• Ana F Pina, Maria João Meneses, Inês Sousa-Lima, Roberto Henriques, João F Raposo, and Maria Paula Macedo.
• iNOVA4Health, NOVA Medical School, Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Lisbon, Portugal.
• Eur. J. Clin. Invest. 2023 Jan 1; 53 (1): e13890e13890.

BackgroundType 2 Diabetes (T2D) diagnosis is based solely on glycaemia, even though it is an endpoint of numerous dysmetabolic pathways. Type 2 Diabetes complexity is challenging in a real-world scenario; thus, dissecting T2D heterogeneity is a priority. Cluster analysis, which identifies natural clusters within multidimensional data based on similarity measures, poses a promising tool to unravel Diabetes complexity.MethodsIn this review, we scrutinize and integrate the results obtained in most of the works up to date on cluster analysis and T2D.ResultsTo correctly stratify subjects and to differentiate and individualize a preventive or therapeutic approach to Diabetes management, cluster analysis should be informed with more parameters than the traditional ones, such as etiological factors, pathophysiological mechanisms, other dysmetabolic co-morbidities, and biochemical factors, that is the millieu. Ultimately, the above-mentioned factors may impact on Diabetes and its complications. Lastly, we propose another theoretical model, which we named the Integrative Model. We differentiate three types of components: etiological factors, mechanisms and millieu. Each component encompasses several factors to be projected in separate 2D planes allowing an holistic interpretation of the individual pathology.ConclusionFully profiling the individuals, considering genomic and environmental factors, and exposure time, will allow the drive to precision medicine and prevention of complications.© 2022 The Authors. European Journal of Clinical Investigation published by John Wiley & Sons Ltd on behalf of Stichting European Society for Clinical Investigation Journal Foundation.

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