Establishing the role of ZBTB20 mutations in GnRH deficiency and impaired neurogenesis in the subventricular zone: a human cohort and animal model study.

Type 2 diabetes mellitus is characterized not only by chronic hyperglycemia but also by substantial heterogeneity in the way individuals respond to food. Even when consuming similar meals, people with comparable glycated hemoglobin levels may exhibit significantly different postprandial glucose excursions, recovery trajectories, and patterns of glycemic variability, generating distinct glycemic phenotypes [,,]. These differences reflect complex interactions between dietary composition and the underlying metabolic characteristics of the individual, including insulin sensitivity, beta-cell function, hepatic glucose regulation, body composition, physical activity, sleep, and circadian biology [,]. Understanding the biological basis of this heterogeneity has become increasingly important as nutritional management shifts from standardized dietary recommendations toward more individualized approaches. Historically, long-term glycemic control has been evaluated primarily using glycated hemoglobin (HbA1c), a robust marker of average glucose exposure over approximately three months [,]. Although HbA1c remains indispensable for diagnosis, risk stratification, and treatment monitoring, it provides limited insight into the dynamic physiological responses that occur throughout the day []. Individuals with similar HbA1c values may experience substantially different postprandial glucose excursions, glycemic variability, and periods of hyperglycemia or hypoglycemia, all of which contribute to metabolic stress and may influence clinical outcomes. Continuous glucose monitoring has transformed the assessment of glycemic control by providing high-resolution measurements of glucose fluctuations under free-living conditions, thereby revealing dimensions of glucose regulation that are not captured by HbA1c alone [,]. Foundational studies of individualized glycemic responses first highlighted an important biological question: why do individuals consuming similar foods often exhibit markedly different glycemic responses? [,] Evidence accumulated over the past decade suggests that postprandial glucose excursions cannot be explained by dietary carbohydrate content alone [,]. Rather, they emerge from interactions between macronutrient composition, meal structure, gastrointestinal physiology, hormonal regulation, insulin action, tissue-specific glucose uptake and disposal, and individual metabolic characteristics [,,]. Although these foundational studies established substantial interindividual variability in glycemic responses, they did not directly validate physiology-based CGM phenotype classifications in adults with type 2 diabetes. These interacting processes produce distinct glycemic phenotypes that become observable through continuous glucose monitoring, yet the physiological interpretation of these phenotypes remains incompletely defined [,].