Predictors and Trends of Diabetic Ketoacidosis at Diagnosis of Type 1 Diabetes Mellitus in Malaysian Children.

Objectives: Previous reports indicate that diabetic ketoacidosis (pDKA) rates in Malaysian children with type 1 diabetes range between 54-75%, which is higher than most European nations. Knowledge of trends and predictors of DKA can be helpful to inform measures to lower the rates of DKA. However, this data is lacking in Malaysian children. Hence, the aim of this study was to determine the predictors and trends of pDKA in Malaysian children at the initial diagnosis of T1DM. Methods: This cross-sectional study examined demographic, clinical and biochemical data of all newly diagnosed Malaysian children aged 0-18 years with T1DM over 11 years from a single centre. Regression analyses determined the predictors and trends. Results: The overall pDKA rate was 73.2%, of which 54.9% were severe DKA. Age ≥5 years (OR 12.29, 95% CI 1.58, 95.58, p= 0.017) and misdiagnosis (OR 3.73, 95% CI 1.36, 10.24 p=0.01) were significant predictors of a DKA presentation. No significant trends in the annual rates of DKA, severe DKA nor children <5 years presenting with DKA were found over the 11-years study period. Conclusion: DKA rates at initial diagnosis of T1DM in Malaysian children are high and severe DKA accounts for a significant burden. Though misdiagnosis and age ≥5 years are predictors of DKA, misdiagnosis can be improved through awareness and education. The lack of downward trends in DKA and severe DKA highlights the urgency to develop measures to curb its rates.

Long-term effect of growth hormone on sleep-disordered breathing in Malaysian children with Prader-Willi syndrome: a retrospective study.

STUDY OBJECTIVES: The effect of recombinant human growth hormone (rhGH) on sleep-disordered breathing (SDB) in Malaysian children with Prader-Willi syndrome (PWS) is under-investigated. We determined (1) the short- and long-term effects of rhGH and (2) factors associated with worsening SDB in children with PWS receiving rhGH. METHODS: This retrospective study included children with PWS (with and without rhGH) who had undergone at least 1 polysomnography. Outcomes measured were the presence of SDB before and after starting rhGH and the progress of SDB with and without rhGH. Serial insulin-like growth factor 1 (IGF-1) measurements were recorded. RESULTS: One-hundred and thirteen polysomnograms were analyzed. The majority (92.3%) of initial polysomnograms showed SDB, with a median (interquartile range) apnea-hypopnea index of 5.0 (2.6, 16.3) events/h. The age for receiving rhGH was a median (IQR) of 1.9 (0.7, 3.4) years. One-third (36.8%) had worsening SDB after initiating rhGH, which was associated with higher IGF-1 levels post-rhGH (P = .007). After a median of 5 years of rhGH, 73.6% maintained or reduced their positive airway pressure settings. Without rhGH, 80% had increased their positive airway pressure settings. Worsening SDB while on rhGH was associated with higher body mass index, lower rhGH dose, higher IGF-1 levels, and non-15q deletion. CONCLUSIONS: The majority of Malaysian children with PWS had SDB. At initiation of rhGH, one-third of patients had worsening SDB, associated with increased IGF-1 levels. Stabilization of SDB was more frequently seen in those receiving long-term rhGH. Worsening SDB while on rhGH was associated with a higher body mass index, receiving a lower dose of rhGH, higher IGF-1 levels, and non-15q deletion. CITATION: Tan YT, Azanan MS, Hng SY, et al. Long-term effect of growth hormone on sleep-disordered breathing in Malaysian children with Prader-Willi syndrome: a retrospective study. J Clin Sleep Med. 2024;20(8):1291-1299.

Is Misdiagnosis of Type 1 Diabetes Mellitus in Malaysian Children a Common Phenomenon?

Background: Children with Type 1 diabetes (T1DM) commonly present in diabetic ketoacidosis (DKA) at initial diagnosis. This is likely due to several factors, one of which includes the propensity for T1DM to be misdiagnosed. The prevalence of misdiagnosis has been reported in non-Asian children with T1DM but not in Asian cohorts. Aim: To report the rate of misdiagnosis and its associated risk factors in Malaysian children and adolescents with T1DM. Methods: A retrospective analysis of children with T1DM below 18 years of age over a 10 year period was conducted. Results: The cohort included 119 children (53.8% female) with a mean age 8.1 SD ± 3.9 years. 38.7% of cases were misdiagnosed, of which respiratory illnesses were the most common (37.0%) misdiagnosis. The rate of misdiagnosis remained the same over the 10 year period. Among the variables examined, younger age at presentation, DKA at presentation, healthcare professional (HCP) contact and admission to the intensive care unit were significantly different between the misdiagnosed and correctly diagnosed groups (p <0.05). Conclusion: Misdiagnosis of T1DM occurs more frequently in Malaysian children <5 years of age. Misdiagnosed cases are at a higher risk of presenting in DKA with increased risk of ICU admission and more likely to have had prior HCP contact. Awareness of T1DM amongst healthcare professionals is crucial for early identification, prevention of DKA and reducing rates of misdiagnosis.

Case Report: Severe Hyponatremia in Infants With Urinary Tract Infection.

Introduction: Many reports on investigations and treatments in UTI, however little, have been mentioned with regard to electrolyte abnormalities. Secondary pseudohypoaldosteronism (PHA) in UTI, though less common, is a known association. Features include hyponatremia and concomitant hyperkalemia. Objectives: We aim to highlight these uncommon sequelae in UTI to avoid incorrect diagnosis and unnecessary investigations. Study Design: Clinical data of patients admitted and referred to a pediatric nephrologist at the University Malaya Medical Center between May 2019 and October 2020 were collated and elaborated. Results and Discussion: We report three infants with hyponatremia and hyperkalemia during UTI episodes. Two infants were known to have posterior urethral valve (PUV) before the onset of UTI and one infant had UTI, which led to investigations confirming the diagnosis of bladder vaginal fistula. The electrolyte derangements were temporary and resolved within 48 to 72 h of treatment with intravenous fluid and appropriate antibiotic therapy. Out of three, only one had a hormonal study, which confirms PHA. Reduced aldosterone activity could be due to absolute reduction in aldosterone titer or lack of aldosterone responsiveness at tubular (other tissues) level. In the latter, aldosterone titer is elevated. The infant in our cohort who had hormonal evaluation had the mentioned electrolyte abnormalities with a markedly elevated aldosterone titer. This demonstrated defective action of the hormone at the level of mineralocorticoid receptor. Although the remaining two infants had no confirmatory hormonal study, all of them recovered within 48 h of hospital admission, after receiving appropriate management for the primary problem, which was UTI. We observed a slower recovery of hyponatremia in relation to hyperkalemia, but none of these infants required salt replacement upon discharge. Conclusion: Infants with severe UTI and deranged electrolytes should be screened for structural abnormality and vice versa. Not all infants require hormonal screening, but those who required prolonged salt replacement or showed involvement of other systems warrant further evaluation.

Adrenal Insufficiency in Children With Nephrotic Syndrome on Corticosteroid Treatment.

Background: Adrenal insufficiency can result from impaired functions at all levels of hypothalamic-pituitary-adrenal (HPA) axis. We here studied risk factors associated with adrenal insufficiency in children receiving prolonged exogenous steroid treatment for nephrotic syndrome. Method:We performed low-dose Synacthen tests (LDSTs, 0.5 µg/m2) in children with steroid-sensitive nephrotic syndrome 4-6 weeks after discontinuation of the corticosteroid therapy. We measured early morning serum cortisol levels at baseline and at intervals of 10, 20, 30, and 60 min following the stimulation test. We defined normal HPA axis stimulation responses as those with peak cortisol cut-off values >550 nmol/L. Result:We enrolled 37 children for this study research. All children enrolled had normal early morning cortisol levels. However, 13 (35.1%) demonstrated HPA axis suppression (by LDST) 4-+6 weeks after discontinuation of oral prednisolone. Nephrotic syndrome diagnosed before 5 years of age (OR, 0.75; 95% CI, 0.57-0.99; p = 0.043), and steroid-dependence [OR, 5.58; 95% confidence interval (CI), 1.06-29.34; p = 0.042] were associated with increased risk of developing adrenal suppression after steroid discontinuation. Conclusion:HPA axis suppression, may go unnoticed without proper screening. A normal early morning cortisol level (275-555 nmol/L) does not exclude adrenal insufficiency in children with steroid-sensitive nephrotic syndrome. Further screening with LDSTs, particularly in children younger than 5 years at diagnosis, may be warranted.