Hostnik Boštjan, Tonin Gašper, Janež Andrej, Klen Jasna
Division of Internal Medicine, Department of Endocrinology, Diabetes and Metabolic Diseases, University Medical Centre Ljubljana, Ljubljana, Slovenia.
Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
Endocrinol Diabetes Metab. 2025 Sep;8(5):e70099. doi: 10.1002/edm2.70099.
Erectile dysfunction (ED) is a highly prevalent complication of diabetes mellitus (DM), significantly impairing quality of life and psychosocial well-being. The prevalence of ED is estimated to be over 3.5 times higher in men with diabetes mellitus compared to those without. The aetiology of diabetic ED is multifactorial, stemming from complex diabetes mellitus-related systemic changes. The pathophysiology of diabetic ED involves interacting pathways, including endothelial dysfunction, accelerated atherosclerosis, autonomic and peripheral neuropathy, structural penile changes, hormonal imbalances, and psychological factors.
A review of the literature was conducted to examine the pathophysiological mechanisms, genetic associations, and treatment modalities related to diabetic ED. Particular attention was given to studies exploring pharmacogenetics and emerging therapeutic interventions.
Management is multimodal, including lifestyle changes, counselling, and pharmacological agents (primarily phosphodiesterase type 5 inhibitors (PDE5Is)), but treatment response varies. Genetic studies have identified associations between ED risk/severity and polymorphisms in several candidate genes, including NOS3 (G894T, T786C, VNTR), ARG1/ARG2 (influencing nitric oxide substrate availability), ACE (I/D polymorphism), AR (CAG repeat length affecting androgen sensitivity), and VEGF (promoter polymorphisms). Pharmacogenetic studies suggest that polymorphisms in NOS3, AR, and VEGF may predict response to PDE5Is or testosterone therapy, while ARG1/ARG2 variations might guide future arginase-targeted therapies. Emerging treatments like low-intensity shockwave therapy, platelet-rich plasma, gene therapy, and stem cell therapy show promise but require more robust evidence.
Diabetic ED is a complex condition driven by multiple pathophysiological mechanisms often influenced by an underlying genetic predisposition. Understanding the interplay between pathophysiology and genetics is crucial for developing personalised treatment strategies. While current therapies offer benefits, variability in response highlights the need for tailored approaches. Further research, especially large-scale pharmacogenetic studies and randomised controlled trials for emerging therapies, is essential to identify reliable biomarkers, optimise treatment selection, and improve outcomes for men with diabetic ED.
勃起功能障碍（ED）是糖尿病（DM）的一种高度常见并发症，严重损害生活质量和心理社会幸福感。据估计，糖尿病男性中ED的患病率比非糖尿病男性高3.5倍以上。糖尿病性ED的病因是多因素的，源于与糖尿病相关的复杂全身变化。糖尿病性ED的病理生理学涉及相互作用的途径，包括内皮功能障碍、动脉粥样硬化加速、自主神经和周围神经病变、阴茎结构改变、激素失衡以及心理因素。
对文献进行综述，以研究与糖尿病性ED相关的病理生理机制、基因关联和治疗方式。特别关注探索药物遗传学和新兴治疗干预措施的研究。
治疗是多模式的，包括生活方式改变、咨询和药物治疗（主要是5型磷酸二酯酶抑制剂（PDE5Is）），但治疗反应各不相同。基因研究已经确定了ED风险/严重程度与几个候选基因多态性之间的关联，包括NOS3（G894T、T786C、VNTR）、ARG1/ARG2（影响一氧化氮底物可用性）、ACE（I/D多态性）、AR（CAG重复长度影响雄激素敏感性）和VEGF（启动子多态性）。药物遗传学研究表明，NOS3、AR和VEGF的多态性可能预测对PDE5Is或睾酮治疗的反应，而ARG1/ARG2的变异可能指导未来以精氨酸酶为靶点的治疗。低强度冲击波治疗、富血小板血浆、基因治疗和干细胞治疗等新兴治疗方法显示出前景，但需要更有力的证据。
糖尿病性ED是一种复杂的病症，由多种病理生理机制驱动，常受潜在遗传易感性影响。了解病理生理学和遗传学之间的相互作用对于制定个性化治疗策略至关重要。虽然目前的治疗方法有好处，但反应的变异性突出了采用量身定制方法的必要性。进一步的研究，特别是大规模药物遗传学研究和针对新兴疗法的随机对照试验，对于确定可靠的生物标志物、优化治疗选择以及改善糖尿病性ED男性的治疗结果至关重要。
