A NEW meta-analysis suggests that diabetes significantly increases the risk of male infertility, with inflammatory pathways emerging as key mechanistic drivers, particularly in Type 2 disease.
Male Infertility Burden Rises with Diabetes
The global prevalence of diabetes mellitus continues to increase, bringing with it a growing burden of long-term complications beyond cardiovascular and metabolic disease. Male infertility is increasingly recognised among these complications, yet the underlying biological mechanisms have remained unclear. In a recent systematic review and meta-analysis, researchers assessed decades of published evidence to clarify the relationship between diabetes and male reproductive dysfunction. Drawing on studies published between 1972 and 2022, the analysis highlights a consistent association between diabetes and impaired male fertility outcomes, reinforcing concerns that chronic metabolic disease may compromise reproductive health. The findings underscore the importance of considering fertility as part of the broader spectrum of diabetes-related complications, particularly in younger men and those of reproductive age.
Male Infertility Risk Differs by Diabetes Type
Using PRISMA-guided methodology, the investigators screened more than 350 studies and included 17 observational studies examining male infertility in Type 1 diabetes (T1D) and Type 2 diabetes (T2D). Meta-analysis of pooled data showed a significant increase in infertility risk among men with diabetes, with subgroup analyses revealing a stronger association for T2D than for T1D. Despite relatively low between-study heterogeneity, the effect estimates were consistent across populations. These findings suggest that insulin resistance, metabolic dysregulation, and longer disease duration in T2D may exert greater detrimental effects on spermatogenesis, semen parameters, or reproductive hormone regulation.
Male Infertility Driven by Inflammatory Pathways
To explore potential mechanisms, the authors also analysed inflammation-focused studies and transcriptomic data. Elevated inflammatory biomarkers, including tumour necrosis factor-alpha (TNF-α), were frequently implicated in diabetes-associated male infertility. Gene expression analyses revealed enrichment of inflammatory signalling pathways alongside altered expression of genes critical for fertility and testicular function. Together, these data support inflammation as a central biological link between diabetes and impaired male reproductive health, providing a plausible mechanistic framework that aligns with broader evidence of chronic low-grade inflammation in diabetes.
This meta-analysis strengthens evidence that diabetes adversely affects male fertility through inflammatory mechanisms, with T2D posing a particularly high risk. Further research is needed to determine whether targeted anti-inflammatory or metabolic interventions could help prevent or mitigate infertility in men with diabetes.
Reference
Hao Y et al. Inflammation-mediated effects of diabetes mellitus on male fertility: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2025;16:1600565.
