Tracer-determined glucose fluxes in health and type 2 diabetes: basal conditions

The role of increases in basal glucose production (EGP) in the pathogenesis of hyperglycaemia in type 2 diabetes (DM2) has been controversial. It is proposed here that the differences arose from: (i) different patient populations at different stages in the evolution of the disease, (ii) a non-steady state due to diurnal variations in EGP, and measurements at different times of day, and (iii) differences in experimental techniques: tracers, priming strategies and methods of calculation. Methodologically we show that (i) non-steady-state methods and (ii) a one-compartment model with volume of distribution estimated from tracer data are necessary in DM2. Studies with sufficient data demonstrated diurnal variations in EGP, with the highest rates in the morning, normalizing by late afternoon. Metabolic clearance rate of glucose (MCR) remained constant. Long-standing DM2 demonstrated increases in glycaemia and relative decreases in morning EGP, probably feedback-induced. A falling MCR, partly secondary to glucotoxicity, likely induced the rise in baseline hyperglycaemia.