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Diabetes mellitus and ovarian cancer: Intersecting pathways and clinical outcomes
Tirath Patel, Sara Kareem Ali, Yusur Jawad, Seba Hasan Haddad, Liyan Mahmoud Al Masri, Aya Rimawi, Reem Ahmed Alraeesi, Hessah Sultan Alkaabi, Muhammad Farhan, Maheen Zahid, Muhammad Ahmad, Neha Choudhary, Muhammad Hashir Nazir, Ayoola Awosika
Tirath Patel, Department of Medicine, Trinity Medical Sciences University School of Medicine, Kingstown VC0100, Saint George, Saint Vincent and the Grenadines
Sara Kareem Ali, Yusur Jawad, Seba Hasan Haddad, Liyan Mahmoud Al Masri, Aya Rimawi, Reem Ahmed Alraeesi, Hessah Sultan Alkaabi, Muhammad Farhan, Department of Medicine, Ajman University, College of Medicine, Ajman 6263, United Arab Emirates
Maheen Zahid, Muhammad Ahmad, Neha Choudhary, Department of Obstetrics and Gynecology, King Edward Medical University, Lahore 54000, Punjab, Pakistan
Muhammad Hashir Nazir, Department of Medicine, King Edward Medical University, Lahore 54000, Punjab, Pakistan
Ayoola Awosika, Department of Family Medicine, University of Illinois College of Medicine Peoria, Bloomington, IL 61601, United States
Author contributions: Patel T, Ali SK, Alraeesi RA, Choudhary N, and Awosika A were involved in conceptualization; Patel T, Ali SK, Rimawi A, Alkaabi HS, and Choudhary N contributed to article screening; Patel T, Ali SK, Jawad Y, Haddad SH, Al Masri LM, Alkaabi HS, Ahmad M, Farhan M, Awosika A, and Choudhary N wrote the first draft; Jawad Y and Ahmad M contributed to literature review, data extraction; Jawad Y, Haddad SH, and Ahmad M contributed to discussion development; Haddad SH contributed to quality assessment; Al Masri LM and Farhan M contributed to data synthesis; Al Masri LM, Rimawi A, Nazir MH, and Farhan M contributed to second draft; Rimawi A contributed to reference management; Alraeesi RA wrote and revied the introduction and discussion sections; Alkaabi HS contributed to formal analysis; Zahid M contributed to data interpretation and manuscript review; Nazir MH and Awosika A contributed to edit and final review; Awosika A was involved in supervising.
AI contribution statement: Paperpal and Grammarly were used during the preparation of this manuscript. The entirety of the main text, including the Abstract, Introduction, Materials and Methods, Results, Discussion, and Conclusion, was written by the authors. No portion of the main text was AI-generated. Paperpal and Grammarly were used solely for language polishing and grammar correction. These tools were not used for translation, data analysis, or writing assistance beyond surface-level grammatical improvements. No AI tool participated in the design of the study or in the interpretation of its results. All intellectual contributions to study design and data interpretation were made exclusively by the authors. No images in the manuscript were generated by AI.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Ayoola Awosika, MD, Department of Family Medicine, University of Illinois College of Medicine Peoria, 1 Illini Drive, Bloomington, IL 61601, United States.
ayoolaawosika@yahoo.com
Received: December 8, 2025
Revised: December 19, 2025
Accepted: March 10, 2026
Published online: May 24, 2026
Processing time: 166 Days and 5.8 Hours
Diabetes mellitus (DM), particularly type 2 diabetes and ovarian cancer (OC) intersect through a complex network of metabolic, inflammatory, and hormonal disturbances that influence tumorigenesis, disease progression, and clinical outcomes. Epidemiologic evidence consistently associates pre-existing DM with higher OC incidence and poorer survival; however, the mechanistic underpinnings remain incompletely defined and substantive knowledge gaps persist. Central to this intersection is the diabetic metabolic milieu, characterized by chronic hyperglycemia, compensatory hyperinsulinemia, and low-grade inflammation, which promotes cellular proliferation, genomic instability, and metastatic potential. Mechanistically, dysregulated insulin and insulin-like growth factor-1 signaling activates the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin axis, driving anti-apoptotic signaling, angiogenesis, and metabolic reprogramming. In parallel, diabetes-associated oxidative stress contributes to DNA damage, defective repair mechanisms, and epigenetic alterations that may accelerate malignant transformation of ovarian or fallopian tube precursor lesions. Despite these insights, critical gaps also remain regarding the influence of contemporary antidiabetic pharmacotherapies - such as metformin, receptor agonist-1 receptor agonists, and sodium-glucose cotransporter-2 inhibitors - on tumor metabolism, chemoresponsiveness, and survival outcomes. The interplay between reproductive hormonal signaling, diabetic metabolic alterations, and immune-stromal remodeling in the ovarian tumor microenvironment is similarly understudied. This review integrates epidemiologic, molecular, and clinical evidence linking DM and OC, evaluates the potential modifying effects of antidiabetic treatments, and highlights priorities for future investigation. Clarifying these intersecting pathways is essential for advancing risk stratification, informing precision therapies, and improving outcomes in this vulnerable population.
Core Tip: Epidemiologic data consistently demonstrate that women with pre-existing diabetes mellitus have higher ovarian cancer incidence and poorer survival, yet the mechanistic underpinnings remain incompletely defined, and substantive knowledge gaps persist. Some biologic linkages uncovered include hyperglycemia, compensatory hyperinsulinemia, and chronic low-grade inflammation, creating a pro-tumorigenic milieu that enhances cellular proliferation, genomic instability, and metastatic potential. And at the molecular level, dysregulated insulin and insulin-like growth factor-1 signaling amplifies phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways, fostering anti-apoptotic signaling, metabolic reprogramming, and angiogenesis.
