Fuelling Life and Managing Surplus: Revisiting Type 2 Diabetes

Abstract

Type 2 Diabetes (T2D) is becoming an increasing global health challenge. Despite intensive efforts to understand its pathophysiology we seem still to be scratching on the surface. Starting from first principles this essay attempts to explore new ways to approach T2D. The premise is that a prolonged nutrient surplus lies at the heart of T2D. Given that homeostasis relies on steady states that require a balance between in- and efflux to maintain the milieu interieur, imbalances between energy uptake and utilisation can only be reconciled by storing unused energy. This explains the link between obesity and T2D. But putting on unlimited reserves is impractical. This is the dilemma the body faces. The natural conclusion is to reduce energy intake or increase expenditure to regain balance. The essay further explores rates of change of fluxes as the medium through which homeostatic control occurs. Steady states are maintained by resisting perturbations and in that way create corridors of control. In closing the essay advocates a pluralistic integrated approach to studying the multi-faceted phenomena that underlie T2D.