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Molecular Aspects of Diabetes and Its Complications

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Department of Endocrinology and Metabolism, Perugia University Hospital Santa Maria Misericordia, Ospedale di Perugia, 06081 Perugia, Italy
Interests: obesity; insulin resistance; adipose tissue; diabetes mellitus, peripheral artery disease; diabetic foot
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Special Issue Information

Dear Colleagues,

The management of diabetes remains a major global health challenge. Despite advances in treatment, diabetes accounts for approximately 6% of total global mortality, with many of these deaths attributable to cardiovascular disease. In addition, diabetes is the leading cause of kidney failure and blindness, as well as a significant cause of non-traumatic lower limb amputations. In recent years, significant progress has been made in understanding the molecular mechanisms underlying both the disruption of glucose homeostasis and the pathophysiology of diabetes-associated complications.

This Special Issue of IJMS invites original research articles and comprehensive reviews that provide insight into type 2 diabetes and its complications. Topics of interest include, but are not limited to, the molecular and preclinical aspects of macrovascular complications—such as atherosclerosis, cardiovascular disease, and peripheral and foot artery disease—as well as microvascular complications including diabetic nephropathy, neuropathy, and retinopathy. Finally, we also aim to highlight the current and emerging therapeutic strategies designed to prevent or mitigate these complications.

We look forward to your valuable contributions.

Dr. Giuseppe Murdolo
Guest Editor

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Keywords

  • obesity
  • insulin resistance
  • type 2 diabetes
  • atherosclerosis
  • endothelial dysfunction
  • cardiovascular disease
  • peripheral artery disease
  • diabetic feet
  • diabetic micoangiopathy
  • diabetic neuropathy
  • regenerative medicine

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Published Papers (1 paper)

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Research

15 pages, 1667 KB  
Article
Iatrogenic Hypoglycemia in Type 2 Diabetes Affects Endothelial Proteins Involved in Cardiovascular Dysfunction
by Edwina Brennan, Abu Saleh Md Moin, Thozhukat Sathyapalan, Laura Dempsey, Stephen L. Atkin and Alexandra E. Butler
Int. J. Mol. Sci. 2026, 27(2), 822; https://doi.org/10.3390/ijms27020822 - 14 Jan 2026
Viewed by 404
Abstract
Hypoglycemia is associated with cardiovascular events reflected by platelet abnormalities. We hypothesized that sequential endothelial changes may occur during hypoglycemia that may enhance cardiovascular risk. In type 2 diabetes (T2D) (n = 23) and controls (n = 23), blood SOMAscan proteomic [...] Read more.
Hypoglycemia is associated with cardiovascular events reflected by platelet abnormalities. We hypothesized that sequential endothelial changes may occur during hypoglycemia that may enhance cardiovascular risk. In type 2 diabetes (T2D) (n = 23) and controls (n = 23), blood SOMAscan proteomic analysis of endothelial proteins at baseline, insulin-induced hypoglycemia and post hypoglycemia to 24 h were examined using repeated-measures linear mixed modeling with a prospective parallel study design. Most endothelial proteins that changed over time did not differ between groups. Baseline levels of P-selectin, plasminogen activator inhibitor-1 (PAI-1; serpine-1), E-selectin and angiopoietin-1 (ANGPT1) were significantly higher, whilst cadherin-5 was lower in T2D. Several proteins exhibited changes versus baseline in both T2D and controls. Under hypoglycemia, decreases in cadherin-5 and soluble angiopoietin-1 receptor (sTie-2) were observed, with increased P-selectin, intercellular adhesion molecule-3 (ICAM3), ANGPT1 and PAI-1. Post hypoglycemia, decreased cadherin-5 and ICAM5 were observed at 2 h and PAI-1 at 4 h, as well as increases in P-selectin at 30 min, 1 h and 24 h and ICAM3 at 24 h. Post hypoglycemia, E-selectin, P-selectin and ICAM3 were significantly lower in T2D patients at 2 h, while PAI-1 was significantly lower at 4 h and ICAM3 was significantly lower at 24 h. Baseline endothelial proteins differed between T2D and controls, which may suggest local endothelial inflammatory activation leading to a pro-thrombotic, destabilized vascular phenotype characteristic of diabetic vasculopathy. Hypoglycemia may exacerbate this towards a pro-adhesive and pro-thrombotic phenotype, worsening endothelial dysfunction. Full article
(This article belongs to the Special Issue Molecular Aspects of Diabetes and Its Complications)
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