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Biochemical Perspectives on Diabetes

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 25 October 2026 | Viewed by 422

Editor


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Guest Editor
ASST Mantova, Specialistica Ambulatoriale Branca Diabetologia, Strada Lago Paiolo 10, 46100 Mantova, Italy
Interests: type 2 diabetes; cardiometabolic risk; metabolic biomarkers; insulin resistance; obesity; MASLD/NAFLD; diabetic complications; real-world clinical research

Special Issue Information

Dear Colleagues,

This Special Issue will provide an updated biochemical perspective on diabetes, spanning from molecular mechanisms to clinically relevant biomarkers and therapeutic implications. We welcome original research, reviews, and translational contributions exploring glucose metabolism, insulin resistance, beta-cell dysfunction, inflammation, oxidative stress, lipid abnormalities, and the biochemical basis of diabetes-related complications. A particular emphasis will be placed on studies addressing cardiovascular, renal, and hepatic involvement, as well as novel laboratory markers that may improve risk stratification, early diagnosis, and personalized treatment. Contributions focused on emerging pathways, metabolic phenotyping, obesity-related mechanisms, and innovative therapeutic targets are also encouraged. By integrating basic, translational, and clinical evidence, this Special Issue will offer a comprehensive overview of the biochemical complexity of diabetes and stimulate multidisciplinary discussions on how biochemical insights can support better prevention, monitoring, and management of the disease.

Dr. Antonio Maria Labate
Guest Editor

Manuscript Submission Information

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Keywords

  • diabetes
  • biochemistry
  • biomarkers
  • insulin resistance
  • cardiometabolic risk
  • inflammation
  • oxidative stress
  • diabetic complications

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Published Papers (1 paper)

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Review

22 pages, 9475 KB  
Review
Molecular Pathways of Cardiometabolic Residual Risk in Type 2 Diabetes: Insulin Resistance, Metaflammation, and Liver–Kidney–Vascular Crosstalk
by Antonio Maria Labate, Elena Cimino, Laura Giacomelli, Stefano Ettori, Oladayo Adigun Oladeji and Barbara Agosti
Int. J. Mol. Sci. 2026, 27(14), 6170; https://doi.org/10.3390/ijms27146170 - 10 Jul 2026
Abstract
Cardiometabolic residual risk in type 2 diabetes mellitus (T2D) persists despite major advances in glucose-lowering therapy, lipid management, blood pressure control, weight reduction, and organ-protective strategies. This residual burden should not be interpreted solely as the consequence of incomplete achievement of conventional therapeutic [...] Read more.
Cardiometabolic residual risk in type 2 diabetes mellitus (T2D) persists despite major advances in glucose-lowering therapy, lipid management, blood pressure control, weight reduction, and organ-protective strategies. This residual burden should not be interpreted solely as the consequence of incomplete achievement of conventional therapeutic targets, but rather as the clinical expression of persistent molecular activity involving multiple interconnected organs and pathways. Insulin resistance, metaflammation, oxidative stress, mitochondrial dysfunction, lipotoxicity, endothelial impairment, hepatic metabolic dysregulation, renal inflammation, fibrotic remodeling, and metabolic memory interact within a dynamic network linking adipose tissue, liver, kidney, immune cells, and vasculature. In this review, we discuss the biochemical and molecular drivers of cardiometabolic residual risk in T2D, with particular emphasis on impaired insulin receptor substrate/PI3K/Akt signaling, stress-kinase activation, NLRP3 inflammasome priming and assembly, MASLD-related lipotoxicity and fibrogenesis, podocyte and tubular injury, endothelial nitric oxide synthase uncoupling, AGE-RAGE signaling, and thrombo-inflammatory vascular injury. These pathways explain why biological vulnerability may persist even when conventional clinical parameters appear adequately controlled. We also examine the role of translational biomarkers and simple clinical indices, including TyG-derived indices, adiposity markers, hepatic steatosis and fibrosis scores, albuminuria, eGFR, and lipid-related markers, as accessible windows into active biological pathways. Finally, we review how contemporary therapeutic strategies may modulate selected components of this residual-risk network. A pathway-centered interpretation of T2D may support more precise residual-risk phenotyping and help move cardiometabolic care beyond isolated target control toward mechanism-based prevention. This review further links these mechanisms to the contemporary cardiovascular–kidney–metabolic (CKM) framework, as defined by the 2026 AHA/ACC/ADA/ASN CKM Guideline, and disaggregates the underlying molecular network into organ-specific pathway cascades that make the causal relationships between metabolic, inflammatory, hepatic, renal, and vascular injury more explicit. Full article
(This article belongs to the Special Issue Biochemical Perspectives on Diabetes)
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