Determination of the Renal Threshold for Glucose Excretion in Familial Renal Glucosuria

Abstract

Background/Aims: Familial Renal Glucosuria (FRG) is characterized by the presence of persistent isolated glucosuria in the absence of hyperglycemia. Mutations in SLC5A2, the gene coding for the sodium-glucose co-transporter 2 (SGLT2), are responsible for FRG. Phenotype/genotype correlations in FRG have mostly relied on the quantification of Urinary Glucose Excretion (UGE), which is dependent on both the filtered glucose load and the renal glucose reabsorptive capacity. In the current work, the renal threshold for glucose excretion (RT_G) was determined in an FRG cohort, with the purpose of characterizing the impact of SGLT2 mutations on renal glucose transport. Methods: From January to December of 2013, eight FRG individuals with identified SLC5A2 mutations were enrolled. Patients were given a Mixed-Meal Tolerance Test during which blood glucose and UGE were measured over a 4 h period and the data was used to calculate RT_G, according to a recently validated protocol. Results: In patients with homozygous mutations, RT_G values were very low, with a mean (SD) of 0.95 (1.17) mmol/l, compared to commonly reported values of approximately 10-11.1 mmol/l in healthy subjects. In subjects with heterozygous mutations, mean (SD) RT_G values were 4.91 (1.23) mmol/l, which are approximately one-half of the values in subjects without mutations. Conclusions: In FRG, mutations in SLC5A2 lead to reductions in RT_G and increases in UGE. Because determination of RT_G is not influenced by the filtered glucose load, the calculated RT_G values provide a more refined measure of the impact of mutations on renal glucose transport than can be obtained from UGE alone.

Six Exonic Variants in the SLC5A2 Gene Cause Exon Skipping in a Minigene Assay

“…Familial renal glucosuria (FRG) is a rare renal tubular disease, which is characterized by persistent glucosuria without aberrant glucose metabolism and any other symptoms of tubular malfunction (Calado et al, 2008;Aires et al, 2015;Wang et al, 2019). The vast majority of FRG patients are associated with SLC5A2 (OMIM 182381) pathogenic variants (Calado et al, 2008;Sada et al, 2019;Wang et al, 2019).…”

Morning Spot Urine Glucose-to-Creatinine Ratios Predict Overnight Urinary Glucose Excretion in Patients With Type 2 Diabetes

“…Elevated urine glucose concentration therefore indicates either the presence of hyperglycemia or a defect in tubular function [1]. Diagnosing diabetes or monitoring glycemic control by assessing the amount of urinary glucose has been replaced by more reliable and accurate blood or plasma glycemic indices.…”

The Relationship between Increases in Morning Spot Urinary Glucose Excretion and Decreases in HbA1C in Patients with Type 2 Diabetes After Taking an SGLT2 Inhibitor: A Retrospective, Longitudinal Study

“…The renal threshold for glucose excretion (RT G ) is the serum glucose concentration at which tubular reabsorption of glucose begins to saturate and glucose first appears in the urine [1]. The cutoff values of RT G are dependent on sodium glucose co-transporter 2 (SGLT2), which is the protein responsible for the majority of filtered glucose reabsorption from the proximal renal tubules.…”