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·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·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·l⁻¹. Median VRT_G was 11.0 mmol·l⁻¹, ranging from 7.8 and 12.1 mmol·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·l⁻¹ renal glucose excretion ranged from 163 μmol·min⁻¹ to 25 μmol·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.

renal threshold for glucose excretion - urinary glucose - splay - tubular transport maximum for glucose - hyperglycaemic glucose-clamp - type 2 diabetes mellitus

References

• 1 Deetjen P, Drexel H, Aczel S. Renal handling of D-Glucose and Other Sugars. In: Massry SG, Glassock RJ, ed. Massry and Glassock's Textbook of Nephrology. Philadelphia: Lippincott Williams & Wilkins 2001: 87-90
• 2 Deetjen P, Baeyer Hv, Drexel H. Renal glucose transport. In: Seldin DW, Giebisch G, ed. The kidney: physiology and pathophysiology. New York: Raven Press 1992: 2873- 2888
• 3 Davison JM, Cheyne GA. Renal reabsorption of glucose.  Lancet. 1972;  1 787-788
• 4 Davison JM, Cheyne GA. History of the measurement of glucose in urine: a cautionary tale.  Med Hist. 1974;  18 194-197
• 5 Shannon JA, Farber S, Troast L. The measurement of glucose Tm in the normal dog.  Am J Physiol. 1941;  133 752-761
• 6 Brodehl J, Franken A, Gellissen K. Maximal tubular reabsorption of glucose in infants and children.  Acta Paediatr Scand. 1972;  61 413-420
• 7 Rohde R, Deetjen P. Glucose reabsorption in the rat kidney. Micro_puncture analysis of tubular glucose concentration during free flow.  Pflugers Arch. 1968;  302 219-232
• 8 Hierholzer K, Fromm M. Funktionen der Nieren. In: Schmidt RF, Thews G, ed. Physiologie des Menschen. Berlin: Springer 1997: 737-777
• 9 Golenhofen K. Physiologie. 1997;  386-392
• 10 Berger M, Sawicki PT. Coma diabeticum. In: Berger M, ed. Diabetes mellitus. München: Urban & Fischer 2000: 387-393
• 11 Bojunga J, Badenhoop K, Althoff PH, Usadel KH. Akute Stoffwechselentgleisungen. In: Mehnert H, Standl E, Usadel KH, Häring HU, ed. Diabetologie in Klinik und Praxis. Stuttgart: Georg Thieme 2003: 376-399
• 12 Grüneklee D. Diagnostik und Therapiekontrolle des Diabetes mellitus. In: Rosak C, ed. Angewandte Diabetologie. Bremen: UNI-MED 2005: 40-65
• 13 Krautzig S. Niere. In: Renz-Polster H, Braun J, ed. Basislehrbuch Innere Medizin. München: Urban & Fischer 2001: 840-913
• 14 Lazarus A. 3. Über alimentäre Glykosurie.  Z Ärztl Fortbild (Jena). 1904;  1 517-520
• 15 Benedict SR, Osterberg E. A method for the determination of sugar in normal urine.  J Biol Chem. 1918;  34 195-201
• 16 Brodehl J, Oemar BS, Hoyer PF. Renal glucosuria.  Pediatr Nephrol. 1987;  1 502-508
• 17 Fine J. Glucose content of normal urine.  Br Med J. 1965;  1 1209-1214
• 18 Folin O. A qualitative (reduction) test for sugar in normal human urine.  J Biol Chem. 1915;  22 327-329
• 19 Gupta RC, Goyal A, Ghosh R, Punjabi M, Singh PP. Normal range for glucose in urine: age-related changes.  Clin Chem. 1982;  28 2335
• 20 Hanusch AW, Kaiser G. A contribution to urinary glucose excretion of metabolically healthy persons.  Dtsch Gesundheitsw. 1968;  23 1888-1892
• 21 Heimsoth VH, Graffe-Achelis C, Banauch D, Vollmar J. Referenzwerte für die Glukosekonzentration im Urin von Erwachsenen.  Med Lab (Stuttg). 1978;  31 236-240
• 22 Heinemann L, Sawicki PT, Niederau CM, Starke AAR. Klinische Chemie. In: Berger M, ed. Diabetes Mellitus. München: Urban & Fischer 2000: 44-65
• 23 Jain S. Reference interval for urinary glucose in elderly subjects.  Clin Chem. 1986;  32 711-712
• 24 Jain S. Reference interval for urinary glucose: effect of age.  Clin Chem. 1986;  32 1426
• 25 Kruse-Jarres JD, Reinauer H, Witt I. Kohlenhydratstoffwechsel. In: Greiling H, Gressner AM, ed. Lehrbuch der klinischen Chemie und Pathobiochemie. Stuttgart: Schattauer 1995: 248-299
• 26 Renschler HE, Weicker H, von Baeyer H. The upper limit of glucose concentration in the urine of healthy subjects].  Dtsch Med Wochenschr. 1965;  90 2349-2353
• 27 Sindoni A. Blood sugar versus urine sugar.  J Am Med Assoc. 1939;  112 2503-2504
• 28 Thomas L. Glucose im Harn und anderen Körperflüssigkeiten. In: Thomas L, ed. Labor und Diagnose. Frankfurt/Main: TH-Books 1998: 141-142
• 29 Butterfield WJ, Keen H, Whichelow MJ. Renal glucose threshold variations with age.  Br Med J. 1967;  4 505-507
• 30 Walford S, Page MM, Allison SP. The influence of renal threshold on the interpretation of urine tests for glucose in diabetic patients.  Diabetes Care. 1980;  3 672-674
• 31 Winter KA. Relationships between blood and urinary sugar and their clinical significance. 1. Methodical studies and results.  Z Gesamte Inn Med. 1973;  28 189-194
• 32 Winter KA. Relationships between blood and urinary sugar and their clinical significance. 2. Clinical significance of marginal blood sugar value determinations.  Z Gesamte Inn Med. 1973;  28 217-222
• 33 Menzel R, Kaisaki PJ, Rjasanowski I, Heinke P, Kerner W, Menzel S. A low renal threshold for glucose in diabetic patients with a mutation in the hepatocyte nuclear factor-1α (HNF-1α) gene.  Diabet Med. 1998;  15 816-820
• 34 Ruhnau B, Faber OK, Borch-Johnsen K, Thorsteinsson B. Renal threshold for glucose in non-insulin-dependent diabetic patients.  Diabetes Res Clin Pract. 1997;  36 27-33
• 35 Mohnike G, Lisewski G, Israel HJ. The threshold point for glucose in diabetes mellitus and renal diabetes.  Z Gesamte Inn Med. 1961;  16 1073-1077
• 36 Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus . Diabetes Care. 1997;  20 1183-1197
• 37 Rule AD, Larson TS, Bergstralh EJ, Slezak JM, Jacobsen SJ, Cosio FG. Using serum creatinine to estimate glomerular filtration rate: accuracy in good health and in chronic kidney disease.  Ann Intern Med. 2004;  141 929-937
• 38 Rave K, Nosek L, Posner J, Heise T, Roggen K, van Hoogdalem E-J. Renal glucose excretion as a function of blood glucose concentration in subjects with type 2 diabetes – results of a hyperglycaemic glucose clamp study.  Nephrol Dial Transplant. 2006;  21 2166-2171
• 39 Johansen K, Svendsen PA, Lorup B. Variations in renal threshold for glucose in Type 1 (insulin-dependent) diabetes mellitus.  Diabetologia. 1984;  26 180-182
• 40 Erkelens DW, Dullaart R, Peuker N. Tubular reabsorption of glucose in quantifying the relation between blood glucose and urinary glucose excretion in diabetic patients.  Neth J Med. 1983;  26 1-9

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