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C\u2010peptide serves an anti\u2010inflammatory and anti\u2010atherogenic role in type 1 diabetes mellitus (T1DM) and early T2DM. C\u2010peptide protects endothelial cells by activating AMP\u2010activated protein kinase \u03b1, thus suppressing the activity of NAD(P)H oxidase activity and reducing reactive oxygen species (ROS) generation. It also prevents apoptosis by regulating hyperglycemia\u2010induced p53 upregulation and mitochondrial adaptor p66shc overactivation, as well as reducing caspase\u20103 activity and promoting expression of B\u2010cell lymphoma\u20102. Additionally, C\u2010peptide suppresses platelet\u2010derived growth factor (PDGF)\u2010beta receptor and p44\/p42 mitogen\u2010activated protein (MAP) kinase phosphorylation to inhibit vascular smooth muscle cells (VSMC) proliferation. It also diminishes leukocyte adhesion by virtue of its capacity to abolish nuclear factor kappa B (NF\u2010kB) signaling, a major pro\u2010inflammatory cascade. Consequently, it is envisaged that supplementation of C\u2010peptide in T1DM might ameliorate or even prevent end\u2010organ damage. In marked contrast, C\u2010peptide increases monocyte recruitment and migration through phosphoinositide 3\u2010kinase (PI\u20103 kinase)\u2010mediated pathways, induces lipid accumulation via peroxisome proliferator\u2010activated receptor \u03b3 upregulation, and stimulates VSMC proliferation and CD4\n                    <jats:sup>+<\/jats:sup>\n                    lymphocyte migration through Src\u2010kinase and PI\u20103K dependent pathways. Thus, it promotes atherosclerosis and microvascular damage in late T2DM. Indeed, C\u2010peptide is now contemplated as a potential biomarker for insulin resistance in T2DM and linked to increased coronary artery disease risk. This shift in the understanding of the pathophysiology of diabetes from being a single hormone deficiency to a dual hormone disorder warrants a careful consideration of the role of C\u2010peptide as a unique molecule with promising diagnostic, prognostic, and therapeutic applications.\n                  <\/jats:p>","DOI":"10.1002\/jcp.31212","type":"journal-article","created":{"date-parts":[[2024,2,3]],"date-time":"2024-02-03T10:09:11Z","timestamp":1706954951000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["C\u2010peptide in diabetes: A player in a dual hormone disorder?"],"prefix":"10.1002","volume":"239","author":[{"given":"Ali","family":"Dakroub","sequence":"first","affiliation":[{"name":"St. Francis Hospital and Heart Center Roslyn New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Dbouk","sequence":"additional","affiliation":[{"name":"Department of Medicine, 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