Building on large population-based cohorts, high-throughput molecular analyses, and novel analytical methodologies, the project has generated fundamental insights into human glycaemic variability, its molecular determinants, and its interactions with diet. These achievements lay the scientific and operational foundation for personalised dietary strategies that account for inter-individual metabolic heterogeneity.
A major accomplishment in this period has been the identification and validation of patterns of glycaemic fluctuations derived from CGM data. Through state-of-the-art analytical approaches, including generative AI models and functional data analysis, we identified glucotypes and show their longitudinal association with long-term glycaemic outcomes such as HbA1c and progression towards type 2 diabetes.
The project has also advanced the understanding of diet–glucose interactions, applying multivariable and functional regression models to link dietary patterns, macronutrient profiles, meal timing, and individual characteristics with glycaemic responses and longer-term outcomes. Analyses show that high glycaemic-load meals, starch-rich or dairy-rich meal compositions, age, BMI, and metabolic status substantially modulate postprandial glucose curves. CGM-derived indicators—such as time above range (TAR ≥130 mg/dL)—were independently predictive of diabetes risk over 10 years, demonstrating their value for early clinical identification and targeted prevention strategies. Collective findings from several high-impact publications confirm that glucotypes capture physiologically meaningful heterogeneity in dietary responses, providing a robust empirical basis for personalised nutritional advice.
Complementing these advancements, the consortium has made significant progress in molecular glycomics and glycoproteomics, a core innovation of GLUCOTYPES. High-throughput N-glycome profiling of 434 serum samples yielded 39 quantifiable glycan peaks, while a newly established plasma glycoproteomics workflow enabled the identification and validation of over 1,000 N-glycopeptides across 54 proteins. This workflow provides high analytical robustness, precise quantification of glycoforms, and scalable processing suitable for large cohorts. In parallel, pilot studies optimized glycomics methodologies for adipose and muscle tissue biopsies, detecting more than 100 glycans per tissue type and revealing biologically relevant differences between adipocytes and mixed-cell tissues. These efforts position GLUCOTYPES to integrate glycan signatures with CGM-derived glucotypes, enabling entirely new avenues for molecular phenotyping, disease risk assessment, and diet-induced glycosylation dynamics.
Operationally, substantial progress has been made in preparing the GAIN precision nutrition trial, which will be the first clinical evaluation of glucotype-based dietary recommendations. The protocol is nearing completion for ethics submission, with detailed work on glucotype assignment, dietary algorithms, and clinical research workflows. This future trial will translate observational findings into interventional evidence, marking a critical step toward clinical implementation.
