PMID- 23585665 OWN - NLM STAT- MEDLINE DCOM- 20130705 LR - 20220310 IS - 1945-7197 (Electronic) IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 98 IP - 5 DP - 2013 May TI - Validation of a novel method for determining the renal threshold for glucose excretion in untreated and canagliflozin-treated subjects with type 2 diabetes mellitus. PG - E867-71 LID - 10.1210/jc.2012-4205 [doi] AB - CONTEXT: The stepwise hyperglycemic clamp procedure (SHCP) is the gold standard for measuring the renal threshold for glucose excretion (RT(G)), 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 RT(G) 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, RT(G) was estimated using measured blood glucose (BG) and urinary glucose excretion (UGE); estimated glomerular filtration rates were also used to determine RT(G) 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 RT(G) values. The concordance correlation coefficient (for all subjects) was 0.94; geometric mean ratios (90% confidence intervals) for RT(G) 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, RT(G) can be accurately estimated from measured BG, UGE, and estimated glomerular filtration rates using an MMTT-based method. FAU - Polidori, David AU - Polidori D AD - Janssen Research & Development, LLC, 3210 Merryfield Row, San Diego, CA 92121, USA. DPolido1@its.jnj.com FAU - Sha, Sue AU - Sha S FAU - Ghosh, Atalanta AU - Ghosh A FAU - Plum-Morschel, Leona AU - Plum-Morschel L FAU - Heise, Tim AU - Heise T FAU - Rothenberg, Paul AU - Rothenberg P LA - eng SI - ClinicalTrials.gov/NCT01273558 PT - Controlled Clinical Trial PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Validation Study DEP - 20130412 PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Blood Glucose) RN - 0 (Glucosides) RN - 0 (Hypoglycemic Agents) RN - 0 (Membrane Transport Modulators) RN - 0 (Sodium-Glucose Transporter 2 Inhibitors) RN - 0 (Thiophenes) RN - 0SAC974Z85 (Canagliflozin) SB - IM MH - Blood Glucose/analysis MH - Body Mass Index MH - Canagliflozin MH - Diabetes Mellitus, Type 2/*drug therapy/metabolism/physiopathology/urine MH - Female MH - Glomerular Filtration Rate/drug effects MH - Glucosides/adverse effects/*therapeutic use MH - Glycosuria/etiology/*prevention & control MH - Humans MH - Hyperglycemia/etiology/prevention & control MH - Hypoglycemic Agents/adverse effects/*therapeutic use MH - Kidney/*drug effects/metabolism/physiopathology MH - Kidney Function Tests MH - Male MH - Membrane Transport Modulators/adverse effects/*therapeutic use MH - Middle Aged MH - Overweight/complications MH - Postprandial Period MH - *Sodium-Glucose Transporter 2 Inhibitors MH - Thiophenes/adverse effects/*therapeutic use PMC - PMC3706739 EDAT- 2013/04/16 06:00 MHDA- 2013/07/06 06:00 PMCR- 2013/04/12 CRDT- 2013/04/16 06:00 PHST- 2013/04/16 06:00 [entrez] PHST- 2013/04/16 06:00 [pubmed] PHST- 2013/07/06 06:00 [medline] PHST- 2013/04/12 00:00 [pmc-release] AID - jc.2012-4205 [pii] AID - 12-4205 [pii] AID - 10.1210/jc.2012-4205 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 2013 May;98(5):E867-71. doi: 10.1210/jc.2012-4205. Epub 2013 Apr 12.