Epidemiologic Characteristics of Children with Diabetic Ketoacidosis Treated in a Pediatric Intensive Care Unit in a 10-Year-Period: Single Centre Experience in Croatia.

Background and Objectives: The incidence of severe and moderate forms of DKA as the initial presentation of type 1 diabetes mellitus (T1D) is increasing, especially during the COVID-19 pandemic. This poses a higher risk of developing cerebral edema as a complication of diabetic ketoacidosis (DKA), as well as morbidity and mortality rates. The aim of this study was to determine the trend and clinical features of children treated in the last 10 years in the Pediatric Intensive Care Unit (PICU) due to the development of DKA. Materials and Methods: This retrospective study was performed in the PICU, Clinical Hospital Centre Rijeka, in Croatia. All children diagnosed with DKA from 2011-2020 were included in this study. Data were received from hospital medical documentation and patient paper history. The number of new cases and severity of DKA were identified and classified using recent International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines. Results: In this investigation period, 194 children with newly diagnosed T1D were admitted to our hospital: 58 of them were treated in the PICU due to DKA; 48 had newly diagnosed T1D (48/58); and ten previously diagnosed T1D (10/58). DKA as the initial presentation of T1D was diagnosed in 24.7% (48/194). Moderate or severe dehydration was present in 76% of the children at hospital admission. Polyuria, polydipsia, and Kussmaul breathing were the most common signs. Three patients (5.2%) developed cerebral edema, of whom one died. Conclusions: During the investigation period a rising trend in T1D was noted, especially in 2020. About one quarter of children with T1D presented with DKA at initial diagnosis in western Croatia, most of them with a severe form. Good education of the general population, along with the patients and families of children with diabetes, is crucial to prevent the development of DKA and thus reduce severe complications.

An extremely high blood glucose level in a child with hyperglycemic hyperosmolar state and type 1 diabetes.

OBJECTIVES: Hyperglycemic hyperosmolar state (HHS) is one of the most severe acute complications of diabetes mellitus (DM) characterized by severe hyperglycemia and hyperosmolality without significant ketosis and acidosis. What is new? Since HHS in the pediatric population is rare and potentially life-threatening, every reported case is very valuable for raising awareness among healthcare professionals. CASE PRESENTATION: A 7-year-old boy with previously diagnosed Joubert syndrome was admitted due to vomiting, polydipsia and polyuria started several days earlier. He was severely dehydrated, and the initial blood glucose level was 115 mmol/L. Based on clinical manifestations and laboratory results, he was diagnosed with T1DM and HHS. The treatment with intravenous fluid was started and insulin administration began later. He was discharged after 10 days without any complications related to HHS. CONCLUSIONS: Since HHS has a high mortality rate, early recognition, and proper management are necessary for a better outcome.

A fatal outcome of complicated severe diabetic ketoacidosis in a 11-year-old girl.

Diabetic ketoacidosis (DKA) is a complex metabolic state characterized by hyperglycemia, metabolic acidosis and ketonuria. Cerebral edema is the most common rare complication of DKA in children. The objective of the study was to emphasize the importance of careful evaluation and monitoring for signs and symptoms of cerebral edema in all children undergoing treatment for DKA. We present a case of 11-year-old girl with a history of diabetes mellitus type I (T1DM) who presented with severe DKA complicated by hypovolemic shock, cerebral edema and hematemesis. Considering the fact that complications of DKA are rare and require a high index of clinical suspicion, early recognition and treatment are crucial for avoiding permanent damage.

Cornelia de Lange syndrome caused by heterozygous deletions of chromosome 8q24: comments on the article by Pereza et al. [2012].

In the March issue of the Journal in 2012, we reported on a girl with Langer-Giedion syndrome (LGS) phenotype and a 7.5 Mb interstitial deletion at 8q23.3q24.13, encompassing the EXT1, but not the TRPS1 gene. Recent discoveries have shown that heterozygous intragenic mutations or contiguous gene deletions including the RAD21 gene, which is located downstream of the TRPS1 gene, are the cause of Cornelia de Lange syndrome-4. Considering that the interstitial deletion in our patient included the RAD21 and 30 other RefSeq genes, we would like to suggest a revision of the diagnosis reported in our previous paper and compare our patient to other reported patients with Cornelia de Lange syndrome-4 caused by heterozygous deletions of chromosome 8q24. © 2015 Wiley Periodicals, Inc.

Incidence of type 1 diabetes mellitus in 0 to 14-yr-old children in Croatia--2004 to 2012 study.

BACKGROUND: The incidence of type 1 diabetes mellitus (T1DM) among children and adolescents increased during the last 50 yr. The T1DM incidence in Croatia was 8.87/100.000/yr over 1995-2003, with an annual increase of 9%, which placed Croatia among countries with moderate risk for T1DM. AIM: To investigate incidence rates and trends of T1DM from 2004 to 2012 in 0 to 14-yr-old Croatian children, and to compare the results with previous studies in Croatia and other European countries. METHODS: T1DM crude incidence rates are estimated for the entire group and three subgroups: 0-4, 5-9, and 10-14 yr. Standardized incidence is calculated using the method of direct standardization according to World Health Organization (WHO) standard world population. The incidence rates by gender, age groups, seasonality, and calendar year, and their interactions were analyzed using Poisson regression model. RESULTS: A total of 1066 cases were ascertained over 2004-2012. The standardized incidence was 17.23/100.000/yr (95% CI: 16.19-18.26), with no significant differences in incidence rates or trends between boys and girls. Statistically significant annual increase of 5.87% (p < 0.001) was found for the whole group, and for the subgroups 5-9 yr (6.82%; p < 0.001) and 10-14 yr (7.47%; p < 0.001). In the youngest subgroup (0-4 yr), annual increase was lower (2.43%; p = 0338) and not statistically significant. CONCLUSION: The incidence of childhood T1DM is increasing in Croatia, thus placing Croatia among countries with high risk for T1DM. The annual increment of 5.87% is considerably lower than 9.0% reported earlier, but still higher than the European average (3.9%). The increase in incidence ceased in youngest children.

Regional differences in incidence and clinical presentation of type 1 diabetes in children aged under 15 years in Croatia.

AIM: To determine regional differences in the incidence, incidence trends, and clinical presentation of type 1 diabetes in children under the age of 15 years in Croatia in a 9-year period (1995-2003). METHODS: We included the patients who had been diagnosed with the disease and had started the insulin treatment before they were 15 years old. Regional differences between eastern, central, and southern Croatia were observed. The gross incidence was expressed by the number of newly diagnosed type 1 diabetes patients in 100000 children of the same age and sex per year, ie, for the 0-14 age group, and for the 0-4, 5-9, and 10-14 subgroups. RESULTS: The highest incidence was observed in southern Croatia (10.91 per 100000/y) and the lowest in central Croatia (8.64 per 100000/y), and in eastern Croatia the incidence was 8.93 per 100000/y. All three regions showed a growing incidence trend, which was significant only in eastern and southern Croatia. There was 35.9% of patients with diabetic ketoacidosis in eastern Croatia, 41.7% in central Croatia, and 31.28% in southern Croatia. CONCLUSION: Croatian regions show differences in the incidence, incidence trends, and disease presentation of type 1 diabetes. A further follow-up is needed to establish whether the regional differences are a consequence of the population dynamics in the observed period or they will continue to exist, pointing to differences in environmental risk factors.

Third case of 8q23.3-q24.13 deletion in a patient with Langer-Giedion syndrome phenotype without TRPS1 gene deletion.

Langer-Giedion syndrome (LGS) is a contiguous gene syndrome caused by a hemizygous deletion on chromosome 8q23.3-q24.11 involving TRPS1 and EXT1 genes. We report on a girl with LGS phenotype and a 7.5 Mb interstitial deletion at chromosome 8q23.3-q24.13. Array-comparative genomic hybridization (a-CGH) revealed a deletion encompassing only the EXT1 and not the TRPS1 gene. Even though the deletion of TRPS1 and EXT1 genes is responsible for craniofacial and skeletal features of LGS, there have been previous reports of patients with LGS phenotype and 8q24 deletions leaving the TRPS1 gene intact. To our knowledge, this is the third such case. Our patient differs from previously reported LGS patients without TRPS1 gene deletion in that she has the typical LGS facial dysmorphism and skeletal abnormalities. However, the girl is of normal height and has only a mild developmental delay. Additionally, she has dyslalia and premature adrenarche classified as Tanner stage 3 premature pubarche which have not yet been described as features of LGS. We examine the molecular breakpoints and phenotypes of our patient and previously reported cases.

Clinical characteristics at presentation of type 1 diabetes mellitus in children younger than 15 years in Croatia.

The aim of the study was to determine the clinical and biochemical characteristics of type 1 diabetes mellitus (DM) at presentation in children younger than 15 years in Croatia during a 9-year period, with special attention to diabetic ketoacidosis (DKA) incidence. The registered data set comprised blood glucose, pH, serum bicarbonate levels, and clinical symptoms at disease manifestation. During the study period, 692 children were diagnosed with type 1 DM. Polydipsia (96.7%), polyuria (96.05%), and weight loss (82.7%) were the most frequent symptoms anticipating disease detection. Enuresis was recorded in 11.55%. A total of 36.41% patients had DKA (pH < 7.3) at disease onset. During the 9-year period, the percentage of children presenting with DKA at time of diagnosis decreased from 41.67% to 33.33% (z = 1.68, p = 0.046). A positive family history of DM, the only factor with an impact on the DKA incidence rate in our population, lowers the probability of the development of ketoacidosis. This study confirms the importance of the detection of the classic symptoms of polyuria, polydipsia, and weight loss in patients with new-onset type 1 DM. The percentage of patients with DKA at diabetes onset decreased during the observed period but is still high and includes one-third of all patients. This is why in every acutely ill child, especially at a younger age, one should evaluate the possibility of type 1 DM to avoid the development of ketoacidosis.

Epidemiology and clinical characteristics of thyroid dysfunction in children and adolescents with type 1 diabetes.

The aim of the study was to evaluate the natural course and potential risk factors of autoimmune thyroiditis (AIT) and thyroid dysfunction, and their influences on growth and glycemic control in children and adolescents with type 1 diabetes mellitus (T1D). The study comprised 148 subjects (age range 1-21 years; males 51%) with T1D. During the interval of 12 years serum levels of thyroid peroxidase (anti-TPO) and thyroglobulin (anti-TG) autoantibodies, thyroid-stimulating hormone (TSH) and tyroksine (T4), were screened annually. Height, weight, body mass index (BMI), glycosylated hemoglobin (HbA1c), insulin dose and the number of severe hypoglycemic episodes, were recorded every 3 months. The mean follow-up was 7 +/- 4.1 years. Prevalence of AIT in subjects with T1D was 15.5%. It was significantly higher in girls (21.9% vs. 9.3%; p = 0.03). The mean age at AIT onset was 11.5 +/- 5.2 years. The mean interval between negative and positive AIT screening was 2.5 +/- 2.3 years. Cumulative incidence of AIT after 6 years of T1D duration was significantly higher in girls (30% vs. 15%; p = 0.03). Prevalence of hypothyroidism was 8.1% with no significant differences in sex distribution. Prevalence of hypothyroidism among subjects with elevated serum thyroid antibodies was 52.2% with significant male preponderance (85.7% vs. 37.5%; p = 0.005). There were no subjects who developed hypothyroidism in absence of thyroid antibodies. Cumulative incidence of hypothyroidism after 3 years from the moment of thyroid antibodies appearance was 55% with significant male preponderance (85% vs. 40%; p = 0.005). The mean interval between T1D onset and hypothyroidism development was 3.3 +/- 2.5 years, and between thyroid antibodies appearance and hypothyreoidism development was 1.7 +/- 1.2 years. The mean age at hypothyroidism onset was 12.7 +/- 5.3 years. There were no differences in growth and metabolic control between patients with and without AIT. The results of the present study confirmed frequent occurrence of AIT and thyroid dysfunction in subjects with T1D. The number of newly diagnosed subjects with AIT reached the peak at the age of puberty. Girls were significantly more predisposed to AIT at any age while amongst subjects with elevated thyroid antibodies boys developed hypothyroidism more frequently. Annual screening of thyroid antibodies in all patients with T1D is recommended, while serum TSH level should be measured in patients with detected thyroid antibodies.