Influence of Familial Renal Glycosuria Due to Mutations in the SLC5A2 Gene on Changes in Glucose Tolerance over Time

PLoS One. 2016 Jan 6;11(1):e0146114. doi: 10.1371/journal.pone.0146114. eCollection 2016.

Abstract

Familial renal glycosuria is an inherited disorder resulting in glucose excretion in the urine despite normal blood glucose concentrations. It is most commonly due to mutations in the SLC5A2 gene coding for the glucose transporter SGLT2 in the proximal tubule. Several drugs have been introduced as means to lower glucose in patients with type 2 diabetes targeting SGLT2 resulting in renal glycosuria, but no studies have addressed the potential effects of decreased renal glucose reabsorption and chronic glycosuria on the prevention of glucose intolerance. Here we present data on a large pedigree with renal glycosuria due to two mutations (c.300-303+2del and p.A343V) in the SLC5A2 gene. The mutations, which in vitro affected glucose transport in a cell line model, and the ensuing glycosuria were not associated with better glycemic control during a follow-up period of more than 10 years. One individual, who was compound heterozygous for mutations in the SLC5A2 gene suffered from severe urogenital candida infections and postprandial hypoglycemia. In conclusion, in this family with familial glycosuria we did not find any evidence that chronic loss of glucose in the urine would protect from deterioration of the glucose tolerance over time.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Candidiasis / complications
  • Candidiasis / diagnosis
  • Candidiasis / pathology
  • DNA, Neoplasm / chemistry
  • DNA, Neoplasm / metabolism
  • Female
  • Gene Deletion
  • Genotype
  • Glucose / metabolism*
  • Glycosuria, Renal / genetics*
  • Glycosuria, Renal / pathology
  • HEK293 Cells
  • Heterozygote
  • Humans
  • Islets of Langerhans / metabolism
  • Middle Aged
  • Molecular Sequence Data
  • Mutation, Missense
  • Pedigree
  • Sequence Alignment
  • Sequence Analysis, DNA
  • Sodium-Glucose Transporter 2 / genetics*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / metabolism
  • Stomach Neoplasms / pathology

Substances

  • DNA, Neoplasm
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Glucose

Grants and funding

This work was supported by grants to the Botnia Study from the Sigrid Juselius Foundation (http://www.sigridjuselius.fi/stiftelse), Folkhälsan Research Foundation (http://www.folkhalsan.fi/startsida/Var-verksamhet/Forskning/), Signe and Ane Gyllenberg Foundation (http://gyllenbergs.fi/en/signe-och-ane-gyllenbergs-stiftelse-en/), Swedish Cultural Foundation in Finland (http://www.kulturfonden.fi/sv/start/), Finnish Diabetes Research Foundation, Foundation for Life and Health in Finland (http://www.livochhalsa.fi/), Finnish Medical Society (http://www.duodecim.fi/web/svenska/hemsida), Paavo Nurmi Foundation, Helsinki University Central Hospital Research Foundation, Perklén Foundation, Ollqvist Foundation, Närpes Health Care Foundation, Ahokas Foundation, a FiDiPro grant (263401) and a Project Grant (267882) from the Academy of Finland (http://www.aka.fi/sv). The study has also been supported by the Municipal Heath Care Center and Hospital in Jakobstad and Health Care Centers in Vasa, Närpes and Korsholm. The research at Lund University is supported by grants to LG: Swedish Research Council (http://www.vr.se/) project grant (2010-3490) and Linnaeus Centre of Excellence grant (2006-237), as well as a European Research Council Advanced Researcher Grant (GA 269045) (http://erc.europa.eu/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.