The Bidirectional Relationship Between Diabetes and Cancer: Mechanistic Insights, Epigenetic Intermediaries, and Therapeutic Approaches.

IF 4.2 3区医学 Q2 Medicine

Diabetes Therapy Pub Date : 2026-10-12 DOI:10.1007/s13300-026-01926-9

Prahallad Mishra, Thyparambil Aravindakshan PramodKumar, Bhagyashree Pradhan, Utpal Ghosh, Pradyumna K Mishra, Pujarini Dash, Ranjit Mohan Anjana, Samir Kumar Patra, Viswanathan Mohan

{"title":"The Bidirectional Relationship Between Diabetes and Cancer: Mechanistic Insights, Epigenetic Intermediaries, and Therapeutic Approaches.","authors":"Prahallad Mishra, Thyparambil Aravindakshan PramodKumar, Bhagyashree Pradhan, Utpal Ghosh, Pradyumna K Mishra, Pujarini Dash, Ranjit Mohan Anjana, Samir Kumar Patra, Viswanathan Mohan","doi":"10.1007/s13300-026-01926-9","DOIUrl":null,"url":null,"abstract":"Objectives: The global rise in diabetes mellitus parallels an increasing cancer burden, highlighting an incompletely understood relationship between these two complex diseases. Accumulating epidemiological evidence indicates that diabetes is associated with an increased incidence and mortality of several site-specific cancers, whereas cancer and its treatment may contribute to dysglycemia and diabetes through diverse mechanisms. In addition, shared metabolic and environmental risk factors further contribute to the observed association between these conditions.Methodology: This narrative review comprehensively examined peer-reviewed literature retrieved from PubMed, Scopus, Web of Science, and Google Scholar, focusing on the epidemiological, mechanistic, and epigenetic links between diabetes and cancer.Results: Beyond shared lifestyle risk factors, converging molecular mechanisms-including chronic hyperglycemia, insulin resistance, low-grade inflammation, oxidative stress, and metabolic reprogramming-provide a biological framework linking diabetes and cancer. Emerging evidence suggests that epigenetic dysregulation acts as a central intermediary in this relationship by integrating metabolic stress with sustained alterations in gene expression through DNA methylation, histone modifications, non-coding RNAs, chromatin remodeling, and epigenetic aging. Diabetes-related epigenetic memory, microbiome-driven epigenetic modulation, and sex-specific epigenetic signatures may further contribute to cancer susceptibility and disease heterogeneity, although the strength of evidence varies across experimental and clinical studies.Conclusions: This review synthesizes current epidemiological, mechanistic, and epigenetic evidence linking diabetes and cancer, with particular emphasis on metabolic-epigenetic crosstalk and clinically relevant signaling pathways. It also critically evaluates the dual metabolic and oncologic effects of antidiabetic and anticancer therapies while highlighting current evidence gaps and the need for precision medicine approaches in the prevention and management of both diseases.","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":" ","pages":""},"PeriodicalIF":4.2000,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Diabetes Therapy","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13300-026-01926-9","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Objectives: The global rise in diabetes mellitus parallels an increasing cancer burden, highlighting an incompletely understood relationship between these two complex diseases. Accumulating epidemiological evidence indicates that diabetes is associated with an increased incidence and mortality of several site-specific cancers, whereas cancer and its treatment may contribute to dysglycemia and diabetes through diverse mechanisms. In addition, shared metabolic and environmental risk factors further contribute to the observed association between these conditions.

Methodology: This narrative review comprehensively examined peer-reviewed literature retrieved from PubMed, Scopus, Web of Science, and Google Scholar, focusing on the epidemiological, mechanistic, and epigenetic links between diabetes and cancer.

Results: Beyond shared lifestyle risk factors, converging molecular mechanisms-including chronic hyperglycemia, insulin resistance, low-grade inflammation, oxidative stress, and metabolic reprogramming-provide a biological framework linking diabetes and cancer. Emerging evidence suggests that epigenetic dysregulation acts as a central intermediary in this relationship by integrating metabolic stress with sustained alterations in gene expression through DNA methylation, histone modifications, non-coding RNAs, chromatin remodeling, and epigenetic aging. Diabetes-related epigenetic memory, microbiome-driven epigenetic modulation, and sex-specific epigenetic signatures may further contribute to cancer susceptibility and disease heterogeneity, although the strength of evidence varies across experimental and clinical studies.

Conclusions: This review synthesizes current epidemiological, mechanistic, and epigenetic evidence linking diabetes and cancer, with particular emphasis on metabolic-epigenetic crosstalk and clinically relevant signaling pathways. It also critically evaluates the dual metabolic and oncologic effects of antidiabetic and anticancer therapies while highlighting current evidence gaps and the need for precision medicine approaches in the prevention and management of both diseases.

查看原文本刊更多论文

糖尿病和癌症之间的双向关系：机制见解、表观遗传中介和治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Diabetes Therapy Medicine-Endocrinology, Diabetes and Metabolism

CiteScore

6.90

自引率

7.90%

发文量

130

审稿时长

6 weeks

期刊介绍： Diabetes Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all areas of diabetes. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Diabetes Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.