title: Influence of Familial Renal Glycosuria Due to Mutations in the SLC5A2 Gene on Changes in Glucose Tolerance over Time.
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.
authors.affiliation: Diabetes and Endocrinology, Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Emilia
authors.initials: E
authors.lastname: Ottosson-Laakso
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Centre, Biomedicum, Helsinki, Finland.|Research Program Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.|Finnish Institute of Molecular Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Tiinamaija
authors.initials: T
authors.lastname: Tuomi
authors.affiliation: Närpes Health Care Center, Närpes, Finland.
authors.forename: Björn
authors.initials: B
authors.lastname: Forsén
authors.affiliation: Närpes Health Care Center, Närpes, Finland.
authors.forename: Monika
authors.initials: M
authors.lastname: Gullström
authors.affiliation: Folkhälsan Institute of Genetics, Folkhälsan Research Centre, Biomedicum, Helsinki, Finland.|Research Program Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.|Abdominal Center Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.|Baker IDI Heart and Diabetes Institute, Melbourne, Australia.
authors.forename: Per-Henrik
authors.initials: PH
authors.lastname: Groop
authors.affiliation: Diabetes and Endocrinology, Department of Clinical Sciences, Lund University, Malmö, Sweden.|Finnish Institute of Molecular Medicine, University of Helsinki, Helsinki, Finland.
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.affiliation: Diabetes and Endocrinology, Department of Clinical Sciences, Lund University, Malmö, Sweden.
authors.forename: Petter
authors.initials: P
authors.lastname: Vikman
mesh_terms: D000595:Amino Acid Sequence; D002177:Candidiasis / Q000150:complications / Q000175:diagnosis / Q000473:pathology; D004273:DNA, Neoplasm / Q000737:chemistry / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D005838:Genotype; D005947:Glucose / Q000378:metabolism*; D006030:Glycosuria, Renal / Q000235:genetics* / Q000473:pathology; D057809:HEK293 Cells; D006579:Heterozygote; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010375:Pedigree; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D051297:Sodium-Glucose Transporter 2 / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology
chemical_list: D004273:DNA, Neoplasm; C089180:SLC5A2 protein, human; D051297:Sodium-Glucose Transporter 2; D005947:Glucose