Nattachet Plengvidhya

Type 2 diabetes is a heterogeneous disease with strong genetic components. We showed earlier that newly diagnosed type 2 diabetes in Thai patients could be categorized into four clusters. This study aimed to determine the evidence of hereditary factors in these type 2 diabetes clusters. A total of 487 subjects who were diagnosed with type 2 diabetes in two years were enrolled in the Siriraj Diabetes Center, Siriraj Hospital Bangkok, Bangkok, Thailand. They were divided into four clusters as previously described. The associations between patients' characteristics, degree of family history of diabetes (FHD), and type 2 diabetes clusters were tested using multinomial logistic regression. Among four clusters of newly diagnosed type 2 diabetes, there were significant differences in characteristics at baseline, including age at diagnosis, BMI, waist circumference, blood sugar levels, vital signs, triglyceride, HDL, calculated LDL, creatinine and eGFR (all p < .05). A relatively young age at the time of diabetes diagnosis was associated with having second-degree relatives with diabetes (p < .05) in all clusters when using mild age-related diabetes (MARD) cluster with no FHD as a control. Patients in the severe insulin-deficient diabetes (SIDD) cluster had more first-degree relatives with diabetes (odds ratio = 1.85; p = .0354), while patients in the metabolic syndrome diabetes (MSD) cluster (odds ratio = 10.73; p < .001) and the mild obesity-related diabetes (MOD) group (odds ratio = 6.66; p = .002), had more second-degree relatives with diabetes. Genetic factors might have various roles in the pathogenesis of type 2 diabetes, at least in newly diagnosed Thai patients. Our findings supported that genetic heterogeneity contributed to clinical heterogeneity or four different clusters. Further studies are needed in a larger sample size of these patients is needed to identify genetic loci associated with each cluster.

Aims/hypothesis: Type 1 diabetes is categorised into autoantibody positive and autoantibody negative. Most type 1 diabetes research has focused on European populations, leaving a gap in understanding in relation to other ethnic groups, including Thai populations. This lack of data is significant given Thailand’s poor prevention and therapeutic management strategies. We aimed to investigate the frequency and distribution of islet autoantibodies among Thai individuals with long-standing type 1 diabetes diagnosed before the age of 30 years. Methods: We conducted a nationwide population-based study involving 48 hospitals in Thailand from May 2020 to September 2023, enrolling 953 participants. Demographic and clinical characteristics of individuals with autoantibody-positive and -negative type 1 diabetes were analysed. The autoantibodies GAD65, IA-2 and ZnT8 were measured using ELISA. A random C-peptide level was detected by electrochemiluminescence immunoassay. Results: Thai individuals with autoantibody-negative type 1 diabetes comprised 34.2% of the population. Among all individuals, the frequency of GAD65, IA-2 and ZnT8 was 56%, 37% and 33%, respectively. Autoantibody-negative individuals with type 1 diabetes were older at diagnosis, had higher BMI and had higher random C-peptide levels compared with autoantibody-positive individuals with type 1 diabetes. Female individuals had a higher prevalence of type 1 diabetes than male individuals (58% vs 42%; p=1.531 × 10⁻⁵). The southern region of Thailand exhibited a distinct pattern of autoantibody frequency compared with other regions (p=0.0001561). Conclusions/interpretation: The frequency, distribution and characteristics of autoantibody-positive and -negative long-standing type 1 diabetes in Thailand showed uniqueness from other populations. This provides insight into the disease that may have implications for type 1 diabetes prediction, treatment and pathogenesis, especially in the Southeast Asian population. Graphical

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 (HbA_1c) 38.8– 46.4 mmol/mol had significantly higher waist circumference (WC) and blood pressure (BP) compared to those with IFG or HbA_1c 38.8– 46.4 mmol/mol alone (P < 0.05). Among three PreDM subgroups, the average age was lowest in the HbA_1c 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.

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 HbA_1c level (12.8± 2.6% vs 10.9± 3.1%, p=0.002) compared to T2DM. Regarding glycemic control, the mean HbA_1c 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 HbA_1c < 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.

BACKGROUND Maturity-onset diabetes of the young (MODY) is the most common form of monogenic diabetes. The disease is transmitted in autosomal dominant mode and diabetes is usually diagnosed before age 25 year. MODY 3 is caused by mutation of hepatocyte nuclear factor (HNF) 1A genes and is the most common MODY subtype. Diagnosis of MODY 3 is crucial since glycemic control can be accomplished by very low dose of sulfonylurea. In this report we described a Thai MODY 3 patient who had excellence plasma glucose control by treating with glicazide 20 mg per day and insulin therapy can be discontinued. CASE SUMMARY A 31-year-old woman was diagnosed diabetes mellitus at 14 years old. The disease was transmitted from her grandmother and mother compatible with autosomal dominant inheritance. Sanger sequencing of proband's DNA identified mutation of HNF1A at codon 203 which changed amino add from arginine to cysteine (R203C). This mutation was carried only by family members who have diabetes. The patient has been treated effectively with a combination of oral hypoglycemic agents and must include a very low dose of glicazide (20 mg/d). Insulin therapy was successfully discontinued. CONCLUSION We demonstrated a first case of pharmacogenetics in Thai MODY 3 patient. Our findings underscore the essential role of molecular genetics in diagnosis and guidance of appropriate treatment of diabetes mellitus in particular patient.