Vol. 33 No. 3 (2026): In Progress

  • Open Access

    Article

    Article ID: 4390

    Not loss of stability but steady-state shift: A systems biology explanation for elevated fasting blood glucose in type 2 diabetes

    by Guanyu Wang

    Advances in Differential Equations and Control Processes, Vol.33, No.3, 2026;

    DOI: https://doi.org/10.59400/adecp4390

    Elevated fasting blood glucose is a hallmark clinical feature of prediabetes and type 2 diabetes, reflecting underlying pathological alterations in the body’s glucose-insulin regulatory system. This study employs a validated mathematical model of the glucose-insulin negative feedback loop to investigate the fundamental mechanisms of this elevation from a systems biology perspective. We specifically analyzed whether hyperglycemia arises from decreased system stability or an upward shift in the steady-state set-point. Our findings demonstrate that the intrinsic stability of the glucose-insulin regulatory system remains largely unchanged from healthy states through early-stage diabetes. Contrary to the hypothesis of stability decay, the essence of elevated fasting glucose is an upward shift of the steady-state level driven primarily by hepatic insulin resistance, which increases basal hepatic glucose output. While system stability is preserved during early progression, the dynamic coupling between glucose and insulin weakens; low-frequency oscillations inherent to the healthy system gradually diminish and eventually disappear as insulin resistance intensifies, signaling a decoupling of dynamics before stability loss. Significant weakening of system stability, characterized by a markedly reduced convergence rate following perturbation, occurs only in late-stage diabetes accompanied by severe pancreatic damage and compromised insulin secretory capacity. These results redefine the pathophysiological understanding of fasting hyperglycemia, suggesting that early therapeutic strategies should target recalibrating the glucose set point and hepatic sensitivity rather than bolstering system stability. This research provides valuable theoretical insights into the pathogenesis of diabetes and highlights potential dynamic biomarkers for monitoring disease progression.

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