INSIGHT of Medicine(phase 20,2024)


1.Prevalence of diabetic kidney disease and the associated factors among patients with type 2 diabetes in a multi-ethnic Asian country

DOI: 10.1038/s41598-024-57723-6

A cross-sectional study was conducted in Malaysia to determine the prevalence of diabetic kidney disease (DKD) and its associated risk factors in patients with type 2 diabetes (T2D). Using data from the National Diabetes Registry, DKD was defined based on albuminuria, decreased glomerular filtration rate, or both. The study included 80,360 patients, with a majority being female (62.2%), Malay (68.4%), and an average age of 61.4 years. The prevalence of DKD among T2D patients was found to be 56.7%. Several risk factors associated with DKD were identified, including increasing age, male sex, Malay ethnicity, longer duration of diabetes, obesity, hypertension, diabetic complications (such as retinopathy and foot ulcer), cardiovascular diseases, poor glucose control, and non-achievement of lipid targets. The findings highlight the importance of targeted interventions to manage modifiable risk factors and prevent the progression of DKD in Malaysia.

2.Integration of polygenic and gut metagenomic risk prediction for common diseases

DOI: 10.1038/s43587-024-00590-7

In a population-based cohort study with long-term e-health record follow-up, the researchers explored the potential of combining genomic and gut metagenomic risk assessment with conventional risk factors for predicting several common diseases. The study focused on coronary artery disease (CAD), type 2 diabetes (T2D), Alzheimer's disease, and prostate cancer. They found that polygenic risk scores (PRSs) based on genomic data enhanced prediction compared to conventional risk factors for all diseases. Gut microbiome scores also improved predictive capacity for CAD, T2D, and prostate cancer when combined with age. Ultimately, integrated risk models that combined PRSs, gut microbiome scores, and conventional risk factors demonstrated the highest predictive performance for all diseases studied, surpassing models based solely on conventional risk factors. This study demonstrates the potential of integrated multiomics approaches in improving risk prediction for common chronic diseases.

3.Visit to visit transition in TXNIP gene methylation and the risk of type 2 diabetes mellitus: a nested case-control study

DOI: 10.1038/s10038-024-01243-8

This study aimed to explore the relationship between changes in methylation levels of the TXNIP gene and the risk of developing type 2 diabetes mellitus (T2DM). The study included 263 individuals who developed T2DM and 263 non-T2DM individuals for comparison. The participants were categorized into different transition groups based on the methylation levels of five specific loci on the TXNIP gene. The findings revealed that individuals who maintained high methylation levels at these loci had a significantly reduced risk of T2DM compared to those with consistently low methylation levels. The reduction in T2DM risk ranged from 61% to 87% across the different loci. The study suggests that maintaining higher methylation levels of specific loci on the TXNIP gene may serve as a potential preventive measure against the development of T2DM.

4.Spatial enhancer activation influences inhibitory neuron identity during mouse embryonic development

DOI: 10.1038/s41593-024-01611-9

In this study, researchers aimed to understand how genetic information in the embryonic basal ganglia determines the development of distinct GABAergic projection neuron and interneuron types in the mammalian telencephalon. Using in vivo CRISPR perturbation, lineage tracing, and ChIP-sequencing analyses, they focused on the transcription factor MEIS2 and its role in cell fate specification. The study found that MEIS2 promotes the development of projection neurons by binding enhancer regions in projection-neuron-specific genes. This activity of MEIS2 requires the presence of DLX5, a homeodomain transcription factor. On the other hand, the transcription factor LHX6 represses the MEIS2-DLX5-dependent activation of projection-neuron-specific enhancers in interneuron precursors. Mutations in Meis2 led to decreased activation of regulatory enhancers, affecting GABAergic differentiation. Overall, the results propose a model where specific transcription factor binding at regulatory elements determines differential gene expression programs, influencing cell fate specification in the mouse ganglionic eminence.

5.Development and characterization of liposomal formulations containing sesquiterpene lactones for the treatment of chronic gout

DOI: 10.1038/s41598-024-57663-1

In this study, researchers aimed to develop liposomal formulations containing eremantholide C and goyazensolide, which are potential therapeutic agents for gout and hyperuricemia. The formulations were characterized and evaluated for encapsulation efficiency, stability, and potential toxicity in Caco-2 cells, as well as their anti-hyperuricemic activity in rats. The liposomal formulations exhibited stability, with efficient encapsulation of the sesquiterpene lactones, indicating their potential for sustained release. They did not exert toxicity in the tested cells but demonstrated an antiproliferative effect. In vivo experiments showed that the liposomes effectively reduced serum uric acid levels. This study represents a promising advancement in the treatment of gout and hyperuricemia, as the liposomal formulations successfully reduced the toxicity associated with the therapeutic agents while maintaining their therapeutic effects.