Dwivedi Jyotsana, Kaushal Shubhi, Wal Pranay, Singh Deependra Pratap, Gupta Priyanka, Sowjanya Pulipati, Gasmi Amin
PSIT- Pranveer Singh Institute of Technology, Pharmacy, Kanpur, India.
Graphic Era Deemed to be University), Pharmacy, Dehradun, Uttarakhand, India.
Curr Gene Ther. 2025 Aug 29. doi: 10.2174/0115665232381943250825055516.
Hereditary forms of diabetes, including Maturity-Onset Diabetes of the Young (MODY) and Neonatal Diabetes Mellitus (NDM), are rare monogenic disorders caused by mutations in genes involved in pancreatic development, beta-cell function, and insulin secretion. Unlike the polygenic nature of type 1 and type 2 diabetes, these forms provide a unique model for precision medicine.
A comprehensive literature review was conducted to explore the molecular genetics, clinical features, diagnostic advancements, and therapeutic strategies related to MODY and NDM. Particular focus was placed on genotype-phenotype correlations and responsiveness to targeted treatments.
Distinct gene mutations such as GCK, HNF1A, and HNF4A in MODY, and KCNJ11, ABCC8, and INS in NDM are associated with specific clinical characteristics and treatment responses. Genetic testing plays a crucial role in early diagnosis and management. For instance, sulfonylurea therapy has effectively replaced insulin in some cases of NDMre with KATP channel mutations. In MODY, accurate genetic classification helps guide the use of oral hypoglycemics or dietary interventions instead of unnecessary insulin therapy.
Understanding the genetic basis of MODY and NDM has enabled clinicians to personalize treatment plans, improving disease outcomes. Genetic diagnosis not only facilitates better classification but also informs prognosis and guides family screening. Despite these advances, challenges remain in access to testing and awareness among healthcare providers.
Molecular insights into MODY and NDM have revolutionized their diagnosis and treatment. Gene-based therapeutic approaches enhance glycemic control and quality of life, marking a significant step toward precision medicine in diabetes care. Ongoing research will be key to further optimizing individualized treatment strategies.
遗传性糖尿病，包括青年发病的成年型糖尿病（MODY）和新生儿糖尿病（NDM），是由参与胰腺发育、β细胞功能和胰岛素分泌的基因突变引起的罕见单基因疾病。与1型和2型糖尿病的多基因性质不同，这些类型为精准医学提供了独特的模型。
进行了全面的文献综述，以探索与MODY和NDM相关的分子遗传学、临床特征、诊断进展和治疗策略。特别关注基因型-表型相关性以及对靶向治疗的反应性。
MODY中的GCK、HNF1A和HNF4A以及NDM中的KCNJ11、ABCC8和INS等不同基因突变与特定的临床特征和治疗反应相关。基因检测在早期诊断和管理中起着关键作用。例如，在一些KATP通道突变的NDM病例中，磺脲类药物治疗已有效取代胰岛素。在MODY中，准确的基因分类有助于指导口服降糖药的使用或饮食干预，而不是进行不必要的胰岛素治疗。
了解MODY和NDM的遗传基础使临床医生能够制定个性化的治疗方案，改善疾病预后。基因诊断不仅有助于更好地分类，还能为预后提供信息并指导家族筛查。尽管取得了这些进展，但在检测的可及性以及医疗保健提供者的认识方面仍然存在挑战。
对MODY和NDM的分子认识彻底改变了它们的诊断和治疗。基于基因的治疗方法可改善血糖控制和生活质量，标志着糖尿病护理向精准医学迈出了重要一步。持续的研究将是进一步优化个体化治疗策略的关键。
