Mechanisms and Physiological Roles of Polymorphisms in Gestational Diabetes Mellitus.

Gestational diabetes mellitus (GDM) is a significant pregnancy complication linked to perinatal complications and an elevated risk of future metabolic disorders for both mothers and their children. GDM is diagnosed when women without prior diabetes develop chronic hyperglycemia due to ß-cell dysfunction during gestation. Global research focuses on the association between GDM and single nucleotide polymorphisms (SNPs) and aims to enhance our understanding of GDM's pathogenesis, predict its risk, and guide patient management. This review offers a summary of various SNPs linked to a heightened risk of GDM and explores their biological mechanisms within the tissues implicated in the development of the condition.

Short-term effects of allulose consumption on glucose homeostasis, metabolic parameters, incretin levels, and inflammatory markers in patients with type 2 diabetes: a double-blind, randomized, controlled crossover clinical trial.

PURPOSE: Allulose is a rare monosaccharide with almost zero calories. There is no study of short-term allulose consumption in patients with type 2 diabetes (T2D). Thus, we aimed to study the effect of allulose consumption for 12 weeks on glucose homeostasis, lipid profile, body composition, incretin levels, and inflammatory markers in patients with T2D. METHODS: A double-blind, randomized, controlled crossover study was conducted on sixteen patients with T2D. Patients were randomly assigned to allulose 7 g twice daily or aspartame 0.03 g twice daily for 12 weeks. After a 2-week washout, patients were crossed over to the other sweetener for an additional 12 weeks. Oral glucose tolerance tests, laboratory measurements, and dual-energy X-ray absorptiometry were conducted before and after each phase. RESULTS: This study revealed that short-term allulose consumption exerted no significant effect on glucose homeostasis, incretin levels, or body composition but significantly increased MCP-1 levels (259 ± 101 pg/ml at baseline vs. 297 ± 108 pg/mL after 12 weeks of allulose, p = 0.002). High-density lipoprotein cholesterol (HDL-C) significantly decreased from 51 ± 13 mg/dl at baseline to 41 ± 12 mg/dL after 12 weeks of allulose, p < 0.001. CONCLUSION: Twelve weeks of allulose consumption had a neutral effect on glucose homeostasis, body composition, and incretin levels. Additionally, it decreased HDL-C levels and increased MCP-1 levels. TRIAL REGISTRATION: This trial was retrospectively registered on the Thai Clinical Trials Registry (TCTR20220516006) on December 5, 2022.

Defective functions of HNF1A variants on BCL2L1 transactivation and beta-cell growth.

Maturity-onset diabetes of the young type 3 (MODY3) is caused by mutations in a gene encoding transcription factor hepatocyte nuclear factor 1-alpha (HNF1A). Although the roles of HNF1A in regulation of hepatic and pancreatic genes to maintain glucose homeostasis were investigated, the functions of HNF1A are not completely elucidated. To better understand the functions of HNF1A, we characterized mutations of HNF1A in Thai MODY3 patients and studied the functions of wild-type HNF1A and variant proteins. We demonstrate for the first time that HNF1A upregulates transactivation of an anti-apoptotic gene BCL2 Like 1 (BCL2L1) and that all the identified HNF1A variants including p.D80V, p.R203C, p.P475L, and p.G554fsX556, reduce this ability. The four HNF1A variants impair HNF1A function in promoting INS-1 cell transition from G1 to S phase of cell cycle, which thereby retard cell growth. This finding indicates the role of HNF1A in beta-cell viability by upregulation of anti-apoptotic gene expression and also reaffirms its role in beta-cell growth through cell cycle control.

Quantitative Proteomics Reveals Differences in the Response of Neutrophils Isolated from Healthy or Diabetic Subjects to Infection with Capsule-Variant Burkholderia thailandensis.

In Thailand, diabetes mellitus is the most significant risk factor for melioidosis, a severe disease caused by Burkholderia pseudomallei. In this study, neutrophils isolated from healthy or diabetic subjects were infected with B. thailandensis E555, a variant strain with a B. pseudomallei-like capsular polysaccharide used here as a surrogate micro-organism for B. pseudomallei. At 2 h post-infection, neutrophil proteins were subjected to 4-plex iTRAQ-based comparative proteomic analysis. A total of 341 proteins were identified in two or more samples, of which several proteins involved in oxidative stress and inflammation were enriched in infected diabetic neutrophils. We validated this finding by demonstrating that infected diabetic neutrophils generated significantly elevated levels of pro-inflammatory cytokines TNFα, IL-6, IL-1ß, and IL-17 compared to healthy neutrophils. Our data also revealed that infected neutrophils from healthy or diabetic individuals undergo apoptotic cell death at distinctly different rates, with infected diabetic neutrophils showing a diminished ability to delay apoptosis and an increased likelihood of undergoing a lytic form of cell death, compared to infected neutrophils from healthy individuals. Increased expression of inflammatory proteins by infected neutrophils could contribute to the increased susceptibility to infection and inflammation in diabetic patients in melioidosis-endemic areas.

Impact of KCNQ1, CDKN2A/2B, CDKAL1, HHEX, MTNR1B, SLC30A8, TCF7L2, and UBE2E2 on risk of developing type 2 diabetes in Thai population.

BACKGROUND: Several type 2 diabetes (T2D) susceptibility loci identified via genome-wide association studies were found to be replicated among various populations. However, the influence of these loci on T2D in Thai population is unknown. The aim of this study was to investigate the influence of eight single nucleotide polymorphisms (SNPs) reported in GWA studies on T2D and related quantitative traits in Thai population. METHODS: Eight SNPs in or near the KCNQ1, CDKN2A/2B, SLC30A8, HHEX, CDKAL1, TCF7L2, MTNR1B, and UBE2E2 genes were genotyped. A case-control association study comprising 500 Thai patients with T2D and 500 ethnically-matched control subjects was conducted. Associations between SNPs and T2D were examined by logistic regression analysis. The impact of these SNPs on quantitative traits was examined by linear regression among case and control subjects. RESULTS: Five SNPs in KCNQ1 (rs2237892), CDK2A/2B (rs108116610, SLC30A8 (rs13266634), TCF7L2 (rs7903146) and MTNR1B (rs1387153) were found to be marginally associated with risk of developing T2D, with odds ratios ranging from 1.43 to 2.02 (p = 0.047 to 3.0 × 10-4) with adjustments for age, sex, and body mass index. Interestingly, SNP rs13266634 of SLC30A8 gene reached statistical significance after correcting for multiple testing (p = 0.0003) (p < 0.006 after Bonferroni correction). However, no significant association was detected between HHEX (rs1111875), CDKAL1 (rs7756992), or UBE2E2 (rs7612463) and T2D. We also observed association between rs10811661 and both waist circumference and waist-hip ratio (p = 0.007 and p = 0.023, respectively). In addition, rs13266634 in SLC30A8 was associated with glycated hemoglobin (p = 0.018), and rs7903146 in TCF7L2 was associated with high-density lipoprotein cholesterol level (p = 0.023). CONCLUSION: Of the eight genes included in our analysis, significant association was observed between KCNQ1, CDKN2A/2B, SLC30A8, TCF7L2, and MTNR1B loci and T2D in our Thai study population. Of these, CDKN2A/2B, SLC30A8, and TCF7L2 genes were also significantly associated with anthropometric, glycemic and lipid characteristics. Larger cohort studies and meta-analyses are needed to further confirm the effect of these variants in Thai population.

PAX4 R192H and P321H polymorphisms in type 2 diabetes and their functional defects.

We have previously identified PAX4 mutations causing MODY9 and a recent genome-wide association study reported a susceptibility locus of type 2 diabetes (T2D) near PAX4. In this study, we aim to investigate the association between PAX4 polymorphisms and T2D in Thai patients and examine functions of PAX4 variant proteins. PAX4 rs2233580 (R192H) and rs712701 (P321H) were genotyped in 746 patients with T2D and 562 healthy normal control subjects by PCR and restriction-fragment length polymorphism method. PAX4 variant proteins were investigated for repressor function on human insulin and glucagon promoters and for cell viability and apoptosis upon high glucose exposure. Genotype and allele frequencies of PAX4 rs2233580 were more frequent in patients with T2D than in control subjects (P=0.001 and 0.0006, respectively) with odds ratio of 1.66 (P=0.001; 95% confidence interval, 1.22-2.27). PAX4 rs712701 was not associated with T2D but it was in linkage disequilibrium with rs2233580. The 192H/321H (A/A) haplotype was more frequent in T2D patients than in controls (9.5% vs 6.6%; P=0.009). PAX4 R192H, but not PAX4 P321H, impaired repression activities on insulin and glucagon promoters and decreased transcript levels of genes required to maintain ß-cell function, proliferation and survival. Viability of ß-cell was reduced under glucotoxic stress condition for the cells overexpressing either PAX4 R192H or PAX4 P321H or both. Thus these PAX4 polymorphisms may increase T2D risk by defective transcription regulation of target genes and/or decreased ß-cell survival in high glucose condition.

Investigation of Monogenic Diabetes Genes in Thai Children with Autoantibody Negative Diabetes Requiring Insulin.

Purpose: The objective of this study was to clarify the phenotypic characteristics of monogenic diabetes abnormalities in Thai children with autoantibody-negative insulin. Patients and Methods: Two hundred and thirty-one Thai type 1 diabetes (T1D) patients out of 300 participants with recent-onset diabetes were analyzed for GAD65 and IA2 pancreatic autoantibodies. A total of 30 individuals with T1D patients with negative autoantibody were screened for 32 monogenic diabetes genes by whole-exome sequencing (WES). Results: All participants were ten men and twenty women. The median age to onset of diabetes was 8 years and 3 months. A total of 20 people with monogenic diabetes carried genes related to monogenic diabetes. The PAX4 (rs2233580) in ten patients with monogenic diabetes was found. Seven variants of WFS1 (Val412Ala, Glu737Lys, Gly576Ser, Cys673Tyr, Arg456His, Lys424Glu, and Gly736fs) were investigated in patients in this study. Furthermore, the pathogenic variant, rs115099192 (Pro407Gln) in the GATA4 gene was found. Most patients who carried PAX4 (c.575G>A, rs2233580) did not have a history of DKA. The pathogenic variant GATA4 variant (c.1220C>A, rs115099192) was found in a patient with a history of DKA. Conclusion: This study demonstrated significant genetic overlap between autoantibody-negative diabetes and monogenic diabetes using WES. All candidate variants were considered disease risk with clinically significant variants. WES screening was the first implemented to diagnose monogenic diabetes in Thai children, and fourteen novel variants were identified in this study and need to be investigated in the future.

The effects of transcription factor 7-like 2 rs7903146 and paired box 4 rs2233580 variants associated with type 2 diabetes on the therapeutic efficacy of hypoglycemic agents.

Aim: This study aims to investigate the effects of the TCF7L2 rs7903146 and PAX4 rs2233580 (R192H) variants associated with T2D on the therapeutic efficacies of various HAs in patients with T2D after follow-up for 3 years. Methods: A total of 526 patients who were followed up at the Diabetic Clinic of Siriraj Hospital during 2016-2019 were enrolled. The variants TCF7L2 rs7903146 and PAX4 rs2233580 (R192H) were genotyped using the RNase H2 enzyme-based amplification (rhAmp) technique and the associations between genotypes and glycemic control after treatments with different combinations HA were evaluated using Generalized Estimating Equations (GEE) analysis. Results: Patients who carried TCF7L2 rs7903146C/T + T/T genotypes when they were treated with biguanide alone had significantly lower fasting plasma glucose (FPG) than those of the patients who carried the C/C genotype (p = 0.01). Patients who carried the PAX4 rs2233580 G/G genotype when they were treated with sulfonylurea alone had significantly lower FPG than those of the patients who carried G/A + A/A genotypes (p = 0.04). Conclusion: Genotypes of TCF7L2 rs7903146 and PAX4 rs2233580 (R192H) variants associated with T2D influence the therapeutic responses to biguanide and sulfonylurea. Different genotypes of these two variants might distinctively affect the therapeutic effects of HAs. This finding provides evidence of pharmacogenetics in the treatment of diabetes.

The genetic polymorphisms and levels of adipokines and adipocytokines that influence the risk of developing gestational diabetes mellitus in Thai pregnant women.

INTRODUCTION: Aberrant immune and inflammatory response is thought to be involved in the pathogenesis of gestational diabetes mellitus (GDM). OBJECTIVE: To investigate the genetic polymorphisms and levels of adipokines/adipocytokines that influence the risk of developing GDM in Thai women. RESEARCH DESIGN & METHODS: This case-control recruited 400 pregnant Thai women. A total of 12 gene polymorphisms at ADIPOQ, adipsin, lipocalin-2, PAI-1, resistin, IL-1ß, IL-4, IL-17A, TGF-ß, IL-10, IL-6, and TNF-α were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay and RNase H2 enzyme-based amplification (rhAmp) SNP assay. Serum levels of adipokines/adipocytokines were evaluated using Luminex assays. RESULTS: Mean age, weight before and during pregnancy, body mass index before and during pregnancy, blood pressure, gestational age at blood collection, and median 50 g glucose challenge test were significantly higher in GDM women than control. Significantly lower adiponectin and higher IL-4 levels were found in GDM compared to controls (p = 0.001 and p = 0.03, respectively). The genotype frequencies of IL-17A (rs3819025) were significantly different between GDM and controls (p = 0.01). Using additive models, IL-17A (rs3819025) and. TNF-α (rs1800629) were found to be independently associated with increased risk of GDM (odds ratio [OR]: 2.867; 95 % confidence interval [CI]: 1.171-7.017; p = 0.021; and OR: 12.163; 95 %CI: 1.368-108.153; p = 0.025, respectively). In GDM with IL-17A (rs3819025), there was a significant negative correlation with lipocalin-2 and PAI-1 levels (p = 0.038 and p = 0.004, respectively). CONCLUSION: The results of this study highlight the need for genetic testing to predict/prevent GDM, and the importance of evaluating adipokine/adipocytokine levels in Thai GDM women.

The Variants in ADIPOQ are Associated with Maternal Circulating Adipokine Profile in Gestational Diabetes Mellitus.

Background: Gestational diabetes mellitus (GDM) is the most common association with hyperglycemia and glucose intolerance during pregnancy. The adipokines play an important to control insulin secretion and glucose. This study aimed to investigate the association between maternal circulating adipokine levels and ADIPOQ gene polymorphism among pregnant women subjects with GDM and normal glucose tolerance (NGT). Methods: Participants including 229 normal pregnant women and 197 GDM pregnant women were enrolled from 2015 to 2018 at Siriraj hospital. Serum adipokine levels including adiponectin, adipsin/factor D, NGAL/Lipocalin-2, total PAI-1, and resistin were measured by immunoassay. ADIPOQ variations were investigated including -11377C/G (rs266729), +45T/G (rs2241766), and +276G/T (rs1501299). Results: Serum adiponectin concentration was also significantly decreased among the GDM who had aged less than 35 years old whereas adipsin levels were significantly lower among the GDM who had aged more than 35 years old. Also, adiponectin and total PAI-1 levels were significantly lower among the GDM who had a BMI of less than 30 kg/m2. The G allele frequency of ADIPOQ +45T/G was significantly different between GDM and controls (p = 0.03). ADIPOQ +45T/G was associated with an increased risk of GDM (odds ratio [OR]: 1.554; 95% confidence interval [CI]: 1.010-2.390; p=0.045). The -11377C/G was affected by the level of adiponectin (p = 0.04). The C allele of -11377C/G SNP declined serum adiponectin levels and may be a risk factor for GDM. Conclusion: This study revealed that genetics play important roles in circulating adipokines among pregnant women. ADIPOQ polymorphisms had significant associations with adiponectin levels in GDM patients.

Long-term multiple metabolic abnormalities among healthy and high-risk people following nonsevere COVID-19.

Few studies have identified the metabolic consequences of the post-acute phase of nonsevere COVID-19. This prospective study examined metabolic outcomes and associated factors in nonsevere, RT-PCR-confirmed COVID-19. The participants' metabolic parameters, the prevalence of long-term multiple metabolic abnormalities (≥ 2 components), and factors influencing the prevalence were assessed at 1, 3, and 6 months post-onset. Six hundred individuals (mean age 45.5 ± 14.5 years, 61.7% female, 38% high-risk individuals) with nonsevere COVID-19 attended at least one follow-up visit. The prevalence of worsening metabolic abnormalities was 26.0% for BMI, 43.2% for glucose, 40.5% for LDL-c, 19.1% for liver, and 14.8% for C-reactive protein. Except for lipids, metabolic-component abnormalities were more prevalent in high-risk hosts than in healthy individuals. The prevalence of multiple metabolic abnormalities at the 6-month follow-up was 41.3% and significantly higher in high-risk than healthy hosts (49.2% vs 36.5%; P = 0.007). Factors independently associated with a lower risk of these abnormalities were being female, having dyslipidemia, and receiving at least 3 doses of the COVID-19 vaccine. These findings suggest that multiple metabolic abnormalities are the long-term consequences of COVID-19. For both high-risk and healthy individuals with nonsevere COVID-19, healthcare providers should monitor metabolic profiles, encourage healthy behaviors, and ensure complete vaccination.

Immune Response after SARS-CoV-2 Infection with Residual Post-COVID Symptoms.

Many patients develop post-acute COVID syndrome (long COVID (LC)). We compared the immune response of LC and individuals with post-COVID full recovery (HC) during the Omicron pandemic. Two hundred ninety-two patients with confirmed COVID infections from January to May 2022 were enrolled. We observed anti-SARS-CoV-2 receptor-binding domain immunoglobulin G, surrogate virus neutralization test, T cell subsets, and neutralizing antibodies against Wuhan, BA.1, and BA.5 viruses (NeuT). NeuT was markedly reduced against BA.1 and BA.5 in HC and LC groups, while antibodies were more sustained with three doses and an updated booster shot than ≤2-dose vaccinations. The viral neutralization ability declined at >84-days after COVID-19 onset (PC) in both groups. PD1-expressed central and effector memory CD4+ T cells, and central memory CD8+ T cells were reduced in the first months PC in LC. Therefore, booster vaccines may be required sooner after the most recent infection to rescue T cell function for people with symptomatic LC.

Dynamics of Antibody Responses after Asymptomatic and Mild to Moderate SARS-CoV-2 Infections: Real-World Data in a Resource-Limited Country.

The dynamics of humoral immune responses of patients after SARS-CoV-2 infection is unclear. This study prospectively observed changes in anti-receptor binding domain immunoglobulin G (anti-RBD IgG) and neutralizing antibodies against the Wuhan and Delta strains at 1, 3, and 6 months postinfection between October 2021 and May 2022. Demographic data, clinical characteristics, baseline parameters, and blood samples of participants were collected. Of 5059 SARS-CoV-2 infected adult patients, only 600 underwent assessment at least once between 3 and 6 months after symptom onset. Patients were categorized as immunocompetent (n = 566), immunocompromised (n = 14), or reinfected (n = 20). A booster dose of a COVID-19 vaccine was strongly associated with maintained or increased COVID-19 antibody levels. The booster dose was also more strongly associated with antibody responses than the primary vaccination series. Among patients receiving a booster dose of a mRNA vaccine or a heterologous regimen, antibody levels remained steady or even increased for 3 to 6 months after symptom onset compared with inactivated or viral vector vaccines. There was a strong correlation between anti-RBD IgG and neutralizing antibodies against the Delta variant. This study is relevant to resource-limited countries for administering COVID-19 vaccines 3 to 6 months after infection.

Prevalence and Characteristics of Prediabetes and Metabolic Syndrome in Seemingly Healthy Persons at a Health Check-Up Clinic.

Purpose: This study investigated the prevalence and characteristics of prediabetes (PreDM) and metabolic syndrome (MetS) in seemingly healthy persons attending a health check-up clinic at a tertiary care hospital. Patients and Methods: This was a cross-sectional study that enrolled 1213 subjects (339 male, 874 female) who underwent an annual health check-up at Siriraj Hospital, Bangkok, Thailand from 2009 to 2019. Factors that independently related to PreDM were analyzed using unconditional logistic regression analysis with adjustments for age, BMI, and gender. Results: The prevalence of PreDM and MetS was 54.3% and 19.7% respectively. Participants with impaired fasting glucose (IFG) and glycated hemoglobin (HbA1c) 38.8-46.4 mmol/mol had significantly higher waist circumference (WC) and blood pressure (BP) compared to those with IFG or HbA1c 38.8-46.4 mmol/mol alone (P < 0.05). Among three PreDM subgroups, the average age was lowest in the HbA1c 38.8-46.4 mmol/mol subgroup (P < 0.001). PreDM participants with MetS were older (p = 0.03), had higher WC, BP, fasting plasma glucose and serum triglyceride level (all P < 0.001) but had lower serum high-density lipoprotein (HDL) cholesterol level (P < 0.001). Multivariate analysis revealed high MetS score, obesity, and low serum HDL cholesterol level to be independently associated with PreDM with odds ratios of 9.02 (95% confidence interval [CI]: 4.03-20.18), 1.8 (95% CI: 1.07-3.04), and 1.42 (95% CI: 1.02-1.96), respectively. Conclusion: The prevalence of PreDM and MetS was relatively high in seemingly healthy persons. Distinct PreDM subgroups with or without MetS exhibited diverse clinical and biochemical features suggesting dissimilar pathogenesis.

Cluster analysis of Thai patients with newly diagnosed type 2 diabetes mellitus to predict disease progression and treatment outcomes : A prospective cohort study.

INTRODUCTION: Type 2 diabetes mellitus (T2D) is highly heterogeneous in disease progression and risk of complications. This study aimed to categorize Thai T2D into subgroups using variables that are commonly available based on routine clinical parameters to predict disease progression and treatment outcomes. RESEARCH DESIGN AND METHODS: This was a cohort study. Data-driven cluster analysis was performed using a Python program in patients with newly diagnosed T2D (n=721) of the Siriraj Diabetes Registry using five variables (age, body mass index (BMI), glycated hemoglobin (HbA1c), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C)). Disease progression and risk of diabetic complications among clusters were compared using the Χ2 and Kruskal-Wallis test. Cox regression and the Kaplan-Meier curve were used to compare the time to diabetic complications and the time to insulin initiation. RESULTS: The mean age was 53.4±11.3 years, 58.9% were women. The median follow-up time was 21.1 months (9.2-35.2). Four clusters were identified: cluster 1 (18.6%): high HbA1c, low BMI (insulin-deficiency diabetes); cluster 2 (11.8%): high TG, low HDL-C, average age and BMI (metabolic syndrome group); cluster 3 (23.3%): high BMI, low HbA1c, young age (obesity-related diabetes); cluster 4 (46.3%): older age and low HbA1c at diagnosis (age-related diabetes). Patients in cluster 1 had the highest prevalence of insulin treatment. Patients in cluster 2 had the highest risk of diabetic kidney disease and diabetic retinopathy. Patients in cluster 4 had the lowest prevalence of diabetic retinopathy, nephropathy, and insulin use. CONCLUSIONS: We were able to categorize Thai patients with newly diagnosed T2D into four clusters using five routine clinical parameters. This clustering method can help predict disease progression and risk of diabetic complications similar to previous studies using parameters including insulin resistance and insulin sensitivity markers.

Clinical Characteristics, Glycemic Control, and Microvascular Complications Compared Between Young-Onset Type 1 and Type 2 Diabetes Patients at Siriraj Hospital - A Tertiary Referral Center.

Purpose: This study aimed to investigate the clinical characteristics, glycemic control, and microvascular complications compared between young-onset type 1 (T1DM) and type 2 diabetes (T2DM) patients at Siriraj Hospital. Patients and Methods: We collected demographic, clinical, glycemic control, and microvascular complication data of young-onset (onset <30 years of age) T1DM and T2DM patients at our center using February 2019-December 2020 data from the Thai Type 1 Diabetes and Diabetes diagnosed Age before 30 years Registry, Care and Network (T1DDAR CN). Results: Of 396 patients, 76% had T1DM and 24% had T2DM. At diagnosis, T1DM were significantly younger (9.7±5.4 vs 16.9±6.4 years, p<0.001), had a lower body mass index (17.2±4.1 vs 30.8±7.9 kg/m2, p<0.001), higher prevalence of diabetic ketoacidosis (DKA) (66.1% vs 13.7%, p<0.001), and higher HbA1c level (12.8±2.6% vs 10.9±3.1%, p=0.002) compared to T2DM. Regarding glycemic control, the mean HbA1c at registry enrollment did not differ between groups (T1DM 8.3±1.8% vs T2DM 8.1±2.2%, p=0.303), but T1DM achieved HbA1c <7% significantly less than T2DM (19.3% vs 47.8%, p<0.001). T1DM showed deterioration of glycemic control during 10-20 years of age, and gradually improved during 20-30 years of age, whereas patients with T2DM showed progressive worsening of glycemic control over time. Concerning microvascular complications, the prevalence of diabetic retinopathy (10.6% vs 9%, p=0.92) and diabetic neuropathy (3.4% vs 5.5%, p=0.514) between T1DM and T2DM was not significantly different. However, T2DM had a significantly higher prevalence of diabetic nephropathy (T1DM 10.1% vs T2DM 40.2%, p<0.001) that developed within a significantly shorter duration of diabetes (T1DM 11.0±6.8 vs T2DM 4.3±5.1 years, p<0.001) compared to T1DM. Conclusion: T1DM had a significantly high prevalence of DKA at presentation, and most T1DM did not achieve the glycemic target, especially during adolescence. T2DM had a significantly higher prevalence of diabetic nephropathy that developed within a shorter duration of diabetes compared to T1DM.

Early diagnosis by antigen test kit and early treatment by antiviral therapy: An ambulatory management strategy during COVID-19 crisis in Thailand.

This study aimed to assess the clinical characteristics of patients who registered at the Siriraj Favipiravir Clinic and to share our experiences in this comparatively unique clinical setting. This retrospective study included patients who registered at the Siriraj Favipiravir Clinic during August 11, 2021 to September 14, 2021. Included adult patients were those with severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019 [COVID-19]) infection confirmed by antigen test kit (ATK) or real-time reverse transcription-polymerase chain reaction, no favipiravir contraindication, no prior COVID-19 treatment, and not receiving care from another medical facility. Demographic data and outcomes were collected and analyzed. Of the 1168 patients (mean age: 44.8 ± 16.4 years, 55.7% female) who registered at the clinic, 117 (10%) did not meet the treatment criteria, and 141 (12%) patients did not pick up their medication. One-third of patients had at least 1 symptom that indicated severe disease. Higher proportion of unvaccinated status (56.7% vs 47.5%, P = .005), higher proportion of persons with risk factors for disease progression (37.7% vs 31.3%, P = .028), and longer duration between the date of clinic registration and the date of positive diagnostic test (3 vs 2 days, P = .004) were significantly more commonly observed in the severe disease group compared to the nonsevere disease group. The duration between symptom onset and the date of clinic registration was significantly longer in the real-time reverse transcription-polymerase chain reaction group than in the ATK group (6 vs 4 days, P < .001). Most patients (90.0%) had completed favipiravir treatment regimen. The improvement and mortality rates were 86.7% and 1.2%, respectively. COVID-19 severity is associated with vaccination status, baseline risk factors, and timing between disease detection and treatment. The use of ATK influences patients to seek treatment significantly earlier in ambulatory setting. Our early diagnosis and antiviral treatment strategy yielded favorable results in an outpatient setting during a COVID-19 outbreak in Thailand.

Early antiviral and supervisory dexamethasone treatment improve clinical outcomes of nonsevere COVID-19 patients.

This study aimed to evaluate the efficacy of early antiviral treatment in preventing clinical deterioration in asymptomatic or mildly symptomatic severe acute respiratory syndrome coronavirus 2 infected (COVID-19) patients in home isolation and to share our experiences with the ambulatory management of nonsevere COVID-19 patients. This retrospective study included mild COVID-19 adult patients confirmed by real-time reverse transcription-polymerase chain reaction. They received care via an ambulatory management strategy between July 2021 and November 2021. Demographic data, clinical progression, and outcomes were collected. Both descriptive and inferential statistics were performed to illustrate the cohort's characteristic and outcomes of the study. Univariable and multivariable logistic regression models were employed to investigate the associations between clinical factors and disease progression. A total of 1940 patients in the Siriraj home isolation system met the inclusion criteria. Their mean age was 42.1 ±â€…14.9 years, with 14.2% older than 60 years, 54.3% female, and 7.1% with a body weight ≥ 90 kg. Only 115 patients (5.9%) had deterioration of clinical symptoms. Two-thirds of these could be managed at home by dexamethasone treatment under physician supervision; however, 38 of the 115 patients (2.0% of the study cohort) needed hospitalization. Early favipiravir outpatient treatment (≤ 5 days from onset of symptoms) in nonsevere COVID-19 patients was significantly associated with a lower rate of symptom deterioration than late favipiravir treatment (50 [4.6%] vs 65 [7.5%] patients, respectively; P = .008; odds ratio 1.669; 95% confidence interval, 1.141-2.441). The unfavorable prognostic factors for symptom deterioration were advanced age, body weight ≥ 90 kg, unvaccinated status, higher reverse transcription-polymerase chain reaction cycle threshold, and late favipiravir treatment. The early delivery of essential treatment, including antiviral and supervisory dexamethasone, to ambulatory nonsevere COVID-19 patients yielded favorable outcomes during the COVID-19 pandemic in Thailand.

SARS-CoV-2 Antibody Response against Mild-to-Moderate Breakthrough COVID-19 in Home Isolation Setting in Thailand.

Background: In December 2021, Omicron replaced Delta as the dominant coronavirus disease 2019 (COVID-19) variant in Thailand. Both variants embody diverse epidemiological trends and immunogenicity. We investigated whether Delta and Omicron patients' biological and clinical characteristics and immunogenicity differed post-COVID-19 infection. Methods: This retrospective cohort study investigated the clinical outcomes and laboratory data of 5181 patients with mild-to-moderate COVID-19 (Delta, 2704; Omicron, 2477) under home isolation. We evaluated anti-receptor-binding domain immunoglobulin G (anti-RBD IgG) and surrogate viral neutralizing (sVNT) activity in 495 individuals post-COVID-19 infection during the Delta pandemic. Results: Approximately 84% of all patients received favipiravir. The median cycle threshold (Ct) values were lower for Omicron patients than Delta patients (19 vs. 21; p < 0.001), regardless of vaccination status. Upper respiratory tract symptoms were more frequent with Omicron patients than Delta patients. There were no significant associations between Ct and Omicron symptoms (95% confidence interval 0.98−1.02). A two-dose vaccine regimen reduced hospital readmission by 10% to 30% and death by under 1%. Anti-RBD IgG and sVNT against Delta were higher among older individuals post-COVID-19 infection. Older individuals expressed anti-RBD IgG and sVNT for a more extended period after two-dose vaccination than other age groups. Conclusions: After a full vaccination course, breakthrough mild-to-moderate Delta and Omicron infections have limited immunogenicity. Prior infections exert reduced protection against later reinfection or infection from novel variants. However, this protection may be sufficient to prevent hospitalization and death, particularly in countries where vaccine supplies are limited.

Incidence and Survival of Hepatocellular Carcinoma in Type 2 Diabetes Patients with Cirrhosis Who Were Treated with and without Metformin.

PURPOSE: To evaluate metformin's benefit on the incidence and survival of hepatocellular carcinoma (HCC) in cirrhosis with type 2 diabetes mellitus (T2DM) patients. PATIENTS AND METHODS: We conducted a retrospective study from 2006 to 2019. The patients were assigned to metformin exposure if they administered metformin at least 3 months after diagnosis of cirrhosis. The outcomes were incidence and survival of HCC in T2DM with cirrhosis treated with metformin compared with those who were not treated with metformin. For the incidence of HCC, the follow-up time was 5 years after cirrhosis was diagnosed. For the survival of HCC, we censored for vital status in June 2019. RESULTS: Of 1061 patients, the patients were divided into 719 patients with metformin exposure and 342 in metformin non-exposure. In metformin exposure, 125 patients (17.4%) developed HCC. In metformin non-exposure, 128 patients (37.4%) developed HCC. Metformin exposure had a significantly lower risk of developing HCC in multivariate analysis HR 0.48 (0.36-0.61); P<0.001. For the survival of HCC, 327 patients were recruited. One-hundred and sixty-two patients were in metformin exposure and 165 patients were in metformin non-exposure. Sixty patients (37%) in metformin exposure died, while 84 patients (50.9%) in metformin non-exposure died. The median survival of metformin exposure and metformin non-exposure were 6.9 years and 3.88 years, respectively; P=0.003. In univariate analysis, the metformin exposure was significantly associated with better survival than in the non-exposure group, HR 0.63 (0.45-0.88); P=0.006. No significant difference was observed in multivariate analysis between two groups, HR 1.07 (0.74-1.54); P=0.72. CONCLUSION: Metformin exposure was associated with a lower incidence of HCC in cirrhosis with T2DM patients and seemed to extend survival. Continuing metformin in patients with cirrhosis with T2DM should be considered if there was no contraindication.