Feedforward–feedback mismatch as a biocybernetic hypothesis for postprandial glycemic dysregulation in type 2 diabetes mellitus
- 1Harbin Wanyu Technology Co., Ltd.
Abstract
Type 2 diabetes mellitus (T2DM) is conventionally attributed to insulin resistance, β-cell dysfunction, abnormal hepatic glucose metabolism, dysregulated glucagon secretion, and impaired incretin signaling. Without challenging these established mechanisms, we propose a complementary biocybernetic hypothesis in which dynamic glycemic abnormalities in a subset of T2DM may additionally involve functional desensitization of a distributed metabolic-sensing network, elevated activation thresholds, weakened predictive feedforward signaling, and increased feedback delay. Potential drivers may include prolonged or repetitive stimulation, sustained metabolic exposure beyond adaptive capacity, inadequate recovery between repeated challenges, and specific nutritional, chemical, metabolic, or physical factors. In parallel, rapid ingestion, limited mastication, or altered food texture may reduce oral–cephalic sensory and mechanical input through a distinct pathway. These upstream disturbances could converge on delayed regulatory initiation, increasing reliance on gastrointestinal and post-absorptive feedback and thereby increasing susceptibility to postprandial overshoot, undershoot, and glycemic oscillation. We further propose metabolic re-sensitization as a testable recovery concept. Reducing candidate desensitizing exposures, restoring physiological stimulus–recovery rhythms, and modifying oral-processing or nutrient-delivery characteristics may lower activation thresholds, increase sensing gain, or advance response timing. The model generates falsifiable predictions: standardized input–output testing should reveal exposure-dependent changes in sensitivity, threshold, or latency, with partial recovery after withdrawal if true desensitization is present; controlled manipulation of mastication or oral processing should alter early regulatory responses if oral–cephalic signaling contributes independently. Failure to reproduce these effects would weaken the corresponding mechanism. This framework is presented as a testable systems-level hypothesis rather than a proven unified etiology of T2DM.
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BibTeX
@article{wan2026feedforwardfeedback,
title = {{Feedforward–feedback mismatch as a biocybernetic hypothesis for postprandial glycemic dysregulation in type 2 diabetes mellitus}},
author = {Yu Wan},
journal = {Frontiers in Endocrinology},
year = {2026},
month = nov,
doi = {10.3389/fendo.2026.1977720},
url = {https://www.frontiersin.org/articles/10.3389/fendo.2026.1977720/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Feedforward–feedback mismatch as a biocybernetic hypothesis for postprandial glycemic dysregulation in type 2 diabetes mellitus
AU - Yu Wan
PY - 2026
DA - 2026/11/09
JO - Frontiers in Endocrinology
DO - 10.3389/fendo.2026.1977720
UR - https://www.frontiersin.org/articles/10.3389/fendo.2026.1977720/full
AB - Type 2 diabetes mellitus (T2DM) is conventionally attributed to insulin resistance, β-cell dysfunction, abnormal hepatic glucose metabolism, dysregulated glucagon secretion, and impaired incretin signaling. Without challenging these established mechanisms, we propose a complementary biocybernetic hypothesis in which dynamic glycemic abnormalities in a subset of T2DM may additionally involve functional desensitization of a distributed metabolic-sensing network, elevated activation thresholds, weakened predictive feedforward signaling, and increased feedback delay. Potential drivers may include prolonged or repetitive stimulation, sustained metabolic exposure beyond adaptive capacity, inadequate recovery between repeated challenges, and specific nutritional, chemical, metabolic, or physical factors. In parallel, rapid ingestion, limited mastication, or altered food texture may reduce oral–cephalic sensory and mechanical input through a distinct pathway. These upstream disturbances could converge on delayed regulatory initiation, increasing reliance on gastrointestinal and post-absorptive feedback and thereby increasing susceptibility to postprandial overshoot, undershoot, and glycemic oscillation. We further propose metabolic re-sensitization as a testable recovery concept. Reducing candidate desensitizing exposures, restoring physiological stimulus–recovery rhythms, and modifying oral-processing or nutrient-delivery characteristics may lower activation thresholds, increase sensing gain, or advance response timing. The model generates falsifiable predictions: standardized input–output testing should reveal exposure-dependent changes in sensitivity, threshold, or latency, with partial recovery after withdrawal if true desensitization is present; controlled manipulation of mastication or oral processing should alter early regulatory responses if oral–cephalic signaling contributes independently. Failure to reproduce these effects would weaken the corresponding mechanism. This framework is presented as a testable systems-level hypothesis rather than a proven unified etiology of T2DM.
SN - 1664-2392
ER -