NDT Advance Access originally published online on April 20, 2006
Nephrology Dialysis Transplantation 2006 21(8):2166-2171; doi:10.1093/ndt/gfl175
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Original Articles: Clinical Nephrology
Renal glucose excretion as a function of blood glucose concentration in subjects with type 2 diabetes—results of a hyperglycaemic glucose clamp study
1 Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany and 2 Johnson & Johnson Pharmaceutical Research & Development, High Wycombe, UK
Correspondence and offprint requests to: Klaus Rave, MD, Profil Institut für Stoffwechselforschung GmbH, Hellersbergstr. 9, 41460 Neuss, Germany. Email: klaus.rave{at}profil-research.de
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 (PRTG) 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) PRTG was 11.0 (1.1) mmol l–1. The within-subject variability of PRTG, i.e. the difference between two assessments, was low, 0.1 (0.0) mmol l–1 while the between-subject variability of PRTG 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.
Keywords: hyperglycaemic glucose clamp; physiology; renal glucose excretion; type 2 diabetes mellitus; urinary glucose
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