Validation of a Novel Method for Determining the Renal Threshold for Glucose Excretion in Untreated and Canagliflozin-treated Subjects With Type 2 Diabetes Mellitus

• Published in: The journal of clinical endocrinology and metabolism Vol. 98; no. 5; pp. E867 - E871
• Main Authors: Polidori, David, Sha, Sue, Ghosh, Atalanta, Plum-Mörschel, Leona, Heise, Tim, Rothenberg, Paul
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01.05.2013; Copyright by The Endocrine Society; Endocrine Society
• Subjects: Blood Glucose - analysis; Body Mass Index; Canagliflozin; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - physiopathology; Diabetes Mellitus, Type 2 - urine; Excretion; Female; Glomerular filtration rate; Glomerular Filtration Rate - drug effects; Glucose; Glucosides - adverse effects; Glucosides - therapeutic use; Glycosuria - etiology; Glycosuria - prevention & control; Humans; Hyperglycemia - etiology; Hyperglycemia - prevention & control; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; JCEM Online: Brief Reports; Kidney - drug effects; Kidney - metabolism; Kidney - physiopathology; Kidney Function Tests; Male; Membrane Transport Modulators - adverse effects; Membrane Transport Modulators - therapeutic use; Middle Aged; Overweight - complications; Postprandial Period; Renal function; Sodium-Glucose Transporter 2 - antagonists & inhibitors; Thiophenes - adverse effects; Thiophenes - therapeutic use
• ISSN: 0021-972X; 1945-7197; 1945-7197
• DOI: 10.1210/jc.2012-4205

Context:The stepwise hyperglycemic clamp procedure (SHCP) is the gold standard for measuring the renal threshold for glucose excretion (RTG), but its use is limited to small studies in specialized laboratories.Objective:The objective of the study was to validate a new method for determining RTG using data obtained during a mixed-meal tolerance test (MMTT) in untreated and canagliflozin-treated subjects with type 2 diabetes mellitus (T2DM).Design:This was an open-label study with 2 sequential parts.Setting:The study was performed at a single center in Germany.Patients:Twenty-eight subjects with T2DM were studied.Interventions:No treatment intervention was given in part 1. In part 2, subjects were treated with canagliflozin 100 mg/d for 8 days. In each part, subjects underwent an MMTT and a 5-step SHCP on consecutive days.Main Outcome Measures:For both methods, RTG was estimated using measured blood glucose (BG) and urinary glucose excretion (UGE); estimated glomerular filtration rates were also used to determine RTG during the MMTT. The methods were compared using the concordance correlation coefficient and geometric mean ratios.Results:In untreated and canagliflozin-treated subjects, the relationship between UGE rate and BG was well described by a threshold relationship. Good agreement was obtained between the MMTT-based and SHCP-derived RTG values. The concordance correlation coefficient (for all subjects) was 0.94; geometric mean ratios (90% confidence intervals) for RTG values (MMTT/SHCP) were 0.93 (0.89–0.96) in untreated subjects and 1.03 (0.78–1.37) in canagliflozin-treated subjects. Study procedures and treatments were generally well tolerated in untreated and canagliflozin-treated subjects.Conclusions:In both untreated and canagliflozin-treated subjects with T2DM, RTG can be accurately estimated from measured BG, UGE, and estimated glomerular filtration rates using an MMTT-based method.