Frequent Self-Monitoring Blood Glucose Correlated to Better Medication Adherence and Glycemic Control in Children with Type 1 Diabetes Mellitus.

Background: Type 1 diabetes mellitus (T1DM) is the most common chronic disease in children, with several severe short and long-term complications. Glycemic control is an important aspect of diabetes management with the most influential factor being compliance with self-monitoring blood glucose (SMBG). Mostly, in Indonesia, the finger stick devices as a glucose monitoring tool were frequently used. About 20% of children follow the recommendation to measure blood glucose four to six times daily. Methods: This is a single center, cross-sectional study that was conducted between July-November 2022. The Population is children with T1DM at the Pediatric Outpatient Clinic of Dr. Soetomo Hospital, Surabaya, Indonesia. Children with T1DM aged 4-18 years were enrolled using consecutive sampling. A compliance questionnaire was used to assess SMBG. Psychosocial conditions were assessed using the Pediatric Symptom Checklist 17, and medication adherence was evaluated using the Adherence to Refills and Medications Scale for Diabetes (ARMS-D). Pearson correlation and linear regression were employed for statistical analyses using Statistical Package for Social Sciences version 21.0, with p < 0.05 indicating statistical significance. Results: A total of 36 children were included in this study. SMBG frequency over 4x per day was significantly associated with increased medication adherence as measured by the ARMS-D score (p = 0.012). Higher SMBG frequency was also correlated with decreased HbA1c (p = 0.014, r = 0.406) and nutritional status (p = 0.031, r = 0.360). Less than 50% of the patients in Indonesia adhered to the recommended guidelines for SMBG (ie, ≥4 times per day). Conclusion: Higher SMBG frequency was correlated with better glycemic control. This finding suggests the need for further support in conducting SMBG based on the national guideline. However, due to it being conducted in a single center, we suggest increasing the sample size or conducting multi-centre collaborations in future studies. Originality/Value: By specifically investigating the relationship between adherence to self-monitoring of blood glucose (SMBG) and glycemic control in children with type 1 diabetes mellitus (T1DM), our study represents a novel contribution to the field of pediatric diabetes management in Indonesia. While previous research has explored similar relationships in other populations, our study focuses exclusively on the unique context of Indonesia, where rates of adherence to SMBG in pediatric patients have not been well studied and are relatively low compared to global standards.

Selenium level correlates negatively with antibodies but positively with thyroid function in children with down syndrome: an Indonesian study.

Background: Children with Down syndrome (DS) are prone to developing autoimmune thyroid disease (AITD). Previous studies found lower selenium (Se) levels in children with AITD. Glutathione peroxidase-3 (GPx3) and selenoprotein-P (SePP) are widely used to measure Se levels. DS children tend to have lower Se levels, the main contributor to hypothyroidism in this population. This study aimed to analyze the Se's role in AITD in Indonesian children with DS. Methods: This cross-sectional study was conducted between February 2021-June 2022 at the Pediatric Outpatient Clinic of Dr Soetomo Hospital. DS children aged 1 month to 18 years were enrolled using consecutive sampling. Thyroid-stimulating hormone, free thyroxine, thyroid peroxidase (TPO-Ab) and thyroglobulin (Tg-Ab) autoantibody, GPx3, and SePP levels were measured in plasma samples using enzyme-linked immunosorbent assays. Statistical analyses used Chi-square, Mann-Whitney, and Spearman's rank correlation (r s). All results with p<0.05 were considered statistically significant. Results: Among 62 children with DS, SePP and GPx3 levels were significantly lower in those with AITD than those without AITD (p=0.013 and p=0.018, respectively). SePP and GPx3 levels correlated significantly with lower TPO-Ab (r s=-0.439 with p=1×10-5 and r s=-0.396 with p=0.001, respectively) and Tg-Ab (r s=-0.474 with p=1×10-5 and r s=-0.410 with p=0.001, respectively) levels. SePP levels correlated significantly with lower thyroid dysfunction incidence (r s=-0.252, p=0.048) in the AITD group. Conclusion: Selenium deficiency contributes to autoimmune process in the thyroid and to thyroid dysfunction in children with Down syndrome. Our findings recommend increasing Se levels through Se-containing foods to reduce the risks of AITD and thyroid dysfunction in DS children with AITD.

Cytotoxic T-lymphocyte-associated protein 4 +49A/G polymorphism in Down syndrome children with Hashimoto's thyroiditis.

Thyroid dysfunction is the most common endocrine disorder in Down syndrome (DS) children. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) is one of the immune regulatory genes that correlates with Hashimoto's thyroiditis (HT). However, studies on CTLA-4 +49A/G in DS children with HT are still limited. We aimed to evaluate CTLA-4 +49A/G gene polymorphism in DS children with HT. This case-control study, conducted from February 2020 to February 2022 at Dr. Soetomo General Hospital, Surabaya, enrolled 40 DS children with HT and 50 healthy children. The DNA sequencing was performed to identify the polymorphism (Sanger sequencing). Thyroid peroxidase antibodies (TPOAb), thyroglobulin antibodies (TgAb), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) levels were analyzed by enzyme-linked immunosorbent assay (ELISA). The mean age of DS children with HT was 1.78 years. Males predominated in the study population. Subjects with GG genotype were diagnosed earliest with hypothyroidism (8 months) compared with other studies. The most common thyroid dysfunction was central hypothyroidism, with TgAb positivity present in all patients. The AA genotype (odds ratio [OR] 0.265, 95% confidence interval [CI] 0.094-0.746; P = 0.012) and A allele (OR 0.472, 95% CI 0.309-0.721; P = 0.0002) were significantly more frequent in the control group. The AG genotype (OR 2.65, 95% CI 0.094-0.746; P = 0.003) and G allele (OR 2.116, 95% CI 1.386-3.23; P = 0.003) were more frequent in the DS with HT group. The age of the subjects in this study was younger than in previous studies. The AG genotype and the G allele were more prevalent in the DS with HT group and may be a risk factor in HT development in DS children. Furthermore, the AA genotype may act as a protective factor against HT in DS children.

Protein tyrosine phosphatase non-receptor type 22 C1858T gene polymorphism in children with down syndrome and autoimmune thyroid diseases.

Autoimmune Thyroid Disease (AIT) is a frequent comorbidity in Down Syndrome (DS). Protein Tyrosine Phosphatase Non- Receptor Type 22 C1858T (PTPN-22 C1858T) gene polymorphisms have a role in the progression of AIT. The study on PTPN- 22 C1858T gene polymorphism as the risk factor of AIT in DS children is still limited. This study aims to evaluate PTPN-22 C1858T polymorphism in Indonesian DS children. A cross-sectional study involving 31 DS children with hypothyroidism (19 boys/12 girls) was conducted for ten months from February to November 2020 at Dr. Soetomo General Hospital Surabaya. The PTPN-22 C1858T gene polymorphism was analyzed using Polymerase Chain Reaction-Restriction-Fragment-Length Polymorphism (PCR-RFLP). Anti-Thyroid Peroxidase (Anti- TPO) and Anti-Thyroglobulin (Anti-TG), FT4, T3, and TSH levels were analyzed using Enzyme-Linked-Immunosorbent-Assay (ELISA). The mean age of the subjects was 19.45±17.3 months. The CT variant of PTPN-22 C1858T was observed in all subjects. The mean level of T3, FT4, and TSH were 1.59±0.45 ng/mL, 0.81±0.57 ng/mL, 0.22±0.21 µU/mL, respectively. Around 83.9% of patients suffered from central hypothyroidism, 12.9% from primary hypothyroidism, and 3.2% from subclinical hypothyroidism. The positive anti-TG and anti-TPO were observed in 96.8% and 58.1%, respectively. CT variant was observed in Indonesian DS children who suffered from hypothyroidism.

The correlation between vitamin D and levels of IFN-γ, NF-κB, thyroid antibodies in down syndrome: study in Indonesian children.

BACKGROUND AND AIM: Vitamin D (VD) reduces interferon-gamma (IFN-γ) production and prevents nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) activation, impacting the inhibition of the autoimmunity process such as autoimmune thyroiditis (AITD). Children with Down syndrome (DS) are reported to have a higher risk of autoimmunity and lower VD levels than non-DS. Therefore, this study aimed to evaluate VD levels in Indonesian DS children and their relationship with marker of AITD. METHODS: This study was conducted on DS children at Dr Soetomo Hospital between February 2021-June 2022. Socio-demographic status, amount of milk, fish and meat consumption, and duration of sun exposure were obtained using a self-report questionnaire. Thyroid hormone (TSH and FT4), thyroid antibody (TPO-Ab and Tg-Ab), 25 (OH)D, IFN-γ, and NF-κB levels were measured using ELISA. RESULTS: Of the 80 participants, 53.75% had sufficient (50.829±17.713 ng/ml) and 46.25% had non-sufficient (20.606±5.974 ng/ml) VD levels. Daily milk consumption, meat and fish consumption were risk factors contributing to VD levels in multivariate analysis [p=0.003, OR=1.007(1.003-1.012); p=0.004, OR=1.816(1.209- 2.728), respectively]. Participants with sufficient VD had significantly higher TPO-Ab (p=0.007) and Tg-Ab (p=0.016). Mean of VD levels were significantly negatively correlated with IFN-γ levels (r =-0.262, p=0.037) and positively correlated with TPO-Ab (r= 0.432, p=1x10-5,) and Tg-Ab (r= 0.375, p=0.001). CONCLUSIONS: Majority of subjects had sufficient VD levels. VD suppresses IFN-g, but is unable to affect NF-κB levels, presumably causing high levels of TPO-Ab and Tg-Ab in sufficient VD patient.

HLA-DQA1 and HLA-DQB1 Gene Polymorphism in Indonesian Children with Type I Diabetes Mellitus.

BACKGROUND: More than 40 genes influence the progression of type 1 diabetes mellitus (T1DM), including human leukocyte antigen (HLA) alleles. Different HLA genotype patterns result in diverse rates of T1DM development. HLA class II DR, DQ, and DP vary among different populations and ethnicities. Data on HLA polymorphism in T1DM in Indonesia are lacking. Therefore, this study was designed to evaluate the gene polymorphism of HLA-DQA1 and HLA-DQB1 in Indonesian children with T1DM. PATIENTS AND METHODS: In this study, 31 patients with T1DM and 31 controls were enrolled from April 2020 to April 2021. This study was conducted at Dr. Soetomo Hospital, Indonesia. We evaluated the gene polymorphism of HLA-DQA1 and HLA-DQB1 using polymerase chain reaction-restriction fragment length polymorphism. The primers used were as follows: for HLA-DQA1, DQAS34: 5'-GGTGTAAACTTGTACCAG-3' (forward) and DQAA261: 5'-ATTGGTAGCAGCGGTAGA-3' (reverse); for HLA-DQB1, DQBS43: 5'-TGCTACT- TCACCAA(C/T)GGG-3' (forward) and DQBA249: 5'-GTAGTTGTGTCTGCA (C/T)AC-3' (reverse). RESULTS: The most common HLA-DQA1 subtype in the T1DM group was 0101/0102 accounting for 67.6%, and 01/03 and 02/03 were found in the T1DM group only. Meanwhile, the most common HLA-DQB1 subtype in the T1DM group was 0301, accounting for 54.8%. Most subjects in this study were Javanese. CONCLUSION: HLA-DQA1 0101/0102 and HLA-DQB1 0301 were commonly found in Indonesian children with T1DM.

Quality of Life Differences in Pre- and Post-Educational Treatment in Type 1 Diabetes Mellitus During COVID-19.

PURPOSE: The coronavirus-19 (COVID-19) pandemic requires the use of online media to ensure monitoring of type 1 diabetes mellitus (T1DM) in children. Thus, this study aims to determine whether online education effectively improves the quality of life (QoL) in children with T1DM during the coronavirus-19 pandemic. PATIENTS AND METHODS: The study, conducted from March to October 2020, utilized the paired t-test before and after online education. Moreover, it adopts the recommended Pediatric Quality of Life Inventory (PedsQL) 3.2 diabetes module for the 33 patients registered in the Pediatric Endocrine Outpatient Clinic of Dr. Soetomo Hospital, Surabaya, Indonesia. RESULTS: The QoL of all children (p = 0.011), parents (p = 0.001), and both children and parents (overall; p = 0.002) have shown significant improvement after the treatment. The QoL of parents, as a subcriterion, improved after the treatment. However, the improvement in the children in subcriterion treatment II (p = 0.186) was not significant. CONCLUSION: Online education has proven to create a better QoL almost in all children with T1DM during the coronavirus-19 pandemic.