Different Forms of Hypothyroidism in Infants with Maternal Graves' Disease: A Case Series.

Infants of mothers with Graves' disease (GD) may develop central hypothyroidism (CH) due to exposure of the foetal hypothalamic-pituitary-thyroid axis to higher-than-normal thyroid hormone concentrations, primary hypothyroidism (PH) due to transplacental passage of maternal thyroid stimulating hormone receptor antibody (TRAb), antithyroid drugs (ATD) or thyroid dysgenesis secondary to maternal uncontrolled hyperthyroidism. We describe two infants with PH and four infants with CH born to mothers with poorly controlled Graves' disease. All infants required levothyroxine and had normal developmental milestones. While national guideline consensus for high thyroid stimulating hormone (TSH) on neonatal screening is well-established, thyroid function tests (TFTs) should be serially monitored in infants with low TSH on screening, as not all mothers with Graves' disease are diagnosed antenatally.

Cardiometabolic risk factors among children who are affected by overweight, obesity and severe obesity.

Background: The increasing severity of obesity is expected to lead to more serious health effects. However, there is limited information on the prevalence and clinical characteristics of cardiometabolic risk factors in severely children affected by obesity in Malaysia. This baseline study aimed to investigate the prevalence of these factors and their association with obesity status among young children. Methods: In this study, a cross-sectional design was employed using the baseline data obtained from the My Body Is Fit and Fabulous at school (MyBFF@school) intervention program involving obese school children. Obesity status was defined using the body mass index (BMI) z-score from the World Health Organization (WHO) growth chart. Cardiometabolic risk factors presented in this study included fasting plasma glucose (FPG), triglycerides (TGs), total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), blood pressure, acanthosis nigricans, insulin resistance (IR), and MetS. MetS was defined using the International Diabetes Federation (IDF) 2007 criteria. Descriptive data were presented accordingly. The association between cardiometabolic risk factors, such as obesity status, and acanthosis nigricans with MetS was measured using multivariate logistic regression, which was adjusted for gender, ethnicity, and strata. Results: Out of 924 children, 38.4% (n = 355) were overweight, 43.6% (n = 403) were obese, and 18% (n = 166) were severely obese. The overall mean age was 9.9 ± 0.8 years. The prevalence of hypertension, high FPG, hypertriglyceridemia, low HDL-C, and the presence of acanthosis nigricans among severely children affected by obesity was 1.8%, 5.4%, 10.2%, 42.8%, and 83.7%, respectively. The prevalence of children affected by obesity who were at risk of MetS in <10-year-old and MetS >10-year-old was observed to be similar at 4.8%. Severely children affected by obesity had higher odds of high FPG [odds ratio (OR) = 3.27; 95% confdence interval (CI) 1.12, 9.55], hypertriglyceridemia (OR = 3.50; 95%CI 1.61, 7.64), low HDL-C (OR = 2.65; 95%CI 1.77, 3.98), acanthosis nigricans (OR = 13.49; 95%CI 8.26, 22.04), IR (OR = 14.35; 95%CI 8.84, 23.30), and MetS (OR = 14.03; 95%CI 3.97, 49.54) compared to overweight and children affected by obesity. The BMI z-score, waist circumference (WC), and percentage body fat showed a significant correlation with triglycerides, HDL-C, the TG: HDL-C ratio, and the homeostatic model assessment for IR (HOMA-IR) index. Conclusions: Severely children affected by obesity exhibit a higher prevalence of and are more likely to develop cardiometabolic risk factors compared to overweight and children affected by obesity. This group of children should be monitored closely and screened periodically for obesity-related health problems to institute early and comprehensive intervention.

Glycaemic Changes Among Children and Adolescents With Type 1 Diabetes Mellitus Before and During Ramadan Fasting Using Continuous Glucose Monitoring.

Objectives: This study described and compared glycaemic changes with the use of the following Continuous Glucose Monitoring (CGM) metrics: time in range, time in hyperglycaemia and time in hypoglycaemia from retrospective CGM data among children and adolescents with Type 1 Diabetes Mellitus (T1DM), before and during Ramadan to better understand the impact of fasting during this season. Methodology: This study was conducted in 2 tertiary centres: Hospital Putrajaya (HPJ) and Hospital Universiti Sains Malaysia (HUSM) from February to May 2020. Muslim T1DM patients between ages 8 to18 who intended to fast during Ramadan were given Ramadan-focused education. CGM iPro2® (Medtronic) was used before and during Ramadan, complemented by finger-prick glucose monitoring or self-monitoring of blood glucose (SMBG). Results: Of the 32 patients, only 24 (12 female) were analysed. Mean age was 13.6 ± 3.1 years old, mean HbAlc was 9.6 ± 1.9% and mean duration of illness was 5.4 ± 3.4 years. Majority (91.7%) were on multiple dose injections (MDI) while only 8.3% were on continuous subcutaneous insulin infusion (CSII). All fasted in Ramadan without acute complications. Retrospective CGM analysis revealed similar results in time in range (TIR), time in hyperglycaemia and time in hypoglycaemia before and during Ramadan, indicating no increased hypoglycaemic or hyperglycaemic events related to fasting. Glycaemic variability before Ramadan as measured by the LBGI, HBGI and MAG, were similar to values during Ramadan. Conclusion: Ramadan fasting among T1DM children and adolescents, by itself, is not associated with short-term glycaemic deterioration. T1DM youths can fast safely in Ramadan with the provision of focused education and regular SMBG.

Effect of obesity and excessive body fat on glycaemic control in paediatric type 1 diabetes.

OBJECTIVES: Excessive adiposity is believed to contribute to insulin resistance, resulting in more complex metabolic outcomes and poorer glycaemic control. This study aimed to determine the prevalence of overweight/obese, excessive adiposity, and metabolic syndrome in type 1 diabetes mellitus (T1DM) children, who were from a relatively overweight/obese population, and to assess the effects on glycaemic control. METHODS: A cross-sectional study was conducted from November 2019 to August 2020 on T1DM children between 6 and 18 years old who attended the Paediatric Endocrine Clinic Putrajaya Hospital. Anthropometry and bioelectrical impedance analysis (Inbody 720) were measured to analyse their effects towards glycated haemoglobin (HbA1c) via SPSS 21. RESULTS: A total of 63 T1DM were recruited with an equal male-to-female ratio. The mean age was 12.4 ± 3.3 years old with a mean HbA1c of 9.8 ± 2.0%. The prevalence of overweight/obese and excessive body fat was 17.5 and 34.9%, respectively. Only 3 (6.8%) fulfilled the metabolic syndrome criteria. The waist circumference had a significant relationship with HbA1c. Every 10 cm increment of waist circumference was predicted to raise HbA1c by 0.8. The odds ratio of having abdominal obesity among T1DM with excessive body fat was 9.3 times. CONCLUSIONS: Abdominal obesity is significantly associated with a poorer glycaemic control in T1DM children. Monitoring of waist circumference should be considered as part of the routine diabetic care.

Prevalence and clinical characteristics of metabolically healthy obese versus metabolically unhealthy obese school children.

Introduction: Children with obesity in the absence of traditional cardiometabolic risk factors (CRF) have been described as metabolically healthy obese (MHO). Children with MHO phenotype has a favorable metabolic profile with normal glucose metabolism, lipids, and blood pressure compared to children with metabolically unhealthy obese (MUO) phenotype. This study aimed to compare several parameters related to obesity between these two groups and to examine the predictors associated with the MHO phenotype. Methods: This study included a cross-sectional baseline data of 193 children with obesity (BMI z-score > +2 SD) aged 8-16 years enrolled in MyBFF@school program, a school-based intervention study conducted between January and December 2014. Metabolic status was defined based on the 2018 consensus-based criteria with MHO children had no CRF (HDL-cholesterol > 1.03 mmol/L, triglycerides ≤ 1.7 mmol/L, systolic and diastolic blood pressure ≤ 90th percentile, and fasting plasma glucose ≤ 5.6 mmol/L). Those that did not meet one or more of the above criteria were classified as children with MUO phenotype. Results: The prevalence of MHO was 30.1% (95% CI 23.7 - 37.1) among schoolchildren with obesity and more common in younger and prepubertal children. Compared to MUO, children with MHO phenotype had significantly lower BMI, lower waist circumference, lower uric acid, higher adiponectin, and higher apolipoprotein A-1 levels (p < 0.01). Multivariate logistic regression showed that adiponectin (OR: 1.33, 95% CI 1.05 - 1.68) and apolipoprotein A-1 (OR: 1.02, 95% CI 1.01 - 1.03) were independent predictors for MHO phenotype in this population. Conclusions: MHO phenotype was more common in younger and prepubertal children with obesity. Higher serum levels of adiponectin and apolipoprotein A-1 increased the possibility of schoolchildren with obesity to be classified into MHO phenotype.

TG: HDL-C Ratio as Insulin Resistance Marker for Metabolic Syndrome in Children With Obesity.

Insulin resistance (IR) is an important variable in the diagnosis of metabolic syndrome (MetS). Currently, IR is not part of the existing pediatric definition of MetS, instead elevated fasting blood glucose (FBG) is measured as an indicator of hyperglycemia. Arguably, many obese children with severe IR are still able to regulate their FBG well. Hence, this study aimed to assess the utility of triglyceride-to-high-density lipoprotein cholesterol (TG : HDL-C) ratio as an IR marker in the modeling of pediatric MetS among children with obesity using structural equation modeling (SEM). A total of 524 blood samples from children with obesity (age 10-16 years old) were analyzed for FBG, lipids, insulin, leptin, and adiponectin. Both exploratory (EFA) and confirmatory factor analysis (CFA) were used to examine TG : HDL-C ratio as an IR marker in pediatric MetS. EFA shows that TG: HDL-C ratio (standardized factor loading = 0.904) groups together with homeostasis model assessment-estimated insulin resistance (HOMA-IR) (standardized factor loading = 0.664), indicating a strong correlation to the IR factor. Replacing FBG with TG: HDL-C ratio improved the modeling of MetS structure in children with obesity. Our MetS model of TG: HDL-C ratio as IR component shows comparable model fitness indices (goodness of fit, Akaike's information criterion, and Bayesian information criterion) with leptin:adiponectin ratio (platinum standard for adiposity:IR marker) model. The least model fit was seen when using FBG as an IR surrogate. TG : HDL-C ratio performed better as IR surrogate in MetS structures (standardized factor loading = 0.39) compared to FBG (standardized factor loading = 0.27). TG: HDL-C ratio may be considered as an IR component in pediatric MetS.

Impact of COVID-19 lockdown on glycaemic control and lifestyle changes in children and adolescents with type 1 and type 2 diabetes mellitus.

AIMS: Malaysia implemented nationwide lockdown from 18th March till 3rd May 2020 to mitigate the spread of coronavirus disease (COVID-19). This study aimed to examine the impact of the lockdown on glycaemic control and lifestyle changes in children and adolescents with type 1 (T1DM) and 2 diabetes mellitus (T2DM) aged less than 18 years old. METHODS: In this cross-sectional study, interviews and a standardised questionnaire comparing lifestyle changes before and during the lockdown were performed in follow-up clinic visits after the lockdown. Anthropometry measurements and glycated haemoglobin (HbA1c) values were compared 3 months prior and after the lockdown. RESULTS: Participants were 93 patients with T1DM (11.08 ± 3.47 years) and 30 patients with T2DM (13.81 ± 2.03 years). Male gender, T2DM and pubertal adolescents were found to have a significant deterioration in glycaemic control. A significant increment of HbA1c was observed in patients with T2DM (8.5 ± 0.40 vs 9.9 ± 0.46%), but not in patients with T1DM (8.6 ± 0.28 vs 8.7 ± 0.33%). Contrarily, there was an improved glycaemic control in pre-pubertal T1DM children likely due to parental supervision during home confinement. Weight and BMI SDS increased in T1DM patients but surprisingly reduced in T2DM patients possibly due to worsening diabetes control. Reduced meal frequency mainly due to skipping breakfast, reduced physical activity level scores, increased screen time and sleep duration were observed in both groups. CONCLUSIONS: Adverse impact on glycaemic control and lifestyle were seen mostly in patients with T2DM and pubertal adolescent boys.

TG : HDL-C Ratio Is a Good Marker to Identify Children Affected by Obesity with Increased Cardiometabolic Risk and Insulin Resistance.

Metabolic syndrome (MetS) is an important predictor of cardiovascular diseases in adulthood. This study aims to examine the clinical utility of triglyceride to high-density lipoprotein ratio (TG : HDL-C) in identifying cardiometabolic risk and insulin resistance (IR) among children with obesity, in comparison with MetS as defined by the International Diabetes Federation (IDF). Data of 232 children with obesity aged 10-16 years were obtained from our study, MyBFF@school study, conducted between January and December 2014. Children were divided into tertiles of TG : HDL-C ratio. The minimum value of the highest tertile was 1.11. Thus, elevated TG : HDL-C ratio was defined as TG : HDL-C ≥1.11. Children with MetS were categorized based on the definition established by the IDF. Out of 232 children, 23 (9.9%) had MetS, out of which 5.6% were boys. Almost twofold of boys and girls had elevated TG : HDL-C ratio compared to MetS: 13.8% vs. 5.6% and 13.8% vs. 4.3%, respectively. Children with elevated TG : HDL-C ratio had lower fasting glucose compared to children with MetS (boys = 5.15 ± 0.4 vs. 6.34 ± 2.85 mmol/l, p=0.02; girls = 5.17 ± 0.28 vs. 6.8 ± 4.3 mmol/l, p=0.03). Additionally, boys with elevated TG : HDL-C ratio had a higher HDL-C level compared to those with MetS (1.08 ± 0.18 vs. 0.96 ± 0.1 mmol/l, p=0.03). There was no significant difference across other MetS-associated risk factors. Overall, TG : HDL-C ratio demonstrated higher sensitivity (42.7% vs. 12.9%) but lower specificity (74.8% vs. 93.2%) than MetS in identifying IR, either in HOMA-IR ≥2.6 for prepubertal children or HOMA-IR ≥4 for pubertal children. TG : HDL-C ratio in children with obesity is thus as useful as the diagnosis of MetS. It should be considered an additional component to MetS, especially as a surrogate marker for IR.

Preserved glucagon-like peptide-1 responses to oral glucose, but reduced incretin effect, insulin secretion and sensitivity in young Asians with type 2 diabetes mellitus.

OBJECTIVE: Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, ß-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM. RESEARCH DESIGN AND METHODS: This case-control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index. Serum glucose, insulin, C peptide and GLP-1 were sampled during 2-hour oral glucose tolerance tests (OGTTs) and 1-hour intravenous glucose tolerance tests (IVGTTs). Insulin sensitivity was derived from the Quantitative Insulin Sensitivity Check Index (QUICKI), Oral Glucose Insulin Sensitivity Index (OGIS) in OGTT and surrogate index of SI from the minimal model (calculated SI, CSI). Acute insulin response (AIR) was obtained from IVGTT. Total BC was computed as incremental area under the curve of insulin/incremental area under the curve of glucose, during OGTT (BCOG) and IVGTT (BCIV), respectively. Disposition index (DI) was calculated using the product of insulin sensitivity and insulin secretion. GLP-1 response to oral glucose was calculated as incremental area under the curve of GLP-1 (ΔAUCGLP-1). Per cent incretin effect was estimated as 100×(BCOG-BCIV)/BCOG). RESULTS: The YT2DM had marked impairment in BC (>80% reduction in AIR and BCOG, p<0.001) and lower QUICKI (p<0.001), OGIS (p<0.001) and CSI (p=0.015) compared with controls. There was no difference in GLP-1 at all time points and ΔAUCGLP-1 but the per cent incretin effect was reduced in the YT2DM compared with controls (12.1±8.93 vs 70.0±4.03, p<0.001). CONCLUSIONS: Asian YT2DM showed similar GLP-1 response to oral glucose as controls but reduced incretin effect, BC and insulin sensitivity. The lack of compensatory mechanisms, as shown by the DI may be partly ascribed to the impaired incretin effect, similar to that of adult T2DM. TRIAL REGISTRATION NUMBER: NMRR-12-1042-13254.

Triglyceride to HDL-C Ratio is Associated with Insulin Resistance in Overweight and Obese Children.

The purpose of this study was to investigate the usefulness of triglyceride to hdl-c ratio (TG:HDL-C) as an insulin resistance (IR) marker for overweight and obese children. A total of 271 blood samples of obese and overweight children aged 9-16 years were analysed for fasting glucose, lipids and insulin. Children were divided into IR and non-insulin resistance, using homeostasis model assessment (HOMA). The children were then stratified by tertiles of TG: HDL-C ratio. The strength between TG:HDL-C ratio and other parameters of IR were quantified using Pearson correlation coefficient (r). Odds ratio was estimated using multiple logistic regression adjusted for age, gender, pubertal stages and IR potential risk factors. Children with IR had significantly higher TG:HDL-C ratio (2.48) (p = 0.01). TG:HDL-C ratio was significantly correlated with HOMA-IR (r = 0.104, p < 0.005) and waist circumference (r = 0.134, p < 0.001). Increasing tertiles of TG:HDL-C ratio showed significant increase in mean insulin level (p = 0.03), HOMA-IR (p = 0.04) and significantly higher number of children with acanthosis nigricans and metabolic syndrome. The odds of having IR was about 2.5 times higher (OR = 2.47; 95% CI 1.23, 4.95; p = 0.01) for those in the highest tertiles of TG:HDL-C ratio. Hence, TG:HDL-C may be a useful tool to identify high risk individuals.