World Journal of Diabetes最新文献

Background: Synaptotagmins (SYTs) are a family of 17 membrane transporters that function as calcium ion sensors during the release of Ca²⁺-dependent neurotransmitters and hormones. However, few studies have reported whether members of the SYT family play a role in glucose uptake in diabetic retinopathy (DR) through Ca²⁺/glucose transporter-1 (GLUT1) and the possible regulatory mechanism of SYTs.

Aim: To elucidate the role of the SYT family in the regulation of glucose transport in retinal pigment epithelial cells and explore its potential as a therapeutic target for the clinical management of DR.

Methods: DR was induced by streptozotocin in C57BL/6J mice and by high glucose medium in human retinal pigment epithelial cells (ARPE-19). Bioinformatics analysis, reverse transcriptase-polymerase chain reaction, Western blot, flow cytometry, ELISA, HE staining, and TUNEL staining were used for analysis.

Results: Six differentially expressed proteins (SYT2, SYT3, SYT4, SYT7, SYT11, and SYT13) were found between the DR and control groups, and SYT4 was highly expressed. Hyperglycemia induces SYT4 overexpression, manipulates Ca²⁺ influx to induce GLUT1 fusion with the plasma membrane, promotes abnormal expression of the glucose transporter GLUT1 and excessive glucose uptake, induces ARPE-19 cell apoptosis, and promotes DR progression. Parkin deficiency inhibits the proteasomal degradation of SYT4 in DR, resulting in SYT4 accumulation and enhanced GLUT1 fusion with the plasma membrane, and these effects were blocked by oe-Parkin treatment. Moreover, dysregulation of the myelin transcription factor 1 (Myt1)-induced transcription of SYT4 in DR further activated the SYT4-mediated stimulus-secretion coupling process, and this process was inhibited in the oe-MYT1-treated group.

Conclusion: Our study reveals the key role of SYT4 in regulating glucose transport in retinal pigment epithelial cells during the pathogenesis of DR and the underlying mechanism and suggests potential therapeutic targets for clinical DR.

Therapy with glucagon-like peptide 1 (GLP1) receptor agonists has raised great interest for its beneficial cardiovascular effects in preventing atherosclerosis and heart failure-related outcomes. However, while evidence about atherosclerosis consistently suggests a cardioprotective potential with class effect, controversies remain on its impact on heart failure. GLP1 receptor agonists appear to prevent hospitalization for new-onset heart failure and reduce symptoms in heart failure with preserved ejection fraction (as demonstrated by the recent STEP-HFpEF Trial). Still, GLP1 agonism has resulted in neutral or even harmful effects in patients with established heart failure with reduced ejection fraction (the LIVE trial). GLP1 receptor agonists benefit the cardiovascular system indirectly through their marked metabolic effects (improved weight management, glycemic control, blood pressure, systemic and tissue inflammation), while direct effects on the heart have been questioned. Nonetheless, weight loss alone achieved through GLP1 receptor agonists has failed in improving left ventricular functions. Tirzepatide is a dual agonist of GLP1 and glucose-dependent insulinotropic polypeptide, representing an innovative treatment option in diabetes with a major impact on weight loss and promising cardiovascular benefits. Whether this class of therapies is going to change the history of heart failure is an ongoing debate.

In this editorial, we comment on the article by Liu et al published in the recent issue of the World Journal of Diabetes (Relationship between GCKR gene rs780094 polymorphism and type 2 diabetes with albuminuria). Type 2 diabetes mellitus (T2DM) is a chronic disorder characterized by dysregulated glucose homeostasis. The persistent elevated blood glucose level in T2DM significantly increases the risk of developing severe complications, including cardiovascular disease, re-tinopathy, neuropathy, and nephropathy. T2DM arises from a complex interplay between genetic, epigenetic, and environmental factors. Global genomic studies have identified numerous genetic variations associated with an increased risk of T2DM. Specifically, variations within the glucokinase regulatory protein (GCKR) gene have been linked to heightened susceptibility to T2DM and its associated complications. The clinical trial by Liu et al further elucidates the role of the GCKR rs780094 polymorphism in T2DM and nephropathy development. Their findings demonstrate that individuals carrying the CT or TT genotype at the GCKR rs780094 locus are at a higher risk of developing T2DM with albuminuria compared to those with the CC genotype. These findings highlight the importance of genetic testing and risk assessment in T2DM to develop effective preventive strategies and personalized treatment plans.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are a growing health burden across a significant portion of the global patient population. However, these conditions seem to have disparate rates and outcomes between different ethnic populations. The combination of MASLD/MASH and type 2 diabetes increases the risk of hepatocellular carcinoma (HCC), and Hispanic patients experience the greatest burden, particularly those in South Texas.

Aim: To compare outcomes between Hispanic and non-Hispanic patients in the United States, while further focusing on the Hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a function of geographical circumstance or if there is a more widespread reason that all clinicians must account for in prognostic consideration.

Methods: This cohort analysis was conducted with data obtained from TriNetX, LLC ("TriNetX"), a global federated health research network that provides access to deidentified medical records from healthcare organizations worldwide. Two cohort networks were used: University of Texas Medical Branch (UTMB) hospital and the United States national database collective to determine whether disparities were related to geographic regions, like Southeast Texas.

Results: This study findings revealed Hispanics/Latinos have a statistically significant higher occurrence of HCC, type 2 diabetes mellitus, and liver fibrosis/cirrhosis in both the United States and the UTMB Hispanic/Latino groups. All-cause mortality in Hispanics/Latinos was lower within the United States group and not statistically elevated in the UTMB cohort.

Conclusion: This would appear to support that Hispanic patients in Southeast Texas are not uniquely affected compared to the national Hispanic population.