Real-world evaluation of care for type 2 diabetes in Malaysia: A cross-sectional analysis of the treatment adherence to guideline evaluation in type 2 diabetes (TARGET-T2D) study.

AIM: Given a lack of data on diabetes care performance in Malaysia, we conducted a cross-sectional study to understand the clinical characteristics, control of cardiometabolic risk factors, and patterns of use of guideline-directed medical therapy (GDMT) among patients with type 2 diabetes (T2D), who were managed at publicly-funded hospitals between December 2021 and June 2022. METHODS: Patients aged ≥18 years with T2D from eight publicly-funded hospitals in the Greater Kuala Lumpur region, who had ≥2 outpatient visits within the preceding year and irrespective of treatment regimen, were eligible. The primary outcome was ≥2 treatment target attainment (defined as either HbA1c <7.0%, blood pressure [BP] <130/80 mmHg, or low-density lipoprotein cholesterol [LDL-C] <1.8 mmol/L). The secondary outcomes were the individual treatment target, a combination of all three treatment targets, and patterns of GDMT use. To assess for potential heterogeneity of study findings, all outcomes were stratified according to prespecified baseline characteristics namely 1) history of atherosclerotic cardiovascular disease (ASCVD; yes/no) and 2) clinic type (Diabetes specialist versus General medicine). RESULTS: Among 5094 patients (mean±SD age 59.0±13.2 years; T2D duration 14.8±9.2 years; HbA1c 8.2±1.9% (66±21 mmol/mol); BMI 29.6±6.2 kg/m2; 45.6% men), 99% were at high/very high cardiorenal risk. Attainment of ≥2 treatment targets was at 18%, being higher in General medicine than in Diabetes specialist clinics (20.8% versus 17.5%; p = 0.039). The overall statin coverage was 90%. More patients with prior ASCVD attained LDL-C <1.4 mmol/L than those without (13.5% versus 8.4%; p<0.001). Use of sodium-glucose cotransporter-2 (SGLT2) inhibitors (13.2% versus 43.2%), glucagon-like peptide-1 receptor agonists (GLP1-RAs) (1.0% versus 6.2%), and insulin (27.7% versus 58.1%) were lower in General medicine than in Diabetes specialist clinics. CONCLUSIONS: Among high-risk patients with T2D, treatment target attainment and use of GDMT were suboptimal.

Combination of multiplex PCR and DHPLC-based strategy for CYP2D6 genotyping scheme in Thais.

OBJECTIVE: To develop CYP2D6 genotyping scheme for accurate allele calling and reliable estimation of functional allele dosage in Thais. DESIGN AND METHODS: We analyzed CYP2D6 copy numbers by pentaplex PCR coupled with semi-quantitative denaturing high performance liquid chromatography (DHPLC)-based technique. Ten common SNPs were genotyped from CYP2D6 gene product using single base extension (SBE) followed by DHPLC analysis. This detection scheme was compared with real-time PCR and conventional PCR-RFLP for cost-effectiveness. RESULTS: The distribution of CYP2D6 gene copy numbers in our population ranged from zero (0.69%), one (7.99%), two (60.07%), three (28.13%) and four (3.13%). The most commonly detected SNPs were related to CYP2D6*10 haplotype. CYP2D6*36 in tandem with CYP2D6*10B is the major rearrangement type in Thais (18.75%). CONCLUSIONS: Multiplex PCR coupled with DHPLC-based strategy is convenient and reliable method for CYP2D6 genotyping offering sufficient allele coverage for Asians. Both cost and analytical time saving were shown and the method could potentially be modified to accommodate CYP2D6 genotyping in other ethnics.

RExPrimer: an integrated primer designing tool increases PCR effectiveness by avoiding 3' SNP-in-primer and mis-priming from structural variation.

BACKGROUND: Polymerase chain reaction (PCR) is very useful in many areas of molecular biology research. It is commonly observed that PCR success is critically dependent on design of an effective primer pair. Current tools for primer design do not adequately address the problem of PCR failure due to mis-priming on target-related sequences and structural variations in the genome. METHODS: We have developed an integrated graphical web-based application for primer design, called RExPrimer, which was written in Python language. The software uses Primer3 as the primer designing core algorithm. Locally stored sequence information and genomic variant information were hosted on MySQLv5.0 and were incorporated into RExPrimer. RESULTS: RExPrimer provides many functionalities for improved PCR primer design. Several databases, namely annotated human SNP databases, insertion/deletion (indel) polymorphisms database, pseudogene database, and structural genomic variation databases were integrated into RExPrimer, enabling an effective without-leaving-the-website validation of the resulting primers. By incorporating these databases, the primers reported by RExPrimer avoid mis-priming to related sequences (e.g. pseudogene, segmental duplication) as well as possible PCR failure because of structural polymorphisms (SNP, indel, and copy number variation (CNV)). To prevent mismatching caused by unexpected SNPs in the designed primers, in particular the 3' end (SNP-in-Primer), several SNP databases covering the broad range of population-specific SNP information are utilized to report SNPs present in the primer sequences. Population-specific SNP information also helps customize primer design for a specific population. Furthermore, RExPrimer offers a graphical user-friendly interface through the use of scalable vector graphic image that intuitively presents resulting primers along with the corresponding gene structure. In this study, we demonstrated the program effectiveness in successfully generating primers for strong homologous sequences. CONCLUSION: The improvements for primer design incorporated into RExPrimer were demonstrated to be effective in designing primers for challenging PCR experiments. Integration of SNP and structural variation databases allows for robust primer design for a variety of PCR applications, irrespective of the sequence complexity in the region of interest. This software is freely available at http://www4a.biotec.or.th/rexprimer.