The Vicious Cycles of Type 2 Diabetes: A Five-Loop Feedback Architecture & Systems-Based Reversal Framework

pe 2 Diabetes Mellitus (T2DM) affects 537 million adults globally with a 0.23% remission rate under standard care. This manuscript presents a paradigm shift: T2DM is not merely a glucose management disorder but a thermodynamic phase transition disorder driven by five self-reinforcing pathological loops: (1) Inflammation/NF-κB/NLRP3, (2) Oxidative Stress/Mitochondrial Dysfunction, (3) Lipotoxicity, (4) IAPP Aggregation, and (5) β-cell Dedifferentiation. We propose the "Hexa-Compound Constellation" (Berberine, Curcumin, Resveratrol, Fisetin, Momordica Charantia, and Luteolin) deployed via a three-tier protocol (Tier 1: Adjunct; Tier 2: Aggressive Reversal; Tier 3: RCT validation) to achieve functional remission (HbA1c