Authors : Gaddam Gurucharan; Chinnem Rama Mohan; Cheemalamarri Venkata Naga Rugvidh; Vavilla Rupesh; Thatiparthi Subramanya Prem Rajiv Kumar

Volume/Issue : Volume 10 - 2025, Issue 9 - September

Google Scholar : https://tinyurl.com/9hbpz5e2

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DOI : https://doi.org/10.38124/ijisrt/25sep990

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Abstract : Monogenic diabetes syndromes subsumed under the rubric of maturity-onset diabetes of the young (MODY) represent a modest yet pathophysiological significant subset of all diabetes diagnoses. The prototypical subtypes of eruptions arise from alterations within the HNF1A (Hepatocyte Nuclear Factor 1-Alpha), HNF4A (Hepatocyte Nuclear Factor 4- Alpha), GCK (Glucokinase), and HNF1B (Hepatocyte Nuclear Factor 1-Beta) genes. Conversely, mutations residing within HNF1C (Hepatocyte Nuclear Factor 1-Gamma), KLF11 (Kruppel-Like Factor 11), PAX4 (Paired Box Gene 4), CEL (Carboxyl Ester Lipase), BLK (B Lymphoid Tyrosine Kinase), ABCC8 (ATP Binding Cassette Subfamily C Member 8), INS (Insulin Gene), and APPL1 (Adaptor Protein, Phosphotyrosine Interacting with PH Domain and Leucine Zipper 1) have only recently been characterized, yielding insufficient mechanistic and clinical data to permit the formulation of standardized diagnostic or management algorithms. This mosaic of clinical phenotypes can easily masquerade as either type 1 or type 2 diabetes, engendering diagnostic inaccuracies whose prevalence varies markedly between geographic and ethnic cohorts. Machine learning (ML) and deep learning (DL) methodologies are uniquely equipped to mitigate persistent obstacles within monogenic diabetes by enhancing subtype differentiation, estimating the pathogenicity of individual genetic alterations, formulating personalized therapeutic regimens, and, in parallel, revealing novel MODY-associated genes well before the intervention threshold in standard clinical practice is reached. By simultaneously processing genomic, longitudinal clinical, and biochemical datasets, multimodal ML models routinely outperform conventional algorithms in diagnostic accuracy, thereby extending the precision of early detection. Maturity-onset diabetes of the young (MODY) encompasses a narrow yet therapeutically consequential segment of the diabetes spectrum, with hereditary alterations in the transcription factors HNF1A and HNF4A, as well as the glucokinase (GCK) gene, constituting the best-characterized historical subclasses. Emerging forms, driven by mutations in HNF1C, KLF11, PAX4, CEL, BLK, ABCC8, INS, and APPL1, are currently under-characterized and proceed in the absence of established testing or therapy protocols. Widespread genetic heterogeneity, compounded by a variable clinical phenotype, predisposes affected individuals to be misclassified as case-type one or case-type two diabetes, perpetuating variable diagnostic yield and investigative accuracy across geographically and ethnically distinct cohorts. Machine learning (ML) and deep learning (DL) stand poised to revolutionize the diagnosis and treatment of monogenic diabetes, particularly in the identification of subtype variations, the assessment of pathogenicity for identified genetic variants, the formulation of individualized therapeutic regimens, and the early identification of previously uncharacterized MODY-associated genes. Recent evidence demonstrates that multimodal ML architectures, which concurrently model genetic profiles, clinical history, and biomarker data, consistently outperform conventional diagnostic protocols in terms of classification precision. Prospective lineages of inquiry will focus on the deployment of federated learning paradigms grounded in extensive global MODY registries, the systematic integration of real-time continuous glucose monitoring records, and the systematic adoption of interpretable AI methodologies to enhance clinician judgment. These converging advancements create the capacity for diabetes management that is not merely individualized but also constructively embedded in established ethical frameworks.

Keywords : MODY, Monogenic Diabetes, Machine Learning, Deep Learning, Precision Medicine, Genetic Variants, Diabetes Classification.

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