OBJECTIVES

In Asia, younger individuals (below age 45) are diagnosed to have type 2 diabetes with increased rates of obesity defined by lower BMI yet with greater visceral adiposity (waist circumference and waisthip ratios). The prevalence data on type 1 diabetes is not well established, considered to be low, but is seen to be increasing as well. This changing phenotype therefore, presents a clinical dilemma in terms of correctly classifying diabetes and deciding on the consequent appropriate treatment. Distinguishing type 1 from type 2 diabetes has become more difficult with type 2 diabetes dramatically increasing in young adults and children. This study aims to define the characteristics of diabetes among young adults in the Philippines to provide a basis for appropriate management amidst changes in diabetes phenotypes seen globally.

METHODS

In this cross-sectional analytic study, we characterized the demographic, metabolic, and autoimmune features of diabetes among young adult Filipinos aged 18 to 45 years old consulting at a tertiary referral center in Manila, Philippines. Baseline serum A1c, FBS, 75-g oral glucose tolerance test, insulin, serum C-peptide, insulin autoantibodies, leptin, adiponectin, lipid profile, and thyroid function tests were obtained from the participants and analyzed. The homeostasis model assessment (HOMA) was used to estimate the insulin sensitivity.

RESULTS

A total of 348 patients with diabetes were included, with females comprising two-thirds of the participants. The mean age at diagnosis of diabetes was 35.9±7.22 years. The mean BMI was 28.12 kg/m2, with median waist to hip ratio (WHR) of 0·93. Metabolic syndrome was found in 60% of participants and 67.82% were obese by body mass index. The mean A1c was 9.07±2.52%. Good glucose control (A1c less than 7.0%) was seen in 23% of participants  while nearly half (48%) had HbA1c which was >9.0%. The median levels of fasting insulin and C-peptide were 12.62 (range 1.33–90.42) mIU/L and 0.78 ng/mL (range 0–16.2), respectively. 

Included participants were diagnosed with diabetes within a year and as such, majority did not have any micro- or macrovascular complications. The most common diabetes complication was sensory neuropathy detected by monofilament testing, which was found in 28% of participants, followed by non-proliferative diabetic retinopathy in 13%. A history of previous diabetic ketoacidosis was found in 10 patients (2.87%). Glutamic acid decarboxylase (GAD) and insulin auto-antibodies were found in 3.2% and 19.3% of participants, respectively. Approximately half (51.73%) of the participants were insulin resistant by HOMA-IR.

CONCLUSION

In contrast with Caucasians and other Asians, diabetes among young Filipino adults is associated with lower BMI but with a similarly high visceral adiposity as shown by an elevated WHR. Metabolic syndrome with insulin resistance as defined by a variety of indices is predominant. Type 1 diabetes with autoantibodies occur in only a small fraction of this population. Data derived from this work can provide a framework for cluster analysis towards personalized management specific to this population.

Human ; Acids ; Adiponectin ; Adiposity ; Adult ; Aged ; Antibodies ; Asia ; Asian ; Asian Continental Ancestry Group ; Autoantibodies ; Body Mass Index ; C-peptide ; Carboxy-lyases ; Child ; Cluster Analysis ; Demography ; Diabetes Complications ; Diabetes Mellitus ; Diabetes Mellitus, Type 1 ; Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis ; Diabetic Retinopathy ; Diagnosis ; Fasting ; Female ; Glucose ; Glucose Tolerance Test ; Glutamate Decarboxylase ; Glutamic Acid ; Insulin ; Insulin Resistance ; Ketosis ; Leptin ; Lipids ; Metabolic Syndrome ; Obesity ; Patients ; Peptides ; Phenotype ; Philippines ; Population ; Prevalence ; Serum ; Therapeutics ; Thyroid Gland ; Thyroid Function Tests ; Young Adult

OBJECTIVES

Diabetic ketoacidosis (DKA) is the most common initial presentation in children with newly diagnosed type 1 diabetes. Severe dehydration/acidosis, shock at admission, and hyperchloremia contribute to acute kidney injury (AKI). This retrospective study was done to determine the proportion of children hospitalized for DKA who had AKI and to compare clinical parameters between children with DKA and with AKI and without AKI to identify the risk factors associated with AKI.

METHODOLOGY

A retrospective review of all DKA admissions with type 1 diabetes was done. AKI was diagnosed as per KDIGO-2012 criteria. The analysis was done using a Chi-square test to assess the association between the status of AKI and other parameters. The Independent t-test was applied for comparison with the mean score between the No AKI / AKI group for numerical variables with normal distribution. A multivariable logistic regression analysis was performed to compare clinical parameters between both groups.

RESULTS

Out of 32 children with DKA, 13 (40.63%) developed AKI. Among them, 9 had AKI at admission and 4 children developed AKI within the first 48 hours of admission. Optimum fluid management resolved AKI in 10 patients, but 3 of them required dialysis. Parameters like higher heart rate (p = 0.0390), higher respiratory rate (p = 0.0402), high leukocyte count (p = 0.0005), severe hyperglycemia (p = 0.0204), severe acidosis (p = 0.0001), hyperchloremia (p = 0.016) and shock at admission (p = 0.0001) were present in children with DKA and AKI.

CONCLUSION

In our study, a high proportion of children with DKA had AKI, which causes prolonged acidosis and hospital stay. Hence, comparing clinical parameters between both groups helps in identifying risk factors associated with AKI in persons with type 1 diabetes with DKA.

Human ; Diabetic Ketoacidosis ; Acute Kidney Injury ; Ketone Bodies ; Hyperglycemia

BACKGROUND

The recent COVID-19 pandemic has led to a rise in the incidence of obesity both in children and adults. Studies on the effect of the pandemic on Type 2 diabetes mellitus (T2DM) trends in children are limited. In this study, we aim to evaluate the frequency, clinical characteristics and demographics of newly-diagnosed paediatric T2DM cases 4 years before and after the pandemic.

METHODOLOGY

The frequency and clinical data of patients aged ≤18 years with newly-diagnosed T2DM in 4 tertiary centers in urban Malaysia from 18 March 2016 till 17 March 2020 (pre-pandemic) and 18 March 2020 till 17 March 2024 (postpandemic) was collected.

RESULTS

Seventy-five (75) patients were recorded with newly-diagnosed T2DM pre-pandemic and fifty-four (54) patients were recorded with newly-diagnosed T2DM post-pandemic. There was no significant increase in T2DM cases and diabetic ketoacidosis (DKA) during pandemic and T2DM cases fell to below pre-pandemic levels in the 3rd and 4th year postpandemic. HbA1c and serum glucose were lower post-pandemic than pre-pandemic: 10.1% vs 11.9%, p = 0.008 and 12.0 mmol/L vs 16.1 mmol/L, p = 0.038 respectively.

CONCLUSION

The incidence of T2DM and DKA did not increase during the pandemic and further declined in year 3 and 4 post-pandemic. Lower HbA1c and serum glucose in the post-pandemic group may suggest improved screening services and greater access to medical care.

Human ; Covid-19 ; Diabetic Ketoacidosis ; Diabetes Mellitus, Type 2 ; Obesity

The occurrence of hyperuricemia is frequently associated with diabetic ketoacidosis (DKA), however, crystalluria from the precipitation of calcium oxalate, uric acid, or urate crystals, is less known. Metabolic derangements during DKA, especially acidic urinary pH and hyperuricosuria are the main risk factors for uric acid crystals and stones. Here we report a case of uric acid crystalluria following the recovery phase of DKA.
Crystalluria ; Uric Acid ; Diabetic Ketoacidosis

OBJECTIVE: To explore the clinical phenotypes and genetic variant in a neonatal case of Mitochondrial DNA depletion syndrome type 13 (MTDPS13). METHODS: Clinical data and results of genetic testing of a neonate admitted to the Children's Hospital of Zhejiang University School of Medicine in January 2023 was retrospectively analyzed. The study was approved by the Medical Ethics Committee of the Children's Hospital of Zhejiang University. RESULTS: The male infant was admitted to the NICU due to tachypnea and persistent lactic acidosis 6 hours after birth. At admission, distinctive facial features were noted. Laboratory tests showed elevated lactic acid (< 30 mmol/L). Whole-exome sequencing revealed that he has harbored homozygous c.141del frameshift mutation of FBXL4 gene, which was unreported previously. The mutation was inherited from both of his parents and classified as likely pathogenic based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). CONCLUSION The clinical phenotypes of this case of MTDPS13 is characterized by lactic acidosis, distinctive facial features, growth retardation and developmental delay, for which the homozygous c.141del variant of the FBXL4 gene may be accountable.
Humans ; Male ; F-Box Proteins/genetics* ; Infant, Newborn ; Ubiquitin-Protein Ligases/genetics* ; DNA, Mitochondrial/genetics* ; Mitochondrial Diseases/genetics* ; Acidosis, Lactic/genetics* ; Mutation ; Phenotype ; Frameshift Mutation ; Exome Sequencing

Diabetic Ketoacidosis/diagnosis* ; Humans ; Child ; Diabetes Mellitus, Type 1/diagnosis* ; China ; Insulin/administration & dosage* ; Hypoglycemic Agents/therapeutic use*

Objectives: This study aims to determine the effect of the COVID-19 pandemic on the incidence, severity, and outcome of children diagnosed with diabetic ketoacidosis admitted in a tertiary pediatric hospital. Materials and Methods: Two groups were identified as the basis for classification: pre-pandemic (2017 to 2019) and COVID-19 pandemic (2020 to 2022). The Mann‐Whitney U test was utilized to test for the differences in continuous variables, while Pearson’s chi‐squared test was used to test for differences in categorical variables. Results: The study involved 136 participants, 63 of whom were recorded in the pre-pandemic period and 73 during the COVID-19 pandemic period. Data revealed no conclusive relationship between sex (p=0.578), age (p=0.225), or height (p=0.876) across the two time frames. However, data showed significant difference between the weight (p=0.007) and BMI (p=0.003) of children with DKA pre-pandemic and during pandemic. This implies that marked changes in weight and BMI reflect possible changes in health behaviors, healthcare access, or other variables that may have altered during the COVID-19 pandemic. Furthermore, there was no discernible difference between pre-pandemic and COVID-19 in terms of severity, incidence, or the amount of time between the onset of symptoms and consultation. Conclusion The demographic and clinical characteristics of patients with DKA across the two study periods indicate a degree of stability in patient profiles. Despite the unique circumstances of the pandemic, patient outcomes in terms of glycemic control and mortality were like those observed pre-pandemic. The significant difference in weight and BMI emphasizes how crucial it is to monitor and respond to modifications in the nutritional status and metabolic health of DKA patients during times of crisis, like the COVID-19 pandemic. Comprehending these changes can provide focused treatments aimed at promoting the best possible health outcomes for susceptible patient groups.
Diabetic Ketoacidosis ; Diabetes Mellitus ; COVID-19

This study aims to analyze the clinical characteristics and genetic variations of two cases with developmental delay and lactic acidosis in a family, and to explore the relationship between genetic variations and clinical features. A retrospective analysis was conducted on the clinical characteristics of two siblings with developmental delay and lactic acidosis who were treated at the Neonatal Department of Children's Hospital of Chongqing Medical University in May 2019 and December 2021, respectively. Whole-exome sequencing was used to detect genetic variations in the affected children. Homology modeling of the BCS1L protein was performed to analyze the structural and functional changes of the protein. The correlation between genetic variations and clinical phenotypes was analyzed. The results showed that the main clinical features of the two affected children in this family were manifestations of mitochondrial respiratory chain complex Ⅲ deficiency, including prematurity, developmental delay, respiratory failure, lactic acidosis, cholestasis, liver dysfunction, renal tubular lesions, coagulation dysfunction, anemia, hypoglycemia, hypotonia, and early death. Whole-exome sequencing revealed a novel deletion mutation c.486_488delGGA (p.E163del) and a novel missense mutation c.992C>T (p.T331I) in the BCS1L gene. Structural analysis of the homology modeling showed that the compound heterozygous mutation had a significant impact on protein function. In conclusion, the novel mutation site c.992C>T (p.T331I) in the BCS1L gene is a "likely pathogenic" mutation, and the compound heterozygous mutation is closely related to the phenotype of mitochondrial respiratory chain complex Ⅲ deficiency.
Humans ; Acidosis, Lactic/genetics* ; Electron Transport Complex III/genetics* ; Retrospective Studies ; Mutation ; Growth Disorders ; ATPases Associated with Diverse Cellular Activities/genetics*

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3^rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB₁, vitaminB₂, vitaminB₆, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.
Humans ; Male ; Acidosis, Lactic ; Brain ; Brain Stem ; Dystonia ; Dystonic Disorders ; Mitochondrial Diseases ; Infant

Humans ; Diabetes Mellitus ; Ketosis ; Magnetic Resonance Imaging