Renal Glucose Excretion and Tubular Reabsorption Rate Related to Blood Glucose in Subjects with Type 2 Diabetes with a Critical Reappraisal of the “Renal Glucose Threshold” Model

Abstract

Until today a "renal threshold for glucose" is described in most medical textbooks. Notwithstanding, low glucose levels are detectable in urine even under euglycaemic conditions - a phenomenon which was observed already in 1904 and labelled as "basal glucosuria". We aimed to characterise renal glucose transport during various steady-state blood glucose levels. Twenty-two subjects with type 2 diabetes and normal renal function underwent two 5-period hyperglycaemic glucose-clamps with blood glucose target levels between 7.8 and 13.3 mmol x l(-1). A virtual renal threshold for glucose excretion (VRT (G)) was calculated for every subject as the highest blood glucose concentration during the glucose-clamps associated with a concomitant urinary glucose level of <2.8 mmol x l(-1). VRT (G) of subjects was classified as low, medium, and high. Each urine sample contained a detectable amount of glucose with a minimal urinary glucose concentration of 0.73 mmol x l(-1). Median VRT (G) was 11.0 mmol x l(-1), ranging from 7.8 and 12.1 mmol x l(-1). With increasing blood glucose renal glucose excretion increased in each subject - but varied considerably between subjects. For example, at a blood glucose concentration of 11 mmol x l(-1) renal glucose excretion ranged from 163 micromol x min(-1) to 25 micromol x min(-1) in subjects exhibiting a low to high VRT (G), thus showing a variability >factor 6. This study reinforces the rejection of the concept of a renal threshold for glucose. Instead, this study shows a substantial variability of renal glucose excretion between subjects with type 2 diabetes.