objectives The prevalence of general overweight and obesity defined by body mass index criteria has greatly increased in Chinese children and adolescents in recent decades. However, few studies have considered the trend in abdominal obesity in Chinese children and adolescents. This study aimed to examine the secular trends in waist circumference (WC), waist-to-height ratio (WHtR) and the prevalence of abdominal obesity among Chinese children and adolescents aged 6–17 years from 1993 to 2015. Methods A total of 11,985 children and adolescents aged 6–17 years participated in the China Health and Nutrition Survey, a continuous cross-sectional survey, conducted from 1993 to 2015. Abdominal obesity was defined as WC≥age- and sex-specific 90th percentile based on the reference from Chinese children and adolescents or WHtR≥0.50. Results After adjustment for age, sex and region, mean WC increased from 60.27 cm in 1993 to 64.31 cm in 2015 (p for trend <0.001), and mean WHtR increased from 0.430 to 0.434 (p for trend <0.05). The prevalence of abdominal obesity defined by WC reference increased from 5.0% in 1993 to 19.3% in 2015 and defined by WHtR reference increased from 6.4% in 1993 to 14.5% in 2015 (p for trend <0.001). Conclusions The prevalence of abdominal obesity among Chinese children and adolescents aged 6–17 years has increased between 1993 and 2015.

Objectives To investigate the optical coherence tomography angiography (OCTA) and specular microscopy (SM) findings in obese children and compare them with healthy ones. Methods In this prospective study, 50 eyes of 25 obese children [body mass index (BMI) ≥95th percentile], 36 eyes of 18 control age- and sex- matched healthy subjects (BMI <85th percentile) were included. Demographic features and ophthalmological examination including OCTA measurements as well as SM findings were assessed. Cellular morphology was observed by noncontact SM and results for corneal endothelial cell density (cells/mm 2 ), coefficient of variation of cell size and percentage of hexagonal cells were obtained. The OCTA was performed with 6 × 6 mm sections for macula and 4.5 × 4.5 mm sections for optic disc in all eyes. Foveal retinal thickness (FRT), retinal nerve fiber layer (RNFL) thickness, vessel density in different sections of retina and optic nerve head were analyzed. Results All SM parameters, RNFL thickness for average, and all quadrants and optic disc radial peripapillary capillary densities were similar between groups. However, FRT, flow area for choriocapillaris, superficial and deep foveal capillary densities were significantly higher in obese group when compared to controls (242.4 ± 18.2 µm vs. 232.1 ± 16.5 µm, p=0.024, 2.2 ± 0.1 mm 2 vs, 2.2 ± 0.0 mm 2 , p=0.042, 22.4 ± 6.9% vs. 15.6 ± 5.5%, p=0.001, and 38.9 ± 7.5% vs. 31.1 ± 8.6 %, p=0.001, respectively). Conclusions Obese children seem to have higher values of FRT, flow area for choriocapillaris, superficial and deep foveal capillary densities. These results may have significant implications for understanding of how childhood obesity could affect retinal microvasculature.

Objectives Children with diabetes are advised to see their diabetes team every 3 months, with interim communication to address insulin dose adjustments. Despite increasing digital accessibility, there is limited data on whether provider–patient communication frequency is associated with glycemic control in pediatric diabetes. We assessed patterns of communication between diabetes clinic visits and whether communication frequency via electronic messaging (EM) and telephone was associated with glycemic control in pediatric diabetes. Methods Retrospective chart review of 267 children with type 1 (T1DM) and type 2 diabetes (T2DM) over a 1-year period (July 2018–June 2019) at an urban academic pediatric diabetes center. Association between frequency of communication (via EM and telephone) and HbA 1c was analyzed using regression analysis. Results Of 267 participants, 224 (84%) had T1DM, 43 (16%) had T2DM, mean age 11.6 years (SD 4), mean duration of diabetes 3.5 years (SD 3.4), and mean HbA 1c 73.8 ± 23 mmol/mol (8.9 ± 2.2%). Most participants (82%) communicated with their diabetes team at least once per year, with a mean number of overall communications of 10.3 ± 13.6 times. Communications were via EM (48%), phone (40%), or both (53%). Participants with more frequent communication had lower HbA 1c values (p=0.007), even when controlling for age, sex, provider, and number of clinic visits per year. We determined that a threshold of three communications per year was associated with a lower HbA 1c (p=0.006). Conclusions More frequent communication with the diabetes team between visits is associated with improved glycemic control. Initiatives to contact diabetes patients between clinic visits may impact their overall glycemic control.

Objectives Type I diabetes mellitus (T1DM) is one of the most common chronic diseases of childhood. Diabetic ketoacidosis (DKA) in this population contributes to significant healthcare utilization, including emergency room visits, hospitalizations, and ICU care. Comorbid psychiatric illnesses (CPI) are additional risks for increased healthcare utilization. While CPI increased risk for DKA hospitalization and readmission, there are no data evaluating the relationship between CPI and hospital outcomes. We hypothesized that adolescents with T1DM and CPI admitted for DKA have increased length of stay (LOS) and higher charges compared to those without CPI. Methods Retrospective review of 2000–2012 Healthcare Cost and Utilization Project’s (HCUP) Kids’ Inpatient Databases (KID). Patients 10–21 years old admitted with ICD-9 codes for DKA or severe diabetes (250.1–250.33) with and without ICD-9 codes for depression (296–296.99, 311) and anxiety (300–300.9). Comparisons of LOS, mortality, and charges between groups (No CPI, Depression and Anxiety) were made with one way ANOVA with Bonferroni correction, independent samples Kruskal-Wallis test with Bonferroni correction and χ 2 . Results There were 79,673 admissions during the study period: 68,573 (86%) No CPI, 8,590 (10.7%) Depression and 12,510 (15.7%) Anxiety. Female patients comprised 58.2% (n=46,343) of total admissions, 66% of the Depression group, and 71% of the Anxiety group. Patients with depression or anxiety were older and had longer LOS and higher mean charges (p<0.001 for both). Conclusion Comorbid depression or anxiety are associated with significantly longer LOS and higher charges in adolescents with T1DM hospitalized for DKA. This study adds to the prior findings of worse outcomes for patients with both T1DM and CPI, emphasizing the importance of identifying and treating these comorbid conditions.

Objective We analyzed the impact of geographic distance from the clinic on adherence to recommended clinic visits and diabetes control among patients with type 1 diabetes (T1D) seen in a pediatric endocrinology clinic serving a rural region in eastern North Carolina. Methods We retrospectively included patients with T1D age ≤20 years seen in our clinic during 2017. Outcomes were tracked until June 2018. Distance from the clinic was determined according to the zone improvement plan (ZIP) code of patient address. Visit adherence was defined based on the number of attended visits during the study period, aiming for 1 every 3 months. Glycated hemoglobin (HbA1c) was measured at the first and last visits during the review period Results The analysis included 368 patients, of whom 218 (59%) completed at least 1 visit every 3 months. The median HbA1c was 9.1 (interquartile range [IQR]: 8.0, 10.3) at the initial visit, and 9.3 (IQR: 8.0, 11.1) at the final visit. Median distance from the clinic was 56 km (IQR: 35, 86). On multivariable logistic regression, greater distance from the clinic was associated with lower odds of visit adherence (odds ratio per 10 km: 0.93; 95% confidence interval: 0.87, 0.99; p=0.030). Neither distance to the clinic nor clinic visit adherence were associated with HbA1c. Conclusions Patients living further away from the clinic were less likely to adhere to the recommended visit schedule, but distance was not correlated with HbA1c levels. Further work is needed to assist families living far from the clinic with adhering to recommended visits.

Objectives Paucity of data from India on care of children with Type 1 diabetes in schools. Aims: To study assess the knowledge, attitude, practices and fear of Type 1 diabetes in school teachers and to assess the impact of an educational model on the fear of teachers and care of children in Type 1 DM at school hours. Methods A community based study, involving school teachers and the intervention being educating them about diabetes conducted. Data pertaining to basic demography, attitude of teachers towards diabetic children, Hypoglycemia fear factor survey- parent version with worries domain and preparedness of school was collected. An education program was conducted on diabetes care in children. Immediately and after three months, the proforma details and HFSP-W scores reassessed. Results Forty two teachers (mean age: 38.7±5.4; M:F ratio 2:40) participated in the study. Post intervention, a higher willingness to have the diabetic child in class (100 vs. 57.1%; p>0.05), better support in daily care (100 vs. 92%; p>0.05), participation in sports activities (100 vs. 7.1%; p<0.05) observed. HFSP-W scores were 38.8±4.5 (pre-intervention), 22.5±4.3 (immediate post intervention) and 29.5±3.2 (at 3months) (p<0.05). To study the determinants of improvement in HFSP-W a regression analysis was performed: presence of glucometer the most likely determining factor (T=1.999, p=0.05). Conclusion There is a significant element of fear in the minds of teachers towards hypoglycemia which improves with a structured education program.

Objectives This study aimed to determine the effects of continuous subcutaneous insulin infusion (CSII) treatment on anthropometric measurements, mean HbA1c, and insulin dosage in patients diagnosed under 5 years of age and compare with multiple-dose injection therapy (MDI). Methods Children with type 1 diabetes mellitus, diagnosed <5 years since 2000 and their 19-year follow-up were evaluated retrospectively. Weight, height, body mass index (BMI), blood pressure, and HbA1c values were recorded for each visit. Results Hundred and five patients (58.1% female, 41.9% male) were included in the study. Sixty-three (60 %) patients were treated by CSII and 42 (40%) by MDI. Mean age at diagnosis was 2.68 ± 1.42 and 3.29 ± 1.30 years respectively. Mean follow-up was 7.42 ± 4.76 and 6.01 ± 4.41 years respectively. For each group, weight standard deviation score (SDS) increased significantly in the first year after the diagnosis (p<0.001), and with the onset of puberty weight SDS decreased significantly (p<0.001). The trend of weight and BMI SDS changes over the years showed similar characteristics in both groups. During follow-up height SDS was similar in both groups except in Tanner stage 5. When puberty was completed, mean height SDS was 0.51 ± 1.03 in CSII and −0.31 ± 0.75 in the MDI group (p: 0.029). Mean HbA1c was significantly lower in the CSII group (7.62 ± 0.82 and 8.17 ± 1.22 respectively). Systolic and diastolic blood pressure change trends during the follow-up were also similar in both groups. Conclusions CSII treatment had positive effects on metabolic control and height SDS in patients with early-onset diabetes without increasing BMI.

Background Children and their mothers, who are usually the primary caregivers, are likely to be distressed due to type 1 diabetes (T1DM). Objectives (1) To assess diabetes-specific distress (DD) perceived by children and adolescents with T1DM and their mothers and association of distress between children and mothers. (2) To study the association of diabetes distress with glycemic control and disease duration. Subjects Children and adolescents with T1DM over eight years and their mothers. Methods Clinical data were recorded. DD was assessed by Problem Associated in Diabetes-Pediatric (PAID-Peds) (range 0–80) and Problem Associated in Diabetes-Parents Revised (PAID-PR) (range 0–72) questionnaires (higher scores indicate higher distress); administered to children and mothers, respectively. Sub-dimensions in questionnaires included diabetes-related emotional problems, and treatment-, food-, and social support-related problems. Correlation analysis (Spearman’s) was performed, and a paired t -test was used to compare PAID-Peds and PAID-PR (SPSS 25). Results Mean PAID-Peds and PAID-PR scores in 67 children and mothers were 24.4 ± 18.1 and 31.9 ± 21.5, respectively (p=0.009), and a significant correlation was noted between their scores (R=0.45, p=0.001). PAID-Peds score was positively associated with HbA1c (R=0.25, p=0.04). Diabetes-related emotional problems of mothers and children (R=0.38, p=0.003), treatment problems (R=0.5, p=0.001), and food problems (R=0.24, p=0.05) correlated positively. Subdimension scores were significantly different in children and mothers except in the social support domain. Conclusion DD was higher in mothers than children; higher distress in children was associated with poor metabolic control. Evaluation of DD needs to be performed in children with T1DM.

Objectives In March 2020, lockdown was imposed in India to combat spread of Coronavirus, which was extended till 31st May. Implementation of lockdown and limited outdoor activities resulted in changes in routines of children with diabetes. The aim of this study was to assess the impact of lockdown on glycemic control, weight and body mass index (BMI) patterns of children with type 1 diabetes (T1DM) from different socio-economic (SE) classes. Methods This observational study included 77 children and youth (5–20 years) with T1DM having disease duration of ≥6 months. Demographic data and investigations were recorded at two time points (post lockdown when the children came for follow up, pre lockdown data from medical records). Results Glycemic control improved (pre lockdown HbA1C 79.4±19.2 vs. post lockdown Hba1C 74.5±16.9 mmol/mol, p<0.05) and there was weight gain post lockdown (pre lockdown weight z-score −0.4±0.8 vs. post lockdown weight z-score −0.2±0.8, p<0.05) without any significant change in BMI and insulin requirements. Improved glycemic was seen in the lower SE group control post lockdown (p<0.05), whereas in higher SE group, it remained unchanged. Children whose parents were at home during lockdown showed an improved glycemic control (p<0.05) as compared to children whose parents continued to work during lockdown (p>0.01) Conclusions During coronavirus lockdown, glycemic control was adequately maintained in children with T1DM, highlighting importance of stronger family support system leading to more steady daily routine.

We aimed to collect data on all paediatric patients who were diagnosed with type 1 diabetes mellitus (T1DM) between the years 2000 and 2019 in Serbia and estimate for the first time its prevalence. Also, the trends of diabetes ketoacidosis (DKA) occurrence at the time of diagnosis are monitored. We collected and retrospectively analysed the data of patients <19 years with newly diagnosed T1DM. T1DM was diagnosed in 3134 patients (53.2% male). Total number of youth <19 years with T1DM was 1735 with prevalence of 135.25/100000 at the end of study period. T1DM was diagnosed most frequently between the ages of 5 and 11 years (42.1%). At the time of diagnosis, 35.7% presented in DKA. The incidence and severity of DKA were more significant at the youngest age (p<0.001). There were significant annual percentage increase (2.2%) in the number of new cases of DKA (p=0.007). Conclusion: This first report of nationwide prevalence of T1DM in youth shows that Serbia is among countries with high prevalence of T1DM in youth. System changes are needed in order to provide better quality of health care to these patients.

Objective To investigate the thyroid volume (Tvol) and to explore factors that affects it among 12 to 15-year-olds attending a rural middle school in east Hangzhou, China. Methods A cross-sectional survey of middle school students attending a rural middle school in east Hangzhou, China was conducted. Height, weight and other physical development related indicators in middle school students were measured. The thyroid size was measured using ultrasound, and the thyroid volume calculated. Results The median (P 25 , P 75 ) of the thyroid volume in 596 middle school students from a rural middle school in east Hangzhou, China was 6.69 (5.66, 7.98) mL. Our study enrolled 305 male students (51.2%) and 291 female students (48.8%). The height, weight and thyroid volume of middle school students increased with age. Univariate analysis revealed that height, weight, body mass index (BMI) and body surface area (BSA) were positive correlated with thyroid volume (p<0.01).The correlation between BSA and thyroid volume was significant (Spearman’s rho=0.473, p<0.01). Multiple linear regression analysis revealed that BSA was positive and significantly correlated with the thyroid volume (p<0.05). Regression equation was Y=−2.532 + 6.186×BSA. Conclusion The thyroid volume is not only affected by age, but it is also affected by growth and development. Goiter cannot only be assessed based on age, gender and thyroid volume. However, this study established that BSA not only presented the strongest correlation with thyroid volume (Spearman’s rho=0.473), but also had a strong correlation with physical development, taking into account the growth and development of middle school students, and showed greater stability. Therefore, we recommend inclusion of BSA as a reference standard in the measurement of the thyroid volume.

Objectives Prevalence of Maternal and congenital hypothyroidism is on the rise. To present the thyroid stimulating hormone screening results in babies born to hypothyroid mothers and assess the burden, aetiology of hypothyroidism in these babies Methods All antenatal mothers attending our hospital during the study period were enrolled into the study. Group I includes 249 term babies born to hypothyroid mothers and group II comprises 2154 newborns born to mothers who are euthyroid. Heel prick thyroid stimulating hormone was done for all newborns on day 3 for both groups. Confirmatory venous testing was done for all for babies in group I and screen positives belonging to group II. Evaluation and therapy done as per standard guidelines. Results Thyroid stimulating hormone values in the two groups are presented. There was significant correlation between peak maternal thyroid stimulating hormone and neonatal day 3 heel prick in group I (r=0.7, P<0.05). The prevalence of positive screening test in groups I and II was 3.8 and 1.03% (p<0.05) whereas corresponding values for confirmed disease was 4.3 and 0.6%, respectively (p<0.05). Aetiological evaluation revealed both transient hypothyroidism (33.3%) and permanent hypothyroidism (66.6%). Conclusion 4.3% of babies born to hypothyroid mothers develop congenital hypothyroidism; aetiology being both transient and permanent. A venous test by 3 weeks is helpful in these babies to improve case identification.

Objectives The purpose of this study was to evaluate the impact of recombinant human growth hormone (rhGH) on the development and progression of scoliosis in patients with idiopathic short stature (ISS). Methods Patients with ISS who underwent rhGH treatment from 1997 to 2017 and were followed up for scoliosis screening with serial radiographic examination were included. For assessing scoliosis development, patients who did not have scoliosis at the time of rhGH treatment were included and followed up to determine whether de novo scoliosis developed during the treatment. For evaluating scoliosis progression, patients who already had scoliosis were analyzed. Univariate and multivariate Cox regression analyses of demographic and radiographic variables were performed to determine the related factors in the development and progression of scoliosis. Results For assessing scoliosis development, 1093 patients were included. The average duration of rhGH treatment was about 2 years. De novo scoliosis developed in 32 patients (3.7%). The analysis revealed that sex (p=0.016) and chronological age (p=0.048) were statistically significant factors associated with scoliosis development. However, no relationship was observed between scoliosis development and rhGH treatment types or duration. Among 67 patients who already had scoliosis at the time of rhGH treatment, 11 (16.4%) showed scoliosis progression. However, the rhGH types and duration also did not affect scoliosis progression. Conclusions De novo scoliosis developed in 3.7% and scoliosis progressed in 16.4% of the patients during rhGH treatment. However, scoliosis development or progression was not affected by the types or duration of rhGH treatment in patients with ISS.

Objectives Although Acute Kidney Injury (AKI) has been described among childhood diabetes ketocidosis (cDKA) there is scarcity of literature on the role of concomitant rhabdomyolysis. Method A retrospective chart review was undertaken (2014–2018) to identify cDKA who developed AKI and had evidence of rhabdomyolysis defined by serum creatine phosphokinase (CPK) > 5 times upper limit of normal. Result 46 cDKA were identified. Ten (22%) developed AKI with 6/10 reaching peak AKI Stage 3 and 8/10 had co-current rhabdomyolysis. In comparison to non rhabdomyolysis group, cDKA with rhabdomyolysis were at presentation significantly more likely to be hypotensive and have higher corrected sodium and calculated osmolality. Subsequently they were more likely to develop lower trough potassium levels during treatment. Five patients, all with rhabdomyolysis, needed dialysis: median duration 9 days (range 4–35). Three children in our cohort died, all from infection complications during treatment, one in AKI only group who did not receive dialysis and two in AKI with rhabdomyolysis on dialysis. Conclusion Rhabdomyolysis was common among our cohort of cDKA with AKI and was associated with high morbidity and mortality. Rapid flux in electrolytes and osmolality may be important precipitating factors. We recommend larger prospective studies exploring the importance of rhabdomyolysis among cDKA with AKI.

Objectives Defects in the IGF-1 receptor gene ( IGF1R ) induce IGF-1 resistance, characterized by intrauterine and postnatal growth retardation, normal or elevated serum IGF-1 levels, and feeding problems. Obesity, idiopathic growth hormone deficiency (IGHD), bone age advancement, and serum IGF-1 level in the lower half of the reference range are very rare clinical features in patients with IGF1R defects. Case presentation In this study, we report the atypical clinical manifestations of IGF1R defects. Short stature girl born small for gestational age were initially diagnosed with IGHD. No catch-up growth was achieved despite sufficiently elevated IGF-1 levels after recombinant human growth hormone (rhGH) treatment. Single nucleotide polymorphism microarray analysis finally confirmed terminal deletion of 15q26.2q26.3 in the subject. Conclusion Intrauterine growth retardation, postnatal growth failure, and IGF-1 resistance during rhGH treatment are homologous features exhibited by affected patients, and may be predictive of IGF1R defects.

Objectives Biallelic mutations in the SLC25A19 gene impair the function of the thiamine mitochondrial carrier, leading to two distinct clinical phenotypes. Homozygosity for the c.530G > C mutation is invariably associated to Amish lethal microcephaly. The second phenotype, reported only in 8 patients homozygous for different non-Amish mutations (c.373G > A, c.580T > C, c.910G > A, c.869T > A, c.576G > C), is characterized by bilateral striatal necrosis and peripheral polyneuropathy. We report a new patient with the non-Amish SLC25A19 phenotype showing compound heterozygosity for the new variant c.673G > A and the known mutation c.373G > A. Case presentation The natural history of non-Amish SLC25A19 deficiency is characterized by acute episodes of fever-induced encephalopathy accompanied by isolated lactic acidosis and Leigh-like features at magnetic resonance imaging (MRI). Acute episodes are prevented by high-dose thiamine treatment (600 mg/day). As shown in the new case, both mild clinical signs and basal ganglia involvement can precede the acute encephalopathic onset of the disease, potentially allowing treatment anticipation and prevention of acute brain damage. Peripheral axonal neuropathy, observed in 7 out of 9 patients, is not improved by thiamine therapy. In two early treated patients, however, peripheral neuropathy did not occur even on long-term follow-up, suggesting a potential preventive role of treatment anticipation also at the peripheral level. Conclusions Non-Amish SLC25A19 deficiency is an extra-rare cause of Leigh syndrome responsive to thiamine treatment. Ex adiuvantibus thiamine treatment is mandatory in any patient with Leigh-like features.

Objectives Activating germline mutations of the thyroid-stimulating hormone receptor (TSHR) are responsible for a rare form of neonatal nonautoimmune hyperthyroidism (NAH). We report the first case of familial neonatal neonatal nonautoimmune associated with c.1856A>G (p.Asp619Gly) variant in the TSHR gene. Case presentation We describe an eight-year-old African-American female presenting with neonatal NAH associated with an inherited heterozygous c.1856A>G (p.Asp619Gly) variant in the TSHR gene. This variant was previously described in one patient presenting with sporadic NAH in adolescence. Our patient was diagnosed with hyperthyroidism in the neonatal period. The mother had a history of hyperthyroidism and had thyroidectomy at the age of 4 years. The patient had goiter and elevated free thyroxine (FT4) and free triiodothyronine (FT3) levels that normalized with methimazole treatment; however, TSH level remained suppressed. Thyroid antibodies were negative. The patient also had bilateral exotropia, a trait shared by the mother and may represent a new association. Conclusions Familial neonatal NAH is associated with heterozygous c.1856A>G (p.Asp619Gly) variant of the TSHR gene.

Objectives Neonatal diabetes mellitus (NDM) is a rare monogenic diabetes form, occurring mainly from ATP-binding cassette subfamily C member 8 ( ABCC8 ) and KCNJ11 mutations. ABCC8 mutations have also been found to cause adult-onset diabetes. What is new?: •Novel ABCC8 mutation in an NDM case •Heterogeneous clinical presentation of diabetes and response to sulfonylurea therapy among family members with the same ABCC8 mutation. Case presentation We report the case of a newborn with NDM and a heterozygous ABCC8 novel variant (c.3835G>A), successfully treated with sulfonylurea. The same ABCC8 variant was found in two other family members, already treated for type 2 diabetes. Conclusions This case demonstrates the variable phenotypic presentation of diabetes due to a novel ABCC8 mutation (c.3835G>A), ranging from transient NDM to adult-onset, insulin-demanding diabetes, among family members. Genetic testing in young individuals with a strong family history of diabetes, presenting with non-autoimmune diabetes is recommended as it can determine prognosis and treatment of affected family members.