Mauro Gitto1,2 · Federica Catapano1,2 · Marco Francone1,2 · Gianluca Mincione1,2 · Vincenzo Scialò1,2 ·Carlo A. Pivato1,2 · Costanza Lisi1,2 · Damiano Regazzoli1,2 · Davide Cao1,2 · Roberta Maria Fiorina1  ·Alessandra Petrelli3,4 · Loredana Bucciarelli4  · Cristian Loretelli3,4 · Gianluigi Condorelli1,2 · Paolo Fiorina3,4,5 · Giulio Stefanini1,2

Received: 4 October 2025 / Accepted: 15 October 2025 / Published online: 4 November 2025 © The Author(s) 2025

Abstract

Background Despite advances in therapeutic strategies a significant proportion of acute coronary syndrome (ACS) patients experience early coronary artery disease (CAD) progression, particularly those with diabetes.

Aim To evaluate CAD progression in diabetic patients treated with glucagon-like peptide 1 receptor agonists (GLP-1Ra) over 1 year after an ACS.

Methods Patients presenting with non–ST-elevation ACS between 2019 and 2022 were enrolled in a prospective registry and underwent serial coronary computed tomography angiography (CCTA) at baseline (after revascularization, during the index hospitalization) and at 1-year follow-up. The primary endpoint was the absolute change (1 year – baseline) in non-culprit lesion plaque burden (ΔPB) on CCTA, with the absolute change in patient percent atheroma volume (ΔPAV) as a key secondary endpoint. A comprehensive lipidomic, metabolomic, and proteomic plasma assessment was also performed in all GLP-1Ra–treated patients and four randomly selected controls.

Results Of 28 diabetic patients, 7 (25%) with 22 coronary plaques were treated with GLP-1Ra, and 21 (75%) with 65 plaques received other antidiabetic agents. In the 1-year observation frame, both ΔPB (-5.8±12.8% vs. -1.1±13.6%, p=0.041) and ΔPAV (-6.1% [-7.3, -1.8] vs. -0.7% [-2.4, 9.8], p=0.039) were significantly lower in GLP-1Ra-treated patients. Total atheroma volume also showed a numerically greater reduction in the GLP-1Ra cohort (0.7 mm³ [-2.5-8.7] vs. 25.0 mm³ [4.8–39.7]), primarily due to a decrease in plaque fibrofatty volume percentage (-2.9±10.1% vs. 1.0±6.8%, p=0.042). Lipi-domic, metabolomic, and proteomic analyses identified reductions in monoacylglycerols and triacylglycerols, increases in diacylglycerols and phosphatidylethanolamine, a shift from carbohydrate metabolism toward lipid metabolism and hormone regulation, and differential expression of proteins involved in complement activation, endothelial function, and cytoskeletal organization in GLP-1Ra–treated patients compared with controls.

Conclusions In diabetic patients with ACS, GLP-1Ra therapy was associated with a significant regression in coronary plaque burden at 1 year, supported by favorable lipidomic, metabolomic, and proteomic changes. These findings suggest a potential role for GLP-1Ra in modifying atherosclerosis progression beyond glycemic control.

Keywords GLP-1 receptor agonists · Diabetes mellitus · Coronary artery disease · Acute coronary syndrome · Plaque regression

Jui M. Desai1  · Lisa R. Letourneau-Freiberg1  · Kristen E. Wroblewski2  · Megan N. Scott3  · Michael E. Msall4  · Siri Atma W. Greeley1,4

Received: 27 February 2025 / Accepted: 4 October 2025 / Published online: 27 January 2026 © The Author(s) 2026

Abstract

Aims Neonatal diabetes mellitus (NDM) occurs before 6–12 months of age and is commonly caused by activating mutations in KCNJ11 (KCNJ11-NDM) or ABCC8. Because of brain expression of these mutant ATP-dependent potassium channels, a spectrum of divergent neurodevelopmental difficulties have been described, including developmental delay, epilepsy, and neonatal diabetes (DEND). However, information on anxiety, social responsiveness, and grit is limited.

Methods Individuals with KCNJ11-NDM (N= 12) and their unaffected siblings (N=12) were recruited through the Uni-versity of Chicago Monogenic Diabetes Registry and participants or their parent/caregiver completedthe Screen for Adult/ Child Anxiety Related Disorder (SCAARED/SCARED), the Social Responsiveness Scale, Second Edition (SRS-2), and the Grit Scale.

Results Mean SRS-2 scores were significantly different between KCNJ11-NDM and sibling controls (P= <0.001 ), with 7/10 affected participants, and 0 /11 siblings, having scores suggestive of autism spectrum disorder (ASD). Differences in anxiety (P=0.69) and grit (P=0.46) were not significant when compared to sibling controls; however, 58% (7/12) of KCNJ11-NDM participants and 40% (4/10) of sibling controls had scores indicating an anxiety disorder by either self- or parent-report.

Conclusions Our results agree with previous studies suggesting significant difficulties with social functioning in KCNJ11- NDM, with 7/10 participants having scores suggestive of ASD, strongly reinforcing the need for early neurodevelopmental screening to allow for prompt support. Our report adds to the knowledge of this population in finding robust grit scores but with a high level of anxiety in both KCNJ11-NDM and unaffected siblings. Although families affected by KCNJ11-NDM may have a high risk of anxiety disorders, it is encouraging that affected and unaffected children exhibit robust self-resiliency that will help support functioning through the challenges of life. Study of additional individuals will help to clarify specific challenges, long-term outcomes, and best approaches for monitoring and support.

Keywords Diabetes mellitus · Potassium channels · Brain · Anxiety · Resilience · Genetics

Daniel Norman1  · Joey Lau1

Received: 22 March 2025 / Accepted: 18 January 2026 © The Author(s) 2026

Abstract

Background Laser capture microdissection (LCM) followed by RNA-sequencing is a powerful, widely applicable tool to analyze the transcriptome in regions of a tissue. Protocols for LCM of transplanted islets of Langerhans, particularly stem cell-derived islets (SC-islets) that have evaluated RNA quality, are lacking. This study demonstrates a robust protocol for LCM of SC-islets in multiple organ sites, generating high quality RNA.

Method SC-islets were transplanted to five organ sites in immunodeficient NOG-mice. Graft-containing organs were then sectioned, fixed in 75% ethanol, stained with the alcohol-based stain cresyl violet, and dehydrated before performing LCM. RNA was then extracted, and quality control was performed.

Results High RIN scores (RNA Integrity Number) were obtained from all organ sites, with the pancreas showing the most robust results, despite its known challenges due to high RNase content. Conversely, organs with small or dispersed grafts, such as the liver and omentum, exhibited lower RIN scores. This is likely due to the size of the dissected area correlating positively with RIN scores, potentially due to a more time-consuming LCM in these sites.

Conclusion Using this novel protocol, high-quality RNA from transplanted SC-islets can be obtained. Smaller and spread-out grafts pose a challenge in obtaining higher quality RNA, although possible.

Keywords Laser capture microdissection · Stem cell-derived islets · RNA quality · Transplantation · Type 1 diabetes

Honghong Zhang¹ · Changlin Zhai¹ · Huilin Hu¹ · Gang Qian¹ · Menghui Mao¹

Received: 1 November 2025 / Accepted: 18 January 2026©The Author(s) 2026

Abstract

Objective This study aimed to investigate gut microbiota composition and metabolic functions in patients with type 2 diabetes mellitus (DM) complicated by myocardial infarction (MI) and to explore potential mechanisms linking the gut microbiome to MI development.

Methods Sixty patients with DM complicated by MI and 52 patients with DM alone were initially recruited.After quality control, 29 DM +MI patients and 33 DM patients were included in the final analysis. Gut microbial profiles were characterized using shotgun metagenomic sequencing and bioinformatics analyses. Microbial diversity, composition, and gene functions were compared between groups based on KEGG, COG, and CAZy annotations.

Results Overall microbial diversity and metabolic profiles were comparable between the two groups; however, significant differences were observed in specific taxa and functional genes.Taxa enriched in the DM +MI group included Bacteroidales, Prevotellaceae, and Lachnospiraceae. In total, 510 KEGG orthology (KO) units and 21 pathways—including ABC transporters, quorum sensing, and general metabolic pathways—differed significantly between groups. Carbohydrate transport and metabolism, as well as glycoside hydrolase activity, represented the most enriched functional categories. Random forest models based on selected microbial species,KO units, and KEGG pathways achieved areas under the curve (AUCs) of0.868, 0.885, and 0.820, respectively.

Conclusion Patients with DM complicated by MI exhibit distinct gut microbial compositions and functional gene signatures compared with patients with DM alone. These microbiome-based markers may contribute to early risk stratification and provide potential targets for microbiota-focused interventions to mitigate MI risk in patients with diabetes.

Keywords Gut microbiome · Type 2 diabetes mellitus · Myocardial infarction · Metagenomics