Type 2 diabetes mellitus: a silent threat to male and female infertility

Malliga Rajendran; Praveen Kumar Chandra Sekar; Ramakrishnan Veerabathiran

Malliga Rajendran Human Cytogenetics and Genomics Laboratory, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, India
Praveen Kumar Chandra Sekar Human Cytogenetics and Genomics Laboratory, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, India
Ramakrishnan Veerabathiran Human Cytogenetics and Genomics Laboratory, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute, Chettinad Academy of Research and Education, Kelambakkam, Tamil Nadu, India

Keywords: type 2 diabetes mellitus, Infertility, Reproductive dysfunction, Genetic polymorphisms

Abstract

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and hyperglycaemia, with global prevalence rising at an alarming rate. Beyond its well-established role in cardiovascular, renal, and neurological complications, T2DM exerts a significant yet often overlooked impact on reproductive health. This review synthesizes current evidence on the relationship between T2DM and infertility in both males and females, exploring epidemiological trends, molecular mechanisms, and clinical implications. T2DM contributes to infertility through endocrine dysfunction, oxidative stress, chronic inflammation, and microvascular damage, disrupting gonadal steroidogenesis, gametogenesis, and implantation. Genetic predisposition plays a critical role, with variants in genes such as PPARG, IRS1, IRS2, and SHBG influencing susceptibility and severity of reproductive impairment. Emerging data suggest that T2DM-induced reproductive dysfunction is mediated by a complex interplay of metabolic, hormonal, and genetic factors, underscoring the need for precision medicine approaches. Despite growing research, significant gaps remain, including a lack of longitudinal studies, underrepresentation of male infertility data, and limited exploration of epigenetic mechanisms. Addressing these gaps through multidisciplinary, multi-omics, and intervention-based studies could improve fertility outcomes in individuals with T2DM.