Use of Continuous Glucose Monitoring with Machine Learning to Identify Metabolic Subphenotypes and Inform Precision Lifestyle Changes

Abstract: The classification of diabetes and prediabetes by static glucose thresholds obscures the pathophysiological dysglycemia heterogeneity, primarily driven by insulin resistance (IR), beta-cell dysfunction, and incretin deficiency. This review demonstrates that continuous glucose monitoring and wearable technologies enable a paradigm shift towards non-invasive, dynamic metabolic phenotyping. We show evidence that machine learning models can leverage high-resolution glucose data from at-home, CGM-enabled oral glucose tolerance tests to accurately predict gold-standard measures of muscle IR and beta-cell function. This personalized characterization extends to real-world nutrition, where an individual's unique postprandial glycemic response (PPGR) to standardized meals, such as the relative glucose spike to potatoes versus grapes, could serve as a biomarker for their metabolic subtype. Moreover, integrating wearable data reveals that habitual diet, sleep, and physical activity patterns, particularly their timing, are uniquely associated with specific metabolic dysfunctions, informing precision lifestyle interventions. The efficacy of dietary mitigators in attenuating PPGR is also shown to be phenotype-dependent. Collectively, this evidence demonstrates that CGM can deconstruct the complexity of early dysglycemia into distinct, actionable subphenotypes. This approach moves beyond simple glycemic control, paving the way for targeted nutritional, behavioral, and pharmacological strategies tailored to an individual's core metabolic defects, thereby paving the way for a new era of precision diabetes prevention.