Background. The purpose of this study was to investigate renal glucose excretion as a function of blood glucose concentration and to evaluate the within-subject variability and between-subject variability in subjects with type 2 diabetes.

Methods. Twenty-two subjects with type 2 diabetes [age 58 (12) years, diabetes duration 7 (6) years, endogenous creatinine clearance 117 (38) ml min⁻¹ 1.73 m⁻²; median (inter-quartile range, IQR)] underwent two five-period hyperglycaemic glucose clamp experiments at intervals of 7–21 days. Starting from an initial blood glucose level of 12.2 mmol l⁻¹, subsequent glucose clamp levels were chosen using an algorithm based on urinary glucose concentrations measured at the end of the preceding glucose clamp period. That is, blood glucose was either stepwise decreased or increased depending on whether urinary glucose concentration was above or below 11.1 mmol l⁻¹, respectively.

Results. As expected, increasing the blood glucose from 7.8 to 13.3 mmol l⁻¹ during the glucose clamps resulted in a steep increase of urinary glucose excretion from 0.06 to 0.77 mmol min⁻¹. With decreasing blood glucose, a measurable glucosuria persisted up to a blood glucose level of 7.8 mmol l⁻¹. When defining the (pseudo)threshold for renal glucose excretion (PRT_G) as the highest blood glucose level during glucose clamps associated with a concomitant glucose concentration in urine of <2.8 mmol l⁻¹, median (IQR) PRT_G was 11.0 (1.1) mmol l⁻¹. The within-subject variability of PRT_G, i.e. the difference between two assessments, was low, 0.1 (0.0) mmol l⁻¹ while the between-subject variability of PRT_G was high, ranging from 7.7 to 12.2 mmol l⁻¹.

Conclusion. Renal glucose excretion increases in a proportional manner with increasing blood glucose. When decreasing blood glucose to euglycaemic blood glucose levels, glucosuria persists so that the classical concept of a renal threshold for glucose excretion cannot be upheld in subjects with type 2 diabetes.