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

Mavinkurve M, Jalaludin MY, Chan EWL, Noordin M, Samingan N, Leong A, et al.

Front Endocrinol (Lausanne), 2021;12:606018.
PMID: 33763028 DOI: 10.3389/fendo.2021.606018

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

Mavinkurve M, Ramzi NH, Jalaludin MYB, Samingan N, Zaini AA

J Clin Res Pediatr Endocrinol, 2024 Dec 04;16(4):411-418.
PMID: 38683019 DOI: 10.4274/jcrpe.galenos.2024.2024-1-8

OBJECTIVE: Previous reports indicate that diabetic ketoacidosis (DKA) rates in Malaysian children with type 1 diabetes mellitus (T1DM) 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 DKA 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 were used to determine predictors and trends.
RESULTS: The overall DKA rate was 73.2%, 54.9% of the DKA cases were severe. Age ≥5 years [odds ratio (OR): 12.29, 95% confidence interval (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 during study period.
CONCLUSION: DKA rates at initial diagnosis of T1DM in Malaysian children are high and severe DKA accounts for a notable proportion of these. Though misdiagnosis and age ≥5 years are predictors of DKA, misdiagnosis can be reduced through better awareness and education. The lack of downward trends in DKA and severe DKA highlights the urgency to develop measures to curb its rates.
Fulltext Case Report: Severe Hyponatremia in Infants With Urinary Tract Infection

Abu Bakar K, Jalaludin MY, Zainal N, Woon SL, Mohd Zikre N, Samingan N, et al.

Front Pediatr, 2021;9:655010.
PMID: 34026690 DOI: 10.3389/fped.2021.655010

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.
Fulltext Adrenal Insufficiency in Children With Nephrotic Syndrome on Corticosteroid Treatment

Abu Bakar K, Khalil K, Lim YN, Yap YC, Appadurai M, Sidhu S, et al.

Front Pediatr, 2020;8:164.
PMID: 32351921 DOI: 10.3389/fped.2020.00164

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

Tan YT, Azanan MS, Hng SY, Eg KP, Jalaludin MY, Thong MK, et al.

J Clin Sleep Med, 2024 Aug 01;20(8):1291-1299.
PMID: 38557309 DOI: 10.5664/jcsm.11140

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.
Maternal lipids are associated with newborn adiposity, independent of GDM status, obesity and insulin resistance: a prospective observational cohort study

Samsuddin S, Arumugam PA, Md Amin MS, Yahya A, Musa N, Lim LL, et al.

BJOG, 2020 03;127(4):490-499.
PMID: 31778255 DOI: 10.1111/1471-0528.16031

OBJECTIVE: To determine the association between maternal lipaemia and neonatal anthropometrics in Malaysian mother-offspring pairs.
DESIGN: Prospective observational cohort study.
SETTING: Single tertiary multidisciplinary antenatal clinic in Malaysia.
POPULATION: A total of 507 mothers: 145 with gestational diabetes mellitus (GDM); 94 who were obese with normal glucose tolerance (NGT) (pre-gravid body mass index, BMI ≥ 27.5 kg/m2 ), and 268 who were not obese with NGT.
METHODS: Maternal demographic, anthropometric, and clinical data were collected during an interview/examination using a structured questionnaire. Blood was drawn for insulin, C-peptide, triglyceride (Tg), and non-esterified fatty acid (NEFA) during the 75-g 2-hour oral glucose tolerance test (OGTT) screening, and again at 36 weeks of gestation. At birth, neonatal anthropometrics were assessed and data such as gestational weight gain (GWG) were extracted from the records.
MAIN OUTCOME MEASURES: Macrosomia, large-for-gestational-age (LGA) status, cohort-specific birthweight (BW), neonatal fat mass (NFM), and sum of skinfold thickness (SSFT) > 90th centile.
RESULTS: Fasting Tg > 95th centile (3.6 mmol/L) at screening for OGTT was independently associated with LGA (adjusted odds ratio, aOR 10.82, 95% CI 1.26-93.37) after adjustment for maternal glucose, pre-gravid BMI, and insulin sensitivity. Fasting glucose was independently associated with a birthweight ratio (BWR) of >90th centile (aOR 2.06, 95% CI 1.17-3.64), but not with LGA status, in this well-treated GDM cohort with pre-delivery HbA1c of 5.27%. In all, 45% of mothers had a pre-gravid BMI of <23 kg/m2 and 61% had a pre-gravid BMI of ≤ 25 kg/m2 , yet a GWG of >10 kg was associated with a 4.25-fold risk (95% CI 1.71-10.53) of BWR > 90th centile.
CONCLUSION: Maternal lipaemia and GWG at a low threshold (>10 kg) adversely impact neonatal adiposity in Asian offspring, independent of glucose, insulin resistance and pre-gravid BMI. These may therefore be important modifiable metabolic targets in pregnancy.
TWEETABLE ABSTRACT: Maternal lipids are associated with adiposity in Asian babies independently of pre-gravid BMI, GDM status, and insulin resistance.