Central Glucostat Reset: A Neurocentric Set Point Hypothesis Explaining Silent Hyperglycemia in Type 2 Diabetes Mellitus

This hypothesis proposes the existence of a central glucose-regulatory network (“Glucostat”) within the brain that maintains blood glucose around a physiological set point, analogous to thermoregulation and osmoregulation. In Type 2 Diabetes Mellitus, this central set point is hypothesized to undergo pathological upward resetting, leading the brain to perceive hyperglycemia as normal and actively defend elevated glucose levels. This framework explains clinical phenomena such as silent hyperglycemia, resistance to glucose-lowering therapies, and symptomatic hypoglycemia at near-normal glucose levels. The hypothesis integrates neuroendocrine and peripheral metabolic pathways and suggests the need for central neuro-metabolic targeting in diabetes This concept was originally developed by the author in 2014 and forms part of the broader Neuro-Endocrine-Peripheral Crosstalk framework in Type 2 Diabetes Mellitus. The foundational elements of this framework, including central neuroendocrine regulation of glucose homeostasis, have been illustrated in the author’s Neuroendocrine Crosstalk Diagram (2022) and further elaborated in the book:“An Introduction to Diabetes” (ISBN: 9789356360846)Authored by:Dr. Aditya Bikram Mishra, MD (Medicine)Senior Fellow in Diabetes (IDF)Dibya Aditya Diabetes Care, Cuttack Keywords Central glucostatGlucose set pointSilent hyperglycemiaNeuroendocrine diabetesHypothalamic glucose sensingType 2 diabetes pathophysiologyAutonomic glucose regulationHyperglycemia adaptationBrain glucose regulationNeuro-metabolic control