Transcriptional profiles associated with coronary artery disease in type 2 diabetes mellitus.

Background: Coronary artery disease (CAD) is a common complication of Type 2 diabetes mellitus (T2DM). Understanding the pathogenesis of this complication is essential in both diagnosis and management. Thus, this study aimed to characterize the presence of CAD in T2DM using molecular markers and pathway analyses. Methods: The study is a sex- and age-frequency matched case-control design comparing 23 unrelated adult Filipinos with T2DM-CAD to 23 controls (DM with CAD). Healthy controls served as a reference. Total RNA from peripheral blood mononuclear cells (PBMCs) underwent whole transcriptomic profiling using the Illumina HumanHT-12 v4.0 expression beadchip. Differential gene expression with gene ontogeny analyses was performed, with supporting correlational analyses using weighted correlation network analysis (WGCNA). Results: The study observed that 458 genes were differentially expressed between T2DM with and without CAD (FDR<0.05). The 5 top genes the transcription factor 3 (TCF3), allograft inflammatory factor 1 (AIF1), nuclear factor, interleukin 3 regulated (NFIL3), paired immunoglobulin-like type 2 receptor alpha (PILRA), and cytoskeleton-associated protein 4 (CKAP4) with AUCs >89%. Pathway analyses show differences in innate immunity activity, which centers on the myelocytic (neutrophilic/monocytic) theme. SNP-module analyses point to a possible causal dysfunction in innate immunity that triggers the CAD injury in T2DM. Conclusion: The study findings indicate the involvement of innate immunity in the development of T2DM-CAD, and potential immunity markers can reflect the occurrence of this injury. Further studies can verify the mechanistic hypothesis and use of the markers.

Variants of SLC2A10 may be Linked to Poor Response to Metformin.

Purpose: A study among Filipinos revealed that only 15% of patients with diabetes achieved glycemic control, and poor response to metformin could be one of the possible reasons. Recent studies demonstrate how genetic variations influence response to metformin. Hence, the present study aimed to determine genetic variants associated with poor response to metformin. Methods: Using a candidate variant approach, 195 adult Filipino participants with newly diagnosed type 2 diabetes mellitus (T2DM) were enrolled in a case-control study. Genomic DNA from blood samples were collected. Allelic and genotypic associations of variants with poor response to metformin were determined using exact statistical methods. Results: Several polymorphisms were nominally associated with poor response to metformin (P uncorr < 0.05). The most notable is the association of multiple variants in the SLC2A10 gene-rs2425911, rs3092412, and rs2425904-with common additive genetic mode of inheritance. Other variants that have possible associations with poor drug response include rs340874 (PROX-AS1), rs815815 (CALM2), rs1333049 (CDKN2B-AS1), rs2010963 (VEGFA), rs1535435 and rs9494266 (AHI1), rs11128347 (PDZRN3), rs1805081 (NPC1), and rs13266634 (SLC30A8). Conclusion: In Filipinos, a trend for the association for several variants was noted, with further observation that several mechanisms may be involved. The results may serve as pilot data for further validation of candidate variants for T2DM pharmacotherapy.

Executive summary of the 2020 clinical practice guidelines for the management of hypertension in the Philippines.

Hypertension is the most common cause of death and disability worldwide with its prevalence rising in low to middle income countries. It remains to be an important cause of morbidity and mortality in the Philippines with poor BP control as one of the main causes. Different societies and groups worked and collaborated together to develop the 2020 Philippine Clinical Practice Guidelines of hypertension arising for the need to come up with a comprehensive local practice guideline for the diagnosis, treatment, and follow up of persons with hypertension. A technical working group was organized into six clusters that analyzed the 30 clinical questions commonly asked in practice, looking into the definition of hypertension, treatment thresholds, blood pressure targets, and appropriate medications to reach targets. This guideline also includes recommendations for the specific management of hypertension among individuals with uncomplicated hypertension, hypertension among those with diabetes, stroke, chronic kidney disease, as well as hypertension among pregnant women and pediatric populations. It also looked into the appropriate screening and monitoring of patients when managing hypertension, and identification of groups who are at high risk for cardiovascular (CV) events. The ADAPTE process was used in developing the statements and recommendations which were then presented to a panel of experts for discussion and approval to come up with the final statements. This guideline aims to aid Filipino healthcare professionals to provide evidence-based care for persons with hypertension and help those with hypertension adequately control their blood pressure and reduce their CV risk.

Adiponectin levels and its association with hyperglycaemia in adult Filipino participants in the 2003--04 National Nutrition and Health Survey.

Our objective was to determine the association of serum adiponectin levels with the presence of IFG or DM in Filipinos. This case control study used sera of adult participants in the Philippines' NNHeS: 2003-04. Subjects were divided into: normoglycaemic control, impaired fasting glucose, and type 2 diabetes mellitus. Seventy-seven prediabetic and 83 diabetic subjects were included in the prediabetic and diabetic groups, respectively. There was no significant difference in adiponectin values between control and prediabetic subjects. Diabetic subjects had significantly lower mean serum adiponectin levels (10.7 versus 14.2 microg/ml, p=0.0198) compared with age- and BMI-matched control subjects. Diabetic subjects were found most frequently (43.53%) in the lowest tertile (1.6-7.2 microg/ml) and least frequently (20%) in the highest tertile (14-84 microg/ml) of adiponectin values. We conclude that Filipinos with diabetes mellitus had significantly lower adiponectin levels compared with normoglycaemic subjects.