Abstract

Type 2 diabetes (T2D) is a multifaceted disease associated with several factors, including diet, genetics, exercise, sleep and gut microbiome. Current diagnostic and monitoring methods based on episodic assays like glycated hemoglobin (HbA1c) fail to capture its full complexity. Here, in a prospective cohort of 1,137 participants in the United States, we analyzed multimodal data from 347 deeply phenotyped individuals (174 normoglycemic, 79 prediabetic and 94 T2D). We found significant differences in the distribution of glucose spike metrics among different diabetes states, with longer expected time for spike resolution and higher values of nocturnal hypoglycemia in T2D. We identified significant correlations between mean glucose level and gut microbiome diversity, and between expected time for spike resolution and resting heart rate. Our multimodal glycemic risk profiles, validated in 1,955 normoglycemic and 114 prediabetic individuals from an independent cohort, improved risk stratification by highlighting substantial variability among individuals with the same value of HbA1c. Such a multimodal approach provides a detailed phenotype that can potentially improve T2D prevention, diagnosis and treatment, and is more informative than HbA1c.

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